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Sample records for faecalis endocarditis linezolid

  1. Enterococcus faecalis infective endocarditis

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    Dahl, Anders; Bruun, Niels Eske

    2013-01-01

    Enterococcus faecalis infective endocarditis (IE) is a disease of increasing importance, with more patients infected, increasing frequency of health-care associated infections and increasing incidence of antimicrobial resistances. The typical clinical presentation is a subacute course with fever...... or ceftriaxone. E. faecalis infective endocarditis continues to be a very serious disease with considerable percentages of high-level gentamicin resistant strains and in-hospital mortality around 20%. Strategies to prevent E. faecalis IE, improve diagnostics, optimize treatment and reduce morbidity...

  2. A severe infective endocarditis successfully treated with linezolid

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    Graziano Antonio Minafra

    2010-03-01

    Full Text Available Despite significant improvements in surgical and medical therapy, prosthetic valve endocarditis (PVE is a diagnostic and therapeutic challenge and is often associated with a severe prognosis. We report a case of a 59-year-old woman, with  PVE and bacterial endocarditis (Streptococcus bovis successfully treated with linezolid. Linezolid is a bacteriostatic oxazolidinone antibiotic that has been proven to be effective for the treatment of patients with pneumonia, skin and soft tissue infections, and infections due to Gram-positive cocci. Linezolid is not yet recognised as a standard therapy for infective endocarditis, but its use becomes a necessity when infection is due to multidrug-resistant microorganisms.

  3. Enterococcus faecalis infective endocarditis

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    Dahl, Anders; Rasmussen, Rasmus V; Bundgaard, Henning

    2013-01-01

    Because of the nephrotoxic effects of aminoglycosides, the Danish guidelines on infective endocarditis were changed in January 2007, reducing gentamicin treatment in enterococcal infective endocarditis from 4 to 6 weeks to only 2 weeks. In this pilot study, we compare outcomes in patients...... with Enterococcus faecalis infective endocarditis treated in the years before and after endorsement of these new recommendations....

  4. Virulence Factors Associated with Enterococcus Faecalis Infective Endocarditis

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    Madsen, Kristian T; Skov, Marianne N; Gill, Sabine

    2017-01-01

    INTRODUCTION: The enterococci are accountable for up to 20% of all cases of infective endocarditis, with Enterococcus faecalis being the primary causative isolate. Infective endocarditis is a life-threatening infection of the endocardium that results in the formation of vegetations. Based...... on a literature review, this paper provides an overview of the virulence factors associated with E. faecalis infective endocarditis. Furthermore, it reports the effects of active or passive immunization against some of these involved factors. INDIVIDUAL VIRULENCE FACTORS: Nine virulence factors have in particular...... been associated with E. faecalis infective endocarditis. Absence of these factors entailed attenuation of strains in both mixed- and mono-bacterial infection endocarditis models as well as in in vitro and ex vivo assays when compared to their virulence factor expressing parental strains. PATHOGENESIS...

  5. Whole transcriptome analysis reveals potential novel mechanisms of low-level linezolid resistance in Enterococcus faecalis.

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    Hua, Ruoyi; Xia, Yun; Wu, Wenyao; Yan, Jia; Yang, Mi

    2018-03-20

    Linezolid is an oxazolidinone antibiotic commonly used to treat serious infections caused by vancomycin-resistant enterococcus. Recently, low-level linezolid resistant Enterococcus faecalis strains have emerged worldwide, but the resistant mechanisms remain undefined. Whole-transcriptome profiling was performed on an E. faecalis strain P10748 with low-level linezolid resistance in comparison with a linezolid-susceptible strain 3138 and the standard control strain ATCC29212. The functions of differentially expressed genes (DEGs) were predicted, with some DEGs potentially involved in drug resistance were validated by PCR and quantitative PCR (qPCR). RNA-Seq on three E. faecalis strains generated 1920 unigenes, with 98% of them assigned to various function groups. A total of 150 DEGs were identified in the linezolid resistant strain P10748 compared to the linezolid susceptible strains 3138 and ATCC29212. Functional analysis indicated a significant transcriptomic shift to membrane transportation and biofilm formation in strain P10748, with three significantly up-regulated DEGs predicted to be associated with drug resistance through active efflux pumps and biofilm formation. The existence of these three DEGs was further confirmed by PCR and qPCR. The significant upregulation of genes associated with efflux pumps and biofilm formation in the linezolid resistant strain suggests their roles in low-level resistance to linezolid in E. faecalis. Copyright © 2018. Published by Elsevier B.V.

  6. Activity of Daptomycin or Linezolid in Combination with Rifampin or Gentamicin against Biofilm-Forming Enterococcus faecalis or E. faecium in an In Vitro Pharmacodynamic Model Using Simulated Endocardial Vegetations and an In Vivo Survival Assay Using Galleria mellonella Larvae

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    Luther, Megan K.; Arvanitis, Marios; Mylonakis, Eleftherios

    2014-01-01

    Enterococci are the third most frequent cause of infective endocarditis. A high-inoculum stationary-phase in vitro pharmacodynamic model with simulated endocardial vegetations was used to simulate the human pharmacokinetics of daptomycin at 6 or 10 mg/kg of body weight/day or linezolid at 600 mg every 12 h (q12h), alone or in combination with gentamicin at 1.3 mg/kg q12h or rifampin at 300 mg q8h or 900 mg q24h. Biofilm-forming, vancomycin-susceptible Enterococcus faecalis and vancomycin-resistant Enterococcus faecium (vancomycin-resistant enterococcus [VRE]) strains were tested. At 24, 48, and 72 h, all daptomycin-containing regimens demonstrated significantly more activity (decline in CFU/g) than any linezolid-containing regimen against biofilm-forming E. faecalis. The addition of gentamicin to daptomycin (at 6 or 10 mg/kg) in the first 24 h significantly improved bactericidal activity. In contrast, the addition of rifampin delayed the bactericidal activity of daptomycin against E. faecalis, and the addition of rifampin antagonized the activities of all regimens against VRE at 24 h. Also, against VRE, the addition of gentamicin to linezolid at 72 h improved activity and was bactericidal. Rifampin significantly antagonized the activity of linezolid against VRE at 72 h. In in vivo Galleria mellonella survival assays, linezolid and daptomycin improved survival. Daptomycin at 10 mg/kg improved survival significantly over that with linezolid against E. faecalis. The addition of gentamicin improved the efficacy of daptomycin against E. faecalis and those of linezolid and daptomycin against VRE. We conclude that in enterococcal infection models, daptomycin has more activity than linezolid alone. Against biofilm-forming E. faecalis, the addition of gentamicin in the first 24 h causes the most rapid decline in CFU/g. Of interest, the addition of rifampin decreased the activity of daptomycin against both E. faecalis and VRE. PMID:24867993

  7. Enterococcus faecalis Endogenous Endophthalmitis from Valvular Endocarditis

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    Sidnei Barge

    2013-01-01

    Full Text Available We report a case of a 74-year-old female, with a mitral heart valve, who presented with pain and blurred vision in the right eye for 2 days. Her visual acuity was light perception (LP in the right eye and 20/40 in the left eye. Slit lamp examination showed corneal edema and hypopyon, and a view of the right fundus was impossible. Echography showed vitreous condensation. One day after presentation, the patient developed acute lung edema requiring hospitalization, so she was not submitted to vitreous tap and intravitreal treatment. The cardiac and systemic evaluations revealed a mitral endocarditis secondary to Enterococcus faecalis. The patient improved systemically with treatment with gentamicin, vancomycin, and linezolid. Her visual acuity remained as no LP, and her intraocular pressure (IOP has been controlled with brimonidine bid despite developing a total cataract with 360° posterior synechia. A cardiac source for endogenous endophthalmitis should be considered in the presence of a prosthetic cardiac valve. The treatment and followup must be made in cooperation with a cardiologist specialist, but the ophthalmologist can play a key role in the diagnosis.

  8. Infectious Endocarditis from Enterococcus faecalis Associated with Tubular Adenoma of the Sigmoid Colon

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    Emilly Caroline de Freitas Silva

    2017-01-01

    Full Text Available Introduction. Enterococcus faecalis (E. faecalis, a constituent of the gut microbiota, can be associated with both colonic lesions and endocarditis. Since this microorganism is one of the endocarditis etiological agents, there is a need for greater study in regard to the association with endocarditis and colonic lesions. Case Presentation. This is the case description of a 53-year-old man with history of prolapse of the anterior mitral valve leaflet who was diagnosed with endocarditis by E. faecalis and treated with ampicillin and gentamicin. Upon investigation by colonoscopy, he was found to have a tubular adenoma with low grade dysplasia. Conclusion. There are a few descriptions in scientific literature of an association between endocarditis by E. faecalis and colonic lesions. However, further studies with significant correlation between the two pathologies are required, so that proper measures can be implemented in clinical practice.

  9. Linezolid as rescue treatment for left-sided infective endocarditis

    DEFF Research Database (Denmark)

    Lauridsen, Trine Kiilerich; Bruun, Louise E; Rasmussen, R V

    2012-01-01

    The increasing number of resistant bacterial strains in infective endocarditis (IE) emphasizes the need for a constant development of antimicrobials. Linezolid is an oxazolidinone with an effect on Gram-positive cocci. Only a few casuistic reports describe its utilization in the treatment of IE...

  10. Efficacy of Linezolid plus Rifampin in an Experimental Model of Methicillin-Susceptible Staphylococcus aureus Endocarditis

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    Dailey, Charlene F.; Pagano, Paul J.; Buchanan, Lewis V.; Paquette, Jennifer A.; Haas, Joseph V.; Gibson, John K.

    2003-01-01

    The efficacy of linezolid, alone or in combination with rifampin, against methicillin-susceptible Staphylococcus aureus in rabbits with experimental endocarditis was investigated. Linezolid (50 or 75 mg/kg of body weight), rifampin, and linezolid (25, 50, or 75 mg/kg) plus rifampin produced statistically significant reductions in bacterial counts compared with those in untreated controls. Plasma or valvular vegetation levels of linezolid in the groups treated with the linezolid-rifampin combi...

  11. Serological diagnosis of experimental Enterococcus faecalis endocarditis

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    Kjerulf, A; Espersen, F; Gutschik, E

    1998-01-01

    A modified rat model of endocarditis with catheterization for 2 days was established in female Lewis rats using different inocula of Enterococcus faecalis (strain no. EF 19) in order to measure IgG antibodies in serum during the course of infection. Increasing the inocula intravenously resulted...

  12. Investigation of mechanisms and molecular epidemiology of linezolid nonsusceptible Enterococcus faecalis isolated from a teaching hospital in China.

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    Li, Bin; Ma, Chuan-Ling; Yu, Xiao; Sun, Yao; Li, Mei-Mei; Ye, Jian-Zhong; Zhang, Ya-Pei; Wu, Qing; Zhou, Tie-Li

    2016-08-01

    The epidemiological and molecular characteristics of eight linezolid nonsusceptible Enterococcus faecalis isolated from a teaching hospital in China (January to July 2014) were investigated. The target site modifications and cfr gene associated with linezolid resistance were not found. Results of the epidemiological investigation indicated that linezolid resistance possibly occurred on several independent occasions and was often not related to linezolid administration. Copyright © 2015. Published by Elsevier B.V.

  13. Endocarditis due to vancomycin-resistant Enterococcus raffinosus successfully treated with linezolid: case report and review of literature Endocarditis por Enterococcus raffinosus resistente a vancomicina exitosamente tratada con linezolid: caso clínico y revisión de la literatura

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    A. Jasovich

    2008-12-01

    Full Text Available Enterococcus raffinosus is scarcely found in clinical samples and even less frequently as etiologic agent of endocarditis. We are herein presenting one case of mitral prosthetic-valve endocarditis in a 77-y-o male due to a vancomycinresistant Enterococcus raffinosus isolate, successfully treated with 6 weeks of linezolid, and a two-year follow up.Enterococcus raffinosus es una especie poco frecuente en materiales clínicos y menos aún como agente etiológico de endocarditis. En este trabajo se presenta un caso de endocarditis de válvula mitral protésica en un paciente de 77 años debida a Enterococcus raffinosus resistente a vancomicina y que fue exitosamente tratada con linezolid durante 6 semanas, con un seguimiento de 2 años.

  14. Risk Factors of Endocarditis in Patients with Enterococcus faecalis Bacteremia

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    Dahl, Anders; Lauridsen, Trine K; Arpi, Magnus

    2016-01-01

    BACKGROUND:  The NOVA score is a recently developed diagnostic tool to identify patients with increased risk of infective endocarditis (IE) among patients with Enterococcus faecalis (EF) bacteremia. We aim to validate an adapted version of the NOVA score and to identify risk factors for IE...

  15. The Fibronectin-Binding Protein EfbA Contributes to Pathogenesis and Protects against Infective Endocarditis Caused by Enterococcus faecalis

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    Singh, Kavindra V.; La Rosa, Sabina Leanti; Somarajan, Sudha R.; Roh, Jung Hyeob

    2015-01-01

    EfbA is a PavA-like fibronectin adhesin of Enterococcus faecalis previously shown to be important in experimental urinary tract infection. Here, we expressed and purified the E. faecalis OG1RF EfbA and confirmed that this protein binds with high affinity to immobilized fibronectin, collagen I, and collagen V. We constructed an efbA deletion mutant and demonstrated that its virulence was significantly attenuated (P endocarditis model. Furthermore, efbA deletion resulted in diminished ability to bind fibronectin (P endocarditis (P = 0.008 versus control). Taken together, our results demonstrate that EfbA is an important factor involved in E. faecalis endocarditis and that rEfbA immunization is effective in preventing such infection, likely by interfering with bacterial adherence. PMID:26351286

  16. First Japanese case of infectious endocarditis due to Enterococcus faecalis small-colony variants.

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    Ogihara, Shinji; Saito, Ryoichi; Sawabe, Etsuko; Hagihara, Michio; Tohda, Shuji

    2016-10-01

    A male patient was admitted to our hospital due to infectious endocarditis. He had been treated with levofloxacin for 6 weeks, sulbactam/cefoperazone for 4 weeks, and benzylpenicillin for 2 days prior to valve replacement surgery. Gram-positive cocci, with morphology consistent with γ-Streptococcus, were detected in blood cultures obtained at admission, as well as in vegetation obtained from the aortic valve. However, the strain could not be identified using biochemical methods. Sequencing of the 16S rRNA gene indicated that the culture was a small-colony variant of Enterococcus faecalis. This is the first case in Japan of infectious endocarditis due to E. faecalis small-colony variants. Small-colony variants are subpopulations of bacteria with slow growth, reduced sugar fermentation, and unstable phenotype. As a result, these strains tend to be misidentified. Further, small-colony variants are associated with recurrent and persistent infections such as prosthetic joint infection and infectious endocarditis. These strains are found in various bacterial species, including Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, and Pseudomonas aeruginosa, but rarely in Enterococcus species. The case highlights the need to be vigilant of E. faecalis small-colony variants, especially in patients who received long-term courses of antibiotics. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  17. Linezolid-resistant enterococci in Polish hospitals: species, clonality and determinants of linezolid resistance.

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    Gawryszewska, I; Żabicka, D; Hryniewicz, W; Sadowy, E

    2017-07-01

    The significant increase of the linezolid-resistant enterococci (LRE) has been observed in Polish hospitals since 2012 and our study aimed at elucidating the possible reasons for this phenomenon. Polish LRE isolates were analysed by multilocus-sequence typing (MLST) and multiple locus variable-number tandem repeat (VNTR) analysis (MLVA), polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP) to establish clonal relatedness and mechanism of linezolid resistance, respectively. Fifty analysed LRE (2008-2015) included mostly Enterococcus faecium (82%) and Enterococcus faecalis (16%). Enterococcus faecium belonged to the hospital-adapted lineages 17/18 and 78, while E. faecalis isolates represented ST6, a hospital-associated type, and ST116, found in both humans and food-production animals. The G2576T 23S rRNA mutation was the most frequent (94%) mechanism of linezolid/tedizolid resistance of LRE. None of the isolates carried the plasmid-associated gene of Cfr methyltransferase, whereas optrA, encoding the ABC-type drug transporter, was identified in two E. faecalis isolates. In these isolates, optrA was located on a plasmid, transferable to both E. faecium and E. faecalis, whose partial (36.3 kb) sequence was 100% identical to the pE394 plasmid, identified previously in China in both clinical and farm animal isolates. The optrA-E. faecium transconjugant displayed a significant growth deficiency, in contrast to the optrA-E. faecalis. Our study indicates the role of mutation acquisition by hospital-adapted clones of enterococci as a major driver of increasing resistance to linezolid and tedizolid. Transferability and apparent lack of a biological cost of resistance suggest that E. faecalis may be a natural reservoir of optrA, an emerging mechanism of oxazolidinone resistance.

  18. In vitro antibacterial activity of tigecycline against clinical isolates of Linezolid-Intermediate (LIE and Linezolid-Resistant Enterococci (LRE by time-kill assay

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    Gustavo Enck Sambrano

    2014-08-01

    Full Text Available Introduction: Enterococci have become the third major leading cause of nosocomial bacteraemia, an infection which is significantly associated with the risk of developing infective endocarditis. Linezolid provides high rates of clinical cure and microbiologic success in complicated infections due to Enterococcus spp. However, several instances of emergence of resistance during linezolid treatment have been reported. The aim of this study was evaluate the activity of tigecycline against Linezolid-Intermediate (LIE and Linezolid-Resistant Enterococcus faecalis (LRE by the time-kill assay. Methods: Five isolates of LRE and two isolates of LIE were used in this study. MICs were determined by broth dilution following the CLSI (2014 guidelines. Time-kill assay was employed to access the in vitro response profile of tigecycline. Results: All seven of the isolates presented MIC of 0.125μg/mL. Tigecycline activity was individually evaluated and in three of the five isolates of LRE it presented bactericidal. Against the other isolates, tigecycline showed bacteriostatic activity. The tigecycline activity was measured according to CLSI criteria. Conclusions: Tigecycline presented both bacteriostatic and bactericidal activity against tested isolates, result not yet described in previous studies. Time and concentrations above MIC were key factors to achieving bactericidal effect. MIC and the tested concentration below it resulted in bacteriostatical effect to enterococci, corroborating previous data.

  19. Successful salvage treatment of native valve Enterococcus faecalis infective endocarditis with telavancin: two case reports.

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    Thompson, Mickala M; Hassoun, Ali

    2017-07-01

    Infective endocarditis (IE) one-year mortality rates approach 40%. Here, we report two native valve Enterococcus faecalis IE cases in patients successfully treated with telavancin. An 88-year-old with mitral valve endocarditis and a penicillin allergy, initially treated with intravenous vancomycin, was switched to telavancin. A 69-year-old, who previously received amoxicillin and intravenous vancomycin for presumed enterococcal bacteraemia, was diagnosed with dual valve endocarditis for which he received telavancin. Both received six weeks of telavancin. Neither had telavancin-related adverse events, evidence of infection at six months, nor required telavancin dosing adjustments. Documented use of novel treatments for serious enterococcal infections is needed.

  20. Linezolid som behandling af infektiøs endokarditis

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    Lauridsen, Trine Kiilerich; Arpi, Magnus; Bruun, Niels Eske

    2010-01-01

    In Denmark enterococci causes 15 to 20% of all endocarditis (IE) cases. The development of multi-resistant bacterial strains has increased the need for new antibiotics. Linezolid is an alternative to conventional treatment of infections with gram positive cocci. In this case report linezolid...

  1. Prevalence and Genetic Diversity of Enterococcus faecalis Isolates from Mineral Water and Spring Water in China

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    Lei Wei

    2017-06-01

    Full Text Available Enterococcus faecalis is an important opportunistic pathogen which is frequently detected in mineral water and spring water for human consumption and causes human urinary tract infections, endocarditis and neonatal sepsis. The aim of this study was to determine the prevalence, virulence genes, antimicrobial resistance and genetic diversity of E. faecalis from mineral water and spring water in China. Of 314 water samples collected from January 2013 to January 2014, 48 samples (15.3% were contaminated E. faecalis. The highest contamination rate occurred in activated carbon filtered water of spring water (34.5%, followed by source water of spring water (32.3% and source water of mineral water (6.4%. The virulence gene test of 58 E. faecalis isolates showed that the detection rates of asa1, ace, cylA, gelE and hyl were 79.3, 39.7, 0, 100, 0%, respectively. All 58 E. faecalis isolates were not resistant to 12 kinds of antibiotics (penicillin, ampicillin, linezolid, quinupristin/dalfopristin, vancomycin, gentamicin, streptomycin, ciprofloxacin, levofloxacin, norfloxacin, nitrofurantoin, and tetracycline. Enterobacterial repetitive intergenic consensus-PCR classified 58 isolates and three reference strains into nine clusters with a similarity of 75%. This study is the first to investigate the prevalence of E. faecalis in mineral water and spring water in China. The results of this study suggested that spring water could be potential vehicles for transmission of E. faecalis.

  2. Resistance mechanisms of linezolid-nonsusceptible enterococci in Korea: low rate of 23S rRNA mutations in Enterococcus faecium.

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    Lee, Sae-Mi; Huh, Hee Jae; Song, Dong Joon; Shim, Hyang Jin; Park, Kyung Sun; Kang, Cheol-In; Ki, Chang-Seok; Lee, Nam Yong

    2017-12-01

    To investigate linezolid-resistance mechanisms in linezolid-nonsusceptible enterococci (LNSE) isolated from a tertiary hospital in Korea. Enterococcal isolates exhibiting linezolid MICs ≥4 mg l -1 that were isolated between December 2011 and May 2016 were investigated by PCR and sequencing for mutations in 23S rRNA or ribosomal proteins (L3, L4 and L22) and for the presence of cfr, cfr(B) and optrA genes.Results/Key findings. Among 135 LNSE (87 Enterococcus faecium and 48 Enterococcus faecalis isolates), 39.1 % (34/87) of E. faecium and 18.8 % (9/48) of E. faecalis isolates were linezolid-resistant. The optrA carriage was the dominant mechanism in E. faecalis: 13 isolates, including 10 E. faecalis [70 % (7/10) linezolid-resistant and 30 % (3/10) linezolid-intermediate] and three E. faecium [33.3 % (1/3) linezolid-resistant and 66.7 % (2/3) linezolid-intermediate], contained the optrA gene. G2576T mutations in the 23S rRNA gene were detected only in E. faecium [14 isolates; 71.4 % (10/14) linezolid-resistant and 28.6 % (4/14) linezolid-intermediate]. One linezolid-intermediate E. faecium harboured a L22 protein alteration (Ser77Thr). No isolates contained cfr or cfr(B) genes and any L3 or L4 protein alterations. No genetic mechanism of resistance was identified for 67.6 % (23/34) of linezolid-resistant E. faecium. A low rate of 23S rRNA mutations and the absence of known linezolid-resistance mechanisms in the majority of E. faecium isolates suggest regional differences in the mechanisms of linezolid resistance and the possibility of additional mechanisms.

  3. Efficacy of Tigecycline Alone and in Combination with Gentamicin in the Treatment of Experimental Endocarditis Due to Linezolid-Resistant Enterococcus faecium

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    Pontikis, Konstantinos; Pefanis, Angelos; Tsaganos, Thomas; Tzepi, Ira-Maria; Carrer, Dionyssia-Pinelopi; Giamarellou, Helen

    2013-01-01

    We evaluated the efficacy of tigecycline in a rabbit model of experimental endocarditis caused by a linezolid-resistant clinical strain of Enterococcus faecium. Tigecycline-treated animals had a 2.8-log10-CFU/g reduction in microbial counts in excised vegetations compared with controls. Addition of gentamicin caused a further arithmetical reduction in colony counts. The therapeutic effect was sustained 5 days after completion of treatment, as shown by relapse studies performed in treatment gr...

  4. Efficacy of tigecycline alone and in combination with gentamicin in the treatment of experimental endocarditis due to linezolid-resistant Enterococcus faecium.

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    Pontikis, Konstantinos; Pefanis, Angelos; Tsaganos, Thomas; Tzepi, Ira-Maria; Carrer, Dionyssia-Pinelopi; Giamarellou, Helen

    2013-07-01

    We evaluated the efficacy of tigecycline in a rabbit model of experimental endocarditis caused by a linezolid-resistant clinical strain of Enterococcus faecium. Tigecycline-treated animals had a 2.8-log10-CFU/g reduction in microbial counts in excised vegetations compared with controls. Addition of gentamicin caused a further arithmetical reduction in colony counts. The therapeutic effect was sustained 5 days after completion of treatment, as shown by relapse studies performed in treatment groups.

  5. Linezolid-resistant clinical isolates of enterococci and Staphylococcus cohnii from a multicentre study in China: molecular epidemiology and resistance mechanisms.

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    Chen, Hongbin; Wu, Weiyuan; Ni, Ming; Liu, Yingmei; Zhang, Jixia; Xia, Fei; He, Wenqiang; Wang, Qi; Wang, Zhanwei; Cao, Bin; Wang, Hui

    2013-10-01

    Genetic characterisation of linezolid-resistant Gram-positive cocci in a multicentre study in China has not been reported previously. To study the mechanism underlying the resistance of linezolid-resistant isolates, nine Enterococcus faecalis, one Enterococcus faecium and three Staphylococcus cohnii isolates with various levels of resistance were collected from five hospitals across China in 2009-2012. The nine E. faecalis isolates were classified into seven sequence types, indicating that these linezolid-resistant E. faecalis isolates were polyclonal. Enterococci isolates had reduced susceptibility to linezolid (MICs of 4-8 mg/L) and had mutation of ribosomal protein L3, with three also having mutation of L4, but without the multidrug resistance gene cfr or the 23S rRNA mutation G2576T. The three S. cohnii isolates were highly resistant to linezolid (MICs of 64 mg/L to >256 mg/L), harboured the cfr gene and had the 23S rRNA mutation G2576T. Southern blotting indicated that the cfr gene of these three isolates resided on different plasmids (pHK01, pRM01 and pRA01). In plasmid pHK01, IS21-558 and the cfr gene were integrated into transposon Tn558. In plasmids pRM01 and pRA01, the cfr gene was flanked by two copies of an IS256-like insertion sequence, indicating that the transferable form of linezolid resistance is conferred by the cfr gene. In conclusion, the emergence of linezolid-resistant Gram-positive cocci in different regions of China is of concern. The cfr gene and the 23S rRNA mutation contribute to high-level linezolid resistance in S. cohnii, and the L3 and L4 mutations are associated with low-level linezolid resistance in enterococci. Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  6. AhrC and Eep Are Biofilm Infection-Associated Virulence Factors in Enterococcus faecalis

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    Guiton, Pascale S.; Barnes, Aaron M. T.; Manias, Dawn A.; Chuang-Smith, Olivia N.; Kohler, Petra L.; Spaulding, Adam R.; Hultgren, Scott J.; Schlievert, Patrick M.; Dunny, Gary M.

    2013-01-01

    Enterococcus faecalis is part of the human intestinal microbiome and is a prominent cause of health care-associated infections. The pathogenesis of many E. faecalis infections, including endocarditis and catheter-associated urinary tract infection (CAUTI), is related to the ability of clinical isolates to form biofilms. To identify chromosomal genetic determinants responsible for E. faecalis biofilm-mediated infection, we used a rabbit model of endocarditis to test strains with transposon insertions or in-frame deletions in biofilm-associated loci: ahrC, argR, atlA, opuBC, pyrC, recN, and sepF. Only the ahrC mutant was significantly attenuated in endocarditis. We demonstrate that the transcriptional regulator AhrC and the protease Eep, which we showed previously to be an endocarditis virulence factor, are also required for full virulence in murine CAUTI. Therefore, AhrC and Eep can be classified as enterococcal biofilm-associated virulence factors. Loss of ahrC caused defects in early attachment and accumulation of biofilm biomass. Characterization of ahrC transcription revealed that the temporal expression of this locus observed in wild-type cells promotes initiation of early biofilm formation and the establishment of endocarditis. This is the first report of AhrC serving as a virulence factor in any bacterial species. PMID:23460519

  7. Conservation of Ebp-type pilus genes among Enterococci and demonstration of their role in adherence of Enterococcus faecalis to human platelets.

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    Nallapareddy, Sreedhar R; Sillanpää, Jouko; Mitchell, Jennifer; Singh, Kavindra V; Chowdhury, Shahreen A; Weinstock, George M; Sullam, Paul M; Murray, Barbara E

    2011-07-01

    Ebp are endocarditis- and biofilm-associated pili of Enterococcus faecalis that are also important in experimental urinary tract infections (UTIs). Our analyses, using available genomes, found that the ebp locus is unique to enterococci. In E. faecalis, the ebp locus is very highly conserved and only 1/473 E. faecalis isolates tested lacked ebpABC, while only 1.2% had the bee pilus locus. No other pilus-encoding operon was identified in 55 available genomes, indicating that the vast majority of E. faecalis strains (unlike Enterococcus faecium and streptococci) have a single pilus locus. Surface expression studies showed that Ebp pili were produced in vitro by 91/91 brain heart infusion (BHI) plus serum-grown E. faecalis isolates and that strain OG1RF expressed pili at even higher levels in rat endocarditis vegetations. However, Ebp expression was restricted to 30 to 72% of E. faecalis cells, consistent with a bistability mode of expression. We also evaluated E. faecalis interactions with human platelets and found that growth of E. faecalis in BHI plus serum significantly enhanced adherence to human platelets and that sortase deletion mutants (the ΔsrtA, Δbps, and ΔbpsΔsrtA mutants) were markedly defective. Further studies identified that Ebp pili, but not the microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) Ace and Fss2, mediate adherence of E. faecalis to platelets. Taken together, our data show that the immunogenic (in human endocarditis patients) and commonly expressed Ebp pili, which are known to be important for experimental endocarditis, are highly conserved and mediate adherence to platelets, suggesting that Ebp pili may be a reasonable immunotherapeutic target for prevention or possibly treatment of endocarditis caused by this species.

  8. Conservation of Ebp-Type Pilus Genes among Enterococci and Demonstration of Their Role in Adherence of Enterococcus faecalis to Human Platelets ▿ †

    Science.gov (United States)

    Nallapareddy, Sreedhar R.; Sillanpää, Jouko; Mitchell, Jennifer; Singh, Kavindra V.; Chowdhury, Shahreen A.; Weinstock, George M.; Sullam, Paul M.; Murray, Barbara E.

    2011-01-01

    Ebp are endocarditis- and biofilm-associated pili of Enterococcus faecalis that are also important in experimental urinary tract infections (UTIs). Our analyses, using available genomes, found that the ebp locus is unique to enterococci. In E. faecalis, the ebp locus is very highly conserved and only 1/473 E. faecalis isolates tested lacked ebpABC, while only 1.2% had the bee pilus locus. No other pilus-encoding operon was identified in 55 available genomes, indicating that the vast majority of E. faecalis strains (unlike Enterococcus faecium and streptococci) have a single pilus locus. Surface expression studies showed that Ebp pili were produced in vitro by 91/91 brain heart infusion (BHI) plus serum-grown E. faecalis isolates and that strain OG1RF expressed pili at even higher levels in rat endocarditis vegetations. However, Ebp expression was restricted to 30 to 72% of E. faecalis cells, consistent with a bistability mode of expression. We also evaluated E. faecalis interactions with human platelets and found that growth of E. faecalis in BHI plus serum significantly enhanced adherence to human platelets and that sortase deletion mutants (the ΔsrtA, Δbps, and ΔbpsΔsrtA mutants) were markedly defective. Further studies identified that Ebp pili, but not the microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) Ace and Fss2, mediate adherence of E. faecalis to platelets. Taken together, our data show that the immunogenic (in human endocarditis patients) and commonly expressed Ebp pili, which are known to be important for experimental endocarditis, are highly conserved and mediate adherence to platelets, suggesting that Ebp pili may be a reasonable immunotherapeutic target for prevention or possibly treatment of endocarditis caused by this species. PMID:21502588

  9. Tedizolid susceptibility in linezolid- and vancomycin-resistant Enterococcus faecium isolates.

    Science.gov (United States)

    Klupp, E-M; Both, A; Belmar Campos, C; Büttner, H; König, C; Christopeit, M; Christner, M; Aepfelbacher, M; Rohde, H

    2016-12-01

    Vancomycin-resistant enterococci (VRE) are of ever-increasing importance, most notably in high-risk patient populations. Therapy options are often limited for these isolates, and apart from tigecycline and daptomycin, oxazolidinone linezolid is frequently administered. The broad usage of linezolid, however, has driven the emergence of linezolid-resistant VRE strains (LR-VRE), further shortening therapeutic options. Second-generation oxazolidinone tedizolid has the advantage of being active against a specific subset of LR-VRE, i.e. isolates expressing the plasmid-encoded chloramphenicol-florfenicol resistance (cfr) gene. Here we tested tedizolid activity in a collection of 30 LR Enterococcus faecium VRE (MIC range 32-256 mg/l) isolated between 2012 and 2015 from clinical and screening specimens. By pulsed field gel electrophoresis (PFGE) isolates were assigned to 16 clonal lineages. In three cases, linezolid-susceptible progenitor isolates of LR-VRE were isolated, thus demonstrating the de-novo emergence of the linezolid-resistant phenotype. PCR did not detect cfr, cfr(B) or novel oxazolidinone resistance gene optrA in LR-VRE. All isolates, however, carried mutations within the 23S rDNA. Compared to linezolid, tedizolid MICs were lower in all isolates (MIC range 2-32 mg/l), but remained above the FDA tedizolid breakpoint for E. faecalis at 0.5 mg/l. Thus, related to the predominant resistance mechanism, tedizolid is of limited value for treatment of most LR-VRE and represents a therapeutic option only for a limited subset of isolates.

  10. Detection of endocarditis bacteria in tonsillar mucosa of Afghan population.

    Science.gov (United States)

    Ruggiero, F; Carbone, D; Mugavero, R; Palmieri, A; Lauritano, D; Baggi, L; Nardone, M; Carinci, F; Martinelli, M

    2018-01-01

    Endocarditis is a cardiovascular disease caused by the inflammation of the inner tissues of the heart, the endocardium, usually of the valves. Bacteraemia is essential in the development of endocarditis, and there are some findings that the main pathogens of endocarditis are viridans group streptococci: Streptococcus oralis, Streptococcus sanguinis, and Enterococcus faecalis. There is strong evidence that endocarditis bacteria are present in the tonsillar microbiota, so that tonsillar infection is associated with an increased risk of endocarditis. The aim of this manuscript is to investigate the presence of the main pathogens of endocarditis in tonsillar microbiota of an Afghan population group. A sample of 80 tonsil swabs were analyzed by quantitative real time PCR to detect endocarditis pathogens and an estimation of the total bacterial load. The median bacterial load in PCR reaction was 1.4x106 (interquartile range 4,7x105 - 2,9x106). Three species, S. Oralis, S. Sanguinis, and E. Faecalis were found in large amounts in all specimens. On the other hand, S. Mitis was never detected. The S. Aureus was found in 3 samples with a prevalence of 0.04 (C.I. 0.01-0.10). The S. Mutans was found in 33 samples with a prevalence of 0.41 (C.I. 0.31-0.52). Endocarditis bacteria has been found into the tonsillar microbiota, so there is sufficient evidence to justify that the oral cavity is a reservoir of endocarditis bacteria that can have a significant impact on the cardiovascular function.

  11. Evaluation of the Enterococcus faecalis Biofilm-Associated Virulence Factors AhrC and Eep in Rat Foreign Body Osteomyelitis and In Vitro Biofilm-Associated Antimicrobial Resistance.

    Directory of Open Access Journals (Sweden)

    Kristi L Frank

    Full Text Available Enterococcus faecalis can cause healthcare-associated biofilm infections, including those of orthopedic devices. Treatment of enterococcal prosthetic joint infection is difficult, in part, due to biofilm-associated antimicrobial resistance. We previously showed that the E. faecalis OG1RF genes ahrC and eep are in vitro biofilm determinants and virulence factors in animal models of endocarditis and catheter-associated urinary tract infection. In this study, we evaluated the role of these genes in a rat acute foreign body osteomyelitis model and in in vitro biofilm-associated antimicrobial resistance. Osteomyelitis was established for one week following the implantation of stainless steel orthopedic wires inoculated with E. faecalis strains OG1RF, ΩahrC, and ∆eep into the proximal tibiae of rats. The median bacterial loads recovered from bones and wires did not differ significantly between the strains at multiple inoculum concentrations. We hypothesize that factors present at the infection site that affect biofilm formation, such as the presence or absence of shear force, may account for the differences in attenuation in the various animal models we have used to study the ΩahrC and ∆eep strains. No differences among the three strains were observed in the planktonic and biofilm antimicrobial susceptibilities to ampicillin, vancomycin, daptomycin, linezolid, and tetracycline. These findings suggest that neither ahrC nor eep directly contribute to E. faecalis biofilm-associated antimicrobial resistance. Notably, the experimental evidence that the biofilm attachment mutant ΩahrC displays biofilm-associated antimicrobial resistance suggests that surface colonization alone is sufficient for E. faecalis cells to acquire the biofilm antimicrobial resistance phenotype.

  12. Impact of the PROVAUR stewardship programme on linezolid resistance in a tertiary university hospital: a before-and-after interventional study.

    Science.gov (United States)

    García-Martínez, Lucrecia; Gracia-Ahulfinger, Irene; Machuca, Isabel; Cantisán, Sara; De La Fuente, Soraya; Natera, Clara; Pérez-Nadales, Elena; Vidal, Elisa; Rivero, Antonio; Rodríguez-Lopez, Fernando; Del Prado, José Ramón; Torre-Cisneros, Julián

    2016-09-01

    There is little evidence of the impact of antimicrobial stewardship programmes on antimicrobial resistance. To study the efficacy and safety of a package of educational and interventional measures to optimize linezolid use and its impact on bacterial resistance. A quasi-experimental study was designed and carried out before and after implementation of a stewardship programme in hospitalized patients with Gram-positive infections treated with linezolid. The intervention reduced linezolid consumption by 76%. The risk of linezolid-resistant CoNS isolates (OR = 0.37; 95% CI = 0.27-0.49; P linezolid use can contribute to reducing the resistance rate of CoNS and E. faecalis to this antibiotic. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. In vitro antimicrobial activity of linezolid tested against vancomycin-resistant enterococci isolated in Brazilian hospitals

    Directory of Open Access Journals (Sweden)

    Reis Adriana O.

    2001-01-01

    Full Text Available The emergence of vancomycin-resistant enterococci (VRE has been described recently in Brazil. This is in contrast to the USA and Europe, where the VRE appeared in the late 1980s. The progressive increase in VRE isolation poses important problems in the antimicrobial therapy of nosocomial infections. Treatment options and effective antimicrobial agents for VRE are often limited and the possibility of transfer of vancomycin genes to other Gram-positive microorganisms continues. In the search for antimicrobial agents for multiresistant Gram-positive cocci, compounds such as linezolid and quinupristin/dalfopristin have been evaluated. The present study was conducted to evaluate the in vitro activity of the oxazolidinone linezolid and 10 other antimicrobial agents, including quinupristin-dalfopristin, against multiresistant enterococci isolated in Brazilian hospitals. Thirty-three vancomycin resistant isolates (17 Enterococcus faecium and 16 E. faecalis, were analyzed. Strains were isolated from patients at São Paulo Hospital, Oswaldo Cruz Hospital, Hospital do Servidor Público Estadual, Santa Marcelina Hospital, Santa Casa de Misericórdia de São Paulo, and Hospital de Clínicas do Paraná. The samples were tested by a broth microdilution method following the National Committee for Clinical Laboratory Standards (NCCLS recommendations. All isolates were molecular typed using pulsed-field gel electrophoresis (PFGE. Linezolid was the most active compound against these multiresistant enterococci, showing 100% inhibition at the susceptible breakpoints. Quinupristin/dalfopristin and teicoplanin showed poor activity against both species. The molecular typing results suggest that there has been interhospital spread of vancomycin resistant E. faecium and E. faecalis among Brazilian hospitals. The results of this study indicate that linezolid is an appropriate therapeutic option for the treatment of vancomycin-resistant enterococci infections in Brazil.

  14. Anterior mitral valve aneurysm: a rare sequelae of aortic valve endocarditis

    Directory of Open Access Journals (Sweden)

    Rajesh Janardhanan

    2016-05-01

    Full Text Available In intravenous drug abusers, infective endocarditis usually involves right-sided valves, with Staphylococcus aureus being the most common etiologic agent. We present a patient who is an intravenous drug abuser with left-sided (aortic valve endocarditis caused by Enterococcus faecalis who subsequently developed an anterior mitral valve aneurysm, which is an exceedingly rare complication. A systematic literature search was conducted which identified only five reported cases in the literature of mitral valve aneurysmal rupture in the setting of E. faecalis endocarditis. Real-time 3D-transesophageal echocardiography was critical in making an accurate diagnosis leading to timely intervention. Learning objectives: • Early recognition of a mitral valve aneurysm (MVA is important because it may rupture and produce catastrophic mitral regurgitation (MR in an already seriously ill patient requiring emergency surgery, or it may be overlooked at the time of aortic valve replacement (AVR. • Real-time 3D-transesophageal echocardiography (RT-3DTEE is much more advanced and accurate than transthoracic echocardiography for the diagnosis and management of MVA.

  15. Anterior mitral valve aneurysm: a rare sequelae of aortic valve endocarditis.

    Science.gov (United States)

    Janardhanan, Rajesh; Kamal, Muhammad Umar; Riaz, Irbaz Bin; Smith, M Cristy

    2016-03-01

    SummaryIn intravenous drug abusers, infective endocarditis usually involves right-sided valves, with Staphylococcus aureus being the most common etiologic agent. We present a patient who is an intravenous drug abuser with left-sided (aortic valve) endocarditis caused by Enterococcus faecalis who subsequently developed an anterior mitral valve aneurysm, which is an exceedingly rare complication. A systematic literature search was conducted which identified only five reported cases in the literature of mitral valve aneurysmal rupture in the setting of E. faecalis endocarditis. Real-time 3D-transesophageal echocardiography was critical in making an accurate diagnosis leading to timely intervention. Early recognition of a mitral valve aneurysm (MVA) is important because it may rupture and produce catastrophic mitral regurgitation (MR) in an already seriously ill patient requiring emergency surgery, or it may be overlooked at the time of aortic valve replacement (AVR).Real-time 3D-transesophageal echocardiography (RT-3DTEE) is much more advanced and accurate than transthoracic echocardiography for the diagnosis and management of MVA. © 2016 The authors.

  16. Conservation of Ebp-Type Pilus Genes among Enterococci and Demonstration of Their Role in Adherence of Enterococcus faecalis to Human Platelets ▿ †

    OpenAIRE

    Nallapareddy, Sreedhar R.; Sillanpää, Jouko; Mitchell, Jennifer; Singh, Kavindra V.; Chowdhury, Shahreen A.; Weinstock, George M.; Sullam, Paul M.; Murray, Barbara E.

    2011-01-01

    Ebp are endocarditis- and biofilm-associated pili of Enterococcus faecalis that are also important in experimental urinary tract infections (UTIs). Our analyses, using available genomes, found that the ebp locus is unique to enterococci. In E. faecalis, the ebp locus is very highly conserved and only 1/473 E. faecalis isolates tested lacked ebpABC, while only 1.2% had the bee pilus locus. No other pilus-encoding operon was identified in 55 available genomes, indicating that the vast majority ...

  17. Is there a need for bacterial endocarditis prophylaxis in patients undergoing gastrointestinal endoscopy?

    Science.gov (United States)

    Patanè, Salvatore

    2014-04-01

    Heart valve repair or replacement is a serious problem. Patients can benefit from an open dialogue between both cardiologists and gastroenterologists for the optimal effective patients care. The focused update on infective endocarditis of the American College of Cardiology/American Heart Association 2008 (ACC/AHA guidelines) and guidelines on the prevention, diagnosis, and treatment of infective endocarditis (new version 2009) of the European Society of Cardiology (ESC guidelines) describe prophylaxis against infective endocarditis (IE) as not recommended for gastroscopy and colonoscopy in the absence of active infection but increasing evidence suggests that the role of IE antibiotic prophylaxis remains a dark side of the cardio-oncology prevention. New evidences concerning infective endocarditis due to Streptococcus bovis, Streptococcus agalactiae, Enterococcus faecalis, Enterococcus faecium, Enterococcus durans, and new findings indicate that there is a need for bacterial endocarditis prophylaxis in patients undergoing gastrointestinal endoscopy especially in elderly patients and in cancer and immunocompromised patients, to avoid serious consequences.

  18. Linezolid-resistant Staphylococcus epidermidis associated with long-term, repeated linezolid use in a pediatric patient.

    Science.gov (United States)

    Ishiwada, Naruhiko; Takaya, Akiko; Kimura, Asahi; Watanabe, Masaharu; Hino, Moeko; Ochiai, Hidemasa; Matsui, Mari; Shibayama, Keigo; Yamamoto, Tomoko

    2016-03-01

    We report an 8-year-old patient with catheter-related bacteremia caused by linezolid-resistant Staphylococcus epidermidis that was isolated after the long-term, repeated use of linezolid. Three S. epidermidis strains isolated from this patient were bacteriologically analyzed. While the strain isolated prior to linezolid initiation was susceptible to linezolid, two strains after linezolid therapy displayed low-level linezolid susceptibility (MIC, 4 mg/L) and linezolid resistance (MIC, 16 mg/L). T2500A mutation in two copies and G2575T mutations in three copies of 23S rRNA were detected in the low-susceptible strain and the resistant strain, respectively. Linezolid-resistant S. epidermidis infection is rare, but may occur with the long-term administration of linezolid. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  19. Rapid Emergence of Resistance to Linezolid during Linezolid Therapy of an Enterococcus faecium Infection▿

    OpenAIRE

    Seedat, Jamela; Zick, Günther; Klare, Ingo; Konstabel, Carola; Weiler, Norbert; Sahly, Hany

    2006-01-01

    We report the emergence of linezolid resistance (MICs of 16 to 32 mg/liter) in clonally related vancomycin-susceptible and -resistant Enterococcus faecium isolates from an intensive care unit patient after 12 days of linezolid therapy. Only linezolid-susceptible isolates of the same clone were detected at 28 days after termination of linezolid therapy.

  20. Assessing outcomes of adult oncology patients treated with linezolid versus daptomycin for bacteremia due to vancomycin-resistant Enterococcus.

    Science.gov (United States)

    Patel, Khilna; Kabir, Rubiya; Ahmad, Samrah; Allen, Steven L

    2016-04-01

    The incidence and severity of vancomycin-resistant Enterococcus blood stream infections continue to rise and is a significant burden in the healthcare setting. Literature thus far is minimal regarding treatment outcomes in patients with malignancy and vancomycin-resistant Enterococcus bacteremia. Appropriate antibiotic selection is vital to treatment success due to high rates of resistance, limited antimicrobials and mortality in this patient population. We conducted this study to determine whether treatment outcomes differed between cancer patients treated with linezolid and those treated with daptomycin for vancomycin-resistant Enterococcus bacteremia. This single-center, retrospective study included adult patients hospitalized on the oncology service with documented vancomycin-resistant Enterococcus faecium or Enterococcus faecalis bacteremia who received at least 48 h of either linezolid or daptomycin as primary treatment. A total of 65 patients were included in the analysis. Thirty-two patients received daptomycin as primary treatment, and 33 patients received linezolid as primary treatment. Twenty-six (76.5%) patients in the linezolid cohort versus 22 (71%) patients in the daptomycin cohort achieved microbiological cure (p = 0.6141). Median length of stay in days (30 vs. 42, p = 0.0714) and mortality (7/32 (20.6%) vs. 8/33 (25.8%), p = 0.6180) were also similar between the linezolid and daptomycin treated patients, respectively. No differences in microbiological cure, length of stay or mortality were identified between the groups. This study suggests that linezolid and daptomycin are each reasonable options for treating vancomycin-resistant Enterococcus bacteremia in oncology patients. Further prospective, randomized controlled trials are needed to assess the optimal treatment for vancomycin-resistant Enterococcus bacteremia in this patient population. © The Author(s) 2014.

  1. Linezolid-Dependent Function and Structure Adaptation of Ribosomes in a Staphylococcus epidermidis Strain Exhibiting Linezolid Dependence

    Science.gov (United States)

    Kokkori, Sofia; Apostolidi, Maria; Tsakris, Athanassios; Pournaras, Spyros

    2014-01-01

    Linezolid-dependent growth was recently reported in Staphylococcus epidermidis clinical strains carrying mutations associated with linezolid resistance. To investigate this unexpected behavior at the molecular level, we isolated active ribosomes from one of the linezolid-dependent strains and we compared them with ribosomes isolated from a wild-type strain. Both strains were grown in the absence and presence of linezolid. Detailed biochemical and structural analyses revealed essential differences in the function and structure of isolated ribosomes which were assembled in the presence of linezolid. The catalytic activity of peptidyltransferase was found to be significantly higher in the ribosomes derived from the linezolid-dependent strain. Interestingly, the same ribosomes exhibited an abnormal ribosomal subunit dissociation profile on a sucrose gradient in the absence of linezolid, but the profile was restored after treatment of the ribosomes with an excess of the antibiotic. Our study suggests that linezolid most likely modified the ribosomal assembly procedure, leading to a new functional ribosomal population active only in the presence of linezolid. Therefore, the higher growth rate of the partially linezolid-dependent strains could be attributed to the functional and structural adaptations of ribosomes to linezolid. PMID:24890589

  2. Linezolid induced retinopathy.

    Science.gov (United States)

    Park, Dae Hyun; Park, Tae Kwann; Ohn, Young-Hoon; Park, Jong Sook; Chang, Jee Ho

    2015-12-01

    While optic neuropathy is a well-known cause of visual disturbances in linezolid-treated patients, the possibility of linezolid-related retinopathy has not been investigated. Here, we report a case of retinopathy demonstrated by multifocal electroretinogram (mfERG) in a linezolid-treated patient. A 61-year-old man with extensively drug-resistant pulmonary tuberculosis treated with linezolid for 5 months presented with painless loss of vision in both eyes. The patient's best corrected visual acuity was 20/50 in the right eye and 20/100 in the left eye. Fundus examination revealed mild disc edema, and color vision was defective in both eyes. Humphrey visual field tests showed a superotemporal field defect in the right eye and central and pericentral field defect in the left eye. Optical coherence tomography (OCT) revealed only mild optic disc swelling. In mfERG, central amplitudes were depressed in both eyes. Four months after the cessation of linezolid, visual acuity was restored to 20/20 right eye and 20/25 left eye. The color vision and visual field had improved. The OCT and mfEFG findings improved as well. Although the clinical features were similar to linezolid-induced optic neuropathy, the mfERG findings suggest the possibility of a retinopathy through cone dysfunction.

  3. Enterococcus faecium small colony variant endocarditis in an immunocompetent patient

    Directory of Open Access Journals (Sweden)

    S. Hernández Egido

    2016-01-01

    Full Text Available Small colony variants (SCV are slow-growing subpopulations of bacteria usually associated with auxotrophism, causing persistent or recurrent infections. Enterococcus faecalis SCV have been seldom described, and only one case of Enterococcus faecium SCV has been reported, associated with sepsis in a leukaemia patient. Here we report the first case described of bacteraemia and endocarditis by SCV E. faecium in an immunocompetent patient.

  4. Five-Year Summary of In Vitro Activity and Resistance Mechanisms of Linezolid against Clinically Important Gram-Positive Cocci in the United States from the LEADER Surveillance Program (2011 to 2015).

    Science.gov (United States)

    Pfaller, Michael A; Mendes, Rodrigo E; Streit, Jennifer M; Hogan, Patricia A; Flamm, Robert K

    2017-07-01

    This report describes linezolid susceptibility testing results for 6,741 Gram-positive pathogens from 60 U.S. sites collected during 2015 for the LEADER Program. In addition, the report summarizes linezolid in vitro activity, resistance mechanisms, and molecular typing obtained for 2011 to 2015. During 2015, linezolid showed potent activity in testing against Staphylococcus aureus , inhibiting >99.9% of 3,031 isolates at ≤2 µg/ml. Similarly, linezolid showed coverage against 99.2% of coagulase-negative staphylococci, 99.7% of enterococci, and 100.0% of Streptococcus pneumoniae , virdans group, and beta-hemolytic streptococcus isolates tested. The overall linezolid resistance rate remained a modest linezolid resistance mechanisms. Increased annual trends for the presence of cfr among Staphylococcus aureus isolates were not observed, but 64.3% (9/14) of the isolates with decreased susceptibility (MIC, ≥4 µg/ml) to linezolid carried this transferrable gene (2011 to 2015). The cfr gene was detected in 21.9% (7/32) of linezolid-resistant staphylococci other than S. aureus from 2011 to 2015. The optrA gene was noted in half (2/4) of the population of linezolid-nonsusceptible Enterococcus faecalis isolates from 2011 to 2015, while linezolid-nonsusceptible Enterococcus faecium isolates showed alterations predominantly (16/16) in the 23S rRNA gene (G2576T). This report confirms a long record of linezolid activity against Gram-positive isolates in the United States since regulatory approval in 2000 and reports the oxazolidinones evolving resistance mechanisms. Copyright © 2017 American Society for Microbiology.

  5. Wide dissemination of linezolid-resistant Staphylococcus epidermidis in Greece is associated with a linezolid-dependent ST22 clone.

    Science.gov (United States)

    Karavasilis, Vasilios; Zarkotou, Olympia; Panopoulou, Maria; Kachrimanidou, Melina; Themeli-Digalaki, Katerina; Stylianakis, Antonios; Gennimata, Vassiliki; Ntokou, Eleni; Stathopoulos, Constantinos; Tsakris, Athanasios; Pournaras, Spyros

    2015-01-01

    Dependence on linezolid was recently described as significant growth acceleration of linezolid-resistant Staphylococcus epidermidis (LRSE) isolates upon linezolid exposure. We investigated the possible contribution of linezolid dependence to LRSE dissemination in Greece. Linezolid resistance rates were estimated in six tertiary hospitals located throughout Greece between 2011 and 2013. Sixty-three randomly selected LRSE recovered in these hospitals during this period were studied. Growth curve analysis was conducted with and without linezolid. Clonality of the isolates was investigated by PFGE and MLST. During the study period, the LRSE rate in the participating hospitals rose significantly from 6.9% to 9% (P = 0.006); the increase was more prominent in ICUs (from 15.1% to 20.9%; P = 0.005). Forty-seven (74.6%) of the 63 LRSE, derived from all study hospitals, clearly exhibited linezolid dependence, growing significantly faster in the presence of 16 and 32 mg/L linezolid. Of note, 61 (96.8%) LRSE exhibited a single macrorestriction pattern and belonged to ST22, which included all linezolid-dependent LRSE. The remaining two LRSE belonged to unique STs. Five of six linezolid-dependent isolates tested also exhibited linezolid dependence upon exposure to 8 mg/L linezolid. Interestingly, five of six ST22 linezolid-non-dependent isolates tested developed linezolid dependence when linezolid exposure preceded growth analysis. The rapid LRSE dissemination in Greek hospitals threatens linezolid activity. The observation that most LRSE belonged to ST22 and expressed dependence on linezolid clearly implies that the spread of linezolid resistance should have been driven by this trait, which provided the LRSE with a selective advantage under linezolid pressure. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. Intrapulmonary penetration of linezolid.

    Science.gov (United States)

    Honeybourne, David; Tobin, Caroline; Jevons, Gail; Andrews, Jenny; Wise, Richard

    2003-06-01

    This study was designed to measure the concentrations of linezolid in bronchial mucosa, pulmonary macrophages and epithelial lining fluid and to compare them with simultaneous blood levels. Ten adult patients undergoing bronchoscopy for diagnostic purposes were given oral linezolid at a dosage of 600 mg twice a day for a total of six doses. Patients with active lung infection were excluded from the study. Flexible bronchoscopy was carried out between 2 and 8 h after the last dose of linezolid. Bronchial biopsies and bronchoalveolar lavage were carried out and a simultaneous blood sample obtained. Linezolid levels were measured using high-performance liquid chromatography (HPLC). Mean concentrations of linezolid were 13.4 mg/L in serum, 10.7 mg/kg in mucosa, 8.1 mg/L in alveolar macrophages and 25.1 mg/L in epithelial lining fluid. The mean site/serum concentration ratios were 0.79 for bronchial mucosa, 0.71 for macrophages and 8.35 for epithelial lining fluid. The MIC90 (< or =4 mg/L) of linezolid for Staphylococcus aureus and Streptococcus pneumoniae was exceeded in serum and bronchial mucosa in all subjects, in epithelial lining fluid in nine subjects and in macrophages in six subjects.

  7. Increasing Incidence of Linezolid-Intermediate or -Resistant, Vancomycin-Resistant Enterococcus faecium Strains Parallels Increasing Linezolid Consumption▿

    OpenAIRE

    Scheetz, Marc H.; Knechtel, Stephanie A.; Malczynski, Michael; Postelnick, Michael J.; Qi, Chao

    2008-01-01

    Clinical enterococcal resistance to linezolid is defined by the presence of the G2576T mutation. We evaluated the incidence of genetically proven linezolid resistance among vancomycin-resistant Enterococcus faecium strains and linezolid consumption for a possible association. A relationship was found (r2 = 0.73, P = 0.03) and predicts increasing resistance with current trends of linezolid use.

  8. Detection of linezolid resistance due to the optrA gene in Enterococcus faecalis from poultry meat from the American continent (Colombia)

    DEFF Research Database (Denmark)

    Cavaco, Lina; Bernal, J F; Zankari, Ea

    2017-01-01

    Three Enterococcus isolates obtained from retail chicken collected in 2010-11 as part of the Colombian Integrated Program for Antimicrobial Resistance Surveillance (COIPARS) showed reduced susceptibility towards linezolid (MIC 8 mg/L). This study aimed at characterizing the isolates resistant......A gene encoding resistance to linezolid and phenicols. Additional screening of 37 enterococci strains from the same study did not detect any further positives. Typing showed that two of the isolates belong to ST59, while the last belongs to ST489. All isolates carry genes encoding resistance to macrolide...

  9. Contribution of the autolysin AtlA to the bactericidal activity of amoxicillin against Enterococcus faecalis JH2-2.

    Science.gov (United States)

    Bravetti, Anne-Lise; Mesnage, Stéphane; Lefort, Agnès; Chau, Françoise; Eckert, Catherine; Garry, Louis; Arthur, Michel; Fantin, Bruno

    2009-04-01

    The bactericidal activity of amoxicillin was investigated against Enterococcus faecalis JH2-2 and against an isogenic mutant deficient in the production of the N-acetylglucosaminidase AtlA. Comparison of the two strains indicated that this autolysin contributes to killing by amoxicillin both in vitro and in a rabbit model of experimental endocarditis.

  10. Linezolid-Dependent Function and Structure Adaptation of Ribosomes in a Staphylococcus epidermidis Strain Exhibiting Linezolid Dependence

    OpenAIRE

    Kokkori, Sofia; Apostolidi, Maria; Tsakris, Athanassios; Pournaras, Spyros; Stathopoulos, Constantinos; Dinos, George

    2014-01-01

    Linezolid-dependent growth was recently reported in Staphylococcus epidermidis clinical strains carrying mutations associated with linezolid resistance. To investigate this unexpected behavior at the molecular level, we isolated active ribosomes from one of the linezolid-dependent strains and we compared them with ribosomes isolated from a wild-type strain. Both strains were grown in the absence and presence of linezolid. Detailed biochemical and structural analyses revealed essential differe...

  11. Clinical Population Pharmacokinetics and Toxicodynamics of Linezolid

    Science.gov (United States)

    Boak, Lauren M.; Rayner, Craig R.; Grayson, M. Lindsay; Paterson, David L.; Spelman, Denis; Khumra, Sharmila; Capitano, Blair; Forrest, Alan; Li, Jian

    2014-01-01

    Thrombocytopenia is a common side effect of linezolid, an oxazolidinone antibiotic often used to treat multidrug-resistant Gram-positive bacterial infections. Various risk factors have been suggested, including linezolid dose and duration of therapy, baseline platelet counts, and renal dysfunction; still, the mechanisms behind this potentially treatment-limiting toxicity are largely unknown. A clinical study was conducted to investigate the relationship between linezolid pharmacokinetics and toxicodynamics and inform strategies to prevent and manage linezolid-associated toxicity. Forty-one patients received 42 separate treatment courses of linezolid (600 mg every 12 h). A new mechanism-based, population pharmacokinetic/toxicodynamic model was developed to describe the time course of plasma linezolid concentrations and platelets. A linezolid concentration of 8.06 mg/liter (101% between-patient variability) inhibited the synthesis of platelet precursor cells by 50%. Simulations predicted treatment durations of 5 and 7 days to carry a substantially lower risk than 10- to 28-day therapy for platelet nadirs of linezolid therapy and large between-patient variability, close monitoring of patients for development of toxicity is important. Dose individualization based on plasma linezolid concentration profiles and platelet counts should be considered to minimize linezolid-associated thrombocytopenia. Overall, oxazolidinone therapy over 5 to 7 days even at relatively high doses was predicted to be as safe as 10-day therapy of 600 mg linezolid every 12 h. PMID:24514086

  12. Surveillance for linezolid resistance via the Zyvox® Annual Appraisal of Potency and Spectrum (ZAAPS) programme (2014): evolving resistance mechanisms with stable susceptibility rates.

    Science.gov (United States)

    Mendes, Rodrigo E; Hogan, Patricia A; Jones, Ronald N; Sader, Helio S; Flamm, Robert K

    2016-07-01

    The objective of this study was to report the linezolid in vitro activity observed during the Zyvox(®) Annual Appraisal of Potency and Spectrum (ZAAPS) programme for 2014. In total, 7541 organisms causing documented infections were consecutively collected in 66 centres in 33 countries, excluding the USA. Susceptibility testing was performed by broth microdilution. Isolates displaying linezolid MIC results of ≥4 mg/L were molecularly characterized. Linezolid inhibited all Staphylococcus aureus at ≤2 mg/L, with MIC50 results of 1 mg/L, regardless of methicillin resistance. A similar linezolid MIC50 result (i.e. 0.5 mg/L) was observed against CoNS, with the vast majority of isolates (99.4%) also inhibited at ≤2 mg/L. Six CoNS that exhibited elevated linezolid MIC values were found to contain alterations in the 23S rRNA and/or L3 ribosomal protein. Linezolid exhibited consistent modal MIC and MIC50 results (1 mg/L) against enterococci, regardless of species or vancomycin resistance. Three Enterococcus faecalis from Galway and Dublin (Ireland) and Kelantan (Malaysia) showed MIC results of 4 to 8 mg/L and carried optrA. All Streptococcus pneumoniae, viridans-group streptococci and β-haemolytic streptococci were inhibited by linezolid at ≤2, ≤2 and ≤1 mg/L, respectively, with equivalent MIC90 results (1 mg/L for all groups). These results document the continued long-term and stable in vitro potency of linezolid and reveal a limited number of isolates with decreased susceptibility to linezolid (i.e. MIC ≥4 mg/L). The latter isolates primarily showed mutations in the 23S rRNA gene and/or L3 protein, but cfr was not detected. Moreover, this study shows that isolates carrying the newly described ABC transporter optrA are not restricted to China. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Resistance to Linezolid

    DEFF Research Database (Denmark)

    Vester, Birte; Ntokou, Eleni

    2017-01-01

    Linezolid is an antimicrobial agent that binds to the bacterial ribosome and thereby inhibits protein synthesis. Soon after its release as a clinical drug, it became clear that bacteria could become resistant to linezolid. The resistance mechanisms are mainly causing alteration of the drug target...... site, but probably efflux might also play a role. The resistance is still rare in surveillance studies, but outbreaks of resistant clones from hospitals have been observed. So far the main mechanisms of resistance are occurrence of mutations in ribosomal genes or obtaining plasmids with a gene coding...... for a methyltransferase providing resistance. The most obvious way to avoid resistance may be development of derivatives of linezolid overcoming the known resistance mechanisms....

  14. Antibiotic resistance and virulence traits in clinical and environmental Enterococcus faecalis and Enterococcus faecium isolates.

    Science.gov (United States)

    Rathnayake, I U; Hargreaves, M; Huygens, F

    2012-07-01

    This study compared virulence and antibiotic resistance traits in clinical and environmental Enterococcus faecalis and Enterococcus faecium isolates. E. faecalis isolates harboured a broader spectrum of virulence determinants compared to E. faecium isolates. The virulence traits Cyl-A, Cyl-B, Cyl-M, gel-E, esp and acm were tested and environmental isolates predominantly harboured gel-E (80% of E. faecalis and 31.9% of E. faecium) whereas esp was more prevalent in clinical isolates (67.8% of E. faecalis and 70.4% of E. faecium). E. faecalis and E. faecium isolated from water had different antibiotic resistance patterns compared to those isolated from clinical samples. Linezolid resistance was not observed in any isolates tested and vancomycin resistance was observed only in clinical isolates. Resistance to other antibiotics (tetracycline, gentamicin, ciprofloxacin and ampicillin) was detected in both clinical and water isolates. Clinical isolates were more resistant to all the antibiotics tested compared to water isolates. Multi-drug resistance was more prevalent in clinical isolates (71.2% of E. faecalis and 70.3% of E. faecium) compared to water isolates (only 5.7% E. faecium). tet L and tet M genes were predominantly identified in tetracycline-resistant isolates. All water and clinical isolates resistant to ciprofloxacin and ampicillin contained mutations in the gyrA, parC and pbp5 genes. A significant correlation was found between the presence of virulence determinants and antibiotic resistance in all the isolates tested in this study (pantibiotic resistant enterococci, together with associated virulence traits, in surface recreational water could be a public health risk. Copyright © 2012 Elsevier GmbH. All rights reserved.

  15. [Consensus document for the treatment of bacteremia and endocarditis caused by methicillin-resistent Staphylococcus aureus. Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica].

    Science.gov (United States)

    Gudiol, Francisco; Aguado, José María; Pascual, Alvaro; Pujol, Miquel; Almirante, Benito; Miró, José María; Cercenado, Emilia; Domínguez, María de Los Angeles; Soriano, Alex; Rodríguez-Baño, Jesús; Vallés, Jordi; Palomar, Mercedes; Tornos, Pilar; Bouza, Emilio

    2009-02-01

    Bacteremia and endocarditis due to methicillin-resistant Staphylococcus aureus (MRSA) are prevalent and clinically important. The rise in MRSA bacteremia and endocarditis is related with the increasing use of venous catheters and other vascular procedures. Glycopeptides have been the reference drugs for treating these infections. Unfortunately their activity is not completely satisfactory, particularly against MRSA strains with MICs > 1 microg/mL. The development of new antibiotics, such as linezolid and daptomycin, and the promise of future compounds (dalvabancin, ceftobiprole and telavancin) may change the expectatives in this field.The principal aim of this consensus document was to formulate several recommendations to improve the outcome of MRSA bacteremia and endocarditis, based on the latest reported scientific evidence. This document specifically analyzes the approach for three clinical situations: venous catheter-related bacteremia, persistent bacteremia, and infective endocarditis due to MRSA.

  16. Activities of Tedizolid and Linezolid Determined by the Reference Broth Microdilution Method against 3,032 Gram-Positive Bacterial Isolates Collected in Asia-Pacific, Eastern Europe, and Latin American Countries in 2014.

    Science.gov (United States)

    Pfaller, Michael A; Flamm, Robert K; Jones, Ronald N; Farrell, David J; Mendes, Rodrigo E

    2016-09-01

    Tedizolid and linezolid in vitro activities against 3,032 Gram-positive pathogens collected in Asia-Pacific, Eastern European, and Latin American medical centers during 2014 were assessed. The isolates were tested for susceptibility by the current reference broth microdilution methods. Due to concern over the effect of MIC endpoint criteria on the results of testing the oxazolidinones tedizolid and linezolid, MIC endpoint values were read by two methods: (i) reading the MIC at the first well where the trailing began without regard for pinpoint trailing, according to CLSI M07-A10 and M100-S26 document instructions for reading linezolid (i.e., 80% inhibition of growth; these reads were designated tedizolid 80 and linezolid 80), and (ii) at 100% inhibition of growth (designated tedizolid 100 and linezolid 100). All Staphylococcus aureus, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus group, and Enterococcus faecalis isolates were inhibited at tedizolid 80 and 100 MIC values of 0.25 and 0.5, 0.25 and 0.25, 0.25 and 0.5, 0.12 and 0.25, and 0.5 and 1 μg/ml, respectively. Generally, MIC50 and MIC90 results for tedizolid 80 and linezolid 80 were one doubling dilution lower than those read at 100% inhibition. Tedizolid was 4- to 8-fold more potent than linezolid against all the isolates tested regardless of the MIC endpoint criterion used. Despite the differences in potency, >99.9% of isolates tested in this survey were susceptible to both linezolid and tedizolid using CLSI and EUCAST interpretive criteria. In conclusion, tedizolid demonstrated greater in vitro potency than linezolid against Gram-positive pathogens isolated from patients in medical centers across the Asia-Pacific region, Eastern Europe, and Latin America. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  17. Pharmacokinetics of linezolid in critically ill patients.

    Science.gov (United States)

    Sazdanovic, Predrag; Jankovic, Slobodan M; Kostic, Marina; Dimitrijevic, Aleksandra; Stefanovic, Srdjan

    2016-06-01

    Linezolid is an oxazolidinone antibiotic active against Gram-positive bacteria, and is most commonly used to treat life-threatening infections in critically ill patients. The pharmacokinetics of linezolid are profoundly altered in critically ill patients, partly due to decreased function of vital organs, and partly because life-sustaining drugs and devices may change the extent of its excretion. This article is summarizes key changes in the pharmacokinetics of linezolid in critically ill patients. The changes summarized are clinically relevant and may serve as rationale for dosing recommendations in this particular population. While absorption and penetration of linezolid to tissues are not significantly changed in critically ill patients, protein binding of linezolid is decreased, volume of distribution increased, and metabolism may be inhibited leading to non-linear kinetics of elimination; these changes are responsible for high inter-individual variability of linezolid plasma concentrations, which requires therapeutic plasma monitoring and choice of continuous venous infusion as the administration method. Acute renal or liver failure decrease clearance of linezolid, but renal replacement therapy is capable of restoring clearance back to normal, obviating the need for dosage adjustment. More population pharmacokinetic studies are necessary which will identify and quantify the influence of various factors on clearance and plasma concentrations of linezolid in critically ill patients.

  18. Assessment of linezolid prescriptions in three French hospitals.

    Science.gov (United States)

    Dentan, C; Forestier, E; Roustit, M; Boisset, S; Chanoine, S; Epaulard, O; Pavese, P

    2017-07-01

    The use of linezolid to treat gram-positive cocci infections is increasing in France. Linezolid is approved in pneumonia and complicated skin and soft tissue infections. Overuse and misuse of linezolid can favor the emergence and spreading of linezolid-resistant strains. We aimed to assess the appropriateness of linezolid use in French hospitals. This is a multicenter, retrospective study conducted in three tertiary care hospitals. Appropriateness of linezolid indications and adequacy (composite score concerning dosage, route of administration and blood monitoring) were assessed. Over a three-month period, all prescriptions of linezolid were extracted and analyzed by two independent infectious disease experts. Among the 81 initial prescriptions that were evaluated, indication was appropriate in 48% of cases. Among those, 51% complied with international guidelines. Fifty-seven percent of the prescriptions were adequate regarding dosage, route of administration and blood monitoring. Overall, 23% of prescriptions combined both appropriateness and adequacy. The most frequent reasons for inappropriateness were the possibility of choosing narrower-spectrum antibiotics and the empirical use of linezolid in severe sepsis or septic shock. Initial treatment was the most frequently appropriate in bone and joint infection cases (p = 0.001). Our study shows that even if modalities of use were mostly correct, appropriateness of linezolid indications is low. Educational programs are mandatory to improve practices, as well as clinical studies to better assess the efficacy and safety of linezolid in clinical situations other than pneumonia or complicated skin and soft tissue infections.

  19. Preclinical Evaluations To Identify Optimal Linezolid Regimens for Tuberculosis Therapy

    Science.gov (United States)

    Drusano, George L.; Adams, Jonathan R.; Rodriquez, Jaime L.; Jambunathan, Kalyani; Baluya, Dodge L.; Brown, David L.; Kwara, Awewura; Mirsalis, Jon C.; Hafner, Richard; Louie, Arnold

    2015-01-01

    ABSTRACT Linezolid is an oxazolidinone with potent activity against Mycobacterium tuberculosis. Linezolid toxicity in patients correlates with the dose and duration of therapy. These toxicities are attributable to the inhibition of mitochondrial protein synthesis. Clinically relevant linezolid regimens were simulated in the in vitro hollow-fiber infection model (HFIM) system to identify the linezolid therapies that minimize toxicity, maximize antibacterial activity, and prevent drug resistance. Linezolid inhibited mitochondrial proteins in an exposure-dependent manner, with toxicity being driven by trough concentrations. Once-daily linezolid killed M. tuberculosis in an exposure-dependent manner. Further, 300 mg linezolid given every 12 hours generated more bacterial kill but more toxicity than 600 mg linezolid given once daily. None of the regimens prevented linezolid resistance. These findings show that with linezolid monotherapy, a clear tradeoff exists between antibacterial activity and toxicity. By identifying the pharmacokinetic parameters linked with toxicity and antibacterial activity, these data can provide guidance for clinical trials evaluating linezolid in multidrug antituberculosis regimens. PMID:26530386

  20. Possible serotonin syndrome with carbidopa-levodopa and linezolid.

    Science.gov (United States)

    Pettit, N N; Alonso, V; Wojcik, E; Anyanwu, E C; Ebara, L; Benoit, J-L

    2016-02-01

    Serotonin syndrome (SS) can occur when linezolid is combined with other serotonergic agents. We report a case of possible SS in an elderly patient receiving linezolid in combination with carbidopa-levodopa (CL). Although certain classes of agents are commonly reported as causing SS among patients receiving linezolid, there are no specific case reports detailing this reaction with CL. Linezolid combined with CL should generally be avoided; however, if linezolid must be used, discontinuation of other agents with serotonergic activity is recommended with careful monitoring for signs and symptoms of SS. © 2016 John Wiley & Sons Ltd.

  1. Therapeutic drug management of linezolid: a missed opportunity for clinicians?

    Science.gov (United States)

    Cattaneo, Dario; Gervasoni, Cristina; Cozzi, Valeria; Castoldi, Simone; Baldelli, Sara; Clementi, Emilio

    2016-12-01

    Some studies have shown that adjustments to the linezolid dose guided by therapeutic drug monitoring (TDM) can reduce interindividual variability in drug exposure and improve linezolid tolerability. In this study, 6 years of linezolid TDM, a diagnostic service for our hospital and others in the Milan (Italy) area, is described. Samples were collected immediately before the morning dose intake (trough concentrations) in steady-state conditions. Linezolid concentrations were quantified by a validated high-performance liquid chromatography (HPLC) method. Four hundred linezolid trough concentrations from 220 patients were collected. A 20-fold variability in linezolid levels was observed. Positive and significant correlations between linezolid trough concentrations and patient age (r = 0.325, P linezolid concentrations with time was observed in a subgroup of patients with more than one TDM assessment. Elderly patients, especially those aged >80 years and with impaired renal function, are at a higher risk of overexposure to linezolid. Despite the observed progressive increase in linezolid concentrations over time, most physicians did not change the drug dose according to the TDM results, even in the presence of frank overexposure to linezolid. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  2. Endocarditis - children

    Science.gov (United States)

    Valve infection - children; Staphylococcus aureus - endocarditis - children; Enterococcus - endocarditis- children; Streptococcus viridians - endocarditis - children; Candida - endocarditis - children; Bacterial endocarditis - children; Infective ...

  3. A novel role for D-alanylation of lipoteichoic acid of enterococcus faecalis in urinary tract infection.

    Directory of Open Access Journals (Sweden)

    Dominique Wobser

    Full Text Available BACKGROUND: Enterococci are the third most common cause of healthcare-associated infections, which include urinary tract infections, bacteremia and endocarditis. Cell-surface structures such as lipoteichoic acid (LTA have been poorly examined in E. faecalis, especially with respect to urinary tract infections (UTIs. The dlt operon is responsible for the D-alanylation of LTA and includes the gene dltA, which encodes the D-alanyl carrier protein ligase (Dcl. The involvement of LTA in UTI infection by E. faecalis has not been studied so far. Here, we examined the role of teichoic acid alanylation in the adhesion of enterococci to uroepithelial cells. RESULTS: In a mouse model of urinary tract infection, we showed that E. faecalis 12030ΔdltA mutant colonizes uroepithelial surfaces more efficiently than wild type bacteria. We also demonstrated that this mutant adhered four fold better to human bladder carcinoma cell line T24 compared to the wild type strain. Bacterial adherence could be significantly inhibited by purified lipoteichoic acid (LTA and inhibition was specific. CONCLUSION: In contrast to bacteraemia model and adherence to colon surfaces, E. faecalis 12030ΔdltA mutant colonized uroepithelial surfaces more efficiently than wild-type bacteria. In the case of the uroepithelial surface the adherence to specific host cells could be prevented by purified LTA. Our results therefore suggest a novel function of alanylation of LTA in E. faecalis.

  4. Multiresistant-MRSA tricuspid valve infective endocarditis with ancient osteomyelitis locus

    Directory of Open Access Journals (Sweden)

    Gambarati Gianpaolo

    2006-07-01

    Full Text Available Abstract Background Methicillin-resistant S. aureus (MRSA with low susceptibility to glycopeptides is uncommon. Case presentation The case of a 50-year-old non-drug addict patient presenting with tricuspid valve infective endocarditis (IE by MRSA resistant to vancomycin and linezolid is presented. There was response only to quinupristin/dalfopristin. He had a motorcycling accident four years before undergoing right above-the-knee amputation and orthopaedic fixation of the left limb. There were multiple episodes of left MRSA-osteomyelitis controlled after surgery and vancomycin therapy. MRSA isolated from the blood at the time of IE presented with the same profile than the isolated four years earlier. Sequential treatment with teicoplanin-cotrimoxazole and Linezolid associated to vancomycin – rifampicin – cotrimoxazole had no improvement. Infection was controlled after 28 days of therapy with quinupristin/dalfopristin. Conclusion The literature presents only a few cases of MRSA IE not susceptible to glycopeptides in not drug addicted patients. This case shows the comparison of a highly-resistant MRSA after previous S. aureus osteomyelitis treated with glycopeptides. This is the first description of successful treatment of resistant-MRSA IE of the tricuspid valve complicated by multiple pulmonary septic infarction with quinupristin/dalfopristin

  5. Infection dynamics of vancomycin and inducible clindamycin resistant Enterococcus faecalis in an Indian teaching hospital

    Directory of Open Access Journals (Sweden)

    Debasmita Dubey

    2015-06-01

    Full Text Available Objective: To do surveillance for vancomycin and inducible clindamycin resistance of Enterococcus faecalis (E. faecalis, a Gram-positive bacterium in a teaching hospital. Methods: E. faecalis strains isolated from clinical samples were screened for vancomycin and inducible clindamycin resistance, i.e., D-test positivity, using vancomycin screen agar and blood agar plates, respectively. For the D-test screening, erythromycin resistant (Er-r and clindamycin sensitive (Cd-s strain were used. Results: Of 265 isolated E. faecalis strains, 159 (60% were vancomycin resistant Enterococcus (VRE and 106 were vancomycin sensitive Enterococcus (VSE. Of 265 strains, 42 were constitutively resistant to clindamycin and erythromycin and of 148 Er-r and Cd-s strains, 87 (32.83% had D-test positivity, while the rest 61 strains were D-test negatives. D-test results examined with 6 hospital factors as bivalents, only 2 factors, the VSE/VRE and the presence/absence of prior antibiotic use > 90 days bivalent were statistically significant. A VRE strain with D-test positivity would be picked up 0.570 2 times more frequently than a strain with VSE and D-test positivity. Also, patients with prior antibiotic use > 90 days had 3.737 5 times more chance of picking up D-test positive strains than patients without any prior antibiotic use. Resistance pattern of E. faecalis strains to individual 14 antibiotics were recorded; the maximum values of resistance were against ampicillin 10 μg/disc and linezolid 30 μg/disc. Student’s t-test for hospital acquired and community acquired data revealed that drug resistant strains were equally prevalent in both sources. Conclusions: Prevalence of 60% VRE in both hospital and adjoining community creates consternation. In total 87 (32.83% strains had D-test positivity; patients who had used antibiotics within the last 90 days have got an ample chance of picking of D-test positive E. faecalis. D-test protocol should be followed with

  6. Infective Endocarditis

    Science.gov (United States)

    ... Center > Infective Endocarditis Menu Topics Topics FAQs Infective Endocarditis En español Infective endocarditis is an infection of ... time, congestive heart failure (CHF). What causes infective endocarditis? The infection that leads to endocarditis can be ...

  7. In vitro activity of daptomycin combined with dalbavancin and linezolid, and dalbavancin with linezolid against MRSA strains.

    Science.gov (United States)

    Aktas, Gulseren; Derbentli, Sengul

    2017-02-01

    Combination therapies have a distinct advantage over monotherapies in terms of their broad spectrum, synergistic effect and prevention of the emergence of drug resistance. In the present study, the in vitro antibacterial activity of daptomycin combinations with linezolid and dalbavancin, and dalbavancin with linezolid were evaluated against 30 clinical MRSA strains. The MICs of all antibiotics were determined using microbroth dilution as described by the CLSI. The in vitro activities of antibiotics in combination were assessed by using a microbroth 'chequerboard' assay. The MIC values of all antibiotics determined were evaluated in accordance with the recommendations of the CLSI for daptomycin and linezolid, and the FDA for dalbavancin. All strains (100%) were found to be susceptible to daptomycin, dalbavancin and linezolid. The MIC 50 , MIC 90 and MIC range values of these antibiotics were determined to be 1, 1 and 0.5-1 mg/L, 0.12, 0.12 and 0.03-0.12 mg/L, and 1, 2 and 1-2 mg/L, respectively. The rates of synergistic effects were 67% for daptomycin combined with dalbavancin and with linezolid, and 60% for dalbavancin combined with linezolid. The results of this study show that in vitro combinations of these new antimicrobials will be effective in the therapy of MRSA infections. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. ANCA-associated pauci-immune glomerulonephritis in a patient with bacterial endocarditis: a challenging clinical dilemma

    OpenAIRE

    Cervi, Andrea; Kelly, Dylan; Alexopoulou, Iakovina; Khalidi, Nader

    2017-01-01

    Purpose: We report the case of a 59-year-old man with chronic hepatitis B and C infection presenting with acute kidney injury and enterococcus faecalis-infective endocarditis (IE). An elevated proteinase-3 (PR3)-ANCA and pauci-immune glomerulonephritis (GN) on renal biopsy were discovered, corresponding to ANCA-mediated GN. We conducted a literature review to assess the role of ANCA in IE and treatment implications. Methods: On systematic review of the literature, we found five previous cases...

  9. Clarithromycin increases linezolid exposure in multidrug-resistant tuberculosis patients

    NARCIS (Netherlands)

    Bolhuis, Mathieu S.; van Altena, Richard; van Soolingen, Dick; de Lange, Wiel C. M.; Uges, Donald R. A.; van der Werf, Tjip S.; Kosterink, Jos G. W.; Alffenaar, Jan-Willem C.

    2013-01-01

    The use of linezolid for the treatment of multidrug-resistant tuberculosis is limited by dose-and time-dependent toxicity. Recently, we reported a case of pharmacokinetic drug drug interaction between linezolid and clarithromycin that resulted in increased linezolid exposure. The aim of this

  10. Activity of linezolid and tedizolid against clinical isolates of methicillin-resistant and methicillin and linezolid resistant Staphylococcus aureus: an in vitro comparison.

    Science.gov (United States)

    Peñuelas, M; Candel, F J; Lejarraga, C; López-González, L; Viñuela-Prieto, J M; López de Mendoza, D

    2016-10-01

    The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in Spain is approximately 20-30%. However, resistance to linezolid is rare, and the main reports are from nosocomial outbreaks. The objective of the present study was to compare the in vitro susceptibility of linezolid with that of tedizolid against MRSA isolates and methicillin-and linezolid-resistant isolates (MLRSA) mediated by the cfr gene. The in vitro susceptibility of linezolid and tedizolid was determined using the E-test with 18 MRSA strains and 18 cfr-mediated MLRSA strains obtained from clinical isolates in the microbiology service of a tertiary university hospital. All MRSA strains were susceptible to both antibiotics. Analysis of the MRSA isolates revealed that the MIC50 and MIC90 of linezolid were 1.5 and 2 mg/L, respectively; those of tedizolid were 0.25 and 0.4 mg/L. The MIC50 and MIC90 of tedizolid remained at 0.75 and 1 mg/L against the MLRSA strains (MIC90 ≥ 8 mg/L). Both for MRSA and for MLRSA, the MICs obtained for tedizolid were at least 2 dilutions lower than those of linezolid, thus demonstrating between 2 and 4 times greater activity in vitro than linezolid.

  11. Sepsis due to linezolid resistant Staphylococcus cohnii and Staphylococcus kloosii: first reports of linezolid resistance in coagulase negative staphylococci from India.

    Science.gov (United States)

    Peer, M A; Nasir, R A; Kakru, D K; Fomda, B A; Bashir, G; Sheikh, I A

    2011-01-01

    Linezolid, a viable alternative to vancomycin against methicillin resistant staphylococcal isolates, has been in use for a decade around the globe. However, resistance against staphylococci remains extremely rare and unreported from most of the Asian countries. Herein, we report two cases of linezolid resistant, coagulase negative staphylococcal sepsis for the first time from India. The first case was an 18-year-old burn patient, who, after a major graft surgery, landed in sepsis, and linezolid resistant Staphylococcus cohnii with an minimum inhibitory concentration (MIC) of >256 μg/ml by both broth microdilution and Etest, was isolated from multiple blood cultures. The second patient was a 60-year-old male with an intracranial bleed and sepsis, from whose blood cultures, linezolid resistant Staphylococcus kloosii was repeatedly isolated. Linezolid MIC was >32 μg/ml by broth microdilution and >16 μg/ml by Etest.

  12. Sepsis due to linezolid resistant Staphylococcus cohnii and Staphylococcus kloosii: First reports of linezolid resistance in coagulase negative staphylococci from India

    Directory of Open Access Journals (Sweden)

    M A Peer

    2011-01-01

    Full Text Available Linezolid, a viable alternative to vancomycin against methicillin resistant staphylococcal isolates, has been in use for a decade around the globe. However, resistance against staphylococci remains extremely rare and unreported from most of the Asian countries. Herein, we report two cases of linezolid resistant, coagulase negative staphylococcal sepsis for the first time from India. The first case was an 18-year-old burn patient, who, after a major graft surgery, landed in sepsis, and linezolid resistant Staphylococcus cohnii with an minimum inhibitory concentration (MIC of >256 μg/ml by both broth microdilution and Etest, was isolated from multiple blood cultures. The second patient was a 60-year-old male with an intracranial bleed and sepsis, from whose blood cultures, linezolid resistant Staphylococcus kloosii was repeatedly isolated. Linezolid MIC was >32 μg/ml by broth microdilution and >16 μg/ml by Etest.

  13. Linezolid-induced thrombocytopenia in two patients with renal dysfunction

    Directory of Open Access Journals (Sweden)

    Engin Melek

    2016-12-01

    Full Text Available Linezolid is an oxazolidinone antibiotic, active against gram positive bacteria that are resistant to other antibiotics including glycopeptides. Thrombocytopenia is an adverse effect of linezolid. Although various risk factors have been suggested, the mechanisms behind this side effect are largely unknown. Here, we report two adolescents with the diagnosis of chronic kidney disease who developed thrombocytopenia following treatment with linezolid. Our purpose in highlighting these cases is to increase the clinical awareness concerning this side effect of linezolid. While it is well known that thrombocytopenia may develop during linezolid treatment, it is relatively unknown that patients with renal dysfunction have an increased risk for the development of thrombocytopenia compared to patients without renal dysfunction. [Cukurova Med J 2016; 41(4.000: 808-810

  14. Linezolid for Infants and Toddlers With Disseminated Tuberculosis: First Steps.

    Science.gov (United States)

    Deshpande, Devyani; Srivastava, Shashikant; Pasipanodya, Jotam G; Bush, Stephen J; Nuermberger, Eric; Swaminathan, Soumya; Gumbo, Tawanda

    2016-11-01

     Infants and toddlers often present with disseminated and lymph node tuberculosis, in which Mycobacterium tuberculosis (Mtb) is predominantly intracellular. Linezolid, used to treat tuberculosis in adults, has not been formally studied in infants. Infants clear linezolid 5 times faster than adults and achieve lower 0- to 24-hour area under the concentration-time curves (AUC 0-24 ).  To mimic intracellular disease, we infected human-derived THP-1 macrophages with Mtb and inoculated hollow fiber systems. We performed dose-effect and dose-scheduling studies in which we recapitulated the linezolid half-life of 3 hours encountered in infants. Repetitive sampling for linezolid pharmacokinetics, Mtb intracellular burden, viable monocyte count, and RNA sequencing reads were performed up to 28 days.  The linezolid extracellular half-life was 2.64 ± 0.38 hours, whereas intracellular half-life was 8.93 ± 1.30 hours (r 2 = 0.89). Linezolid efficacy was linked to the AUC 0-24 to minimum inhibitory concentration (MIC) ratio (r 2 = 0.98). The exposure associated with maximal Mtb kill was an AUC 0-24 /MIC of 23.37 ± 1.16. We identified a 414-gene transcript on exposure to toxic linezolid doses. The largest number of genes mapped to ribosomal proteins, a signature hitherto not associated with linezolid toxicity. The second-largest number of differentially expressed genes mapped to mitochondrial enzyme inhibition. Linezolid AUC 0-24 best explained the mitochondrial gene inhibition, with 50% inhibition at 94 mg × hour/L (highest r 2 = 0.98).  We identified the linezolid AUC 0-24 /MIC target for optimal efficacy against pediatric intracellular tuberculosis, and an AUC 0-24 threshold associated with mitochondrial inhibition. These constitute a therapeutic window to be targeted for optimal linezolid doses in children with tuberculosis. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

  15. Linezolid susceptibility in Helicobacter pylori, including strains with multidrug resistance.

    Science.gov (United States)

    Boyanova, Lyudmila; Evstatiev, Ivailo; Gergova, Galina; Yaneva, Penka; Mitov, Ivan

    2015-12-01

    Only a few studies have evaluated Helicobacter pylori susceptibility to linezolid. The aim of the present study was to assess linezolid susceptibility in H. pylori, including strains with double/multidrug resistance. The susceptibility of 53 H. pylori strains was evaluated by Etest and a breakpoint susceptibility testing method. Helicobacter pylori resistance rates were as follows: amoxicillin, 1.9%; metronidazole, 37.7%; clarithromycin, 17.0%; tetracycline, 1.9%; levofloxacin, 24.5%; and linezolid (>4 mg/L), 39.6%. The linezolid MIC50 value was 31.2-fold higher than that of clarithromycin and 10.5-fold higher than that of levofloxacin; however, 4 of 11 strains with double/multidrug resistance were linezolid-susceptible. The MIC range of the oxazolidinone agent was larger (0.125-64 mg/L) compared with those in the previous two reports. The linezolid resistance rate was 2.2-fold higher in metronidazole-resistant strains and in strains resistant to at least one antibiotic compared with the remaining strains. Briefly, linezolid was less active against H. pylori compared with clarithromycin and levofloxacin, and linezolid resistance was linked to resistance to metronidazole as well as to resistance to at least one antibiotic. However, linezolid activity against some strains with double/multidrug resistance may render the agent appropriate to treat some associated H. pylori infections following in vitro susceptibility testing of the strains. Clinical trials are required to confirm this suggestion. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  16. Human Bile Reduces Antimicrobial Activity of Selected Antibiotics against Enterococcus faecalis and Escherichia coli In Vitro.

    Science.gov (United States)

    Wulkersdorfer, Beatrix; Jaros, David; Eberl, Sabine; Poschner, Stefan; Jäger, Walter; Cosentini, Enrico; Zeitlinger, Markus; Schwameis, Richard

    2017-08-01

    It has been known from previous studies that body fluids, such as cerebrospinal fluid, lung surfactant, and urine, have a strong impact on the bacterial killing of many anti-infective agents. However, the influence of human bile on the antimicrobial activity of antibiotics is widely unknown. Human bile was obtained and pooled from 11 patients undergoing cholecystectomy. After sterilization of the bile fluid by gamma irradiation, its effect on bacterial killing was investigated for linezolid (LZD) and tigecycline (TGC) against Enterococcus faecalis ATCC 29212. Further, ciprofloxacin (CIP), meropenem (MEM), and TGC were tested against Escherichia coli ATCC 25922. Time-kill curves were performed in pooled human bile and Mueller-Hinton broth (MHB) over 24 h. Bacterial counts (in CFU per milliliter after 24 h) of bile growth controls were approximately equal to MHB growth controls for E. coli and approximately 2-fold greater for E. faecalis , indicating a promotion of bacterial growth by bile for the latter strain. Bile reduced the antimicrobial activity of CIP, MEM, and TGC against E. coli as well as the activity of LZD and TGC against E. faecalis This effect was strongest for TGC against the two strains. Degradation of TGC in bile was identified as the most likely explanation. These findings may have important implications for the treatment of bacterial infections of the gallbladder and biliary tract and should be explored in more detail. Copyright © 2017 American Society for Microbiology.

  17. Outbreak of bacterial endocarditis associated with an oral surgery practice: New Jersey public health surveillance, 2013 to 2014.

    Science.gov (United States)

    Ross, Kathleen M; Mehr, Jason S; Greeley, Rebecca D; Montoya, Lindsay A; Kulkarni, Prathit A; Frontin, Sonya; Weigle, Trevor J; Giles, Helen; Montana, Barbara E

    2018-03-01

    In October and November 2014, the New Jersey Department of Health received reports of 3 patients who developed Enterococcus faecalis endocarditis after undergoing surgical procedures at the same oral surgery practice in New Jersey. Bacterial endocarditis is an uncommon but life-threatening condition; 3 patients with enterococcal endocarditis associated with a single oral surgery practice is unusual. An investigation was initiated because of the potential ongoing public health risk. Public health officials conducted retrospective surveillance to identify additional patients with endocarditis associated with the practice. They interviewed patients using a standardized questionnaire. An investigative public health team inspected the office environment, interviewed staff, and reviewed medical records. Public health officials identified 15 confirmed patients with enterococcal endocarditis of those patients who underwent procedures from December 2012 through August 2014. Among these patients, 12 (80%) underwent cardiac surgery. One (7%) patient died from complications of endocarditis and subsequent cardiac surgery. Breaches of recommended infection prevention practices were identified that might have resulted in transmission of enterococci during the administration of intravenous sedation, including failure to perform hand hygiene and failure to maintain aseptic technique when performing procedures and handling medications. This investigation highlights the importance of adhering to infection prevention recommendations in dental care settings. No additional patients with endocarditis were identified after infection prevention and control recommendations were implemented. Infection prevention training should be emphasized at all levels of professional dental training. All dental health care personnel establishing intravenous treatment and administering intravenous medications should be trained in safe injection practices. Copyright © 2018 American Dental Association

  18. A retrospective study of the risk factors for linezolid-induced thrombocytopenia and anemia.

    Science.gov (United States)

    Hanai, Yuki; Matsuo, Kazuhiro; Ogawa, Miki; Higashi, Ayaka; Kimura, Itsuki; Hirayama, Shinobu; Kosugi, Takayoshi; Nishizawa, Kenji; Yoshio, Takashi

    2016-08-01

    Myelosuppression is major treatment-related adverse events of linezolid therapy and result in treatment termination in some cases. We aimed to identify the risk factors for linezolid-induced thrombocytopenia and anemia. We retrospectively retrieved demographic and laboratory data from the medical records of 221 Japanese patients who were undergoing linezolid therapy. Thrombocytopenia and anemia were defined as an unexplained reduction of >30% in the patient's platelet count and hemoglobin level, respectively, from the baseline. Thrombocytopenia developed in 48.4% of patients, and anemia developed in 10.4% of patients during linezolid therapy. In multivariate analysis, creatinine clearance (adjusted odds ratio = 0.94 [0.92-0.95], P linezolid therapy (1.14 [1.07-1.21], P linezolid-induced thrombocytopenia. Patients with creatinine clearance rates of linezolid-induced thrombocytopenia. In addition, a high incidence of linezolid-induced thrombocytopenia was even detected among the patients that had received linezolid therapy for linezolid therapy (1.04 [1.01-1.07], P = 0.011) was shown to be a risk factor for anemia, and a high incidence of anemia was seen among the patients who received linezolid for >15 days. In conclusion, we recommend that among patients receiving linezolid therapy the platelet counts of those with risk factors for linezolid-induced thrombocytopenia should be monitored closely throughout treatment, and the hemoglobin levels of patients that receive linezolid for >15 days should be carefully monitored on a weekly basis to detect anemia. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  19. Emergence of linezolid-resistant coagulase-negative staphylococci in an intensive care unit.

    Science.gov (United States)

    Balandin, Bárbara; Lobo, Beatriz; Orden, Beatriz; Román, Federico; García, Elena; Martínez, Rocío; Valdivia, Miguel; Ortega, Alfonso; Fernández, Inmaculada; Galdos, Pedro

    2016-01-01

    The aim of this study was to report the emergence of linezolid-resistant coagulase-negative staphylococci (CoNS) in an intensive care unit. An observational study was conducted in critically ill patients with colonization or infection by linezolid-resistant CoNS between January 2010 and December 2014. We analyzed the epidemiological and clinical features, and the mechanism of resistance to linezolid. We also evaluated the association between the incidence of linezolid-resistant CoNS strains and the consumption of linezolid in the study period. During the study period 49 patients had a linezolid-resistant CoNS strain isolated from clinical samples (blood in 42 cases, urine in 6, peritoneal fluid in 1). Molecular study showed a combination of mechanisms of resistance. Most patients were critically ill (APACHE II score = 21.9 ± 8.3) and nearly all had undergone surgery and invasive procedures, and had prior exposure to antibiotics. Linezolid-resistant CoNS were considered to be contaminants in 42 patients and associated with infection in 7 patients, comprising bacteremia and septic shock in most of them. They were successfully treated with glycopeptides or daptomycin. A modest significant correlation was observed between the decrease in linezolid consumption and the lower incidence of resistant isolates. Linezolid-resistant CoNS had emerged in critically ill patients with severe underlying diseases and prior antibiotic exposure. Most isolates represented colonization; however, linezolid-resistant CoNS can produce serious infections in critically ill patients. Glycopeptides and daptomycin seem to provide useful alternatives for therapy of these infections. A relationship was found between linezolid consumption and the incidence of linezolid-resistant CoNS strains.

  20. Population pharmacokinetics and pharmacodynamics of linezolid-induced thrombocytopenia in hospitalized patients.

    Science.gov (United States)

    Tsuji, Yasuhiro; Holford, Nicholas H G; Kasai, Hidefumi; Ogami, Chika; Heo, Young-A; Higashi, Yoshitsugu; Mizoguchi, Akiko; To, Hideto; Yamamoto, Yoshihiro

    2017-08-01

    Thrombocytopenia is among the most important adverse effects of linezolid treatment. Linezolid-induced thrombocytopenia incidence varies considerably but has been associated with impaired renal function. We investigated the pharmacodynamic mechanism (myelosuppression or enhanced platelet destruction) and the role of impaired renal function (RF) in the development of thrombocytopenia. The pharmacokinetics of linezolid were described with a two-compartment distribution model with first-order absorption and elimination. RF was calculated using the expected creatinine clearance. The decrease platelets by linezolid exposure was assumed to occur by one of two mechanisms: inhibition of the formation of platelets (PDI) or stimulation of the elimination (PDS) of platelets. About 50% of elimination was found to be explained by renal clearance (normal RF). The population mean estimated plasma protein binding of linezolid was 18% [95% confidence interval (CI) 16%, 20%] and was independent of the observed concentrations. The estimated mixture model fraction of patients with a platelet count decreased due to PDI was 0.97 (95% CI 0.87, 1.00), so the fraction due to PDS was 0.03. RF had no influence on linezolid pharmacodynamics. We have described the influence of weight, renal function, age and plasma protein binding on the pharmacokinetics of linezolid. This combined pharmacokinetic, pharmacodynamic and turnover model identified that the most common mechanism of thrombocytopenia associated with linezolid is PDI. Impaired RF increases thrombocytopenia by a pharmacokinetic mechanism. The linezolid dose should be reduced in RF. © 2017 The British Pharmacological Society.

  1. Linezolid is Associated with Improved Early Outcomes of Childhood Tuberculous Meningitis.

    Science.gov (United States)

    Li, Huimin; Lu, Jie; Liu, Jinrong; Zhao, Yuhong; Ni, Xin; Zhao, Shunying

    2016-06-01

    Linezolid serves as an important component for the treatment of drug-resistant tuberculosis although there is little published data about linezolid use in children, especially in childhood tuberculous meningitis (TBM). In this study, we retrospectively reviewed records of childhood TBM patients who started treatment between January 2012 and August 2014. A total of 86 childhood TBM patients younger than 15 years old were enrolled. Out of 86 children, 36 (41.9%) received the regimen containing linezolid. Thirty-two (88.9%) of 36 linezolid-treated cases had favorable outcomes, and 35 (70.0%) cases were successfully treated in the control group. The frequency of favorable outcome of linezolid group was significantly higher than that of control group (P = 0.037). In addition, compared with cases with fever clearance time of 4 weeks (P = 0.000) than linezolid group. Furthermore, there was no significant difference in the frequency of adverse events between the two regimens (P = 0.896). In addition, the patients with adverse events were more likely to have treatment failure, the P value of which was 0.008. Our data demonstrate that linezolid improves early outcome of childhood TBM. The low frequency of linezolid-associated adverse effects highlights the promising prospects of its use for treatment of childhood TBM.

  2. Fungal Endocarditis.

    Science.gov (United States)

    Yuan, Shi-Min

    2016-01-01

    Fungal endocarditis is a rare and fatal condition. The Candida and Aspergillus species are the two most common etiologic fungi found responsible for fungal endocarditis. Fever and changing heart murmur are the most common clinical manifestations. Some patients may have a fever of unknown origin as the onset symptom. The diagnosis of fungal endocarditis is challenging, and diagnosis of prosthetic valve fungal endocarditis is extremely difficult. The optimum antifungal therapy still remains debatable. Treating Candida endocarditis can be difficult because the Candida species can form biofilms on native and prosthetic heart valves. Combined treatment appears superior to monotherapy. Combination of antifungal therapy and surgical debridement might bring about better prognosis.

  3. Preparation and biodistribution of [131I]linezolid in animal model infection and inflammation

    International Nuclear Information System (INIS)

    Yurt Lambrecht, F.; Durkan, K.; Unak, P.; Bayrak, E.; Yilmaz, O.

    2009-01-01

    Linezolid is the first of new class of antibiotics, the oxazolidinones, and exhibits activity against many gram-positive organisms, including vancomycin-resistant Enterococcus faecium, methicillin-resistant Staphylococcus aureus, and penicillin-resistant Streptococcus pneumoniae. Aim of the study: Linezolid was to label with I-131 and potential of the radiolabeled antibiotic was to investigate in inflamed rats with S. aureus (S. aureus) and sterile inflamed rats with turpentine oil. Linezolid was labeled with I-131 by iodogen method. Biodistribution of [ 131 I]linezolid was carried out in bacterial inflamed and sterile inflamed rats. Radiolabeling yield of [ 131 I]linezolid was determined as 85 ± 1% at pH 2. After injecting of [ 131 I]linezolid into bacterial inflamed and sterile inflamed rats, radiolabeled linezolid was rapidly removed from the circulation via the kidneys. Binding of [ 131 I]linezolid to bacterial inflamed muscle (T/NT = 77.48 at 30 min) was five times higher than binding to sterile inflamed muscle (T/NT = 14.87 at 30 min) of rats. [ 131 I]linezolid showed good localization in bacterial inflamed tissue. It was demonstrated that [ 131 I]linezolid can be used to detect S. aureus inflammation in rats. (author)

  4. Investigations of the pathogenesis of Staphylococcus aureus and Enterococcus faecalis in an experimental footpad infection model in broiler breeders

    DEFF Research Database (Denmark)

    Thoefner, Ida; Olsen, Rikke Heidemann; Poulsen, Louise Ladefoged

    2016-01-01

    in the central foot pad. Birds underwent full post mortem and bacteriological investigation 3, 7 and 14 days after infection. Inoculation of the S. aureus resulted in systemic lesions (sepsis, endocarditis and arthritis) as well as injection site abscesses. The lesions and bacterial re-isolation in the birds...... receiving the S. aureus originating from bumble foot were restricted to the footpad only. Similar to the S. aureus the E. faecalis infected birds contracted both systemic and local lesions. Bacterial re-isolation was demonstrated in a pattern similar to the pathological findings. Both systemic and local...

  5. Linezolid desensitization for a patient with multiple medication hypersensitivity reactions.

    Science.gov (United States)

    Bagwell, Autumn D; Stollings, Joanna L; White, Katie D; Fadugba, Olajumoke O; Choi, Jane J

    2013-01-01

    To describe a case in which a linezolid desensitization protocol was successfully used for a polymicrobial surgical wound infection in a patient with multiple drug hypersensitivity reactions. A 24-year-old woman with vocal cord dysfunction requiring tracheostomy was admitted for a surgical wound infection following a tracheostomy fistula closure procedure. The patient reported multiple antibiotic allergies including penicillins (rash), sulfonamides (rash), vancomycin (anaphylaxis), azithromycin (rash), cephalosporins (anaphylaxis), levofloxacin (unspecified), clindamycin (unspecified), and carbapenems (unspecified). Gram stain of the purulent wound drainage demonstrated mixed gram-negative and gram-positive flora, and bacterial cultures were overgrown with Proteus mirabilis, which precluded identification of other pathogens. Following failed test doses of linezolid, tigecycline, and daptomycin, all of which resulted in hypersensitivity reactions, a 16-step linezolid desensitization protocol was developed and successfully implemented without adverse reactions. The patient completed a 2-week course of antibiotic therapy that included linezolid upon finishing the desensitization protocol. Linezolid is useful in treating complicated and uncomplicated skin and soft tissue infections caused by gram-positive bacteria. With precautions, including premedication, a monitored nursing unit, and immediate availability of an emergency anaphylaxis kit, drug desensitization allows patients the ability to safely use medications to which they may have an immediate hypersensitivity reaction. Minimal data exist on linezolid desensitization protocols. Linezolid desensitization can be a viable option in patients requiring antimicrobial therapy for complicated gram-positive skin infections.

  6. Linezolid induced black hairy tongue: a rare side effect.

    Science.gov (United States)

    Aijazi, Ishma; Abdulla, Fadhil M

    2014-01-01

    Linezolid induced black hairy tongue is a rare benign reversible side effect of linezolid therapy. We report a case of a 61 year old diabetic lady who developed thrombocytopenia and black hairy discoloration of the tongue after being prescribed linezolid for foot osteomyelitis by the orthopaedic surgeon. Patient was encouraged to practice good oral dental hygiene, advised to use a soft tooth brush, regular mouth wash and baking soda containing tooth paste. The condition resolved four weeks after cessation of the antibiotic therapy.

  7. Endocarditis

    Science.gov (United States)

    ... lining of the heart. The most common type, bacterial endocarditis, occurs when germs enter your heart. These germs ... another part of your body, often your mouth. Bacterial endocarditis can damage your heart valves. If untreated, it ...

  8. Bicytopenia, especially thrombocytopenia in hemodialysis and non-hemodialysis patients treated with linezolid therapy.

    Science.gov (United States)

    Kato, Hideo; Hamada, Yukihiro; Hagihara, Mao; Hirai, Jun; Yamagishi, Yuka; Matsuura, Katsuhiko; Mikamo, Hiroshige

    2015-10-01

    One of the major adverse events associated with linezolid treatment is pancytopenia. However, there are few reports about the tolerability of linezolid among patients undergoing hemodialysis. This study retrospectively investigated the frequency of bicytopenia (thrombocytopenia and erythropenia) secondary to linezolid treatment in patients undergoing and not-undergoing hemodialysis. In total, 181 patients treated with linezolid from January 2010 to July 2012 at Aichi Medical University Hospital were divided into three groups; patients undergoing hemodialysis (HD group), those with creatinine clearance (CLCR) of linezolid therapy were compared among three groups. Thrombocytopenia (linezolid therapy. In particular, the PLT nadir in HD group occurred earlier than that in non-HD groups (HD, 11.5 days [4-31 days]; CLCR linezolid treatment in patients undergoing hemodialysis. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  9. Pharmacokinetics of linezolid in bone tissue investigated by in vivo microdialysis

    DEFF Research Database (Denmark)

    Stolle, L.B.; Plock, N.; Joukhadar, C.

    2008-01-01

    Pharmacokinetics of unbound anti-infectives in bone is difficult to characterize. The aim of this study was to assess the feasibility of the microdialysis technique to cancellous bone for single dose pharmacokinetic investigations of the anti-infective linezolid. Serial bone biopsies (left tibia......) and microdialysate samples (right tibia: 2 catheters) as well as plasma and bone marrow samples were obtained from 10 pigs. The concentrations of linezolid reached bacteriostatic levels in plasma, bone marrow, bone biopsies and microdialysates. With the use of microdialysis we here present the first results...... for unbound linezolid bone penetration. Unbound linezolid concentrations in bone obtained by microdialysis were lower than might have been expected from previous bone biopsy studies. To achieve effective concentrations (24 h) for susceptible organisms the chosen dose of linezolid might not be sufficient...

  10. Linezolid: a promising option in the treatment of Gram-positives.

    Science.gov (United States)

    Zahedi Bialvaei, Abed; Rahbar, Mohammad; Yousefi, Mehdi; Asgharzadeh, Mohammad; Samadi Kafil, Hossein

    2017-02-01

    Linezolid, an oxazolidinone antimicrobial agent that acts by inhibiting protein synthesis in a unique fashion, is used in the treatment of community-acquired pneumonia, skin and soft-tissue infections and other infections caused by Gram-positive bacteria including VRE and methicillin-resistant staphylococci. Currently, linezolid resistance among these pathogens remains low, commonly linezolid susceptibility testing for this important agent and should be taken into account when considering its therapeutic use. Considering the importance of linezolid in the treatment of infections caused by Gram-positive bacteria, this review was undertaken to optimize the clinical use of this antibiotic. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Toxicity to sensory neurons and Schwann cells in experimental linezolid-induced peripheral neuropathy.

    Science.gov (United States)

    Bobylev, Ilja; Maru, Helina; Joshi, Abhijeet R; Lehmann, Helmar C

    2016-03-01

    Peripheral neuropathy is a common side effect of prolonged treatment with linezolid. This study aimed to explore injurious effects of linezolid on cells of the peripheral nervous system and to establish in vivo and in vitro models of linezolid-induced peripheral neuropathy. C57BL/6 mice were treated with linezolid or vehicle over a total period of 4 weeks. Animals were monitored by weight, nerve conduction studies and behavioural tests. Neuropathic changes were assessed by morphometry on sciatic nerves and epidermal nerve fibre density in skin sections. Rodent sensory neuron and Schwann cell cultures were exposed to linezolid in vitro and assessed for mitochondrial dysfunction. Prolonged treatment with linezolid induced a mild, predominantly small sensory fibre neuropathy in vivo. Exposure of Schwann cells and sensory neurons to linezolid in vitro caused mitochondrial dysfunction primarily in neurons (and less prominently in Schwann cells). Sensory axonopathy could be partially prevented by co-administration of the Na(+)/Ca(2+) exchanger blocker KB-R7943. Clinical and pathological features of linezolid-induced peripheral neuropathy can be replicated in in vivo and in vitro models. Mitochondrial dysfunction may contribute to the axonal damage to sensory neurons that occurs after linezolid exposure. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Tratamiento quirúrgico de la endocarditis infecciosa Surgical treatment of infective endocarditis

    Directory of Open Access Journals (Sweden)

    Milvio Ramírez López

    2010-09-01

    Full Text Available La cirugía constituye un ataque vigoroso a la incompetencia valvular que ocasiona las graves complicaciones hemodinámicas que se observan en la endocarditis infecciosa. Se presenta una breve revisión de las diferentes técnicas quirúrgicas que se emplean para el tratamiento de la endocarditis infecciosa de la válvula mitral nativa, utilización de homoinjertos mitrales, tratamiento quirúrgico de la endocarditis infecciosa de la válvula aórtica y de la endocarditis infecciosa de prótesis valvular aórtica, homoinjertos criopreservados, prótesis sin soporte valvular y otros tipos de prótesis, así como de otras técnicas que se pueden emplear en caso de no contar con homoinjertos. Se revisan las técnicas que se utilizan en la endocarditis infecciosa de la válvula tricúspide y la conducta quirúrgica en la endocarditis por cables de marcapasos o desfibriladores automáticos implantables.Surgery is a strong attack to valvular incompetence causing the severe hemodynamic complications seen in infective endocarditis. This is a brief review of the different surgical techniques used in the treatment of infective endocarditis of native mitral valve, utilization of mitral homografts, surgical treatment of the infective endocarditis of the aortic valve and the infective endocarditis of the aortic valvular prosthesis, cryopreservation of the homografts, prosthesis without valvular support and other types of prostheses, as well as of other techniques that could be used if the homografts are not available. Techniques used in the infective endocarditis of tricuspid valve are reviewed and the surgical behavior in the endocarditis provoked by the pacemakers cables or implanted automated defibrillators.

  13. Current status of taxonomic groups of oral streptococci in endocarditis. Can virulence factors discriminate between endocarditis and non-endocarditis strains?

    DEFF Research Database (Denmark)

    Larsen, Tove; Fiehn, Nils-Erik; Gutschik, Ernö

    1999-01-01

    streptococcal isolates from the oral cavities of periodontal patients without endocarditis. Subsequently, surface hydrophobicity was assessed by hydrophobic interaction chromatography, production of extracellular dextran was determined by precipitation, and non-specific proteolytic activity was evaluated......OBJECTIVE: Infective endocarditis is frequently caused by oral streptococci, especially Streptococcus sanguis. In this group, many strains have recently been reclassified on the basis of new taxonomic schemes. The purpose of this study was to classify oral streptococci from patients with infective...... and non-endocarditis isolates. CONCLUSIONS: The present study showed that infective endocarditis may be caused by a variety of oral streptococcal species. The possible virulence factors investigated were found in the same proportions in endocarditis and non-endocarditis isolates, and thus did not seem...

  14. Anti-inflammatory effects of linezolid on carrageenan-induced paw edema in rats.

    Science.gov (United States)

    Matsumoto, Kazuaki; Obara, Shigeaki; Kuroda, Yuko; Kizu, Junko

    2015-12-01

    The immunomodulatory activity of linezolid has recently been reported using in vitro experimental models. However, the anti-inflammatory activity of linezolid has not yet been demonstrated using in vivo experimental models. Therefore, the aim of the present study was to demonstrate the anti-inflammatory activity of linezolid and other anti-MRSA agents using the carrageenan-induced rat paw edema model. The pretreatment with 50 mg/kg linezolid significantly suppressed edema rates, compared with control (5% glucose), with edema rates at 0.5 and 3 h after the administration of carrageenan being 17.3 ± 3.5 and 30.8 ± 3.0%, respectively. On the other hand, edema rates were not suppressed by the pretreatments with 50 mg/kg vancomycin, teicoplanin, arbekacin, and daptomycin. Furthermore, we demonstrated that linezolid exhibited anti-inflammatory activity in a concentration-dependent manner. These effects were observed at linezolid concentrations that are achievable in human serum with conventional dosing. In conclusion, the results of the present study suggest that the anti-inflammatory activities of linezolid, in addition to its antimicrobial effects, have a protective effect against destructive inflammatory responses in areas of inflammation. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  15. Linezolid-induced lactic acidosis: the thin line between bacterial and mitochondrial ribosomes.

    Science.gov (United States)

    Santini, Alessandro; Ronchi, Dario; Garbellini, Manuela; Piga, Daniela; Protti, Alessandro

    2017-07-01

    Linezolid inhibits bacterial growth by targeting bacterial ribosomes and by interfering with bacterial protein synthesis. Lactic acidosis is a rare, but potentially lethal, side effect of linezolid. Areas covered: The pathogenesis of linezolid-induced lactic acidosis is reviewed with special emphasis on aspects relevant to the recognition, prevention and treatment of the syndrome. Expert opinion: Linezolid-induced lactic acidosis reflects the untoward interaction between the drug and mitochondrial ribosomes. The inhibition of mitochondrial protein synthesis diminishes the respiratory chain enzyme content and thus limits aerobic energy production. As a result, anaerobic glycolysis and lactate generation accelerate independently from tissue hypoxia. In the absence of any confirmatory test, linezolid-induced lactic acidosis should be suspected only after exclusion of other, more common, causes of lactic acidosis such as hypoxemia, anemia or low cardiac output. Normal-to-high whole-body oxygen delivery, high venous oxygen saturation and lack of response to interventions that effectively increase tissue oxygen provision all suggest a primary defect in oxygen use at the mitochondrial level. During prolonged therapy with linezolid, blood drug and lactate levels should be regularly monitored. The current standard-of-care treatment of linezolid-induced lactic acidosis consists of drug withdrawal to reverse mitochondrial intoxication and intercurrent life support.

  16. Investigation of Linezolid Resistance in Staphylococci and Enterococci

    Science.gov (United States)

    Gallegos, Michael; Alspaugh, Debbie

    2016-01-01

    The objective of this study was to investigate an apparent increase in linezolid-nonsusceptible staphylococci and enterococci following a laboratory change in antimicrobial susceptibility testing from disk diffusion to an automated susceptibility testing system. Isolates with nonsusceptible results (n = 27) from Vitek2 were subjected to a battery of confirmatory testing which included disk diffusion, Microscan broth microdilution, Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution, gradient diffusion (Etest), 23S rRNA gene sequencing, and cfr PCR. Our results show that there is poor correlation between methods and that only 70 to 75% of isolates were confirmed as linezolid resistant with alternative phenotypic testing methods (disk diffusion, Microscan broth microdilution, CLSI broth microdilution, and Etest). 23S rRNA gene sequencing identified mutations previously associated with linezolid resistance in 16 (59.3%) isolates, and the cfr gene was detected in 3 (11.1%) isolates. Mutations located at positions 2576 and 2534 of the 23S rRNA gene were most common. In addition, two previously undescribed variants (at positions 2083 and 2345 of the 23S rRNA gene) were also identified and may contribute to linezolid resistance. PMID:26935728

  17. Aerococcus christensenii native aortic valve subacute bacterial endocarditis (SBE) presenting as culture negative endocarditis (CNE) mimicking marantic endocarditis.

    Science.gov (United States)

    Jose, Anita; Cunha, Burke A; Klein, Natalie C; Schoch, Paul E

    2014-01-01

    This is a case report of an adult who presented with apparent culture negative endocarditis (CNE) thought to be marantic endocarditis due to a B-cell lymphoproliferative disorder. This was a most perplexing case and was eventually diagnosed as subacute bacterial endocarditis (SBE) due to a rare slow growing organism. Against the diagnosis of SBE was the lack of fever, hepatomegaly, peripheral manifestations and microscopic hematuria. Also, against a diagnosis of SBE was another explanation for the patient's abnormal findings, e.g., elevated ferritin levels, elevated α1/α2 globulins on SPEP, an elevated alkaline phosphatase, flow cytometry showing B-lymphocytes expressing CD5, and a bone lesion in the right iliac. Findings compatible with both SBE and marantic endocarditis due to a B-cell lymphoproliferative disorder included an elevated ESR, and splenomegaly. Blood cultures eventually became positive during hospitalization. We report a case of native aortic valve (AV) subacute bacterial endocarditis (SBE) due to Aerococcus christensenii mimicking marantic endocarditis due to a B-cell lymphoproliferative disorder. To the best of our knowledge, this is the first reported case of native AV SBE due to A. christensenii presenting as marantic endocarditis. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Linezolid as treatment for pulmonary Mycobacterium avium disease.

    Science.gov (United States)

    Deshpande, Devyani; Srivastava, Shashikant; Pasipanodya, Jotam G; Gumbo, Tawanda

    2017-09-01

    To identify the pharmacokinetic/pharmacodynamic parameters and exposures of linezolid in the treatment of pulmonary Mycobacterium avium complex (MAC) disease. Human-derived monocytes infected with MAC were inoculated into hollow-fibre systems for dose-effect and dose-scheduling studies. We mimicked linezolid concentration-time profiles achieved in adult human lungs treated for 28 days. Sampling to confirm that the intended linezolid pharmacokinetics had been achieved, and for enumeration of MAC colony-forming units, was performed based on repetitive sampling from each system over the 28 days. We then performed 10 000 patient Monte Carlo simulations to identify doses associated with optimal effect in the clinic. Linezolid achieved a hitherto unprecedented feat of at least 1.0 log10 cfu/mL reduction. Efficacy was most closely linked to the AUC0-24/MIC ratio. The AUC0-24/MIC ratio associated with no change in bacterial burden or bacteriostasis was 7.82, while that associated with 1.0 log10 cfu/mL kill was 42.06. The clinical dose of 600 mg/day achieved or exceeded the bacteriostasis exposure in 98.73% of patients. The proportion of 10 000 patients treated with the standard 1200 mg/day who achieved the exposure for 1.0 log10 cfu/mL kill was 70.64%, but was 90% for 1800 mg/day. The proposed MIC breakpoint for linezolid is 16 mg/L, with which 49%-80% of clinical isolates would be considered resistant. Linezolid is associated with a bactericidal effect in pulmonary MAC that is greater than that seen with other recommended drugs. However, because of the MIC distribution, doses that would optimize the bactericidal effect would be associated with a high adverse event rate. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. Endocarditis in Greenland with special reference to endocarditis caused by Streptococcus pneumoniae

    DEFF Research Database (Denmark)

    Madsen, Rasmus Gaarde; Ladefoged, Karin; Kjaergaard, Jens Jørgen

    2009-01-01

    OBJECTIVES: The aim of this retrospective study was to determine the incidence and outcome of infectious endocarditis in Greenland with an emphasis on pneumococcal endocarditis. STUDY DESIGN: Retrospective, non-interventional study. METHODS: Review of files and medical history of all patients...... with infectious endocarditis from the Patient Registry in Greenland in the 11-year period 1995-2005. RESULTS: There were 25 cases of endocarditis, giving an incidence rate of 4.0/100,000 per year. Twenty-four percent of these cases were caused by Streptoccous pneumonia, which is significantly more frequent than...... in studies on Caucasian populations, where pneumococcal infection was seen in 1-3% of endocarditis cases. The overall mortality rate was 12%. Pneumococcal endocarditis (PE) had the clinical characteristics of fulminant disease with frequent heart failure, complications and need for surgery. Among cases...

  20. Characterization of Vancomycin Reactions and Linezolid Utilization in the Pediatric Population.

    Science.gov (United States)

    Lin, Samantha K; Mulieri, Kevin M; Ishmael, Faoud T

    Red man syndrome (RMS) occurs because of non-IgE-mediated histamine release. Unlike vancomycin allergy, which necessitates the use of an alternative drug (often linezolid), RMS does not typically preclude further vancomycin use. Care should be taken to differentiate these reaction types from one another to prevent unnecessary vancomycin avoidance. To characterize vancomycin reaction types in our population, and to determine whether having a reaction consistent with RMS is associated with otherwise unexplained vancomycin avoidance and linezolid use. We retrospectively reviewed charts for children with documented vancomycin reactions. We classified the in-hospital reactions via an objective analysis and estimated the prevalence of different reaction types. We then identified children who received linezolid over 3 years, and investigated reasons for linezolid use instead of vancomycin. Of the 78 in-hospital reactions we characterized, 72 (92%) were objectively consistent with RMS, 5 we could not objectively classify (2 most likely RMS, 3 more suspicious for possible IgE-mediated allergy), and 1 was a non-RMS/non-IgE reaction. Of 60 children who received linezolid, 19 had previous reactions consistent with RMS, which should not preclude further vancomycin. Nevertheless, only 7 of 19 (37%) had a clear explanation for receiving linezolid instead of vancomycin compared with 32 of 39 (82%) children without previous vancomycin reactions (P linezolid utilization. We propose that this may be related to how reactions appear in the electronic medical record. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  1. Infective Endocarditis: Identification of Catalase-Negative, Gram-Positive Cocci from Blood Cultures by Partial 16S rRNA Gene Analysis and by Vitek 2 Examination.

    Science.gov (United States)

    Abdul-Redha, Rawaa Jalil; Kemp, Michael; Bangsborg, Jette M; Arpi, Magnus; Christensen, Jens Jørgen

    2010-01-01

    Streptococci, enterococci and Streptococcus-like bacteria are frequent etiologic agents of infective endocarditis and correct species identification can be a laboratory challenge. Viridans streptococci (VS) not seldomly cause contamination of blood cultures. Vitek 2 and partial sequencing of the 16S rRNA gene were applied in order to compare the results of both methods. STRAINS ORIGINATED FROM TWO GROUPS OF PATIENTS: 149 strains from patients with infective endocarditis and 181 strains assessed as blood culture contaminants. Of the 330 strains, based on partial 16S rRNA gene sequencing results, 251 (76%) were VS strains, 10 (3%) were pyogenic streptococcal strains, 54 (16%) were E. faecalis strains and 15 (5%) strains belonged to a group of miscellaneous catalase-negative, Gram-positive cocci. Among VS strains, respectively, 220 (87,6%) and 31 (12,3%) obtained agreeing and non-agreeing identifications with the two methods with respect to allocation to the same VS group. Non-agreeing species identification mostly occurred among strains in the contaminant group, while for endocarditis strains notably fewer disagreeing results were observed.Only 67 of 150 strains in the mitis group strains obtained identical species identifications by the two methods. Most VS strains belonging to the groups of salivarius, anginosus, and mutans obtained agreeing species identifications with the two methods, while this only was the case for 13 of the 21 bovis strains. Pyogenic strains (n=10), Enterococcus faecalis strains (n=54) and a miscellaneous group of catalase-negative, Gram-positive cocci (n=15) seemed well identified by both methods, except that disagreements in identifications in the miscellaneous group of strains occurred for 6 of 15 strains.

  2. Infective Endocarditis

    Science.gov (United States)

    ... Venous Thromboembolism Aortic Aneurysm More Infective Endocarditis Updated:Mar 29,2018 View an illustration of endocarditis Infective ... procedure. Web Booklets on Congenital Heart Defects These online publications describe many defects and the procedures used ...

  3. A cfr-positive clinical staphylococcal isolate from India with multiple mechanisms of linezolid-resistance

    Directory of Open Access Journals (Sweden)

    Vineeth Rajan

    2014-01-01

    Full Text Available Background & objectives: Linezolid, a member of the oxazolidinone class of antibiotics, has been an effective therapeutic option to treat severe infections caused by multidrug resistant Gram positive bacteria. Emergence of linezolid resistant clinical strains is a serious issue in the healthcare settings worldwide. We report here the molecular characterization of a linezolid resistant clinical isolate of Staphylococcus haemolyticus from India. Methods: The species of the clinical isolate was identified by 16S rRNA gene sequencing. The minimum inhibitory concentrations (MICs of linezolid, clindamycin, chloramphenicol and oxacillin were determined by E-test method. To elucidate the mechanism of linezolid-resistance, presence of cfr gene (chloramphenicol florfenicol resistance and mutations in 23S rRNA and ribosomal proteins (L3, L4 and L22 were investigated. Staphylococcal Cassette Chromosome mec (SCCmec typing was performed by multiplex PCR. Results: The study documented a rare clinical S. haemolyticus strain with three independent mechanisms of linezolid-resistance. The strain carried cfr gene, the only known transmissible mechanism of linezolid-resistance. The strain also possessed resistance-conferring mutations such as G 2576 T in domain V of 23S rRNA gene and Met 156 Thr in L3 ribosomal protein. The other ribosomal proteins (L4 and L22 did not exhibit mutations accountable for linezolid-resistance. Restriction digestion by NheI revealed that all the alleles of 23S rRNA gene were mutated. The isolate showed elevated MIC values (>256 ΅g ml -[1] of linezolid, clindamycin, chloramphenicol and oxacillin. Methicillin resistance was conferred by type I SCCmec element. The strain also harboured lsa(B gene which encodes an ABC transporter that can efflux clindamycin. Interpretation & conclusions: The present study reports the first clinical strain from India with transmissible and multiple mechanisms of linezolid-resistance. Judicious use of

  4. [A study of population pharmacokinetics of linezolid in Chinese].

    Science.gov (United States)

    Zhang, L; Bai, N; Liu, Y N; Wang, R

    2016-12-12

    Objective: To study the population pharmacokinetic (PPK) profiles of linezolid in Chinese healthy volunteers and infected patients. Methods: Linezolid 600 mg was administered to 31 Chinese healthy volunteers with a single dose and to 57 infected patients every 12 h for at least 5 doses. High performance liquid chromatography was applied to determine the plasma concentration of linezolid. Nonlinear mixed-effects modeling method was applied to analyze the PPK profiles. Results: For healthy volunteers with single dose of linezolid, 2-compartment with linear elimination model was the most appropriate structural pharmacokinetic model. The population typical value of apparent volume of central compartment was 26.99 L, volume of peripheral compartment was 22.22 L, apparent clearance of central compartment was 7.99 L/h, and clearance of peripheral compartment was 101.28 L/h. For each 1 kg deviation of weight from the mean value, 0.62 L of volume of peripheral compartment was correlated. For Chinese infected patients with multiple doses of linezolid, 1-compartment with linear elimination model was the most appropriate structural pharmacokinetic model. The population typical value of apparent volume was 38.85 L, and apparent clearance was 4.70 L/h. For each 1 kg deviation of weight from the mean value, 0.79 L of volume, as well as 0.04 L/h of clearance were correlated. For each 1 year deviation of age from the mean value, -0.045 L/h of clearance was correlated. Conclusions: The pharmacokinetic profiles of linezolid in Chinese simulate a 2-compartment with linear elimination model when single dose is administrated, and the weight is linearly positive-correlated to volume. While a 1-compartment with linear elimination model is appropriate when multiple doses are administrated, and the weight is linearly positive-correlated to volume and clearance, but the age is linearly negative-correlated to clearance.

  5. Two cases of serious rhabdomyolysis during linezolid treatment.

    Science.gov (United States)

    Lechner, Arno M; Past, Eva; Porsche, Ulla; Kern, Jan M; Hoppe, Uta; Pretsch, Ingrid

    2017-08-01

    Linezolid is an oxazolidinone antibiotic with activity against gram-positive organisms, particularly methicillin-resistant Staphylococcus aureus (MRSA). To the best of our knowledge, there are only two case reports on rhabdomyolysis in patients treated with linezolid. Here, we describe two cases of serious rhabdomyolysis: one in a patient with septic community-acquired (CA)-MRSA pneumonia and a second case in a patient with suspected catheter-related blood stream infection.

  6. Emergence of linezolid resistant Staphylococcus aureus in Bastar tribal region, India

    Directory of Open Access Journals (Sweden)

    Mohammad Fareed Khan

    2012-09-01

    Full Text Available Methicillin resistant Staphylococcus aureus(MRSA is a well-known threat to the healthcaresystems for its increasing global prevalence, intrinsicability of resistance to ß-lactam and cephalosporin,and for acquiring resistance to multipleclasses of other antibiotics, causing difficult-totreatinfections with significant increase in morbidity,mortality and treatment cost. Although forsevere MRSA infections vancomycin is describedas the first-line intravenous drug, vancomycinresistantand intermediate isolates of S. aureus(VRSA & VISA have been increasingly reportedthroughout the world. The therapeutic and lifesavingoption for VRSA and VISA infections remainlinezolid, first antimicrobial of oxazolidinonegroup available since 2000. The first case of linezolid-resistant staphylococci appeared within 1year after linezolid was approved for therapeuticuse.1 Although linezolid resistance in S. aureusis uncommon, emergence has been shown fromsome parts of the world.2 From India, first casereport of linezolid resistance was published in2011 from Kashmir.3 This is the first report fromthe Chattisgarh state in Central India where wefound two linezolid-resistant Staphylococcus aureusisolates which were cultured in March 2011from pus samples collected from the male surgicalward of Maharani Hospital, Jagdalpur, Bastar.

  7. Variability of linezolid concentrations after standard dosing in critically ill patients: a prospective observational study

    Science.gov (United States)

    2014-01-01

    Introduction Severe infections in intensive care patients show high morbidity and mortality rates. Linezolid is an antimicrobial drug frequently used in critically ill patients. Recent data indicates that there might be high variability of linezolid serum concentrations in intensive care patients receiving standard doses. This study was aimed to evaluate whether standard dosing of linezolid leads to therapeutic serum concentrations in critically ill patients. Methods In this prospective observational study, 30 critically ill adult patients with suspected infections received standard dosing of 600 mg linezolid intravenously twice a day. Over 4 days, multiple serum samples were obtained from each patient, in order to determine the linezolid concentrations by liquid chromatography tandem mass spectrometry. Results A high variability of serum linezolid concentrations was observed (range of area under the linezolid concentration time curve over 24 hours (AUC24) 50.1 to 453.9 mg/L, median 143.3 mg*h/L; range of trough concentrations (Cmin) linezolid concentrations over 24 hours and at single time points (defined according to the literature as AUC24  400 mg*h/L and Cmin > 10 mg/L) were observed for 7 of the patients. Conclusions A high variability of linezolid serum concentrations with a substantial percentage of potentially subtherapeutic levels was observed in intensive care patients. The findings suggest that therapeutic drug monitoring of linezolid might be helpful for adequate dosing of linezolid in critically ill patients. Trial registration Clinicaltrials.gov NCT01793012. Registered 24 January 2013. PMID:25011656

  8. Infective Endocarditis and Cancer Risk

    Science.gov (United States)

    Sun, Li-Min; Wu, Jung-Nan; Lin, Cheng-Li; Day, Jen-Der; Liang, Ji-An; Liou, Li-Ren; Kao, Chia-Hung

    2016-01-01

    Abstract This study investigated the possible relationship between endocarditis and overall and individual cancer risk among study participants in Taiwan. We used data from the National Health Insurance program of Taiwan to conduct a population-based, observational, and retrospective cohort study. The case group consisted of 14,534 patients who were diagnosed with endocarditis between January 1, 2000 and December 31, 2010. For the control group, 4 patients without endocarditis were frequency matched to each endocarditis patient according to age, sex, and index year. Competing risks regression analysis was conducted to determine the effect of endocarditis on cancer risk. A large difference was noted in Charlson comorbidity index between endocarditis and nonendocarditis patients. In patients with endocarditis, the risk for developing overall cancer was significant and 119% higher than in patients without endocarditis (adjusted subhazard ratio = 2.19, 95% confidence interval = 1.98–2.42). Regarding individual cancers, in addition to head and neck, uterus, female breast and hematological malignancies, the risks of developing colorectal cancer, and some digestive tract cancers were significantly higher. Additional analyses determined that the association of cancer with endocarditis is stronger within the 1st 5 years after endocarditis diagnosis. This population-based cohort study found that patients with endocarditis are at a higher risk for colorectal cancer and other cancers in Taiwan. The risk was even higher within the 1st 5 years after endocarditis diagnosis. It suggested that endocarditis is an early marker of colorectal cancer and other cancers. The underlying mechanisms must still be explored and may account for a shared risk factor of infection in both endocarditis and malignancy. PMID:27015220

  9. Linezolid-Associated Optic Neuropathy in Drug-Resistant Tuberculosis Patients in Mumbai, India.

    Science.gov (United States)

    Mehta, Salil; Das, Mrinalini; Laxmeshwar, Chinmay; Jonckheere, Sylvie; Thi, Sein Sein; Isaakidis, Petros

    2016-01-01

    Patients on linezolid-containing drug-resistant TB (DR-TB) regimen often develop adverse-events, particularly peripheral and optic neuropathy. Programmatic data and experiences of linezolid-associated optic neuropathy from high DR-TB burden settings are lacking. The study aimed to determine the frequency of and risk-factors associated with linezolid-associated optic neuropathy and document the experiences related to treatment/care of DR-TB patients on linezolid-containing regimens. This was a retrospective cohort study using routine clinical and laboratory data in Médecins Sans Frontières (MSF) HIV/DR-TB clinic in collaboration with Lilavati Hospital & Research Center, Mumbai, India. All DR-TB patients on linezolid-containing treatment regimens were included in the study and underwent routine evaluations for systemic and/or ocular complaints. Ophthalmological evaluation by a consultant ophthalmologist included visual-acuity screening, slit-lamp examination and dilated fundus examination. During January 2013-April 2016, 86 of 136 patients (with/without HIV co-infection) initiated linezolid-containing DR-TB treatment. The median age of these 86 patients was 25 (20-35) years and 47% were males. 20 percent of them had HIV co-infection. Of 86, 24 (27.9%) had at least one episode of ocular complaints (the majority blurred-vision) and among them, five (5.8%) had optic neuropathy. Patients received appropriate treatment and improvements were observed. None of the demographic/clinical factors were associated with optic neuropathy in Poissons or multivariate binary logistic-regression models. This is the first report focusing on optic neuropathy in a cohort of complex DR-TB patients, including patients co-infected with HIV, receiving linezolid-containing regimens. In our study, one out of four patients on linezolid had at least one episode of ocular complaints; therefore, systematic monitoring of patients by primary physicians/nurses, and access to specialized diagnostic

  10. Linezolid-Associated Optic Neuropathy in Drug-Resistant Tuberculosis Patients in Mumbai, India

    Science.gov (United States)

    Mehta, Salil; Das, Mrinalini; Laxmeshwar, Chinmay; Jonckheere, Sylvie; Thi, Sein Sein; Isaakidis, Petros

    2016-01-01

    Background Patients on linezolid-containing drug-resistant TB (DR-TB) regimen often develop adverse-events, particularly peripheral and optic neuropathy. Programmatic data and experiences of linezolid-associated optic neuropathy from high DR-TB burden settings are lacking. The study aimed to determine the frequency of and risk-factors associated with linezolid-associated optic neuropathy and document the experiences related to treatment/care of DR-TB patients on linezolid-containing regimens. Methods This was a retrospective cohort study using routine clinical and laboratory data in Médecins Sans Frontières (MSF) HIV/DR-TB clinic in collaboration with Lilavati Hospital & Research Center, Mumbai, India. All DR-TB patients on linezolid-containing treatment regimens were included in the study and underwent routine evaluations for systemic and/or ocular complaints. Ophthalmological evaluation by a consultant ophthalmologist included visual-acuity screening, slit-lamp examination and dilated fundus examination. Results During January 2013-April 2016, 86 of 136 patients (with/without HIV co-infection) initiated linezolid-containing DR-TB treatment. The median age of these 86 patients was 25 (20–35) years and 47% were males. 20 percent of them had HIV co-infection. Of 86, 24 (27.9%) had at least one episode of ocular complaints (the majority blurred-vision) and among them, five (5.8%) had optic neuropathy. Patients received appropriate treatment and improvements were observed. None of the demographic/clinical factors were associated with optic neuropathy in Poissons or multivariate binary logistic-regression models. Discussion This is the first report focusing on optic neuropathy in a cohort of complex DR-TB patients, including patients co-infected with HIV, receiving linezolid-containing regimens. In our study, one out of four patients on linezolid had at least one episode of ocular complaints; therefore, systematic monitoring of patients by primary physicians

  11. Linezolid in the treatment of drug-resistant tuberculosis: the challenge of its narrow therapeutic index.

    Science.gov (United States)

    Wasserman, Sean; Meintjes, Graeme; Maartens, Gary

    2016-10-01

    Linezolid is an oxazolidinone with potent activity against M tuberculosis, and improves culture conversion and cure rates when added to treatment regimens for drug resistant tuberculosis. However, linezolid has a narrow therapeutic window, and the optimal dosing strategy that minimizes the substantial toxicity associated with linezolid's prolonged use in tuberculosis treatment has not been determined, limiting the potential impact of this anti-mycobacterial agent. This paper aims to review and summarize the current knowledge on linezolid for the treatment of drug-resistant tuberculosis. The focus is on the pharmacokinetic-pharmacodynamic determinants of linezolid's efficacy and toxicity in tuberculosis, and how this relates to defining an optimal dose. Mechanisms of linezolid toxicity and resistance, and the potential role of therapeutic drug monitoring are also covered. Expert commentary: Prospective pharmacokinetic-pharmacodynamic studies are required to define optimal therapeutic targets and to inform improved linezolid dosing strategies for drug-resistant tuberculosis.

  12. Mechanisms of Linezolid Resistance among Coagulase-Negative Staphylococci Determined by Whole-Genome Sequencing

    Science.gov (United States)

    Tewhey, Ryan; Gu, Bing; Kelesidis, Theodoros; Charlton, Carmen; Bobenchik, April; Hindler, Janet; Schork, Nicholas J.

    2014-01-01

    ABSTRACT Linezolid resistance is uncommon among staphylococci, but approximately 2% of clinical isolates of coagulase-negative staphylococci (CoNS) may exhibit resistance to linezolid (MIC, ≥8 µg/ml). We performed whole-genome sequencing (WGS) to characterize the resistance mechanisms and genetic backgrounds of 28 linezolid-resistant CoNS (21 Staphylococcus epidermidis isolates and 7 Staphylococcus haemolyticus isolates) obtained from blood cultures at a large teaching health system in California between 2007 and 2012. The following well-characterized mutations associated with linezolid resistance were identified in the 23S rRNA: G2576U, G2447U, and U2504A, along with the mutation C2534U. Mutations in the L3 and L4 riboproteins, at sites previously associated with linezolid resistance, were also identified in 20 isolates. The majority of isolates harbored more than one mutation in the 23S rRNA and L3 and L4 genes. In addition, the cfr methylase gene was found in almost half (48%) of S. epidermidis isolates. cfr had been only rarely identified in staphylococci in the United States prior to this study. Isolates of the same sequence type were identified with unique mutations associated with linezolid resistance, suggesting independent acquisition of linezolid resistance in each isolate. PMID:24915435

  13. Resistance to Linezolid Caused by Modifications at Its Binding Site on the Ribosome

    Science.gov (United States)

    Long, Katherine S.

    2012-01-01

    Linezolid is an oxazolidinone antibiotic in clinical use for the treatment of serious infections of resistant Gram-positive bacteria. It inhibits protein synthesis by binding to the peptidyl transferase center on the ribosome. Almost all known resistance mechanisms involve small alterations to the linezolid binding site, so this review will therefore focus on the various changes that can adversely affect drug binding and confer resistance. High-resolution structures of linezolid bound to the 50S ribosomal subunit show that it binds in a deep cleft that is surrounded by 23S rRNA nucleotides. Mutation of 23S rRNA has for some time been established as a linezolid resistance mechanism. Although ribosomal proteins L3 and L4 are located further away from the bound drug, mutations in specific regions of these proteins are increasingly being associated with linezolid resistance. However, very little evidence has been presented to confirm this. Furthermore, recent findings on the Cfr methyltransferase underscore the modification of 23S rRNA as a highly effective and transferable form of linezolid resistance. On a positive note, detailed knowledge of the linezolid binding site has facilitated the design of a new generation of oxazolidinones that show improved properties against the known resistance mechanisms. PMID:22143525

  14. Linezolid and dexamethasone experience in a serious case of listeria rhombencephalitis.

    Science.gov (United States)

    Yılmaz, Pakize Ö; Mutlu, Nevzat M; Sertçelik, Ahmet; Baştuğ, Aliye; Doğu, Cihangir; Kışlak, Sümeyye

    2016-01-01

    Listeria rhombencephalitis is a rare cause of brain stem encephalitis. We report a case with a history of immunosupressive therapy due to Takayasu's arteritis that was treated with corticosteroids and linezolid for Listeria rhombencephalitis. A 63-year-old woman was admitted to the hospital with fever, headache, nausea, and vomiting. The patient's body temperature was 38°C, and she had a stiff neck. Listeria monocytogenes was isolated from the cerebrospinal fluid (CSF), and penicillin G and gentamicin treatment was initiated. Linezolid and dexamethasone were added. Due to hematuria and thrombocytopenia, the linezolid was discontinued. In immunocompromised patients with CNS infections, Listeria rhombencephalitis should be suspected. Linezolid can be used in combination with dexamethasone. Copyright © 2016 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

  15. Evaluation of the stability of linezolid in aqueous solution and commonly used intravenous fluids

    Directory of Open Access Journals (Sweden)

    Taylor R

    2017-07-01

    Full Text Available Rachel Taylor, Bruce Sunderland, Giuseppe Luna, Petra Czarniak School of Pharmacy, Faculty of Health Sciences, Curtin University, Bentley, WA, Australia Purpose: The aim was to evaluate the stability of linezolid in commonly used intravenous fluids and in aqueous solution to determine the kinetics of degradation and shelf-life values at alkaline pH values. Methods: Forced degradation studies were performed on linezolid in solution to develop a validated high-performance liquid chromatography analysis. Sodium chloride 0.9%, sodium lactate, and glucose 5% and glucose 10% solution containing 2.0 mg/mL linezolid were stored at 25.0°C (±0.1°C for 34 days. The effect of temperature on the stability of linezolid in 0.1 M sodium hydroxide solution was investigated to determine the activation energy. The degradation rates of linezolid at selected pH values at 70.0°C and the influence of ionic strength were also examined. Activation energy data were applied to determine the shelf-life values at selected pH values, and a pH rate profile was constructed over the pH range of 8.7–11.4. The stability of intravenous linezolid (Zyvox® solution was evaluated by storing at 70.0°C for 72 hours. Results: Linezolid was found to maintain >95.0% of its initial concentration after storage at 25.0°C for 34 days in sodium lactate, 0.9% in sodium chloride, and 5% and 10% in glucose solutions. Linezolid was degraded at alkaline pH values by first-order kinetics. Activation energy data showed that temperature, but not ionic strength, influenced the degradation rate significantly. An activation energy of 58.22 kJ/mol was determined for linezolid in 0.1 M sodium hydroxide solution. Linezolid was least stable at high pH values and at elevated temperatures. It was determined that linezolid has adequate stability for the preparation of intravenous fluids for clinical administration. Conclusion: Linezolid was found to have a shelf life of 34 days at 25°C when added to

  16. Frequency of ace, epa and elrA Genes in Clinical and Environmental Strains of Enterococcus faecalis.

    Science.gov (United States)

    Lysakowska, Monika Eliza; Denys, Andrzej; Sienkiewicz, Monika

    2012-12-01

    Surface proteins play an important role in the pathogenesis of enterococcal infections. Some of them are candidates for a vaccine, e.g., the frequency of endocarditis in rats vaccinated with Ace protein was 75 % as 12 opposed to 100 % in those who weren't. However, there are other components of enterococcal cells, such as Epa antigens or internalin-like proteins, which may be used in the prophylaxis of infections caused by them. However, also other virulence factors and resistance to antibiotics are important during enterococcal infection. Therefore, the relevance of ace, epa, elrA, other virulence genes, as well as resistance to antibiotics was investigated. 161 Enterococcus faecalis strains isolated from teaching hospitals in Lodz, cultured according to standard microbiological methods, were investigated for the presence of genes encoding surface proteins by PCR. Results were analyzed with χ(2) test. The elrA gene was found in all clinical and environmental strains, the ace gene was also widespread among E. faecalis (96.9 %). Both tested epa genes were found in the majority of isolates (83.25 %). There was correlation between the presence of esp and ace genes (p = 0.046) as well as between epa and agg genes (p = 0.0094; χ(2) test). The presence of the genes encoding surface proteins investigated in our study in the great majority of isolates implies that they would appear to be required during E. faecalis infection. Therefore, they could be excellent targets in therapy of enterococcal infections or, as some studies show, candidates for vaccines.

  17. Predictors of Inadequate Linezolid Concentrations after Standard Dosing in Critically Ill Patients.

    Science.gov (United States)

    Taubert, Max; Zoller, Michael; Maier, Barbara; Frechen, Sebastian; Scharf, Christina; Holdt, Lesca-Miriam; Frey, Lorenz; Vogeser, Michael; Fuhr, Uwe; Zander, Johannes

    2016-09-01

    Adequate linezolid blood concentrations have been shown to be associated with an improved clinical outcome. Our goal was to assess new predictors of inadequate linezolid concentrations often observed in critically ill patients. Fifty-two critically ill patients with severe infections receiving standard dosing of linezolid participated in this prospective observational study. Serum samples (median, 32 per patient) were taken on four consecutive days, and total linezolid concentrations were quantified. Covariates influencing linezolid pharmacokinetics were identified by multivariate analysis and a population pharmacokinetic model. Target attainment (area under the concentration-time curve over 12 h [AUC12]/MIC ratio of >50; MIC = 2 mg/liter) was calculated for both the study patients and a simulated independent patient group (n = 67,000). Target attainment was observed for only 36% of the population on both days 1 and 4. Independent covariates related to significant decreases of linezolid concentrations included higher weight, creatinine clearance rates, and fibrinogen and antithrombin concentrations, lower concentrations of lactate, and the presence of acute respiratory distress syndrome (ARDS). Linezolid clearance was increased in ARDS patients (by 82%) and in patients with elevated fibrinogen or decreased lactate concentrations. In simulated patients, most covariates, including fibrinogen and lactate concentrations and weight, showed quantitatively minor effects on target attainment (difference of ≤9% between the first and fourth quartiles of the respective parameters). In contrast, the presence of ARDS had the strongest influence, with only ≤6% of simulated patients reaching this target. In conclusion, the presence of ARDS was identified as a new and strong predictor of insufficient linezolid concentrations, which might cause treatment failure. Insufficient concentrations might also be a major problem in patients with combined alterations of other covariate

  18. Linezolid Dose That Maximizes Sterilizing Effect While Minimizing Toxicity and Resistance Emergence for Tuberculosis.

    Science.gov (United States)

    Srivastava, Shashikant; Magombedze, Gesham; Koeuth, Thearith; Sherman, Carleton; Pasipanodya, Jotam G; Raj, Prithvi; Wakeland, Edward; Deshpande, Devyani; Gumbo, Tawanda

    2017-08-01

    Linezolid has an excellent sterilizing effect in tuberculosis patients but high adverse event rates. The dose that would maximize efficacy and minimize toxicity is unknown. We performed linezolid dose-effect and dose-scheduling studies in the hollow fiber system model of tuberculosis (HFS-TB) for sterilizing effect. HFS-TB units were treated with several doses to mimic human-like linezolid intrapulmonary pharmacokinetics and repetitively sampled for drug concentration, total bacterial burden, linezolid-resistant subpopulations, and RNA sequencing over 2 months. Linezolid-resistant isolates underwent whole-genome sequencing. The expression of genes encoding efflux pumps in the first 1 to 2 weeks revealed the same exposure-response patterns as the linezolid-resistant subpopulation. Linezolid-resistant isolates from the 2nd month of therapy revealed mutations in several efflux pump/transporter genes and a LuxR-family transcriptional regulator. Linezolid sterilizing effect was linked to the ratio of unbound 0- to 24-h area under the concentration-time curve (AUC 0-24 ) to MIC. Optimal microbial kill was achieved at an AUC 0-24 /MIC ratio of 119. The optimal sterilizing effect dose for clinical use was identified using Monte Carlo simulations. Clinical doses of 300 and 600 mg/day (or double the dose every other day) achieved this target in 87% and >99% of 10,000 patients, respectively. The susceptibility breakpoint identified was 2 mg/liter. The simulations identified that a 300-mg/day dose did not achieve AUC 0-24 s associated with linezolid toxicity, while 600 mg/day achieved those AUC 0-24 s in linezolid dose of 300 mg/day performed well and should be compared to 600 mg/day or 1,200 mg every other day in clinical trials. Copyright © 2017 Srivastava et al.

  19. Structural Basis for Linezolid Binding Site Rearrangement in the Staphylococcus aureus Ribosome.

    Science.gov (United States)

    Belousoff, Matthew J; Eyal, Zohar; Radjainia, Mazdak; Ahmed, Tofayel; Bamert, Rebecca S; Matzov, Donna; Bashan, Anat; Zimmerman, Ella; Mishra, Satabdi; Cameron, David; Elmlund, Hans; Peleg, Anton Y; Bhushan, Shashi; Lithgow, Trevor; Yonath, Ada

    2017-05-09

    An unorthodox, surprising mechanism of resistance to the antibiotic linezolid was revealed by cryo-electron microscopy (cryo-EM) in the 70S ribosomes from a clinical isolate of Staphylococcus aureus This high-resolution structural information demonstrated that a single amino acid deletion in ribosomal protein uL3 confers linezolid resistance despite being located 24 Å away from the linezolid binding pocket in the peptidyl-transferase center. The mutation induces a cascade of allosteric structural rearrangements of the rRNA that ultimately results in the alteration of the antibiotic binding site. IMPORTANCE The growing burden on human health caused by various antibiotic resistance mutations now includes prevalent Staphylococcus aureus resistance to last-line antimicrobial drugs such as linezolid and daptomycin. Structure-informed drug modification represents a frontier with respect to designing advanced clinical therapies, but success in this strategy requires rapid, facile means to shed light on the structural basis for drug resistance (D. Brown, Nat Rev Drug Discov 14:821-832, 2015, https://doi.org/10.1038/nrd4675). Here, detailed structural information demonstrates that a common mechanism is at play in linezolid resistance and provides a step toward the redesign of oxazolidinone antibiotics, a strategy that could thwart known mechanisms of linezolid resistance. Copyright © 2017 Belousoff et al.

  20. What Is Infective Endocarditis?

    Science.gov (United States)

    ANSWERS by heart Cardiovascular Conditions What Is Infective Endocarditis? Infective (bacterial) endocarditis (IE) is an infection of either the heart’s inner lining (endocardium) or the heart valves. Infective endocarditis is a serious — and sometimes fatal — illness. Two ...

  1. Retrospective study of tolerability and efficacy of linezolid in patients with multidrug-resistant tuberculosis (1998-2014).

    Science.gov (United States)

    Ramírez-Lapausa, Marta; Pascual Pareja, José Francisco; Carrillo Gómez, Raquel; Martínez-Prieto, Mónica; González-Ruano Pérez, Patricia; Noguerado Asensio, Arturo

    2016-02-01

    Although linezolid is known to be effective when used as an adjunct therapy in the treatment of patients with multidrug-resistant tuberculosis (MDR-TB), the clinical experience is limited. In this study the efficacy and adverse effects of linezolid treatment were evaluated. A retrospective study of tolerability and efficacy of linezolid in MDR-TB patients was performed in Madrid, Spain. Demographic characteristics, microbiological and clinical features and data on treatment tolerability were collected. Regimens were constructed with a target of prescribing, at least, five anti-tuberculosis agents likely to be effective. Linezolid, at a dosage of 1200 or 600 mg daily, was included to complete the treatment if no other sensitive drugs were available. Vitamin B6 was used to reduce toxicity. Treatment outcome and clinical status at last contact were compared between patients with linezolid-containing regimens and with those without linezolid-containing regimens. During the period 1998-2014, 55 patients with MDR-TB received treatment. In 21 of these patients, linezolid was added. The median of linezolid administration was 23.9 months (IQT 13.1-24.7). Patients using linezolid showed a greater resistance to drugs, with a median of 6 (IQR 5-7) compared with those who did not use it, with a median of 4 drugs (IQR 3-5) (plinezolid group (73.5 days) did not differ significantly from those in the non-linezolid group (61 days) (p=0.29). There were no significant differences in the outcomes of the two patient groups. There were no reported adverse events in 81% of patients assigned to linezolid therapy. Only four patients developed toxicity attributed to linezolid. The most serious adverse event in these patients was anemia observed in the two patients treated with 1200 mg per day. One of them also developed moderate paresthesia. In both cases the dosage was reduced to 600 mg per day, with improvement of the anemia and paresthesias. No patients stopped linezolid therapy. A daily

  2. Accumulation of multiple mutations in linezolid-resistant Staphylococcus epidermidis causing bloodstream infections; in silico analysis of L3 amino acid substitutions that might confer high-level linezolid resistance.

    Science.gov (United States)

    Ikonomidis, Alexandros; Grapsa, Anastasia; Pavlioglou, Charikleia; Demiri, Antonia; Batarli, Alexandra; Panopoulou, Maria

    2016-12-01

    Fifty-six Staphylococcus epidermidis clinical isolates, showing high-level linezolid resistance and causing bacteremia in critically ill patients, were studied. All isolates belonged to ST22 clone and carried the T2504A and C2534T mutations in gene coding for 23SrRNA as well as the C189A, G208A, C209T and G384C missense mutations in L3 protein which resulted in Asp159Tyr, Gly152Asp and Leu94Val substitutions. Other silent mutations were also detected in genes coding for ribosomal proteins L3 and L22. In silico analysis of missense mutations showed that although L3 protein retained the sequence of secondary motifs, the tertiary structure was influenced. The observed alteration in L3 protein folding provides an indication on the putative role of L3-coding gene mutations in high-level linezolid resistance. Furthermore, linezolid pressure in health care settings where linezolid consumption is of high rates might lead to the selection of resistant mutants possessing L3 mutations that might confer high-level linezolid resistance.

  3. Resistance to Linezolid Caused by Modifications at Its Binding Site on the Ribosome

    DEFF Research Database (Denmark)

    Long, Katherine S.; Vester, Birte

    2012-01-01

    Linezolid is an oxazolidinone antibiotic in clinical use for the treatment of serious infections of resistant Gram-positive bacteria. It inhibits protein synthesis by binding to the peptidyl transferase center on the ribosome. Almost all known resistance mechanisms involve small alterations...... to the linezolid binding site, so this review will therefore focus on the various changes that can adversely affect drug binding and confer resistance. High-resolution structures of linezolid bound to the 50S ribosomal subunit show that it binds in a deep cleft that is surrounded by 23S rRNA nucleotides. Mutation...... of 23S rRNA has for some time been established as a linezolid resistance mechanism. Although ribosomal proteins L3 and L4 are located further away from the bound drug, mutations in specific regions of these proteins are increasingly being associated with linezolid resistance. However, very little...

  4. ENDOCARDITIS IN SYSTEMIC LUPUS ERYTHEMATOSUS

    Directory of Open Access Journals (Sweden)

    AMEL Harzallah

    2017-04-01

    Full Text Available Endocarditis is one of the most prevalent forms of cardiac involvement in patients with lupus, as it is considered as one a life-threatening complication. Libman-Sacks endocarditis is common. Infective endocarditis can also cause complications within immunocompromised patients. The aim of this study is to determine particularities of endocarditis in patients with lupus and to look for distinguishing features between infectious or immunological origin. A retrospective study was conducted on patients with lupus presenting endocarditis. Lupus was diagnosed according to the American college of rheumatology criteria. The diagnosis of endocarditis was made based on the modified Duke criteria. The present case report studies seven cases of endocarditis. Six of these patients are women and the other one is a man. They are aged meanly of 29.4 years (extremes: 20-36. Fever was present in all the cases with a new cardiac murmur in six cases and a modification of its intensity in one case. Biologic inflammatory syndrome was present in six cases. Cardiac ultrasound performed in six cases made the diagnosis of endocarditis which involved the left heart valves in five cases and the right heart valves in one case. Valvular insufficiency was identified in six patients. The valve involvement was mitral in two cases, mitro-aortic in two others, aortic in the fifth one and tricuspid in the sixth one. Endocarditis was infectious in 4 cases, thanks to positive blood culture. The germs identified were gram negative bacilli in two cases, anaerobic organism in one case and gram positive cocci in one case. Candida albicans was isolated in one case. Libman-Sacks endocarditis was objectified in three cases. A combination of Libman-Sacks endocarditis with infectious endocarditis was diagnosed in one case. The treatment consisted of antibiotics in four cases with surgery in two cases. The outcome was favorable in five cases and fatal in the two others. Endocarditis in lupus

  5. Linezolid-induced optic neuropathy with a rare pathological change in the inner retina.

    Science.gov (United States)

    Ishii, Nobuhito; Kinouchi, Reiko; Inoue, Masatomo; Yoshida, Akitoshi

    2016-12-01

    We report a case of linezolid-induced optic neuropathy with transient microcystic spaces in the inner retina. We observed the retina using Fourier-domain optical coherence tomography (FD-OCT) in a patient with linezolid-induced optic neuropathy. A 49-year-old woman presented to our department with a 1-week history of bilateral photophobia. At the first visit, her best-corrected visual acuity (VA) was 0.6 in the right eye and 0.5 in the left eye. She had moderate optic disk edema and central scotomas bilaterally. FD-OCT showed bilateral microcystic spaces in the retina. Microcystic spaces were seen in the retinal nerve fiber layer (RNFL) and at the border of the RNFL and the retinal ganglion cell layer. Magnetic resonance imaging and laboratory tests showed no positive findings except for an elevated lactic acid level. One week after the first visit, the VA levels decreased to 0.06 and 0.07 in the right and left eyes, respectively. Because the patient had a 7-month history of linezolid treatment for persistent pyogenic arthritis, we suspected linezolid-induced optic neuropathy and immediately terminated treatment with this drug. The optic disk edema and the microcystic spaces in the retina resolved, and the VA improved to 1.2 at 6 weeks after linezolid withdrawal. Microcystic spaces, which resolved with linezolid withdrawal, were observed in linezolid-induced optic neuropathy. The microcystic spaces in the inner retina can be the first retinal sign of some optic neuropathies.

  6. Comparing the ocular surface effects of topical vancomycin and linezolid for treating bacterial keratitis.

    Science.gov (United States)

    Akova Budak, Berna; Baykara, Mehmet; Kıvanç, Sertaç Argun; Yilmaz, Hakan; Cicek, Serhat

    2016-01-01

    Vancomycin is the gold standard in combination therapy for severe and resistant gram-positive keratitis and in particular for Methicillin-resistant Staphylococcus aureus (MRSA) infections. The aim of this study was to report the ocular surface toxicity and scoring in patients whose treatment shifted to topical linezolid/ceftazidime from topical vancomycin/ceftazidime due to their vancomycin intolerance. A retrospective, interventional case series of bacterial keratitis was treated with topical linezolid (one drop of 0.2% solution per eye), administered hourly until epithelization and then gradually decreased. The number and extent of punctate epithelial erosions were noted across the entire surface of the cornea. Ocular discomfort was assessed by means of (a) patient-reported pain upon instillation of the medication (vancomycin/linezolid), (b) reported burning sensation between doses and (c) reported foreign-body sensation. No ocular surface toxicity related to linezolid use was noted. Patients were followed for at least 2 months after treatment between April and December 2013. Of the seven patients included in the study (age range: 2-88 years; five females, two males), complete epithelization and resolution was achieved in five patients. One patient was treated with linezolid after penetrating keratoplasty. The second culture of another patient with impending perforation despite linezolid/ceftazidime therapy yielded Fusarium spp., so he underwent tectonic keratoplasty. The mean ocular surface score was 9.4 ± 1.6 during vancomycin treatment and 5.9 ± 1.3 during linezolid treatment after discontinuation of vancomycin. The topical linezolid score was significantly lower (p = 0.027). Topical linezolid may be better tolerated, according to the mean ocular surface score, than topical vancomycin by some patients and can be considered an alternative for patients who do not well tolerate vancomycin.

  7. EFFECT OF LINEZOLID ALONE AND IN COMBINATION WITH OTHER ANTIBIOTICS, ON METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS.

    Science.gov (United States)

    Yehia, Hoda; El Said, Manal; Azmy, Magda; Badawy, Moushira; Mansy, Soheir; Gohar, Hamida; Madany, Nadia

    2016-04-01

    The prevalence of methicillin-resistant Staphyloccoccus aureus (MRSA) strains has presented a new challenge in antimicrobial medication. Linezolid is a new drug with potent activity on Gram-positive pathogens such as MRSA. The aim of the study was to investigate the in vitro activity of linezolid alone and in combination with imipenem, vancomycin or rifampicin to determine the most active therapy against MRSA strains. Twenty clinical MRSA strains were isolated from patients admitted to inpatient departments and outpatient clinics of Theodor Bilharz Research Institute. Standard strain MRSA ATCC 43300 was included as a control. The MICs of MRSA strains to linezolid, vancomycin, imipenem and rifampicin were evaluated using E test. Time-kill curve were used to assess the in vitro activity of linezolid (at 8x MIC) alone and in combination with imipenem (at 32x MIC), vancomycin or rifampicin (at 8x MIC). Scanning and transmission electron microscopy were performed to compare bacterial morphological alterations owing to the different combi- nations. Time-kill studies showed synergistic effect when linezolid combined with imipenem was tested against all the MRSA strains. Linezolid plus vancomycin or rifampicin combinations did not display any synergism or antagonism. Scanning and transmission electron microscopy observations confirmed the interactions observed in time kill experiments. Linezolid in combination with subinhibitory concentrations of imipenem can be bactericidal against MRSA strains and appears to be a promising combination for the treatment of MRSA infections. No synergistic activity was seen when the linezolid and vancomycin or rifampicin were combined. Linezolid could prevent the emergence of mutants resistant to rifampicin

  8. Linezolid extracorporeal removal during haemodialysis with high cut-off membrane in critically ill patients.

    Science.gov (United States)

    Villa, Gianluca; Cassetta, Maria Iris; Tofani, Lorenzo; Valente, Serafina; Chelazzi, Cosimo; Falsini, Silvia; De Gaudio, Angelo Raffaele; Novelli, Andrea; Ronco, Claudio; Adembri, Chiara

    2015-10-01

    Continuous venovenous haemodialysis with high cut-off membrane (HCO-CVVHD) is often used in critically ill septic patients with acute kidney injury (AKI) to sustain renal function and to remove circulating inflammatory mediators. The aim of this study was to analyse the extracorporeal removal of linezolid and related alterations in pharmacokinetic/pharmacodynamic (PK/PD) parameters during HCO-CVVHD. Three critically ill septic patients with AKI, treated with linezolid and HCO-CVVHD, were prospectively observed. To calculate the extracorporeal clearance of linezolid and the PK parameters, effluent, pre-filter and post-filter samples were contemporaneously collected before linezolid infusion, just after 1-h infusion (maximum serum concentration; C(max)), at 3 h and 6 h after dosing, and before the next dose (trough serum concentration; C(min)). Linezolid C(max) and C(min) (pre-filter) ranged from 10.4-23.5 mg/L and from 2.9-10.3 mg/L. The dialysate saturation coefficient was 0.66-0.85 and the extracorporeal clearance with a diffusive dose of 35 m L/kg/h ranged from 2.1-2.5 L/h. Total linezolid clearance was between 1.7 L/h and 6.3 L/h. The total area under the plasma concentration-time curve (AUC0-∞) ranged from 95.1 mgh/L to 352.9 mgh/L, in accordance with the different clinical conditions. AUCfree/MIC ratios were always linezolid total clearance, the clinical features of critically ill septic patients appear to be mainly responsible for the high variability of linezolid serum concentrations. Copyright © 2015. Published by Elsevier B.V.

  9. Linezolid Surveillance Results for the United States (LEADER Surveillance Program 2014).

    Science.gov (United States)

    Flamm, Robert K; Mendes, Rodrigo E; Hogan, Patricia A; Streit, Jennifer M; Ross, James E; Jones, Ronald N

    2016-04-01

    Thelinezolidexperience andaccuratedetermination ofresistance (LEADER) surveillance program has monitored linezolid activity, spectrum, and resistance since 2004. In 2014, a total of 6,865 Gram-positive pathogens from 60 medical centers from 36 states were submitted. The organism groups evaluated wereStaphylococcus aureus(3,106), coagulase-negative staphylococci (CoNS; 797), enterococci (855),Streptococcus pneumoniae(874), viridans group streptococci (359), and beta-hemolytic streptococci (874). Susceptibility testing was performed by reference broth microdilution at the monitoring laboratory. Linezolid-resistant isolates were confirmed by repeat testing. PCR and sequencing were performed to detect mutations in 23S rRNA, L3, L4, and L22 proteins and acquired genes (cfrandoptrA). The MIC50/90forStaphylococcus aureuswas 1/1 μg/ml, with 47.2% of isolates being methicillin-resistantStaphylococcus aureus Linezolid was active against allStreptococcus pneumoniaestrains and beta-hemolytic streptococci with a MIC50/90of 1/1 μg/ml and against viridans group streptococci with a MIC50/90of 0.5/1 μg/ml. Among the linezolid-nonsusceptible MRSA strains, one strain harboredcfronly (MIC, 4 μg/ml), one harbored G2576T (MIC, 8 μg/ml), and one containedcfrand G2576T with L3 changes (MIC, ≥8 μg/ml). Among CoNS, 0.75% (six isolates) of all strains demonstrated linezolid MIC results of ≥4 μg/ml. Five of these were identified asStaphylococcus epidermidis, four of which containedcfrin addition to the presence of mutations in the ribosomal proteins L3 and L4, alone or in combination with 23S rRNA (G2576T) mutations. Six enterococci (0.7%) were linezolid nonsusceptible (≥4 μg/ml; five with G2576T mutations, including one with an additionalcfrgene, and one strain withoptrAonly). Linezolid demonstrated excellent activity and a sustained susceptibility rate of 99.78% overall. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  10. Lack of an Effect of Standard and Supratherapeutic Doses of Linezolid on QTc Interval Prolongation▿†

    Science.gov (United States)

    Damle, Bharat; LaBadie, Robert R.; Cuozzo, Cheryl; Alvey, Christine; Choo, Heng Wee; Riley, Steve; Kirby, Deborah

    2011-01-01

    A double-blind, placebo-controlled, four-way crossover study was conducted in 40 subjects to assess the effect of linezolid on corrected QT (QTc) interval prolongation. Time-matched, placebo-corrected QT intervals were determined predose and at 0.5, 1 (end of infusion), 2, 4, 8, 12, and 24 h after intravenous dosing of linezolid 600 and 1,200 mg. Oral moxifloxacin at 400 mg was used as an active control. The pharmacokinetic profile of linezolid was also evaluated. At each time point, the upper bound of the 90% confidence interval (CI) for placebo-corrected QTcF values (i.e., QTc values adjusted for ventricular rate using the correction methods of Fridericia) for linezolid 600 and 1,200-mg doses were 5 ms, indicating that the study was adequately sensitive to assess QTc prolongation. The pharmacokinetic profile of linezolid at 600 mg was consistent with previous observations. Systemic exposure to linezolid increased in a slightly more than dose-proportional manner at supratherapeutic doses, but the degree of nonlinearity was small. At a supratherapeutic single dose of 1,200 mg of linezolid, no treatment-related increase in adverse events was seen compared to 600 mg of linezolid, and no clinically meaningful effects on vital signs and safety laboratory evaluations were noted. PMID:21709083

  11. Shewanella putrefaciens infective endocarditis

    Directory of Open Access Journals (Sweden)

    Jonathan Constant

    2014-11-01

    Full Text Available Shewanella putrefaciens rarely causes infection in humans. In the last few decades a growing number of cases have been described. The following report outlines the case of a 40-year-old immunocompetent white man with S. putrefaciens infective endocarditis. This is the first known case of infective endocarditis due to an apparently monomicrobial S. putrefaciens infection, and the second known case of S. putrefaciens-related infective endocarditis worldwide.

  12. [Linezolid-induced Apoptosis through Mitochondrial Damage and Role of Superoxide Dismutase-1 in Human Monocytic Cell Line U937].

    Science.gov (United States)

    Fujii, Satoshi; Muraoka, Sanae; Miyamoto, Atsushi; Sakurai, Koichi

    2018-01-01

     Cytopenia is a major adverse event associated with linezolid therapy. The objective of this study was to examine whether the cytotoxicity of linezolid to eukaryotic cells was associated with mitochondrial dysfunction and apoptosis-like cell death in human leukemic monocyte lymphoma cell line U937. Apoptosis-like cell death was clearly observed when cells were incubated with linezolid, depending on the duration and linezolid concentration. Mitochondrial membrane potential of cells treated with linezolid collapsed in a short period of time, but the number of mitochondria did not decrease. Cytotoxicity of linezolid was relieved by the knockdown of superoxide dismutase-1 in U937 cells. On the other hand, no autophagy was observed in cells treated with linezolid. These results suggest that mitochondrial damages would be linked to the induction of apoptosis in U937 cells treated with linezolid and that its mechanism does not involve autophagy.

  13. ENDOCARDITIS WITH AN UNCOMMON GERM

    Directory of Open Access Journals (Sweden)

    M. Gharouni

    2006-07-01

    Full Text Available Enterococci are normal inhabitants of gastrointestinal tract, being responsible for 5 to 18% of infective endocarditis and the incidence appears to be increasing. Eleven patients with enterococcal endocarditis were studied. In a case series group, 10 men (average 57 years and one woman (37 years were studied. Two patients had rheumatic heart disease, 5 patients arteriosclerotic disease and one patient chronic renal failure on hemodialysis. Ten patients were treated with ampicillin and gentamycin. Valve replacement was performed in 3 patients with aortic valve endocarditis, one on 8th day and two at the end of the treatment. Overall clinical cure was achieved in 9 patients. Two relapses occurred and 2 patients died as a result of refractory congestive heart failure and cerebral emboli. All of the enterococcal endocarditis cases were community acquired. In conclusion, infective endocarditis in patients with preexistent valvular heart disease, community acquisition and non specific symptoms with bacteriuria should be considered as enterococcal endocarditis.

  14. Global analysis of the impact of linezolid onto virulence factor production in S. aureus USA300.

    Science.gov (United States)

    Bonn, Florian; Pané-Farré, Jan; Schlüter, Rabea; Schaffer, Marc; Fuchs, Stephan; Bernhardt, Jörg; Riedel, Katharina; Otto, Andreas; Völker, Uwe; van Dijl, Jan Maarten; Hecker, Michael; Mäder, Ulrike; Becher, Dörte

    2016-05-01

    The translation inhibitor linezolid is an antibiotic of last resort against Gram-positive pathogens including methicillin resistant strains of the nosocomial pathogen Staphylococcus aureus. Linezolid is reported to inhibit production of extracellular virulence factors, but the molecular cause is unknown. To elucidate the physiological response of S. aureus to linezolid in general and the inhibition of virulence factor synthesis in particular a holistic study was performed. Linezolid was added to exponentially growing S. aureus cells and the linezolid stress response was analyzed with transcriptomics and quantitative proteomics methods. In addition, scanning and transmission electron microscopy experiments as well as fluorescence microscopy analyses of the cellular DNA and membrane were performed. As previously observed in studies on other translation inhibitors, S. aureus adapts its protein biosynthesis machinery to the reduced translation efficiency. For example the synthesis of ribosomal proteins was induced. Also unexpected results like a decline in the amount of extracellular and membrane proteins were obtained. In addition, cell shape and size changed after linezolid stress and cell division was diminished. Finally, the chromosome was condensed after linezolid stress and lost contact to the membrane. These morphological changes cannot be explained by established theories. A new hypothesis is discussed, which suggests that the reduced amount of membrane and extracellular proteins and observed defects in cell division are due to the disintegration of transertion complexes by linezolid. Copyright © 2016 Elsevier GmbH. All rights reserved.

  15. Lyme Endocarditis.

    Science.gov (United States)

    Paim, Ana C; Baddour, Larry M; Pritt, Bobbi S; Schuetz, Audrey N; Wilson, John W

    2018-03-29

    We describe a case of Lyme endocarditis which, to our knowledge, is the first reported case confirmed by molecular diagnostics in the United States. Valvular involvement as a manifestation of Lyme carditis is rare 4 . The first case describing a possible association between Lyme disease and cardiac valvular disease in the United States was published in 1993 5 . Since that time, there have been 2 cases of Lyme endocarditis confirmed by Borrelia positive 16S rRNA polymerase chain reaction (PCR) and sequencing from valvular tissue 8,10 and reported from Europe. We present the case of a 68-year-old male with progressive dyspnea had mitral valve perforation with severe mitral valve insufficiency and perforation seen on transesophageal echocardiogram. Subsequently resected valve tissue had sings of acute inflammation without organisms seen. Although blood and valve tissue cultures were negative, 16S rRNA PCR and sequencing demonstrated Borrelia burgdorferi. Lyme endocarditis can be a challenging diagnosis to confirm, given the rarity of cases and the need for molecular tools of resected valve tissue. It should be included among diagnostic possibilities in patients with culture-negative endocarditis who have exposure to ticks in endemic and emerging areas of Lyme disease. Copyright © 2018. Published by Elsevier Inc.

  16. Linezolid-associated optic neuropathy in a pediatric patient with Mycobacterium nonchromogenicum: A case report.

    Science.gov (United States)

    González Saldaña, Napoleón; Galvis Trujillo, Diego Mauricio; Borbolla Pertierra, Ana Maria; Mondragón Pineda, Ana Ivette; Juárez Olguín, Hugo

    2017-12-01

    Toxic optic neuropathies are alterations of the optic nerve and can be caused by environmental, pharmacological, or nutritional agents. It is about a 7-year-old male patient, a native of the State of Mexico, Mexico who was diagnosed with cervical mycobacterial lymphadenitis that required management with linezolid. After 7 months of treatment, visual acuity of the left eye decreased and was accompanied by headache. Neuroinfection and other central nervous system affections were discarded. An adverse effect related to treatment with linezolid was suspected, and linezolid was suspended. The symptoms subsided after discontinuation; however, the patient continued to show decreased visual acuity of the left eye, assessed by his ability to count 2 fingers. The right eye remained unaffected. Neurotoxicity can be decreased by reducing the total dose of linezolid or by administrating it in an intermittent form. To avoid progression and loss of vision, we suggest frequent periodic ophthalmological evaluation in patients treated with linezolid. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  17. INFECTIVE ENDOCARDITIS: MODERN COURSE

    Directory of Open Access Journals (Sweden)

    T. L. Vinogradova

    2014-07-01

    Full Text Available The paper presents the characteristic features of the modern course of infective endocarditis. Unresolved questions of classification of diseaseand drug therapy are discussed. Clearly defined indications for surgical treatment of endocarditis.

  18. In Vitro Activity of PNU-100766 (Linezolid), a New Oxazolidinone Antimicrobial, against Nocardia brasiliensis

    Science.gov (United States)

    Vera-Cabrera, Lucio; Gómez-Flores, Alejandra; Escalante-Fuentes, Wendy G.; Welsh, Oliverio

    2001-01-01

    The in vitro activity of a novel oxazolidinone, linezolid, was studied by comparing the activity of linezolid with those of amikacin, trimethoprim-sulfamethoxazole, and amoxicillin-clavulanic acid against 25 strains of Nocardia brasiliensis isolated from patients with mycetoma. All N. brasiliensis strains tested were sensitive to linezolid (MIC at which 90% of strains are inhibited [MIC90], 2 μg/ml; MIC50, 1 μg/ml). This antimicrobial might constitute a good alternative for treatment of actinomycetoma. PMID:11709356

  19. Risk factors associated with high linezolid trough plasma concentrations.

    Science.gov (United States)

    Morata, L; De la Calle, C; Gómez-Cerquera, J M; Manzanedo, L; Casals, G; Brunet, M; Cobos-Trigueros, N; Martínez, J A; Mensa, J; Soriano, A

    2016-06-01

    The major concern of linezolid is the adverse events. High linezolid trough serum concentration (Cmin) has been associated with toxicity. The aim of this study was to analyze factors associated with high Cmin. Main clinical characteristics of 104 patients treated with 600 mg/12 hours of linezolid were retrospectively reviewed. Samples were obtained just before the next dose after at least three doses and within the first 8 days of treatment. High Cmin was considered when it was >8 mg/L. Univariate and multivariate analysis were performed. 34.6% patients had a Cmin >8 mg/L, and they were older and had more frequently an estimated glomerular filtration by MDRD 8 was the renal function. Patients with an eGF 80 mL/min (OR: 4.273) and there was a trend towards a high Cmin in patients with eGF between 40-80 mL/min (OR: 2.109). High Cmin were frequent, especially in patients with MDRD <40 mL/min. Therapeutic drug monitoring could be useful to avoid toxicity in patients with renal dysfunction.

  20. The efficacy and safety of linezolid and glycopeptides in the treatment of Staphylococcus aureus infections.

    Directory of Open Access Journals (Sweden)

    Jinjian Fu

    Full Text Available To assess the effectiveness and safety of linezolid in comparison with glycopeptides (vancomycin and teicoplanin for the treatment of Staphylococcus aureus infections, we conducted a meta-analysis of relevant randomized controlled trials. A thorough search of Pubmed and other databases was performed. Thirteen trials on 3863 clinically assessed patients were included. Linezolid was slightly more effective than glycopeptides in the intent-to-treat population (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01-1.10, was more effective in clinically assessed patients (OR 95% CI: 1.38, 1.17-1.64 and in all microbiologically assessed patients (OR 95% CI: 1.38, 1.15-1.65. Linezolid was associated with better treatment in skin and soft-tissue infections (SSTIs patients (OR 95% CI: 1.61, 1.22-2.12, but not in bacteraemia (OR 95% CI: 1.24, 0.78-1.97 or pneumonia (OR 95% CI: 1.25, 0.97-1.60 patients. No difference of mortality between linezolid and glycopeptides was seen in the pooled trials (OR 95% CI: 0.98, 0.83-1.15. While linezolid was associated with more haematological (OR 95% CI: 2.23, 1.07-4.65 and gastrointestinal events (OR 95% CI: 2.34, 1.53-3.59, a significantly fewer events of skin adverse effects (OR 95% CI: 0.27, 0.16-0.46 and nephrotoxicity (OR 95% CI: 0.45, 0.28-0.72 were recorded in linezolid. Based on the analysis of the pooled data of randomized control trials, linezolid should be a better choice for treatment of patients with S. aureus infections, especially in SSTIs patients than glycopeptides. However, when physicians choose to use linezolid, risk of haematological and gastrointestinal events should be taken into account according to the characteristics of the specific patient populations.

  1. Daptomycin versus linezolid for the treatment of vancomycin-resistant enterococcal bacteraemia: implications of daptomycin dose.

    Science.gov (United States)

    Chuang, Y-C; Lin, H-Y; Chen, P-Y; Lin, C-Y; Wang, J-T; Chang, S-C

    2016-10-01

    Treatment options for vancomycin-resistant enterococci (VRE) bloodstream infection are limited. Studies comparing daptomycin or linezolid in treating VRE bloodstream infection have conflicting results and suggest daptomycin underdosing. The responses to different daptomycin doses have not been studied. We conducted a multicentre prospective cohort study to compare linezolid and daptomycin (≥6 mg/kg) for the treatment of VRE bloodstream infection. The primary outcome was 14-day mortality. We used multivariate logistic regression analysis for outcome analysis and a generalized additive model for dose-dependent response estimation. Two hundred twelve patients were included (daptomycin, n = 141; linezolid, n = 71). All-cause 14-day mortality was higher in the daptomycin group (36.9% vs. 21.1%; p 0.03). After adjusting for confounders in logistic regression, mortality was lower in the linezolid group (adjusted odds ratio (aOR), 0.45; 95% confidence interval (CI), 0.21-0.96; p 0.04). The generalized additive model showed that higher-dose daptomycin (≥9 mg/kg) was associated with better survival than lower-dose daptomycin (6-9 mg/kg). Logistic regression showed that linezolid (aOR, 0.36; 95% CI, 0.17-0.79; p 0.01) and higher-dose daptomycin (aOR, 0.26; 95% CI, 0.09-0.74; p 0.01) independently predicted lower mortality compared to lower-dose daptomycin. Linezolid was not superior to higher-dose daptomycin in terms of mortality (aOR, 1.40; 95% CI, 0.45-4.37; p 0.57). Higher-dose daptomycin had lower mortality than lower-dose daptomycin. Despite higher mortality for lower-dose daptomycin than linezolid, linezolid conferred no survival benefit compared to higher-dose daptomycin. Our findings suggest that the recommended daptomycin dose is suboptimal for treating VRE bacteraemia. Copyright © 2016. Published by Elsevier Ltd.

  2. Infective endocarditis in children: an update.

    Science.gov (United States)

    Dixon, Garth; Christov, Georgi

    2017-06-01

    Infective endocarditis in children remains a clinical challenge. Here, we review the impact of the updated 2015 American Heart Association and European Society of Cardiology guidelines on management as well as the significance of the new predisposing factors, diagnostic and treatment options, and the impact of the 2007-2008 change in prophylaxis recommendations. The new 2015 infective endocarditis guidelines introduced the endocarditis team, added the new imaging modalities of computer tomography and PET-computer tomography into the diagnostic criteria and endorsed the concept of safety of relatively early surgical treatment. The impact of the restriction of infective endocarditis prophylaxis since the 2007-2008 American Heart Association and National Institute for Health and Care Excellence recommendations is uncertain, with some studies showing no change and other more recent studies showing increased incidence. The difficulties in adjusting for varying confounding factors are discussed. The relative proportion of the device-related infective endocarditis is increasing. Special attention is paid to relatively high incidence of percutaneous pulmonary valve implantation-related infective endocarditis with low proportion of positive echo signs, disproportionate shift in causative agents, and unusual complication of acute obstruction. The significance of incomplete neoendothelialization on the risk of infective endocarditis on intracardiac devices is also discussed. The impact of changes in the infective endocarditis prophylaxis recommendations in pediatric patients is still uncertain. The device-related infective endocarditis has increasing importance, with the incidence on transcatheter implanted bovine jugular vein pulmonary valves being relatively high. The use of novel imaging, laboratory diagnostic techniques, and relatively early surgery in particular circumstances is important for management of paediatric infective endocarditis.

  3. Propionibacterium endocarditis: a case series from the International Collaboration on Endocarditis Merged Database and Prospective Cohort Study

    NARCIS (Netherlands)

    Lalani, Tahaniyat; Person, Anna K.; Hedayati, Susan S.; Moore, Laura; Murdoch, David R.; Hoen, Bruno; Peterson, Gail; Shahbaz, Hasan; Raoult, Didier; Miro, Jose M.; Olaison, Lars; Snygg-Martino, Ulrika; Suter, Fredy; Spelman, Dennis; Eykyn, Susannah; Strahilevitz, Jacob; van der Meer, Jan T.; Verhagen, Dominique; Baloch, Khaula; Abrutyn, Elias; Cabell, Christopher H.

    2007-01-01

    Propionibacterium species are occasionally associated with serious systemic infections such as infective endocarditis. In this study, we examined the clinical features, complications and outcome of 15 patients with Propionibacterium endocarditis using the International Collaboration on Endocarditis

  4. The Emergence of Linezolid Resistance among Enterococci in Intestinal Microbiota of Treated Patients Is Unrelated to Individual Pharmacokinetic Characteristics

    Science.gov (United States)

    Nguyen, T. T.; Defrance, G.; Massias, L.; Alavoine, L.; Lefort, A; Noel, V.; Senneville, E.; Doucet-Populaire, F.; Mentré, F.; Andremont, A.; Duval, X.

    2014-01-01

    Linezolid is an antimicrobial agent for the treatment of multiresistant Gram-positive infections. We assessed the impact of linezolid on the microbiota and the emergence of resistance and investigated its relationship with plasma pharmacokinetics of the antibiotic. Twenty-eight patients were treated for the first time with linezolid administered orally (n = 17) or parenterally (n = 11) at 600 mg twice a day. Linezolid plasma pharmacokinetic analysis was performed on day 7. Colonization by fecal enterococci, pharyngeal streptococci, and nasal staphylococci were assessed using selective media with or without supplemental linezolid. The resistance to linezolid was characterized. The treatment led to a decrease of enterococci, staphylococci, and streptococci in the fecal (P = 0.03), nasal, and pharyngeal (P linezolid resistance during treatment was observed only in the intestinal microbiota and unrelated to pharmacokinetic parameters. However, colonization by Gram-positive bacteria was reduced as a result of treatment in all microbiotas. PMID:24566182

  5. Endocarditis in adults with bacterial meningitis

    NARCIS (Netherlands)

    Lucas, Marjolein J.; Brouwer, Matthijs C.; van der Ende, Arie; van de Beek, Diederik

    2013-01-01

    Endocarditis may precede or complicate bacterial meningitis, but the incidence and impact of endocarditis in bacterial meningitis are unknown. We assessed the incidence and clinical characteristics of patients with meningitis and endocarditis from a nationwide cohort study of adults with

  6. Effects of continuous renal replacement therapy on linezolid pharmacokinetic/pharmacodynamics: a systematic review.

    Science.gov (United States)

    Villa, Gianluca; Di Maggio, Paola; De Gaudio, A Raffaele; Novelli, Andrea; Antoniotti, Riccardo; Fiaccadori, Enrico; Adembri, Chiara

    2016-11-19

    Major alterations in linezolid pharmacokinetic/pharmacodynamic (PK/PD) parameters might be expected in critically ill septic patients with acute kidney injury (AKI) who are undergoing continuous renal replacement therapy (CRRT). The present review is aimed at describing extracorporeal removal of linezolid and the main PK-PD parameter changes observed in critically ill septic patients with AKI, who are on CRRT. Citations published on PubMed up to January 2016 were systematically reviewed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. All authors assessed the methodological quality of the studies and consensus was used to ensure studies met inclusion criteria. In-vivo studies in adult patients with AKI treated with linezolid and on CRRT were considered eligible for the analysis only if operational settings of the CRRT machine, membrane type, linezolid blood concentrations and main PK-PD parameters were all clearly reported. Among 68 potentially relevant articles, only 9 were considered eligible for the analysis. Across these, 53 treatments were identified among the 49 patients included (46 treated with high-flux and 3 with high cut-off membranes). Continuous veno-venous hemofiltration (CVVH) was the most frequent treatment performed amongst the studies. The extracorporeal clearance values of linezolid across the different modalities were 1.2-2.3 L/h for CVVH, 0.9-2.2 L/h for hemodiafiltration and 2.3 L/h for hemodialysis, and large variability in PK/PD parameters was reported. The optimal area under the curve/minimum inhibitory concentration (AUC/MIC) ratio was reached for pathogens with an MIC of 4 mg/L in one study only. Wide variability in linezolid PK/PD parameters has been observed across critically ill septic patients with AKI treated with CRRT. Particular attention should be paid to linezolid therapy in order to avoid antibiotic failure in these patients. Strategies to improve the effectiveness of

  7. A simple high-performance liquid chromatography for the determination of linezolid in human plasma and saliva.

    Science.gov (United States)

    Hara, Shuuji; Uchiyama, Masanobu; Yoshinari, Masami; Matsumoto, Taichi; Jimi, Shiro; Togawa, Atsushi; Takata, Tohru; Takamatsu, Yasushi

    2015-09-01

    Linezolid is an antimicrobial agent for the treatment of multiresistant Gram-positive infections. A practical high-performance liquid chromatography method was developed for the determination of linezolid in human plasma and saliva. Linezolid and an internal standard (o-ethoxybenzamide) were extracted from plasma and saliva with ethyl acetate and analyzed on a Capcell Pak C18 MG column with UV detection at 254 nm. The calibration curve was linear through the range 0.5-50 µg/mL using a 200 μL sample volume. The intra- and interday precisions were all plasma and 5.60% for saliva. The accuracies ranged from 98.8 to 110% for both matrices. The mean recoveries of linezolid were 80.8% for plasma and 79.0% for saliva. This method was used to determine the plasma and saliva concentrations of linezolid in healthy volunteers who were orally administered a 600 mg dose of linezolid. Our liquid-liquid extraction procedure is easy and requires a small volume of plasma or saliva (200 μL). This small volume can be advantageous in clinical pharmacokinetic studies, especially if children participate. Copyright © 2015 John Wiley & Sons, Ltd.

  8. Endocarditis in adults with bacterial meningitis.

    Science.gov (United States)

    Lucas, Marjolein J; Brouwer, Matthijs C; van der Ende, Arie; van de Beek, Diederik

    2013-05-21

    Endocarditis may precede or complicate bacterial meningitis, but the incidence and impact of endocarditis in bacterial meningitis are unknown. We assessed the incidence and clinical characteristics of patients with meningitis and endocarditis from a nationwide cohort study of adults with community-acquired bacterial meningitis in the Netherlands from 2006 to 2012. Endocarditis was identified in 24 of 1025 episodes (2%) of bacterial meningitis. Cultures yielded Streptococcus pneumoniae in 13 patients, Staphylococcus aureus in 8 patients, and Streptococcus agalactiae, Streptococcus pyogenes, and Streptococcus salivarius in 1 patient each. Clues leading to the diagnosis of endocarditis were cardiac murmurs, persistent or recurrent fever, a history of heart valve disease, and S aureus as the causative pathogen of bacterial meningitis. Treatment consisted of prolonged antibiotic therapy in all patients and surgical valve replacement in 10 patients (42%). Two patients were treated with oral anticoagulants, and both developed life-threatening intracerebral hemorrhage. Systemic (70%) and neurological (54%) complications occurred frequently, leading to a high proportion of patients with unfavorable outcome (63%). Seven of 24 patients (29%) with meningitis and endocarditis died. Endocarditis is an uncommon coexisting condition in bacterial meningitis but is associated with a high rate of unfavorable outcome.

  9. Rapid Acquisition of Linezolid Resistance in Methicillin-Resistant Staphylococcus aureus: Role of Hypermutation and Homologous Recombination.

    Science.gov (United States)

    Iguchi, Shigekazu; Mizutani, Tomonori; Hiramatsu, Keiichi; Kikuchi, Ken

    2016-01-01

    We previously reported the case of a 64-year-old man with mediastinitis caused by Staphylococcus aureus in which the infecting bacterium acquired linezolid resistance after only 14 days treatment with linezolid. We therefore investigated relevant clinical isolates for possible mechanisms of this rapid acquisition of linezolid resistance. Using clinical S. aureus isolates, we assessed the in vitro mutation rate and performed stepwise selection for linezolid resistance. To investigate homologous recombination, sequences were determined for each of the 23S ribosomal RNA (23S rRNA) loci; analyzed sequences spanned the entirety of each 23S rRNA gene, including domain V, as well as the 16S-23S intergenic spacer regions. We additionally performed next-generation sequencing on clinical strains to identify single-nucleotide polymorphisms compared to the N315 genome. Strains isolated from the patient prior to linezolid exposure (M5-M7) showed higher-level linezolid resistance than N315, and the pre-exposure strain (M2) exhibited more rapid acquisition of linezolid resistance than did N315. However, the mutation rates of these and contemporaneous clinical isolates were similar to those of N315, and the isolates did not exhibit any mutations in hypermutation-related genes. Sequences of the 23S rRNA genes and 16S-23S intergenic spacer regions were identical among the pre- and post-exposure clinical strains. Notably, all of the pre-exposure isolates harbored a recQ missense mutation (Glu69Asp) with respect to N315; such a lesion may have affected short sequence recombination (facilitating, for example, recombination among rrn loci). We hypothesize that this mechanism contributed to rapid acquisition of linezolid resistance. Hypermutation and homologous recombination of the ribosomal RNA genes, including 23S rRNA genes, appear not to have been sources of the accelerated acquisition of linezolid resistance observed in our clinical case. Increased frequency of short sequence

  10. Nuclear medicine imaging in endocarditis

    International Nuclear Information System (INIS)

    Ivancevic, V.; Munz, D.L.

    1999-01-01

    Infective endocarditis is a serious disease which requires early diagnosis and adequate therapy. Echocardiography plays a key role in diagnosis and follow-up. Subacute infective endocarditis, however, is often difficult to prove echocardiographically due to its more subtle morphological changes. Also, echocardiography cannot reliably differentiate florid vegetations from residual structural changes of the affected valves in cured patients. Therefor, scintigraphy of infection and inflammation has been investigated as a complementary tool in diagnosis and follow-up of infective endocarditis. Immunoscintigraphy with the 99m Tc labelled anti granulocyte antibody in SPECT technique is complementary to echocardiography and seems to assess the floridity of the underlying inflammatory process. The combined use of both imaging modalities allows detection of virtually all cases of subacute infective endocarditis. SPECT immunoscintigraphy with the anti granulocyte antibody seems useful in doubtful cases of infective endocarditis, especially, if echocardiography is non-diagnostic and valve pathology pre-existing. the method may be used for follow-up and monitoring antibiotic therapy

  11. Nuclear medicine imaging in endocarditis

    Energy Technology Data Exchange (ETDEWEB)

    Ivancevic, V.; Munz, D.L. (Univ. Hospital Charite' , Humboldt Univ., Berlin (Germany). Clinic for Nuclear Medicine)

    1999-03-01

    Infective endocarditis is a serious disease which requires early diagnosis and adequate therapy. Echocardiography plays a key role in diagnosis and follow-up. Subacute infective endocarditis, however, is often difficult to prove echocardiographically due to its more subtle morphological changes. Also, echocardiography cannot reliably differentiate florid vegetations from residual structural changes of the affected valves in cured patients. Therefor, scintigraphy of infection and inflammation has been investigated as a complementary tool in diagnosis and follow-up of infective endocarditis. Immunoscintigraphy with the [sup 99m]Tc labelled anti granulocyte antibody in SPECT technique is complementary to echocardiography and seems to assess the floridity of the underlying inflammatory process. The combined use of both imaging modalities allows detection of virtually all cases of subacute infective endocarditis. SPECT immunoscintigraphy with the anti granulocyte antibody seems useful in doubtful cases of infective endocarditis, especially, if echocardiography is non-diagnostic and valve pathology pre-existing. the method may be used for follow-up and monitoring antibiotic therapy.

  12. Bartonella Endocarditis and Pauci-Immune Glomerulonephritis

    Science.gov (United States)

    Raybould, Jillian E.; Raybould, Alison L.; Morales, Megan K.; Zaheer, Misbah; Lipkowitz, Michael S.; Timpone, Joseph G.; Kumar, Princy N.

    2016-01-01

    Abstract Among culture-negative endocarditis in the United States, Bartonella species are the most common cause, with Bartonella henselae and Bartonella quintana comprising the majority of cases. Kidney manifestations, particularly glomerulonephritis, are common sequelae of infectious endocarditis, with nearly half of all Bartonella patients demonstrating renal involvement. Although a pauci-immune pattern is a frequent finding in infectious endocarditis–associated glomerulonephritis, it is rarely reported in Bartonella endocarditis. Anti–neutrophil cytoplasmic antibody (ANCA) positivity can be seen with many pathogens causing endocarditis and has been previously reported with Bartonella species. In addition, ANCA-associated vasculitis can also present with renal and cardiac involvement, including noninfectious valvular vegetations and pauci-immune glomerulonephritis. Given the overlap in their clinical presentation, it is difficult to differentiate between Bartonella endocarditis and ANCA-associated vasculitis but imperative to do so to guide management decisions. We present a case of ANCA-positive Bartonella endocarditis with associated pauci-immune glomerulonephritis that was successfully treated with medical management alone. PMID:27885316

  13. Successful treatment of methicillin-resistant Staphylococcus aureus osteomyelitis with combination therapy using linezolid and rifampicin under therapeutic drug monitoring.

    Science.gov (United States)

    Ashizawa, Nobuyuki; Tsuji, Yasuhiro; Kawago, Koyomi; Higashi, Yoshitsugu; Tashiro, Masato; Nogami, Makiko; Gejo, Ryuichi; Narukawa, Munetoshi; Kimura, Tomoatsu; Yamamoto, Yoshihiro

    2016-05-01

    Linezolid is an effective antibiotic against most gram-positive bacteria including drug-resistant strains such as methicillin-resistant Staphylococcus aureus. Although linezolid therapy is known to result in thrombocytopenia, dosage adjustment or therapeutic drug monitoring of linezolid is not generally necessary. In this report, however, we describe the case of a 79-year-old woman with recurrent methicillin-resistant S. aureus osteomyelitis that was successfully treated via surgery and combination therapy using linezolid and rifampicin under therapeutic drug monitoring for maintaining an appropriate serum linezolid concentration. The patient underwent surgery for the removal of the artificial left knee joint and placement of vancomycin-impregnated bone cement beads against methicillin-resistant S. aureus after total left knee implant arthroplasty for osteoarthritis. We also initiated linezolid administration at a conventional dose of 600 mg/h at 12-h intervals, but reduced it to 300 mg/h at 12-h intervals on day 9 because of a decrease in platelet count and an increase in serum linezolid trough concentration. However, when the infection exacerbated, we again increased the linezolid dose to 600 mg/h at 12-h intervals and performed combination therapy with rifampicin, considering their synergistic effects and the control of serum linezolid trough concentration via drug interaction. Methicillin-resistant S. aureus infection improved without reducing the dose of or discontinuing linezolid. The findings in the present case suggest that therapeutic drug monitoring could be useful for ensuring the therapeutic efficacy and safety of combination therapy even in patients with osteomyelitis who require long-term antibiotic administration. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  14. Linezolid Trough Concentrations Correlate with Mitochondrial Toxicity-Related Adverse Events in the Treatment of Chronic Extensively Drug-Resistant Tuberculosis.

    Science.gov (United States)

    Song, Taeksun; Lee, Myungsun; Jeon, Han-Seung; Park, Yumi; Dodd, Lori E; Dartois, Véronique; Follman, Dean; Wang, Jing; Cai, Ying; Goldfeder, Lisa C; Olivier, Kenneth N; Xie, Yingda; Via, Laura E; Cho, Sang Nae; Barry, Clifton E; Chen, Ray Y

    2015-11-01

    Long-term linezolid use is limited by mitochondrial toxicity-associated adverse events (AEs). Within a prospective, randomized controlled trial of linezolid to treat chronic extensively drug-resistant tuberculosis, we serially monitored the translational competence of mitochondria isolated from peripheral blood of participants by determining the cytochrome c oxidase/citrate synthase activity ratio. We compared this ratio with AEs associated with mitochondrial dysfunction. Linezolid trough concentrations were determined for 38 participants at both 600 mg and 300 mg doses. Those on 600 mg had a significantly higher risk of AE than those on 300 mg (HR 3·10, 95% CI 1·23-7 · 86). Mean mitochondrial function levels were significantly higher in patients before starting linezolid compared to their concentrations on 300 mg (P = 0·004) or 600 mg (P linezolid trough concentrations were associated with lower mitochondrial function levels (Spearman's ρ = - 0.48; P = 0.005). Mitochondrial toxicity risk increased with increasing linezolid trough concentrations, with all patients with mean linezolid trough > 2 μg/ml developing an AE related to mitochondrial toxicity, whether on 300 mg or 600 mg. Therapeutic drug monitoring may be useful to prevent the development of mitochondrial toxicity associated with long-term linezolid use.

  15. Molecular imaging in Libman-Sacks endocarditis

    DEFF Research Database (Denmark)

    Dahl, Anders; Schaadt, Bente K; Santoni-Rugiu, Eric

    2015-01-01

    cardiothoracic surgery and pathologic examinations showed characteristic morphology of Libman-Sacks vegetations. All microbiological examinations including blood cultures, microscopy, culture and 16s PCR of the valve were negative and the diagnosis of Libman-Sacks endocarditis was convincing. It is difficult...... to distinguish Libman-Sacks endocarditis from culture-negative infective endocarditis (IE). Molecular imaging techniques are being used increasingly in cases of suspected IE but no studies have previously reported the use in patients with Libman-Sacks endocarditis. In the present case, (18)F-FDG-PET-CT clearly...

  16. Estimating the cost-effectiveness of linezolid for the treatment of methicillin-resistant Staphylococcus aureus nosocomial pneumonia in Taiwan.

    Science.gov (United States)

    Lin, Po-Chang; Wang, Bruce C M; Kim, Richard; Magyar, Andrew; Lai, Chung-Chih; Yang, Ya-Wen; Huang, Yhu-Chering

    2016-02-01

    Methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia (NP) is associated with higher resource utilization, increased hospital stays, and mortality. We present a health economics model to understand the impact of using linezolid as the first-line treatment of MRSA NP in Taiwan. We developed a cost-effectiveness model to estimate the costs and clinical outcomes of using linezolid 600 mg b.i.d. versus vancomycin 15 mg/kg b.i.d. as the first-line treatment of MRSA NP in Taiwan. The model is a decision-analytic analysis in which a MRSA-confirmed patient is simulated to utilize one of the treatments, using data from a clinical trial. Within each treatment arm, the patient can or cannot achieve clinical cure. Regardless of whether the clinical cure was achieved or not, the patient may or may not have experienced an adverse event. The per-protocol results for clinical cure were 57.6% and 46.6% for linezolid and vancomycin, respectively. The total cost of linezolid was $376 more per patient than that of vancomycin. Drug costs were higher for linezolid than for vancomycin ($1108 vs. $233), and hospitalization costs were lower ($4998 vs. $5496). With higher cost and higher cure rates for linezolid, the incremental cost per cure was $3421. This study projects linezolid to have higher drug costs, lower hospital costs, and higher overall costs compared with vancomycin. This is balanced against the higher clinical cure rate for linezolid. Depending on the willingness to pay for clinical cure, linezolid could be cost effective as the first-line treatment of NP in Taiwan. Copyright © 2015. Published by Elsevier B.V.

  17. Comparison of Linezolid and Vancomycin for Methicillin-Resistant Staphylococcus aureus Pneumonia: Institutional Implications.

    Science.gov (United States)

    Tong, ManShan C; Wisniewski, Christopher S; Wolf, Bethany; Bosso, John A

    2016-07-01

    Recent studies suggesting clinical superiority of linezolid over vancomycin in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia led to a change in our institution's clinical pathway/order form for hospital-acquired pneumonia, positioning linezolid as the preferred agent. Our objective was to assess the impact of this change within our institution. Retrospective electronic medical records review. The analysis for this observational study included eligible patients admitted to our medical center between May 1, 2011, and August 31, 2014, with ICD-9 codes for MRSA and pneumonia. Included patients were at least 18 years of age and had vancomycin or linezolid initiated at least 2 days after admission and continued for at least 2 consecutive days. The primary end points were extent of antibiotic use before and after order form change and length of stay (LOS) and hospital charges in the two treatment groups. A secondary aim was to detect any gross discrepancies in patient outcomes such as treatment duration, mechanical ventilation duration, all-cause mortality rate, nephrotoxicity, and 30-day readmission between the two treatment groups. Outcomes in 227 patients were assessed. Linezolid use increased 16.2% subsequent to the change in the order form. Although not statistically significant, the median hospital admission charge was $6200 lower in patients treated with linezolid compared with those treated with vancomycin ($25,900 vs $32,100). Hospital LOS was significantly associated with Charlson Comorbidity Index score (plinezolid treatment, and these patients were more likely to be discharged (shorter LOS). Although linezolid use increased markedly with this pathway/order form change, no negative institutional consequences or unfavorable patient outcomes were detected, justifying the change in policy from these perspectives. © 2016 Pharmacotherapy Publications, Inc.

  18. Aerococcus viridans Native Valve Endocarditis

    Directory of Open Access Journals (Sweden)

    Wenwan Zhou

    2013-01-01

    Full Text Available Aerococcus viridans is an infrequent human pathogen and few cases of infective endocarditis have been reported. A case involving a 69-year-old man with colon cancer and hemicolectomy 14 years previously, without recurrence, is reported. A diagnosis of native mitral valve endocarditis was established on the basis of clinical presentation, characteristic echocardiographic findings and pathological specimen examination after urgent valve replacement. A viridans endocarditis appears to be particularly virulent, requiring a surgical approach in four of 10 cases reported and death in one of nine. Given the aggressive nature of A viridans endocarditis and the variable time to diagnosis (a few days to seven months, prompt recognition of symptoms and echocardiography, in addition to blood cultures, should be performed when symptoms persist.

  19. Endocarditis de Libman-Sacks

    Directory of Open Access Journals (Sweden)

    Carolina Saldarriaga

    2015-05-01

    Se reporta el caso de un paciente de género masculino, de 63 años, quien manifestó signos y síntomas compatibles con endocarditis infecciosa, y cuyos diferentes estudios demostraron una endocarditis de Libman-Sacks que respondió de forma favorable al tratamiento inmunosupresor.

  20. Analysis of linezolid and tigecycline as candidates for local prophylaxis via antibiotic-loaded bone cement.

    Science.gov (United States)

    Nichol, T; Smith, T J; Townsend, R; Stockley, I; Akid, R

    2017-02-01

    To assess the Gram-positive-specific antibiotic linezolid and the broad-spectrum antibiotic tigecycline for use in local antibiotic delivery via antibiotic-loaded bone cement. Linezolid and tigecycline were added to Biomet bone cement at varying concentrations. Antibiotic elution over 1 week was quantified by HPLC-MS. The effect of wear on elution over 51 h was determined using a modified TE-66 wear tester. Eluted antibiotics were used to determine the MICs for a panel of clinically relevant bacteria. The impact strength of antibiotic-loaded samples was determined using a Charpy-type impact testing apparatus. Cytotoxicity of eluted antibiotics against MG-63 cells was evaluated using an MTT assay. Linezolid and tigecycline eluted from bone cement to clinically relevant levels within 1 h and retained activity over 1 week. Mechanical wear significantly reduced elution of tigecycline, but had little effect on elution of linezolid. Linezolid showed low cytotoxicity towards MG-63 cells with ≤300 mg/mL resulting in >50% cell activity. Cytotoxicity of tigecycline was higher, with an IC 50 of 5-10 mg/L. Linezolid and tigecycline retain activity after elution from bone cement. The concentration of tigecycline may need to be carefully controlled due to cytotoxicity. The effect of wear on bone cement may need to be considered if tigecycline is to be used for local delivery. Up to 10% linezolid can be added without affecting the impact strength of the bone cement. These results are promising indications for future investigation of these antibiotics for use in local antibiotic delivery strategies. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Infective endocarditis associated with Bartonella henselae: A case series

    Directory of Open Access Journals (Sweden)

    Akio Nakasu

    Full Text Available Organisms in the genus Bartonella are cause of blood culture-negative endocarditis. Bartonella infective endocarditis is being increasingly reported worldwide; however, reports from Japan are limited. Here, we report five cases of infective endocarditis associated with Bartonella henselae. All patients had a history of contact with cats or fleas; this information helped achieve an appropriate diagnosis. Keywords: Infective endocarditis, Blood culture-negative endocarditis, Bartonella henselae, Infection, Bartonella, Endocarditis

  2. Optimization of linezolid treatment regimens for Gram-positive bacterial infections based on pharmacokinetic/pharmacodynamic analysis.

    Science.gov (United States)

    Yang, Minjie; Zhang, Jing; Chen, Yuancheng; Liang, Xiaoyu; Guo, Yan; Yu, Jicheng; Zhu, Demei; Zhang, Yingyuan

    2017-01-01

    To optimize linezolid treatment regimens for Gram-positive bacterial infections based on pharmacokinetic/pharmacodynamic analysis. The minimum inhibitory concentration (MIC) distribution of 572 Gram-positive strains from patients with clinically confirmed infections was analyzed. Using the Monte Carlo simulation method, the cumulative fraction of response and probability of target attainment were determined for linezolid regimens of 600 mg q.12h and q.8h Results: Linezolid dosage of 600 mg q.12h yielded >90% cumulative fraction of response and probability of target attainment for staphylococcal infections with an MIC of ≤1 mg/l, enterococcal infections with higher MIC values required 600 mg q.8h. Linezolid 600 mg q.12h is still the clinically recommended empirical dosage for Gram-positive bacterial infections. However, as bacterial MICs increase, 600 mg q.8h may be required to achieve better efficacy.

  3. Lymphangiogenesis is increased in heart valve endocarditis.

    Science.gov (United States)

    Niinimäki, Eetu; Mennander, Ari A; Paavonen, Timo; Kholová, Ivana

    2016-09-15

    Inflammation-associated lymphangiogenesis (IAL) has been identified as part of several acute and chronic inflammation. Sparse data exist on lymphatics during endocarditis. Fifty-two patients with surgically resected valves were included. Endocarditis was present in 18 aortic and 10 mitral valves. Controls consisted of 15 degenerative aortic and 9 degenerative mitral valves. There were 22 males with endocarditis and 17 males in controls. The mean age was 58 (SD 15) years with endocarditis vs. 62 (SD 13) years for controls. Lymphatics were detected by podoplanin antibody immunohistochemistry and morphometrical analysis was performed. The lymphatic density in endocarditis was 833 (SD 529) vessels/mm(2) (range 0-1707) as compared with 39 (SD 60) vessels/mm(2) (range 0-250) in controls (p=0.000). In endocarditis, the mean lymphatic size was 153 (SD 372) μm(2) ranging from 1 to 2034μm(2), whereas it was 30 (SD 29) μm(2), with maximum 90μm(2) and minimum 2μm(2) in controls (p=0.000). IAL is increased in valves with endocarditis as compared with controls. Lymphatics in heart valves may provide a novel means for treatment strategies against endocarditis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Fungal Endocarditis: Update on Diagnosis and Management.

    Science.gov (United States)

    Pasha, Ahmed Khurshid; Lee, Justin Z; Low, See-Wei; Desai, Hem; Lee, Kwan S; Al Mohajer, Mayar

    2016-10-01

    Fungal endocarditis is an extremely debilitating disease associated with high morbidity and mortality. Candida spp. are the most common isolated organisms in fungal endocarditis. It is most prevalent in patients who are immunosuppressed and intravenous drug users. Most patients present with constitutional symptoms, which are indistinguishable from bacterial endocarditis, hence a high index of suspicion is required for pursuing diagnosis. Diagnosis of fungal endocarditis can be very challenging: most of the time, blood cultures are negative or take a long time to yield growth. Fungal endocarditis mandates an aggressive treatment strategy. A medical and surgical combined approach is the cornerstone of therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Infective endocarditis, 1984 through 1993

    DEFF Research Database (Denmark)

    Benn, Marianne; Hagelskjaer, L H; Tvede, M

    1997-01-01

    To characterize the epidemiology and the clinical and microbiological spectrum of infective endocarditis in a Danish population.......To characterize the epidemiology and the clinical and microbiological spectrum of infective endocarditis in a Danish population....

  6. Clinical update on linezolid in the treatment of Gram-positive bacterial infections

    Science.gov (United States)

    Ager, Sally; Gould, Kate

    2012-01-01

    Gram-positive pathogens are a significant cause of morbidity and mortality in both community and health care settings. Glycopeptides have traditionally been the antibiotics of choice for multiresistant Gram-positive pathogens but there are problems with their use, including the emergence of glycopeptide-resistant strains, tissue penetration, and achieving and monitoring adequate serum levels. Newer antibiotics such as linezolid, a synthetic oxazolidinone, are available for the treatment of resistant Gram-positive bacteria. Linezolid is active against a wide range of Gram-positive bacteria and has been generally available for the treatment of Gram-positive infections since 2000. There are potential problems with linezolid use, including its bacteriostatic action and the relatively high incidence of reported adverse effects, particularly with long-term use. Long-term use may also be complicated by the development of resistance. However, linezolid has been shown to be clinically useful in the treatment of several serious infections where traditionally bacteriocidal agents have been required and many of its adverse effects are reversible on cessation. It has also been shown to be a cost-effective treatment option in several studies, with its high oral bioavailability allowing an early change from intravenous to oral formulations with consequent earlier patient discharge and lower inpatient costs. PMID:22787406

  7. Simple strategy to assess linezolid exposure in patients with multi-drug-resistant and extensively-drug-resistant tuberculosis.

    Science.gov (United States)

    Kamp, Jasper; Bolhuis, Mathieu S; Tiberi, Simon; Akkerman, Onno W; Centis, Rosella; de Lange, Wiel C; Kosterink, Jos G; van der Werf, Tjip S; Migliori, Giovanni B; Alffenaar, Jan-Willem C

    2017-06-01

    Linezolid is used increasingly for the treatment of multi-drug-resistant (MDR) and extensively-drug-resistant (XDR) tuberculosis (TB). However, linezolid can cause severe adverse events, such as peripheral and optical neuropathy or thrombocytopenia related to higher drug exposure. This study aimed to develop a population pharmacokinetic model to predict the area under the concentration curve (AUC) for linezolid using a limited number of blood samples. Data from patients with MDR-/XDR-TB who received linezolid and therapeutic drug monitoring as part of their TB treatment were used. Mw\\Pharm 3.82 (Mediware, Zuidhorn, The Netherlands) was used to develop a population pharmacokinetic model and limited sampling strategy (LSS) for linezolid. LSS was evaluated over a time span of 6 h. Blood sampling directly before linezolid administration and 2 h after linezolid administration were considered to be the most clinically relevant sampling points. The model and LSS were evaluated by analysing the correlation between AUC 12h,observed and AUC 12h,estimated . In addition, LSS was validated with an external group of patients with MDR-/XDR-TB from Sondalo, Italy. Fifty-two pharmacokinetic profiles were used to develop the model. Thirty-three profiles with a 300 mg dosing regimen and 19 profiles with a 600 mg dosing regimen were obtained. Model validation showed prediction bias of 0.1% and r 2 of 0.99. Evaluation of the most clinically relevant LSS showed prediction bias of 4.8% and r 2 of 0.97. The root mean square error corresponding to the most relevant LSS was 6.07%. The developed LSS could be used to enable concentration-guided dosing of linezolid. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  8. Complicated infective endocarditis: a case series.

    Science.gov (United States)

    Kim, Joo Seop; Kang, Min-Kyung; Cho, A Jin; Seo, Yu Bin; Kim, Kun Il

    2017-05-08

    Infective endocarditis is associated with not only cardiac complications but also neurologic, renal, musculoskeletal, and systemic complications related to the infection, such as embolization, metastatic infection, and mycotic aneurysm. We report three cases (the first patient is Chinese and the other two are Koreans) of complicated infective endocarditis; two of the cases were associated with a mycotic aneurysm, and one case was associated with a splenic abscess. One case of a patient with prosthetic valve endocarditis was complicated by intracerebral hemorrhage caused by mycotic aneurysm rupture. A second case of a patient with right-sided valve endocarditis associated with a central catheter was complicated by an abdominal aortic mycotic aneurysm. The third patient had a splenic infarction and abscess associated with infected cardiac thrombi. Complicated infective endocarditis is rare and is associated with cardiac, neurologic, renal, musculoskeletal, and systemic complications related to infection, such as embolization, metastatic infection, and mycotic aneurysm. Infective endocarditis caused by Staphylococcus aureus is more frequently associated with complications. Because the mortality rate increases when complications develop, aggressive antibiotic therapy and surgery, combined with specific treatments for the complications, are necessary.

  9. Linezolid induced black hairy tongue

    OpenAIRE

    Govindan Balaji; B Maharani; Velappan Ravichandran; Thiyagarajan Parthasarathi

    2014-01-01

    Black hairy tongue (BHT) also called as lingua villosa nigra, is a self limiting benign condition characterized by hypertrophy and elongation of filiform papillae of tongue with brown or black discoloration. Smoking, poor oral hygiene, xerostomia, using peroxide containing mouth washes, substance abuse and drugs (steroids, methyldopa, olanzapine, etc) are the predisposing factors. However its occurrence in relation to linezolid ingestion among south Indians has not been reported in PubMed dat...

  10. ORF Alignment: NC_004668 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_004668 gi|29376585 >1pq4B 1 288 29 305 1e-52 ... ref|NP_815739.1| endocarditis spe...cific antigen [Enterococcus faecalis V583] ... gb|AAO81809.1| endocarditis specific antigen ...

  11. Limited Sampling Strategies for Therapeutic Drug Monitoring of Linezolid in Patients With Multidrug-Resistant Tuberculosis

    NARCIS (Netherlands)

    Alffenaar, Jan-Willem C.; Kosterink, Jos G. W.; van Altena, Richard; van der Werf, Tjip S.; Uges, Donald R. A.; Proost, Johannes H.

    Introduction: Linezolid is a potential drug for the treatment of multidrug-resistant tuberculosis but its use is limited because of severe adverse effects such as anemia, thrombocytopenia, and peripheral neuropathy. This study aimed to develop a model for the prediction of linezolid area. under the

  12. Complicaciones neurológicas de la endocarditis infecciosa: controversias Neurological complications of infective endocarditis: controversies

    Directory of Open Access Journals (Sweden)

    Federico A Silva

    2011-07-01

    Full Text Available En la endocarditis infecciosa aguda se describen complicaciones neurológicas entre 20% y 40% de los casos, lo cual representa un importante factor que predice morbimortalidad, secuelas y discapacidad. Esta entidad se caracteriza por un amplio espectro clínico debido a su compleja fisiopatología, que involucra entre otros, fenómenos inflamatorios, inmunes, infecciosos y embólicos. A pesar de la notable frecuencia de las complicaciones neurológicas en la endocarditis infecciosa, dadas especialmente por enfermedad cerebrovascular y neuroinfecciones, aun existen controversias acerca de algunos aspectos diagnósticos y terapéuticos, en parte por la poca evidencia disponible, las cuales se discuten a continuación, a partir de una serie de casos atendidos en la Fundación Cardiovascular de Colombia.Neurological complications of acute infective endocarditis are described in 20%-40% of cases, representing an important predictive factor of morbidity, mortality, sequels and disability. Acute endocarditis is characterized by a wide clinical spectrum due to its complex physiopathology that involves inflammatory, immune, infectious and embolic phenomena. Despite the remarkable frequency of neurological complications in the infective endocarditis especially by cerebrovascular disease and neuroinfections, there are still some controversies about some diagnostic and therapeutic aspects, partly because of the little evidence available. This paper describes a number of cases seen in the Fundación Cardiovascular de Colombia and discusses some aspects related with the diagnosis and treatment of the neurological complications of acute endocarditis.

  13. Optimal Clinical Doses of Faropenem, Linezolid, and Moxifloxacin in Children With Disseminated Tuberculosis: Goldilocks.

    Science.gov (United States)

    Srivastava, Shashikant; Deshpande, Devyani; Pasipanodya, Jotam; Nuermberger, Eric; Swaminathan, Soumya; Gumbo, Tawanda

    2016-11-01

     When treated with the same antibiotic dose, children achieve different 0- to 24-hour area under the concentration-time curves (AUC 0-24 ) because of maturation and between-child physiological variability on drug clearance. Children are also infected by Mycobacterium tuberculosis isolates with different antibiotic minimum inhibitory concentrations (MICs). Thus, each child will achieve different AUC 0-24 /MIC ratios when treated with the same dose.  We used 10 000-subject Monte Carlo experiments to identify the oral doses of linezolid, moxifloxacin, and faropenem that would achieve optimal target exposures associated with optimal efficacy in children with disseminated tuberculosis. The linezolid and moxifloxacin exposure targets were AUC 0-24 /MIC ratios of 62 and 122, and a faropenem percentage of time above MIC >60%, in combination therapy. A linezolid AUC 0-24 of 93.4 mg × hour/L was target for toxicity. Population pharmacokinetic parameters of each drug and between-child variability, as well as MIC distribution, were used, and the cumulative fraction of response (CFR) was calculated. We also considered drug penetration indices into meninges, bone, and peritoneum.  The linezolid dose of 15 mg/kg in full-term neonates and infants aged up to 3 months and 10 mg/kg in toddlers, administered once daily, achieved CFR ≥ 90%, with linezolid AUC 0-24 associated with toxicity. The moxifloxacin dose of 25 mg/kg/day achieved a CFR > 90% in infants, but the optimal dose was 20 mg/kg/day in older children. The faropenem medoxomil optimal dosage was 30 mg/kg 3-4 times daily.  The regimen and doses of linezolid, moxifloxacin, and faropenem identified are proposed to be adequate for all disseminated tuberculosis syndromes, whether drug-resistant or -susceptible. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

  14. Effect of Linezolid on Hematologic Recovery in Newly Diagnosed Acute Myeloid Leukemia Patients Following Induction Chemotherapy.

    Science.gov (United States)

    Nedved, Adrienne N; DeFrates, Sean R; Hladnik, Lindsay M; Stockerl-Goldstein, Keith E

    2016-10-01

    Assess the effects of linezolid on hematologic outcomes in newly diagnosed patients with acute myeloid leukemia (AML) following induction chemotherapy. Single-center, retrospective, observational, cohort study. Large, tertiary care academic medical center. A total of 225 patients ≥ 18 years admitted between December 2010 and 2013 with newly diagnosed AML were assessed for inclusion. Patients were identified through the use of ICD-9 codes and chemotherapy ordered via the computerized physician order entry system. Sixty-eight patients met inclusion criteria and were grouped into two arms based on antimicrobial treatment: LZD group (linezolid plus gram-negative antimicrobial, n=21) or control group (vancomycin or daptomycin plus gram-negative antimicrobial, n=47). The LZD group received linezolid ≥ 72 hours. The control group received vancomycin or daptomycin ≥ 72 hours. If patients switched extended gram-positive therapy, they were included in the LZD group as long as they had received ≥ 72 hours of linezolid. The primary end point of time to neutrophil recovery was not statistically different (28 days for LZD group vs 26 days for control group; p=0.675). The preplanned subgroup analysis of patients who received ≥ 14 days of linezolid demonstrated statistically similar median times to neutrophil recovery (29 days for LZD group vs 26 days for control group; p=0.487). Total duration of extended gram-positive antimicrobial therapy was significantly longer in the LZD group (27 days vs 16 days; plinezolid for extended gram-positive antimicrobial coverage following induction chemotherapy. This study provides new insight with a primary focus on the effects of hematologic outcomes when using linezolid in a well-defined acute leukemia population. Further study is warranted with larger populations to assess the potential adverse effects linezolid may have in patients with acute leukemia. © 2016 Pharmacotherapy Publications, Inc.

  15. The origin of endodontic Enterococcus faecalis explored by comparison of virulence factor patterns and antibiotic resistance to that of isolates from stool samples, blood cultures and food.

    Science.gov (United States)

    Vidana, R; Rashid, M U; Özenci, V; Weintraub, A; Lund, B

    2016-04-01

    To elucidate the origin of Enterococcus faecalis isolated from secondary root canal infections and the possibility for a foodborne transmission by comparing them to strains recovered from food, blood and stool regarding putative virulence factors and antibiotic susceptibility profiles, where strains from common origin were hypothesized to harbour similar characteristics. A total of 108 E. faecalis strains recovered in the county of Stockholm, Sweden, were screened using PCR for putative virulence factors esp, cylA, gelE/gelatinase-negative phenotype (ef1841/fsrC), efaA, ace and asa1. The minimum inhibitory concentration (MIC) for ampicillin, piperacillin-tazobactam, imipenem, gentamicin, vancomycin, ciprofloxacin and linezolid was determined using the agar dilution method. Next to strains from blood, the food isolates presented the highest average number of virulence determinants and were frequently enriched with asa1 coding for aggregation substance. None of the endodontic strains carried cylA, and the gelatinase-negative phenotype caused by a deletion dominated the group. Altogether, the most prevalent genes were gelE, efaA and ace, and a combination of them was equally present in approximately 80% of the strains from food, stool and root canals in comparison with 43.3% of the blood isolates. High-level resistance to ciprofloxacin and gentamicin was observed in 30% of the blood isolates, whereas the isolates from other origins, with single exceptions, were susceptible to all tested antibiotics. Evidence for a foodborne transmission, explaining the high reported prevalence of E. faecalis in root filled teeth, could not be determined based on the similarities in virulence factor patterns and antibiotic susceptibility. The only linkage between isolates from food and root canals consisted of a shared common combination of the genes gelE, efaA and ace. The high occurrence of putative virulence traits in food isolates questions the safety of E. faecalis in food

  16. Efficacy of Linezolid and Fosfomycin in Catheter-Related Biofilm Infection Caused by Methicillin-Resistant Staphylococcus aureus

    Science.gov (United States)

    Chai, Dong; Liu, Xu; Wang, Rui; Bai, Yan; Cai, Yun

    2016-01-01

    As long-standing clinical problems, catheter-related infections and other chronic biofilm infections are more difficult to treat due to the high antibiotic resistance of biofilm. Therefore, new treatments are needed for more effective bacteria clearance. In this study, we evaluated the antibacterial activities of several common antibiotics alone and their combinations against biofilm-embedded methicillin-resistant staphylococcus aureus (MRSA) infections, both in vitro and in vivo. In brief, fosfomycin, levofloxacin, and rifampin alone or in combination with linezolid were tested in vitro against planktonic and biofilm-embedded MRSA infection in three MRSA stains. The synergistic effects between linezolid and the other three antibiotics were assessed by fractional inhibitory concentration index (FICI) and time-kill curves, where the combination of linezolid plus fosfomycin showed the best synergistic effect in all strains. For further evaluation in vivo, we applied the combination of linezolid and fosfomycin in a catheter-related biofilm rat model and found that viable bacteria counts in biofilm were significantly reduced after treatment (P linezolid and fosfomycin treatment had improved therapeutic effects on biofilm-embedded MRSA infection both in vitro and in vivo, which provided important basis for new clinical therapy development. PMID:27366751

  17. Time interval between infective endocarditis first symptoms and diagnosis: relationship to infective endocarditis characteristics, microorganisms and prognosis.

    Science.gov (United States)

    N'Guyen, Yohan; Duval, Xavier; Revest, Matthieu; Saada, Matthieu; Erpelding, Marie-Line; Selton-Suty, Christine; Bouchiat, Coralie; Delahaye, François; Chirouze, Catherine; Alla, François; Strady, Christophe; Hoen, Bruno

    2017-03-01

    To analyze the characteristics and outcome of infective endocarditis (IE) according to the time interval between IE first symptoms and diagnosis. Among the IE cases of a French population-based epidemiological survey, patients having early-diagnosed IE (diagnosis of IE within 1 month of first symptoms) were compared with those having late-diagnosed IE (diagnosis of IE more than 1 month after first symptoms). Among the 486 definite-IE, 124 (25%) had late-diagnosed IE whereas others had early-diagnosed IE. Early-diagnosed IE were independently associated with female gender (OR = 1.8; 95% CI [1.0-3.0]), prosthetic valve (OR= 2.6; 95% CI [1.4-5.0]) and staphylococci as causative pathogen (OR = 3.7; 95% CI [2.2-6.2]). Cardiac surgery theoretical indication rates were not different between early and late-diagnosed IE (56.3% vs 58.9%), whereas valve surgery performance was lower in early-diagnosed IE (41% vs 53%; p = .03). In-hospital mortality rates were higher in early-diagnosed IE than in late-diagnosed IE (25.1% vs 16.1%; p endocarditis, which time interval between first symptoms and diagnosis was less than one month, were mainly due to Staphylococcus aureus in France. Staphylococcus aureus infective endocarditis were associated with septic shock, transient ischemic attack or stroke and higher mortality rates than infective endocarditis due to other bacteria or infective endocarditis, which time interval between first symptoms and diagnosis was more than one month. Infective endocarditis, which time interval between first symptoms and diagnosis was more than one month, were accounting for one quarter of all infective endocarditis in our study and were associated with vertebral osteomyelitis and a higher rate of cardiac surgery performed for hemodynamic indication than other infective endocarditis.

  18. Global analysis of the impact of linezolid onto virulence factor production in S. aureus USA300

    NARCIS (Netherlands)

    Bonn, Florian; Pane-Farre, Jan; Schlueter, Rabea; Schaffer, Marc; Fuchs, Stephan; Bernhardt, Joerg; Riedel, Katharina; Otto, Andreas; Voelker, Uwe; van Dijl, Jan Maarten; Hecker, Michael; Maeder, Ulrike; Becher, Doerte

    The translation inhibitor linezolid is an antibiotic of last resort against Gram-positive pathogens including methicillin resistant strains of the nosocomial pathogen Staphylococcus aureus. Linezolid is reported to inhibit production of extracellular virulence factors, but the molecular cause is

  19. Modeling the economic impact of linezolid versus vancomycin in confirmed nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Patel, Dipen A; Shorr, Andrew F; Chastre, Jean; Niederman, Michael; Simor, Andrew; Stephens, Jennifer M; Charbonneau, Claudie; Gao, Xin; Nathwani, Dilip

    2014-07-22

    We compared the economic impacts of linezolid and vancomycin for the treatment of hospitalized patients with methicillin-resistant Staphylococcus aureus (MRSA)-confirmed nosocomial pneumonia. We used a 4-week decision tree model incorporating published data and expert opinion on clinical parameters, resource use and costs (in 2012 US dollars), such as efficacy, mortality, serious adverse events, treatment duration and length of hospital stay. The results presented are from a US payer perspective. The base case first-line treatment duration for patients with MRSA-confirmed nosocomial pneumonia was 10 days. Clinical treatment success (used for the cost-effectiveness ratio) and failure due to lack of efficacy, serious adverse events or mortality were possible clinical outcomes that could impact costs. Cost of treatment and incremental cost-effectiveness per successfully treated patient were calculated for linezolid versus vancomycin. Univariate (one-way) and probabilistic sensitivity analyses were conducted. The model allowed us to calculate the total base case inpatient costs as $46,168 (linezolid) and $46,992 (vancomycin). The incremental cost-effectiveness ratio favored linezolid (versus vancomycin), with lower costs ($824 less) and greater efficacy (+2.7% absolute difference in the proportion of patients successfully treated for MRSA nosocomial pneumonia). Approximately 80% of the total treatment costs were attributed to hospital stay (primarily in the intensive care unit). The results of our probabilistic sensitivity analysis indicated that linezolid is the cost-effective alternative under varying willingness to pay thresholds. These model results show that linezolid has a favorable incremental cost-effectiveness ratio compared to vancomycin for MRSA-confirmed nosocomial pneumonia, largely attributable to the higher clinical trial response rate of patients treated with linezolid. The higher drug acquisition cost of linezolid was offset by lower treatment failure

  20. Erysipelothrix Rhusiopathiae Endocarditis and Presumed Osteomyelitis

    Directory of Open Access Journals (Sweden)

    Marc Romney

    2001-01-01

    Full Text Available Erysipelothrix rhusiopathiae is known to cause infections in humans following exposure to decaying organic matter or animals colonized with the organism, such as swine and fish. Invasive infections with this organism are unusual and are manifested primarily as infective endocarditis. The present report is believed to be the first to report a case of E rhusiopathiae endocarditis and presumptive osteomyelitis. E rhusiopathiae appears to have intrinsic resistance to vancomycin. Because vancomycin is often used empirically for the treatment of endocarditis, rapid differentiation of E rhusiopathiae> from other Gram-positive organisms is critical. In patients with endocarditis caused by a Gram-positive bacillus and epidemiological risk factors for E rhusiopathiae exposure, empirical treatment with vancomycin should be reconsidered.

  1. Comparative Evaluation of Serotonin Toxicity among Veterans Affairs Patients Receiving Linezolid and Vancomycin

    Science.gov (United States)

    Patel, N.; Rivera, A.; Tristani, L.; Lazariu, V.; Vandewall, H.; McNutt, L. A.

    2013-01-01

    Despite the theoretical risk of serotonin toxicity (ST) with linezolid, “real-world” clinical evaluations of the risk of ST in patients receiving linezolid have been limited to case reports and noncomparator studies. An observational, matched-cohort study was conducted to evaluate the risk of ST among hospitalized patients who received linezolid or vancomycin at the Upstate New York Veterans Affairs Healthcare Network (Veterans Integrated Service Network 2 [VISN-2]). Matching criteria included VISN-2 hospital, hospital ward, prior hospital length of stay, age, and baseline platelet counts. The patients' electronic medical records were evaluated for symptoms consistent with ST and the Hunter serotonin toxicity criteria (HSTC) using an intensive, natural word search algorithm. The study included 251 matched pairs. Demographics and comorbidities were similar between groups. Over half of the study population received at least one concurrent medication with serotonergic activity. Receipt of agents with serotonergic activity was more pronounced in the vancomycin group, and the higher frequency was due to concomitant antihistamine and antiemetic use. Antidepressant use, including selective serotonin reuptake inhibitors (SSRIs), was similar between groups. No patients in either group were found to meet the criteria using the word search algorithm for ST. Fewer linezolid patients than vancomycin patients met the HSTC overall (3.2% versus 8.8%) and when stratified by receipt of a concurrent serotonergic agent (4.3% versus 12.4%). Of the patients meeting the HSTC, most had past or present comorbidities that may have contributed to or overlapped the HSTC. This study of hospitalized patients revealed comparably low frequencies of adverse events potentially related to ST among patients who received linezolid or vancomycin. PMID:24041888

  2. Sequential antimicrobial treatment with linezolid for neurosurgical infections: efficacy, safety and cost study.

    Science.gov (United States)

    Martín-Gandul, Cecilia; Mayorga-Buiza, M J; Castillo-Ojeda, E; Gómez-Gómez, M J; Rivero-Garvía, M; Gil-Navarro, M V; Márquez-Rivas, F J; Jiménez-Mejías, M E

    2016-10-01

    Evidence for the effectiveness of linezolid in neurosurgical infections (NSIs) is growing. The comfortable oral dosage and tolerance of linezolid opens the possibility for sequential antimicrobial treatment (SAT) in stable patients after a period of intravenous treatment. To evaluate the efficacy and safety of SAT with oral linezolid in patients with NSI and to analyse the cost implications, an observational, non-comparative, prospective cohort study was conducted on clinically stable consecutive adult patients at the Neurosurgical Service. Following intravenous treatment, patients were discharged with SAT with oral linezolid. A total of 77 patients were included. The most common NSIs were: 41 surgical wound infections, 20 subdural empyemas, 18 epidural abscesses, and 16 brain abscesses. Forty-four percent of patients presented two or more concomitant NSIs. Aetiological agents commonly isolated were: Propionibacterium acnes (36 %), Staphylococcus aureus (23 %), Staphylococcus epidermidis (21 %) and Streptococcus spp. (13 %). The median duration of the SAT was 15 days (range, 3-42). The SAT was interrupted in five cases due to adverse events. The remainder of the patients were cured at the end of the SAT. A total of 1,163 days of hospitalisation were saved. An overall cost reduction of €516,188 was attributed to the SAT. Eight patients with device infections did not require removal of the device, with an additional cost reduction of €190,595. The mean cost saving per patient was €9,179. SAT with linezolid was safe and effective for the treatment of NSI. SAT reduces hospitalisation times, which means significant savings of health and economic resources.

  3. Overexpression of Enterococcus faecalis elr operon protects from phagocytosis.

    Science.gov (United States)

    Cortes-Perez, Naima G; Dumoulin, Romain; Gaubert, Stéphane; Lacoux, Caroline; Bugli, Francesca; Martin, Rebeca; Chat, Sophie; Piquand, Kevin; Meylheuc, Thierry; Langella, Philippe; Sanguinetti, Maurizio; Posteraro, Brunella; Rigottier-Gois, Lionel; Serror, Pascale

    2015-05-25

    Mechanisms underlying the transition from commensalism to virulence in Enterococcus faecalis are not fully understood. We previously identified the enterococcal leucine-rich protein A (ElrA) as a virulence factor of E. faecalis. The elrA gene is part of an operon that comprises four other ORFs encoding putative surface proteins of unknown function. In this work, we compared the susceptibility to phagocytosis of three E. faecalis strains, including a wild-type (WT), a ΔelrA strain, and a strain overexpressing the whole elr operon in order to understand the role of this operon in E. faecalis virulence. While both WT and ΔelrA strains were efficiently phagocytized by RAW 264.7 mouse macrophages, the elr operon-overexpressing strain showed a decreased capability to be internalized by the phagocytic cells. Consistently, the strain overexpressing elr operon was less adherent to macrophages than the WT strain, suggesting that overexpression of the elr operon could confer E. faecalis with additional anti-adhesion properties. In addition, increased virulence of the elr operon-overexpressing strain was shown in a mouse peritonitis model. Altogether, our results indicate that overexpression of the elr operon facilitates the E. faecalis escape from host immune defenses.

  4. Infective endocarditis and cancer in the elderly.

    Science.gov (United States)

    García-Albéniz, Xabier; Hsu, John; Lipsitch, Marc; Logan, Roger W; Hernández-Díaz, Sonia; Hernán, Miguel A

    2016-01-01

    Little is known about the magnitude of the association between infective endocarditis and cancer, and about the natural history of cancer patients with concomitant diagnosis of infective endocarditis. We used the SEER-Medicare linked database to identify individuals aged 65 years or more diagnosed with colorectal, lung, breast, or prostate cancer, and without any cancer diagnosis (5% random Medicare sample from SEER areas) between 1992 and 2009. We identified infective endocarditis from the ICD-9 diagnosis of each admission recorded in the Medpar file and its incidence rate 90 days around cancer diagnosis. We also estimated the overall survival and CRC-specific survival after a concomitant diagnosis of infective endocarditis. The peri-diagnostic incidence of infective endocarditis was 19.8 cases per 100,000 person-months for CRC, 5.7 cases per 100,000 person-months for lung cancer, 1.9 cases per 100,000 person-months for breast cancer, 4.1 cases per 100,000 person-months for prostate cancer and 2.4 cases per 100,000 person-months for individuals without cancer. Two-year overall survival was 46.4% (95% CI 39.5, 54.5%) for stage I-III CRC patients with concomitant endocarditis and 73.1% (95 % CI 72.9, 73.3%) for those without it. In this elderly population, the incidence of infective endocarditis around CRC diagnosis was substantially higher than around the diagnosis of lung, breast and prostate cancers. A concomitant diagnosis of infective endocarditis in patients with CRC diagnosis is associated with shorter survival.

  5. Changes in Whole-Body Oxygen Consumption and Skeletal Muscle Mitochondria During Linezolid-Induced Lactic Acidosis.

    Science.gov (United States)

    Protti, Alessandro; Ronchi, Dario; Bassi, Gabriele; Fortunato, Francesco; Bordoni, Andreina; Rizzuti, Tommaso; Fumagalli, Roberto

    2016-07-01

    To better clarify the pathogenesis of linezolid-induced lactic acidosis. Case report. ICU. A 64-year-old man who died with linezolid-induced lactic acidosis. Skeletal muscle was sampled at autopsy to study mitochondrial function. Lactic acidosis developed during continuous infusion of linezolid while oxygen consumption and oxygen extraction were diminishing from 172 to 52 mL/min/m and from 0.27 to 0.10, respectively. Activities of skeletal muscle respiratory chain complexes I, III, and IV, encoded by nuclear and mitochondrial DNA, were abnormally low, whereas activity of complex II, entirely encoded by nuclear DNA, was not. Protein studies confirmed stoichiometric imbalance between mitochondrial (cytochrome c oxidase subunits 1 and 2) and nuclear (succinate dehydrogenase A) DNA-encoded respiratory chain subunits. These findings were not explained by defects in mitochondrial DNA or transcription. There were no compensatory mitochondrial biogenesis (no induction of nuclear respiratory factor 1 and mitochondrial transcript factor A) or adaptive unfolded protein response (reduced concentration of heat shock proteins 60 and 70). Linezolid-induced lactic acidosis is associated with diminished global oxygen consumption and extraction. These changes reflect selective inhibition of mitochondrial protein synthesis (probably translation) with secondary mitonuclear imbalance. One novel aspect of linezolid toxicity that needs to be confirmed is blunting of reactive mitochondrial biogenesis and unfolded protein response.

  6. Endocarditis Caused by Rhodotorula Infection

    OpenAIRE

    Simon, Matthew S.; Somersan, Selin; Singh, Harjot K.; Hartman, Barry; Wickes, Brian L.; Jenkins, Stephen G.; Walsh, Thomas J.; Schuetz, Audrey N.

    2014-01-01

    Rhodotorula is an emerging opportunistic fungal pathogen that is rarely reported to cause endocarditis. We describe a case involving a patient who developed endocarditis due to Rhodotorula mucilaginosa and Staphylococcus epidermidis, proven by culture and histopathology. The case illustrates the unique diagnostic and therapeutic challenges relevant to Rhodotorula spp.

  7. Endocarditis caused by Rhodotorula infection.

    Science.gov (United States)

    Simon, Matthew S; Somersan, Selin; Singh, Harjot K; Hartman, Barry; Wickes, Brian L; Jenkins, Stephen G; Walsh, Thomas J; Schuetz, Audrey N

    2014-01-01

    Rhodotorula is an emerging opportunistic fungal pathogen that is rarely reported to cause endocarditis. We describe a case involving a patient who developed endocarditis due to Rhodotorula mucilaginosa and Staphylococcus epidermidis, proven by culture and histopathology. The case illustrates the unique diagnostic and therapeutic challenges relevant to Rhodotorula spp.

  8. Gemella morbillorum Endocarditis

    Directory of Open Access Journals (Sweden)

    Serap Ural

    2014-01-01

    Full Text Available Infective endocarditis caused by Gemella morbillorum is a rare disease. In this report 67-year-old male patient with G. morbillorum endocarditis was presented. The patient was hospitalized as he had a fever of unknown origin and in the two of the three sets of blood cultures taken at the first day of hospitalization G. morbillorum was identified. The transthoracic echogram revealed 14 × 10 mm vegetation on the aortic noncoronary cuspis. After 4 weeks of antibiotic therapy, the case was referred to the clinic of cardiovascular surgery for valve surgery.

  9. Infective Endocarditis and Cancer Risk: A Population-Based Cohort Study.

    Science.gov (United States)

    Sun, Li-Min; Wu, Jung-Nan; Lin, Cheng-Li; Day, Jen-Der; Liang, Ji-An; Liou, Li-Ren; Kao, Chia-Hung

    2016-03-01

    This study investigated the possible relationship between endocarditis and overall and individual cancer risk among study participants in Taiwan.We used data from the National Health Insurance program of Taiwan to conduct a population-based, observational, and retrospective cohort study. The case group consisted of 14,534 patients who were diagnosed with endocarditis between January 1, 2000 and December 31, 2010. For the control group, 4 patients without endocarditis were frequency matched to each endocarditis patient according to age, sex, and index year. Competing risks regression analysis was conducted to determine the effect of endocarditis on cancer risk.A large difference was noted in Charlson comorbidity index between endocarditis and nonendocarditis patients. In patients with endocarditis, the risk for developing overall cancer was significant and 119% higher than in patients without endocarditis (adjusted subhazard ratio = 2.19, 95% confidence interval = 1.98-2.42). Regarding individual cancers, in addition to head and neck, uterus, female breast and hematological malignancies, the risks of developing colorectal cancer, and some digestive tract cancers were significantly higher. Additional analyses determined that the association of cancer with endocarditis is stronger within the 1st 5 years after endocarditis diagnosis.This population-based cohort study found that patients with endocarditis are at a higher risk for colorectal cancer and other cancers in Taiwan. The risk was even higher within the 1st 5 years after endocarditis diagnosis. It suggested that endocarditis is an early marker of colorectal cancer and other cancers. The underlying mechanisms must still be explored and may account for a shared risk factor of infection in both endocarditis and malignancy.

  10. Linezolid Decreases Susceptibility to Secondary Bacterial Pneumonia Post-Influenza Infection in Mice Through its Effects on Interferon-γ

    Science.gov (United States)

    Breslow-Deckman, Jessica M.; Mattingly, Cynthia M.; Birket, Susan E.; Hoskins, Samantha N.; Ho, Tam N.; Garvy, Beth A.; Feola, David J.

    2013-01-01

    Influenza infection predisposes patients to secondary bacterial pneumonia that contributes significantly to morbidity and mortality. While this association is well documented, the mechanisms that govern this synergism are poorly understood. A window of hyporesponsiveness following influenza infection has been associated with a substantial increase in local and systemic IFNγ concentrations. Recent data suggests that the oxazolidinone antibiotic linezolid decreases IFNγ and TNFα production in vitro from stimulated peripheral blood mononuclear cells. We therefore sought to determine whether linezolid would reverse immune hyporesponsiveness after influenza infection in mice through its effects on IFNγ. In vivo dose response studies demonstrated that oral linezolid administration sufficiently decreased bronchoalveolar lavage fluid levels of IFNγ at day 7 post-influenza infection in a dose-dependent manner. The drug also decreased morbidity as measured by weight loss compared to vehicle-treated controls. When mice were challenged intranasally with S. pneumoniae 7 days after infection with influenza, linezolid pre-treatment led to decreased IFNγ and TNFα production, decreased weight loss, and lower bacterial burdens at 24 hours post bacterial infection in comparison to vehicle-treated controls. To determine whether these effects were due to suppression of IFNγ, linezolid-treated animals were given intranasal instillations of recombinant IFNγ before challenge with S. pneumoniae. This partially reversed the protective effects observed in the linezolid-treated mice, suggesting that the modulatory effects of linezolid are mediated partially by its ability to blunt IFNγ production. These results suggest that IFNγ, and potentially TNFα, may be useful drug targets for prophylaxis against secondary bacterial pneumonia following influenza infection. PMID:23833238

  11. Laboratory Diagnosis of Infective Endocarditis

    Science.gov (United States)

    Liesman, Rachael M.; Pritt, Bobbi S.; Maleszewski, Joseph J.

    2017-01-01

    ABSTRACT Infective endocarditis is life-threatening; identification of the underlying etiology informs optimized individual patient management. Changing epidemiology, advances in blood culture techniques, and new diagnostics guide the application of laboratory testing for diagnosis of endocarditis. Blood cultures remain the standard test for microbial diagnosis, with directed serological testing (i.e., Q fever serology, Bartonella serology) in culture-negative cases. Histopathology and molecular diagnostics (e.g., 16S rRNA gene PCR/sequencing, Tropheryma whipplei PCR) may be applied to resected valves to aid in diagnosis. Herein, we summarize recent knowledge in this area and propose a microbiologic and pathological algorithm for endocarditis diagnosis. PMID:28659319

  12. Efficacy of Linezolid and Fosfomycin in Catheter-Related Biofilm Infection Caused by Methicillin-Resistant Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Dong Chai

    2016-01-01

    Full Text Available As long-standing clinical problems, catheter-related infections and other chronic biofilm infections are more difficult to treat due to the high antibiotic resistance of biofilm. Therefore, new treatments are needed for more effective bacteria clearance. In this study, we evaluated the antibacterial activities of several common antibiotics alone and their combinations against biofilm-embedded methicillin-resistant staphylococcus aureus (MRSA infections, both in vitro and in vivo. In brief, fosfomycin, levofloxacin, and rifampin alone or in combination with linezolid were tested in vitro against planktonic and biofilm-embedded MRSA infection in three MRSA stains. The synergistic effects between linezolid and the other three antibiotics were assessed by fractional inhibitory concentration index (FICI and time-kill curves, where the combination of linezolid plus fosfomycin showed the best synergistic effect in all strains. For further evaluation in vivo, we applied the combination of linezolid and fosfomycin in a catheter-related biofilm rat model and found that viable bacteria counts in biofilm were significantly reduced after treatment (P<0.05. In summary, we have shown here that the combination of linezolid and fosfomycin treatment had improved therapeutic effects on biofilm-embedded MRSA infection both in vitro and in vivo, which provided important basis for new clinical therapy development.

  13. Endocarditis in Greenland with special reference to endocarditis caused by Streptococcus pneumoniae

    DEFF Research Database (Denmark)

    Madsen, Rasmus Gaarde; Ladefoged, Karin; Kjaergaard, Jens Jørgen

    2009-01-01

    in studies on Caucasian populations, where pneumococcal infection was seen in 1-3% of endocarditis cases. The overall mortality rate was 12%. Pneumococcal endocarditis (PE) had the clinical characteristics of fulminant disease with frequent heart failure, complications and need for surgery. Among cases...... with PE, 67% needed acute valve replacement and the mortality rate was 33%. CONCLUSIONS: The high incidence rate, clinical characteristics and grave prognosis of PE are consistent with another study of an Inuit population in Alaska....

  14. Pharmacokinetic/pharmacodynamic evaluation of linezolid for the treatment of staphylococcal infections in critically ill patients.

    Science.gov (United States)

    Dong, Haiyan; Xie, Jiao; Wang, Taotao; Chen, Lihong; Zeng, Xiaoyan; Sun, Jinyao; Wang, Xue; Dong, Yalin

    2016-09-01

    Several studies have demonstrated that the ideal therapeutic effect of linezolid cannot be achieved in critically ill patients with the recommended standard dosing regimen of 600 mg every 12 h (q12h). Moreover, the optimal strategy for successful treatment is still lacking. This study analysed factors influencing the efficacy of linezolid treatment and determined the target for successful treatment by logistic regression in 27 critically ill patients with staphylococcal infection who received linezolid 600 mg q12h. The results showed that only the 24-h area under the concentration-time curve to minimum inhibitory concentration (AUC24/MIC) ratio was significantly associated with staphylococcal eradication. Reaching 80% bacterial eradication required an AUC24/MIC of 120.5, defining the therapeutic target. Different dosing regimens were evaluated using Monte Carlo simulation to determine the optimal dosage strategy for linezolid. Although the probability of target attainment (PTA) was high (>99.9%) for the standard dosing regimen at MIC ≤ 1 mg/L, the PTA was almost 0 at MIC = 2 mg/L, thus the dosing regimen required adjustment. In addition, if the dosing regimen was adjusted to 600 mg every 8 h or 600 mg every 6 h, the major staphylococci (except for MRSA and MSSA) exhibited a cumulative fraction of response of >80%, showing a higher treatment success. These findings indicate that a strategy of high linezolid dosage may be needed to increase the probability of successful treatment at MIC > 1 mg/L. The role of therapeutic drug monitoring should be encouraged for optimising linezolid exposure in critically ill patients. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  15. Comparative Efficacy of Ceftaroline with Linezolid against Staphylococcus Aureus and Methicillin Resistant Staphylococcus Aureus

    International Nuclear Information System (INIS)

    Hafeez, A.; Munir, T.; Rehman, S.; Najeeb, S.; Gilani, M.; Latif, M.; Ansari, M.; Saad, N.

    2015-01-01

    Objective:To compare the in vitro antimicrobial efficacy of ceftaroline with linezolid against Staphylococcus aureus and methicillin resistant Staphylococcus aureus. Study Design: Quasi-experimental study. Place and Duration of Study: Microbiology Department, Army Medical College, Rawalpindi, from January to December 2013. Methodology: Clinical samples from respiratory tract, blood, pus and various catheter tips routinely received in the Department of Microbiology, Army Medical College, Rawalpindi were innoculated on blood and MacConkey agar. Staphylococcus aureus was identified by colony morphology, Gram reaction, catalase test and coagulase test. Methicillin resistant Staphylococcus aureus detection was done by modified Kirby Bauer disc diffusion method using cefoxitin disc (30g) and the isolates were considered methicillin resistant if the zone of inhibition around cefoxitin disc was /sup 2/ 21 mm. Bacterial suspensions of 56 Staphylococcus aureus isolates and 50 MRSA isolates were prepared, which were standardized equal to 0.5 McFarland's turbidity standard and inoculated on Mueller-Hinton agar plates followed by application of ceftaroline and linezolid disc (Oxoid, UK), according to manufacturer's instructions. The plates were then incubated at 37 Degree C aerobically for 18 - 24 hours. Diameters of inhibition zone were measured and interpretated as per Clinical and Laboratory Standards Institute (CLSI) guidelines. Results: Out of 106 isolates all of the 56 Staphylococcus aureus (100%) were sensitive to ceftaroline and linezolid. However, out of 50 methicillin resistant Staphylococcus aureus, 48 (96%) were sensitive to ceftaroline whereas, 49 (98%) were sensitive to linezolid. Conclusion: Ceftaroline is equally effective as linezolid against Staphylococcus aureus and methicillin resistant Staphylococcus aureus. (author)

  16. Polymorphic solidification of Linezolid confined in electrospun PCL fibers for controlled release in topical applications.

    Science.gov (United States)

    Tammaro, Loredana; Saturnino, Carmela; D'Aniello, Sharon; Vigliotta, Giovanni; Vittoria, Vittoria

    2015-07-25

    Poly(ϵ-caprolactone) (PCL) membranes loaded with Linezolid, chemically N-[[(5S)-3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide (empirical formula C16H20FN3O4) have been prepared by electrospinning technique, at different Linezolid concentrations (0.5, 1, 2.5 and 5%, w/w). Structural characterization, morphological analysis and the study of the mechanical properties have been performed on loaded membranes and compared with neat PCL membranes. Linezolid embedded in the membranes is prevalently amorphous, with a low crystallinity showing a different polymorphic form respect to the usual Form I and Form II. The release kinetics of the drug were studied by spectrophotometric analysis (UV-vis). It allowed to discriminate between Linezolid molecules on the surface and encapsulated into the fibers. The antibacterial activity of the electrospun membranes was effective to inhibit Staphylococcus aureus. The properties of the loaded membranes and their capability for local delivery of the antibiotic make them good candidates as drug release devices for topical use. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Nonbacterial thrombotic endocarditis presenting as intracerebral hemorrhage.

    Science.gov (United States)

    Wigger, Olivier; Windecker, Stephan; Bloechlinger, Stefan

    2016-12-01

    Nonbacterial thrombotic endocarditis is a rare cause of valvular heart disease, most commonly associated with advanced malignancy. The morbidity of this kind of endocarditis lies in its tendency to embolize, while the valve function is usually preserved. The central nervous system is the most common site of embolization, leading to ischemic stroke. We report a case of nonbacterial thrombotic endocarditis complicated by intracerebral hemorrhage as the first manifestation of adenocarcinoma of the lung. The endocarditis led to severe aortic regurgitation. In view of the advanced stage of lung cancer, the patient refused further therapy. He passed away 3 weeks after first diagnosis of the adenocarcinoma.

  18. Examination of bedaquiline- and linezolid-resistant Mycobacterium tuberculosis isolates from the Moscow region.

    Science.gov (United States)

    Zimenkov, Danila V; Nosova, Elena Yu; Kulagina, Elena V; Antonova, Olga V; Arslanbaeva, Liaisan R; Isakova, Alexandra I; Krylova, Ludmila Yu; Peretokina, Irina V; Makarova, Marina V; Safonova, Svetlana G; Borisov, Sergey E; Gryadunov, Dmitry A

    2017-07-01

    To study the isolates with acquired resistance to bedaquiline and linezolid that were obtained from patients enrolled in a clinical study of a novel therapy regimen for drug-resistant TB in Moscow, Russia. Linezolid resistance was detected using MGIT 960 with a critical concentration of 1 mg/L. The MIC of bedaquiline was determined using the proportion method. To identify genetic determinants of resistance, sequencing of the mmpR ( Rv0678 ), atpE , atpC , pepQ , Rv1979c , rrl , rplC and rplD loci was performed. A total of 85 isolates from 27 patients with acquired resistance to linezolid and reduced susceptibility to bedaquiline (MIC ≥0.06 mg/L) were tested. Most mutations associated with a high MIC of bedaquiline were found in the mmpR gene. We identified for the first time two patients whose clinical isolates had substitutions D28N and A63V in AtpE, which had previously been found only in in vitro -selected strains. Several patients had isolates with elevated MICs of bedaquiline prior to treatment; four of them also bore mutations in mmpR , indicating the presence of some hidden factors in bedaquiline resistance acquisition. The C154R substitution in ribosomal protein L3 was the most frequent in the linezolid-resistant strains. Mutations in the 23S rRNA gene (g2294a and g2814t) associated with linezolid resistance were also found in two isolates. Heteroresistance was identified in ∼40% of samples, which reflects the complex nature of resistance acquisition. The introduction of novel drugs into treatment must be accompanied by continuous phenotypic susceptibility testing and the analysis of genetic determinants of resistance. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. Serious complications after infective endocarditis

    DEFF Research Database (Denmark)

    Gill, Sabine

    2010-01-01

    The objective of the present study was to review all cases of infective endocarditis at our hospital between 2002 and 2006 concerning the bacteriological aetiology and outcomes.......The objective of the present study was to review all cases of infective endocarditis at our hospital between 2002 and 2006 concerning the bacteriological aetiology and outcomes....

  20. Exploiting CRISPR-Cas to manipulate Enterococcus faecalis populations.

    Science.gov (United States)

    Hullahalli, Karthik; Rodrigues, Marinelle; Palmer, Kelli L

    2017-06-23

    CRISPR-Cas provides a barrier to horizontal gene transfer in prokaryotes. It was previously observed that functional CRISPR-Cas systems are absent from multidrug-resistant (MDR) Enterococcus faecalis , which only possess an orphan CRISPR locus, termed CRISPR2, lacking cas genes. Here, we investigate how the interplay between CRISPR-Cas genome defense and antibiotic selection for mobile genetic elements shapes in vitro E. faecalis populations. We demonstrate that CRISPR2 can be reactivated for genome defense in MDR strains. Interestingly, we observe that E. faecalis transiently maintains CRISPR targets despite active CRISPR-Cas systems. Subsequently, if selection for the CRISPR target is present, toxic CRISPR spacers are lost over time, while in the absence of selection, CRISPR targets are lost over time. We find that forced maintenance of CRISPR targets induces a fitness cost that can be exploited to alter heterogeneous E. faecalis populations.

  1. Musculoskeletal manifestations of bacterial endocarditis

    Directory of Open Access Journals (Sweden)

    Érika Bevilaqua Rangel

    2000-09-01

    Full Text Available CONTEXT: The incidence of staphylococcal infection has been increasing during the last 20 years. OBJECTIVE: Report a case of staphylococcal endocarditis preceded by musculoskeletal manifestations, which is a rare form of clinical presentation. DESIGN: Case report. CASE REPORT: A 45-year-old-man, without addictions and without known previous cardiopathy, was diagnosed as having definitive acute bacterial endocarditis due to Staphylococcus aureus. Its etiology was community-acquired, arising from a non-apparent primary focus. In addition, the musculoskeletal symptoms preceded the infective endocarditis (IE by about 1 month, which occurred together with other symptoms, e.g. mycotic aneurysms and petechiae. Later, the patient showed perforation of the mitral valve and moderate mitral insufficiency with clinical control.

  2. Primary Mural Endocarditis Without Valvular Involvement.

    Science.gov (United States)

    Tahara, Mai; Nagai, Tomoo; Takase, Yoshiyuki; Takiguchi, Shunichi; Tanaka, Yoshiaki; Kunihara, Takashi; Arakawa, Junko; Nakaya, Kazuhiro; Hamabe, Akira; Gatate, Youdou; Kujiraoka, Takehiko; Tabata, Hirotsugu; Katsushika, Shuichi

    2017-03-01

    Primary mural endocarditis is an extremely rare infection in which nonvalvular endocardial involvement is seen without any cardiac structural abnormalities such as ventricular septal defects. The rapid and precise diagnosis of this disease remains challenging. We present 2 cases (67- and 47-year-old male patients) of pathologically confirmed primary mural endocarditis that could have been detected by initial transthoracic echocardiography in the emergency department. Transthoracic echocardiography and transesophageal echocardiography play critical roles in the early recognition and confirmation of primary mural endocarditis. © 2017 by the American Institute of Ultrasound in Medicine.

  3. Synthesis of Linezolid Metabolites PNU-142300 and PNU-142586 toward the Exploration of Metabolite-Related Events.

    Science.gov (United States)

    Hanaya, Kengo; Matsumoto, Kazuaki; Yokoyama, Yuta; Kizu, Junko; Shoji, Mitsuru; Sugai, Takeshi

    2017-01-01

    Linezolid (1) is an oxazolidinone antibiotic that is partially metabolized in vivo via ring cleavage of its morpholine moiety to mainly form two metabolites, PNU-142300 (2) and PNU-142586 (3). It is supposed that accumulation of 2 and 3 in patients with renal insufficiency may cause thrombocytopenia, one of the adverse effects of linezolid. However, the poor availability of 2 and 3 has hindered further investigation of the clinical significance of the accumulation of these metabolites. In this paper, we synthesized metabolites 2 and 3 via a common synthetic intermediate, 4; this will encourage further exploration of events related to these metabolites and lead to improved clinical use of linezolid.

  4. Simple strategy to assess linezolid exposure in patients with multi-drug-resistant and extensively-drug-resistant tuberculosis

    NARCIS (Netherlands)

    Kamp, Jasper; Bolhuis, Mathieu S.; Tiberi, Simon; Akkerman, Onno W.; Centis, Rosella; de lange, Wiel C.; Kosterink, Jos G.; van der Werf, Tjip S.; Migliori, Giovanni B.; Alffenaar, Jan-Willem C.

    Linezolid is used increasingly for the treatment of multi-drug-resistant (MDR) and extensively-drug-resistant (XDR) tuberculosis (TB). However, linezolid can cause severe adverse events, such as peripheral and optical neuropathy or thrombocytopenia related to higher drug exposure. This study aimed

  5. Bartonella henselae endocarditis in Laos - 'the unsought will go undetected'.

    Directory of Open Access Journals (Sweden)

    Sayaphet Rattanavong

    2014-12-01

    Full Text Available Both endocarditis and Bartonella infections are neglected public health problems, especially in rural Asia. Bartonella endocarditis has been described from wealthier countries in Asia, Japan, Korea, Thailand and India but there are no reports from poorer countries, such as the Lao PDR (Laos, probably because people have neglected to look.We conducted a retrospective (2006-2012, and subsequent prospective study (2012-2013, at Mahosot Hospital, Vientiane, Laos, through liaison between the microbiology laboratory and the wards. Patients aged >1 year admitted with definite or possible endocarditis according to modified Duke criteria were included. In view of the strong suspicion of infective endocarditis, acute and convalescent sera from 30 patients with culture negative endocarditis were tested for antibodies to Brucella melitensis, Mycoplasma pneumoniae, Bartonella quintana, B. henselae, Coxiella burnetii and Legionella pneumophila. Western blot analysis using Bartonella species antigens enabled us to describe the first two Lao patients with known Bartonella henselae endocarditis.We argue that it is likely that Bartonella endocarditis is neglected and more widespread than appreciated, as there are few laboratories in Asia able to make the diagnosis. Considering the high prevalence of rheumatic heart disease in Asia, there is remarkably little evidence on the bacterial etiology of endocarditis. Most evidence is derived from wealthy countries and investigation of the aetiology and optimal management of endocarditis in low income countries has been neglected. Interest in Bartonella as neglected pathogens is emerging, and improved methods for the rapid diagnosis of Bartonella endocarditis are needed, as it is likely that proven Bartonella endocarditis can be treated with simpler and less expensive regimens than "conventional" endocarditis and multicenter trials to optimize treatment are required. More understanding is needed on the risk factors for

  6. Endocarditis infecciosa de válvula pulmonar nativa

    OpenAIRE

    Franco Romaní R; Fernando Atencia M; José Cuadra A

    2007-01-01

    La endocarditis infecciosa en válvulas derechas es predominantemente en la válvula tricuspídea, mientras la válvula pulmonar es excepcionalmente afectada (menos de 1,5%), por lo que son pocos los casos reportados en la literatura mundial. Las manifestaciones clínicas de endocarditis en válvula pulmonar no son las clásicas de endocarditis infecciosa, como son los síntomas de embolismo séptico pulmonar. La endocarditis aislada de válvula pulmonar nativa es inusual en personas que no consumen dr...

  7. Epidemiology of infective endocarditis in a large Belgian non-referral hospital.

    Science.gov (United States)

    Poesen, K; Pottel, H; Colaert, J; De Niel, C

    2014-06-01

    Guidelines for diagnosis of infective endocarditis are largely based upon epidemiological studies in referral hospitals. Referral bias, however, might impair the validity of guidelines in non-referral hospitals. Recent studies in non-referral care centres on infective endocarditis are sparse. We conducted a retrospective epidemiological study on infective endocarditis in a large non-referral hospital in a Belgian city (Kortrijk). The medical record system was searched for all cases tagged with a putative diagnosis of infective endocarditis in the period 2003-2010. The cases that fulfilled the modified Duke criteria for probable or definite infective endocarditis were included. Compared to referral centres, an older population with infective endocarditis, and fewer predisposing cardiac factors and catheter-related infective endocarditis is seen in our population. Our patients have fewer prosthetic valve endocarditis as well as fewer staphylococcal endocarditis. Our patients undergo less surgery, although mortality rate seems to be highly comparable with referral centres, with nosocomial infective endocarditis as an independent predictor of mortality. The present study suggests that characteristics of infective endocarditis as well as associative factors might differ among non-referral hospitals and referral hospitals.

  8. Linezolid Versus Vancomycin in the Empiric Treatment of Nosocomial Pneumonia: A Cost-Utility Analysis Incorporating Results from the ZEPHyR Trial.

    Science.gov (United States)

    Collins, Curtis D; Schwemm, Ann K

    2015-07-01

    To examine the cost-effectiveness of vancomycin versus linezolid in the empiric treatment of nosocomial pneumonias incorporating results from a recent prospective, double-blind, multicenter, controlled trial in adults with suspected methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia. A decision-analytic model examining the cost-effectiveness of linezolid versus vancomycin for the empiric treatment of nosocomial pneumonia was created. Publicly available cost, efficacy, and utility data populated relevant model variables. A probabilistic sensitivity analysis varied parameters in 10,000 Monte-Carlo simulations, and univariate sensitivity analyses assessed the impact of model uncertainties and the robustness of our conclusions. Results indicated that the cost per quality-adjusted life-year (QALY) increased 6% ($22,594 vs. $23,860) by using linezolid versus vancomycin for nosocomial pneumonia. The incremental cost per QALY gained by using linezolid over vancomycin was $6,089, and the incremental cost per life saved was $68,615 with the use of linezolid. Vancomycin dominated linezolid in the subset of patients with documented MRSA. The incremental cost per QALY gained using linezolid if no mortality benefit exists between agents or a 60-day time horizon was analyzed was $19,608,688 and $443,662, respectively. Linezolid may be a cost-effective alternative to vancomycin in the empiric treatment of patients with suspected MRSA nosocomial pneumonia; however, results of our model were highly variable on a number of important variables and assumptions including mortality differences and time frame analyzed. Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  9. Zygomycotic infective endocarditis in pregnancy.

    Science.gov (United States)

    Vaideeswar, Pradeep; Shah, Rushabh

    Under the circumstances of cardiovascular adaptations and immunomodulation, an uncommon but disastrous complication of infective endocarditis (IE) can occur in pregnancy. Almost all the cases reported earlier were caused by bacteria. We report a fatal case of zygomycotic valvular and mural endocarditis in a young non-diabetic primigravida with a positive hepatitis B serology. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Bacterial Endocarditis and Cerebrovascular Disease.

    Science.gov (United States)

    Silver, Brian; Behrouz, Réza; Silliman, Scott

    2016-12-01

    Cerebrovascular complications of endocarditis occur in 25-70% of patients with infective endocarditis. The cornerstone of treatment is early initiation of antibiotic treatment, which significantly reduces the risk of embolization after 1 week of treatment. In general, thrombolysis and anticoagulation of these patients should be avoided, while antiplatelet therapy may be considered in those with other indications. Endovascular treatment of acute septic emboli is uncertain, but a few case reports have demonstrated benefit. Other complications of infective endocarditis include intracerebral hemorrhage, which may be predicted by the presence of two or more cerebral microbleeds on gradient echo sequences. Intracranial mycotic aneurysms can often be managed with serial imaging and coiled if there is evidence of failure to reduce in size, or enlargement.

  11. Concentration-Dependent Synergy and Antagonism of Linezolid and Moxifloxacin in the Treatment of Childhood Tuberculosis: The Dynamic Duo.

    Science.gov (United States)

    Deshpande, Devyani; Srivastava, Shashikant; Nuermberger, Eric; Pasipanodya, Jotam G; Swaminathan, Soumya; Gumbo, Tawanda

    2016-11-01

     No treatment regimens have been specifically designed for children, in whom tuberculosis is predominantly intracellular. Given their activity as monotherapy and their ability to penetrate many diseased anatomic sites that characterize disseminated tuberculosis, linezolid and moxifloxacin could be combined to form a regimen for this need.  We examined microbial kill of intracellular Mycobacterium tuberculosis (Mtb) by the combination of linezolid and moxifloxacin multiple exposures in a 7-by-7 mathematical matrix. We then used the hollow fiber system (HFS) model of intracellular tuberculosis to identify optimal dose schedules and exposures of moxifloxacin and linezolid in combination. We mimicked pediatric half-lives and concentrations achieved by each drug. We sampled the peripheral compartment on days 0, 7, 14, 21, and 28 for Mtb quantification, and compared the slope of microbial kill of Mtb by these regimens to the standard regimen of isoniazid, rifampin, and pyrazinamide, based on exponential decline regression.  The full exposure-response surface identified linezolid-moxifloxacin zones of synergy, antagonism, and additivity. A regimen based on each of these zones was then used in the HFS model, with observed half-lives of 4.08 ± 0.66 for linezolid and 3.80 ± 1.34 hours for moxifloxacin. The kill rate constant was 0.060 ± 0.012 per day with the moxifloxacin-linezolid regimen in the additivity zone vs 0.083 ± 0.011 per day with standard therapy, translating to a bacterial burden half-life of 11.52 days vs 8.53 days, respectively.  We identified doses and dose schedules of a linezolid and moxifloxacin backbone regimen that could be highly efficacious in disseminated tuberculosis in children. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

  12. Endocarditis : Improving the chain of care

    NARCIS (Netherlands)

    Gomes, Anna

    2018-01-01

    Infectieuze endocarditis is een levensbedreigende ziekte dat een agressief diagnostisch en therapeutisch beleid vereist. Aangezien dit in de huidige praktijk nog niet optimaal geïmplementeerd is, is er behoefte aan verbetering van de zorg voor patiënten met (een verdenking op) endocarditis. Wegens

  13. Mutations in 23S rRNA at the Peptidyl Transferase Center and Their Relationship to Linezolid Binding and Cross-Resistance

    DEFF Research Database (Denmark)

    Long, Katherine; Munck, Christian

    2010-01-01

    The oxazolidinone antibiotic linezolid targets the peptidyl transferase center (PTC) on the bacterial ribosome. Thirteen single and four double 23S rRNA mutations were introduced into a Mycobacterium smegmatis strain with a single rRNA operon. Converting bacterial base identity by single mutations...... at positions 2032, 2453, and 2499 to human cytosolic base identity did not confer significantly reduced susceptibility to linezolid. The largest decrease in linezolid susceptibility for any of the introduced single mutations was observed with the G2576U mutation at a position that is 7.9 Å from linezolid....... Smaller decreases were observed with the A2503G, U2504G, and G2505A mutations at nucleotides proximal to linezolid, showing that the degree of resistance conferred is not simply inversely proportional to the nucleotide-drug distance. The double mutations G2032A-C2499A, G2032A-U2504G, C2055A-U2504G, and C...

  14. Haemophilus segnis endocarditis

    DEFF Research Database (Denmark)

    Bangsborg, Jette Marie; Tvede, M; Skinhøj, P

    1988-01-01

    Haemophilus segnis is a rarely recognised commensal in the oropharynx. We wish to report the first published case of endocarditis caused by H. segnis. The patient, a 76-year-old female did not recover until after 2 courses of ampicillin given for a total of 57 days. In the second course of treatm......Haemophilus segnis is a rarely recognised commensal in the oropharynx. We wish to report the first published case of endocarditis caused by H. segnis. The patient, a 76-year-old female did not recover until after 2 courses of ampicillin given for a total of 57 days. In the second course...

  15. Endocarditis in left ventricular assist device

    Science.gov (United States)

    Thyagarajan, Braghadheeswar; Kumar, Monisha Priyadarshini; Sikachi, Rutuja R; Agrawal, Abhinav

    2016-01-01

    Summary Heart failure is one of the leading causes of death in developed nations. End stage heart failure often requires cardiac transplantation for survival. The left ventricular assist device (LVAD) has been one of the biggest evolvements in heart failure management often serving as bridge to transplant or destination therapy in advanced heart failure. Like any other medical device, LVAD is associated with complications with infections being reported in many patients. Endocarditis developing secondary to the placement of LVAD is not a frequent, serious and difficult to treat condition with high morbidity and mortality. Currently, there are few retrospective studies and case reports reporting the same. In our review, we found the most common cause of endocarditis in LVAD was due to bacteria. Both bacterial and fungal endocarditis were associated with high morbidity and mortality. In this review we will be discussing the risk factors, organisms involved, diagnostic tests, management strategies, complications, and outcomes in patients who developed endocarditis secondary to LVAD placement. PMID:27672540

  16. Activity of moxifloxacin and linezolid against Mycobacterium tuberculosis in combination with potentiator drugs verapamil, timcodar, colistin and SQ109.

    Science.gov (United States)

    de Knegt, Gerjo J; van der Meijden, Aart; de Vogel, Corné P; Aarnoutse, Rob E; de Steenwinkel, Jurriaan E M

    2017-03-01

    Current treatment for tuberculosis (TB) is complicated by the emergence of multidrug resistant TB (MDR-TB). As a result, there is an urgent need for new powerful anti-TB regimens and novel strategies. In this study, we aimed to potentiate a moxifloxacin + linezolid backbone as treatment for MDR-TB with the efflux pump inhibitors verapamil and timcodar as well as with drugs that act on mycobacterial cell wall stability such as colistin and SQ109. Using a time-kill kinetics assay, the activities of moxifloxacin, linezolid, verapamil, timcodar, colistin and SQ109 as single drugs against Mycobacterium tuberculosis were evaluated. In addition, the activity of the moxifloxacin + linezolid backbone in combination with one of the potentiator drugs was assessed. As little as 0.125 mg/L moxifloxacin achieved 99% killing of M. tuberculosis after 6 days of exposure. Linezolid showed moderate killing but 99% killing was not achieved. Verapamil, timcodar and colistin only resulted in killing with the highest concentrations tested but 99% killing was not achieved. SQ109 resulted in complete elimination after 1 day of exposure to 256 mg/L and in 99% elimination after 6 days of exposure to 1 mg/L. Furthermore, colistin added to the moxifloxacin + linezolid backbone resulted in increased elimination, whereas verapamil, timcodar and SQ109 showed no added value to the backbone. This finding that colistin potentiates the activity of the moxifloxacin + linezolid backbone against M. tuberculosis suggests its potential role in further studies on the applicability of a moxifloxacin + linezolid treatment of MDR-TB. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  17. Successful Treatment of Necrotizing Fasciitis and Streptococcal Toxic Shock Syndrome with the Addition of Linezolid

    Directory of Open Access Journals (Sweden)

    Hana Rac

    2017-01-01

    Full Text Available Necrotizing fasciitis is a deep-seated subcutaneous tissue infection that is commonly associated with streptococcal toxic shock syndrome (TSS. Surgical debridement plus penicillin and clindamycin are the current standard of care. We report a case of necrotizing fasciitis and streptococcal TSS where linezolid was added after a failure to improve with standard therapy. Briefly after isolation of Streptococcus pyogenes from tissue cultures, the patient underwent two surgical debridement procedures and was changed to standard of care therapy. While the patient was hemodynamically stable, the patient’s wounds, leukocytosis, and thrombocytopenia all progressively worsened. After initiation of linezolid, the patient slowly improved clinically. The present report is the first to highlight the role of linezolid in streptococcal necrotizing fasciitis and TSS not improving with standard therapy.

  18. Crystal Structure of the Oxazolidinone Antibiotic Linezolid Bound to the 50S Ribosomal Subunit

    Energy Technology Data Exchange (ETDEWEB)

    Ippolito,J.; Kanyo, Z.; Wang, D.; Franceschi, F.; Moore, P.; Steitz, T.; Duffy, E.

    2008-01-01

    The oxazolidinone antibacterials target the 50S subunit of prokaryotic ribosomes. To gain insight into their mechanism of action, the crystal structure of the canonical oxazolidinone, linezolid, has been determined bound to the Haloarcula marismortui 50S subunit. Linezolid binds the 50S A-site, near the catalytic center, which suggests that inhibition involves competition with incoming A-site substrates. These results provide a structural basis for the discovery of improved oxazolidinones active against emerging drug-resistant clinical strains.

  19. Linezolid and tiamulin cross-resistance in Staphylococcus aureus mediated by point mutations in the peptidyl transferase center.

    Science.gov (United States)

    Miller, Keith; Dunsmore, Colin J; Fishwick, Colin W G; Chopra, Ian

    2008-05-01

    Oxazolidinone and pleuromutilin antibiotics are currently used in the treatment of staphylococcal infections. Although both antibiotics inhibit protein synthesis and have overlapping binding regions on 23S rRNA, the potential for cross-resistance between the two classes through target site mutations has not been thoroughly examined. Mutants of Staphylococcus aureus resistant to linezolid were selected and found to exhibit cross-resistance to tiamulin, a member of the pleuromutilin class of antibiotics. However, resistance was unidirectional because mutants of S. aureus selected for resistance to tiamulin did not exhibit cross-resistance to linezolid. This contrasts with the recently described PhLOPS(A) phenotype, which confers resistance to both oxazolidinones and pleuromutilins. The genotypes responsible for the phenotypes we observed were examined. Selection with tiamulin resulted in recovery of mutants with changes in the single-copy rplC gene (Gly155Arg, Ser158Leu, or Arg149Ser), whereas selection with linezolid led to recovery of mutants with changes (G2576U in 23S rRNA) in all five copies of the multicopy operon rrn. In contrast, cross-resistance to linezolid was exhibited by tiamulin-resistant mutants generated in a single-copy rrn knockout strains of Escherichia coli, illustrating that the copy number of 23S rRNA is the limiting factor in the selection of 23S rRNA tiamulin-resistant mutants. The interactions of linezolid and tiamulin with the ribosome were modeled to seek explanations for resistance to both classes in the 23S rRNA mutants and the lack of cross-resistance between tiamulin and linezolid following mutation in rplC.

  20. Variable Linezolid Exposure in Intensive Care Unit Patients-Possible Role of Drug-Drug Interactions.

    Science.gov (United States)

    Töpper, Christoph; Steinbach, Cathérine L; Dorn, Christoph; Kratzer, Alexander; Wicha, Sebastian G; Schleibinger, Michael; Liebchen, Uwe; Kees, Frieder; Salzberger, Bernd; Kees, Martin G

    2016-10-01

    Standard doses of linezolid may not be suitable for all patient groups. Intensive care unit (ICU) patients in particular may be at risk of inadequate concentrations. This study investigated variability of drug exposure and its potential sources in this population. Plasma concentrations of linezolid were determined by high-performance liquid chromatography in a convenience sample of 20 ICU patients treated with intravenous linezolid 600 mg twice daily. Ultrafiltration applying physiological conditions (pH 7.4/37°C) was used to determine the unbound fraction. Individual pharmacokinetic (PK) parameters were estimated by population PK modeling. As measures of exposure to linezolid, area under the concentration-time curve (AUC) and trough concentrations (Cmin) were calculated and compared with published therapeutic ranges (AUC 200-400 mg*h/L, Cmin 2-10 mg/L). Coadministered inhibitors or inducers of cytochrome P450 and/or P-glycoprotein were noted. Data from 18 patients were included into the PK evaluation. Drug exposure was highly variable (median, range: AUC 185, 48-618 mg*h/L, calculated Cmin 2.92, 0.0062-18.9 mg/L), and only a minority of patients had values within the target ranges (6 and 7, respectively). AUC and Cmin were linearly correlated (R = 0.98), and classification of patients (underexposed/within therapeutic range/overexposed) according to AUC or Cmin was concordant in 15 cases. Coadministration of inhibitors was associated with a trend to higher drug exposure, whereas 3 patients treated with levothyroxine showed exceedingly low drug exposure (AUC ∼60 mg*h/L, Cmin linezolid is highly variable and difficult to predict in ICU patients, and therapeutic drug monitoring seems advisable. PK drug-drug interactions might partly be responsible and should be further investigated; protein binding appears to be stable and irrelevant.

  1. Ethambutol/Linezolid Toxic Optic Neuropathy.

    Science.gov (United States)

    Libershteyn, Yevgeniya

    2016-02-01

    To report a rare toxic optic neuropathy after long-term use of two medications: ethambutol and linezolid. A 65-year-old man presented to the Miami Veterans Affairs Medical Center in December 2014 for evaluation of progressive vision decrease in both eyes. The patient presented with best-corrected visual acuities of 20/400 in the right eye and counting fingers at 5 feet in the left eye. Color vision was significantly reduced in both eyes. Visual fields revealed a cecocentral defect in both eyes. His fundus and optic nerve examination was unremarkable. Because vision continued to decline after discontinuation of ethambutol, linezolid was also discontinued, after which vision, color vision, and visual fields improved. Because of these findings, the final diagnosis was toxic optic neuropathy. Final visual outcome was 20/30 in the right eye and 20/40 in the left eye. Drug-associated toxic optic neuropathy is a rare but vision-threatening condition. Diagnosis is made based on an extensive case history and careful clinical examination. The examination findings include varying decrease in vision, normal pupils and extraocular muscles, and unremarkable fundoscopy, with the possibility of swollen optic discs in the acute stage of the optic neuropathy. Other important findings descriptive of toxic optic neuropathy include decreased color vision and cecocentral visual field defects. This case illustrates the importance of knowledge of all medications and/or substances a patient consumes that may cause a toxic reaction and discontinuing them immediately if the visual functions are worsening or not improving.

  2. Acute bacterial endocarditis. Optimizing surgical results.

    Science.gov (United States)

    Larbalestier, R I; Kinchla, N M; Aranki, S F; Couper, G S; Collins, J J; Cohn, L H

    1992-11-01

    Acute bacterial endocarditis continues to be a condition with high morbidity. Although the majority of patients are treated by high-dose antibiotics, a high-risk patient group requires surgical intervention, which is the subject of this article. From 1972 to 1991, 3,820 patients underwent heart valve replacement at the Brigham and Women's Hospital, Boston. Of this group, 158 patients underwent surgery for acute bacterial endocarditis: 109 had native valve endocarditis (NVE), and 49 had prosthetic valve endocarditis (PVE). There were 108 men and 50 women with a mean age of 49 years (range, 16-79 years); 64% were New York Heart Association functional class IV before surgery, and 12% of the group had a history of intravenous drug abuse. In both NVE and PVE groups, Streptococcus was the predominant infecting agent. Uncontrolled sepsis, progressive congestive failure, peripheral emboli, and echocardiographically demonstrated vegetations were the most common indications for surgery. Eighty-five percent of patients had a single-valve procedure, 15% had a multivalve procedure, and 34 patients had other associated major cardiac procedures. The operative mortality was 6% in NVE and 22% in PVE. Long-term survival at 10 years was 66% for NVE and 29% for PVE. Freedom from recurrent endocarditis at 10 years was 85% for NVE and 82% for PVE. The main factors associated with decreased survival overall were PVE and nonstreptococcal infection. The morbidity and mortality after surgical treatment of acute endocarditis depend on the site, the severity, and the subject infected. Early aggressive surgical intervention is indicated to optimize surgical results, especially in patients with nonstreptococcal infection or PVE.

  3. The challenge of staphylococcal pacemaker endocarditis in a patient with transposition of the great arteries endocarditis in congenital heart disease

    International Nuclear Information System (INIS)

    Ch'ng, Julie; Chan, William; Lee, Paul; Joshi, Subodh; Grigg, Leanne E.; Ajani, Andrew E.

    2003-01-01

    Staphylococcus aureus is a leading cause of septicaemia and infective endocarditis. The overall incidence of staphylococcal bacteraemia is increasing, contributing to 16% of all hospital-acquired bacteraemias. The use of cardiac pacemakers has revolutionized the management of rhythm disturbances, yet this has also resulted in a group of patients at risk of pacemaker lead endocarditis and seeding in the range of 1% to 7%. We describe a 26-year-old man with transposition of the great arteries who had a pacemaker implanted and presented with S. aureus septicaemia 2 years postpacemaker implantation and went on to develop pacemaker lead endocarditis. This report illustrates the risk of endocarditis in the population with congenital heart disease and an intracardiac device

  4. [Rare diagnostics of infective endocarditis after kidney transplantation].

    Science.gov (United States)

    Dedinská, Ivana; Skalová, Petra; Mokáň, Michal; Martiaková, Katarína; Osinová, Denisa; Pindura, Miroslav; Palkoci, Blažej; Vojtko, Marián; Hubová, Janka; Kadlecová, Denisa; Lendová, Ivona; Zacharovský, Radovan; Pekar, Filip; Kaliská, Lucia

    2016-01-01

    Infective endocarditis in a patient after kidney transplantation is a serious infective complication which increases the risk of loss of the graft and also the mortality of patients. The most important predisposing factor is the immunosuppressive therapy - mainly induction immunosuppression.Material and case description: 250 patients underwent kidney transplantation throughout the period of 12 years in the Transplant Center Martin. This set of patients included 5 patients (2 %) after heart valve replacement. We present the case of a patient after kidney transplantation with development of endocarditis of the bioprosthesis of the aortic valve one month after successful kidney transplantation. Diagnostics of endocarditis by standard procedures (examination by transthoracic echocardiogram, transesophageal echocardiography, hemocultures) was unsuccessful. We rarely diagnosed endocarditis only by PET-CT examination with a consequent change of the antibiotic treatment and successful managing of this post-transplant complication. Endocarditis after kidney transplantation is a serious complication which significantly worsens the mortality of patients. The risk of development of infective endocarditis after transplantation is also increased by induction, mainly by antithymocyte globulin. Diagnostics only by PET-CT examination is rare; however, in this case it fundamentally changed the approach to the patient and led to a successful treatment.

  5. Characteristics and prognosis of pneumococcal endocarditis: a case-control study.

    Science.gov (United States)

    Daudin, M; Tattevin, P; Lelong, B; Flecher, E; Lavoué, S; Piau, C; Ingels, A; Chapron, A; Daubert, J-C; Revest, M

    2016-06-01

    Case series have suggested that pneumococcal endocarditis is a rare disease, mostly reported in patients with co-morbidities but no underlying valve disease, with a rapid progression to heart failure, and high mortality. We performed a case-control study of 28 patients with pneumococcal endocarditis (cases), and 56 patients with non-pneumococcal endocarditis (controls), not matched for sex and age, during the years 1991-2013, in one referral centre. Alcoholism (39.3% versus 10.7%; p endocarditis. Cardiac surgery was required in 64.3% of patients with pneumococcal endocarditis, much earlier than in patients with non-pneumococcal endocarditis (mean time from symptom onset, 14.1 ± 18.2 versus 69.0 ± 61.1 days). In-hospital mortality rates were similar (7.1% versus 12.5%). Streptococcus pneumoniae causes rapidly progressive endocarditis requiring life-saving early cardiac surgery in most cases. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  6. Bacterial Clearance and Endocarditis in American Opossums

    Science.gov (United States)

    Musher, Daniel M.; Richie, Yvonne

    1974-01-01

    The American opossum is the only experimental animal that regularly develops bacterial endocarditis spontaneously. There was no relation between the ability of opossums to clear bacteria from the bloodstream and the subsequent development of endocarditis. PMID:4208530

  7. Complex long-distance effects of mutations that confer linezolid resistance in the large ribosomal subunit

    Science.gov (United States)

    Fulle, Simone; Saini, Jagmohan S.; Homeyer, Nadine; Gohlke, Holger

    2015-01-01

    The emergence of multidrug-resistant pathogens will make current antibiotics ineffective. For linezolid, a member of the novel oxazolidinone class of antibiotics, 10 nucleotide mutations in the ribosome have been described conferring resistance. Hypotheses for how these mutations affect antibiotics binding have been derived based on comparative crystallographic studies. However, a detailed description at the atomistic level of how remote mutations exert long-distance effects has remained elusive. Here, we show that the G2032A-C2499A double mutation, located > 10 Å away from the antibiotic, confers linezolid resistance by a complex set of effects that percolate to the binding site. By molecular dynamics simulations and free energy calculations, we identify U2504 and C2452 as spearheads among binding site nucleotides that exert the most immediate effect on linezolid binding. Structural reorganizations within the ribosomal subunit due to the mutations are likely associated with mutually compensating changes in the effective energy. Furthermore, we suggest two main routes of information transfer from the mutation sites to U2504 and C2452. Between these, we observe cross-talk, which suggests that synergistic effects observed for the two mutations arise in an indirect manner. These results should be relevant for the development of oxazolidinone derivatives that are active against linezolid-resistant strains. PMID:26202966

  8. [Clinical Characteristics and Evolution of Recurrent Infectious Endocarditis in non Drug Addicts].

    Science.gov (United States)

    Rodríguez, M; Anguita, M; Castillo, J M; Torres, F; Siles, J R; Mesa, D; Franco, M; García-Alegría, J; Concha, M; Vallés, F

    2001-09-01

    Recurrence of infection is observed in a high proportion of patients who have had infective endocarditis in the past. The aim of our study was to evaluate the possible differences between the first and the recurrent episodes of endocarditis, as well as to assess the outcome and prognosis of patients with recurrent endocarditis. We reviewed a series of 13 episodes of recurrent endocarditis from among 196 cases of infective endocarditis involving non-drug-addict patients in two hospitals from 1987 to 2000. There were no differences between recurrent and first episodes of endocarditis according to age, sex, heart valve involved or causal microorganisms. Prosthetic valve endocarditis was more common in patients with recurrent endocarditis (86% versus 27%; p < 0.001). Although there were no differences in the rate of complications or early surgery, overall mortality was significantly higher in patients with recurrent endocarditis (53% versus 27%: p < 0.05). When early and late mortality were analysed separately, the differences did not achieve significance. Recurrent endocarditis was frequent in our series (7% of all cases). The features were similar to those of the first episode except for a higher rate of prosthetic valve endocarditis and a higher overall mortality.

  9. Aggregatibacter aphrophilus pacemaker endocarditis: a case report.

    Science.gov (United States)

    Patel, Sahil R; Patel, Nishi H; Borah, Amit; Saltzman, Heath

    2014-12-08

    Aggregatibacter bacteria are a rare cause of endocarditis in adults. They are part of a group of organisms known as HACEK--Haemophilus, Aggregatibacter, Cardiobacter, Eikenella, and Kingella. Among these organisms, several Haemophilus species have been reclassified under the genus Aggregatibacter. Very few cases of Aggregatibacter endocarditis in patients with pacemaker devices have been reported. We present here what we believe to be the first case of Aggregatibacter aphrophilus pacemaker endocarditis. A 62-year-old African American male with a medical history significant for dual-chamber pacemaker placement in 1996 for complete heart block with subsequent lead manipulation in 2007, presented to his primary care doctor with fever, chills, night sweats, fatigue, and ten-pound weight loss over a four-month period. Physical examination revealed a new murmur and jugular venous distension which prompted initiation of antibiotics for suspicion of endocarditis. Both sets of initial blood cultures were positive for A. aphrophilus. Transesophageal echocardiogram revealed vegetations on the tricuspid valve and the right ventricular pacemaker lead (Figure 1). This case highlights the importance of identifying rare causes of endocarditis and recognizing that treatment may not differ from the standard treatment for typical presentations. The patient received intravenous ceftriaxone for his endocarditis for a total of six weeks. Upon device removal, temporary jugular venous pacing wires were placed. After two weeks of antibiotic treatment and no clinical deterioration, a new permanent pacemaker was placed and the patient was discharged home. This is the first case of A. aphrophilus endocarditis in a patient with a permanent pacemaker. Our patient had no obvious risk factors other than poor dentition and a history of repeated pacemaker lead manipulation. This suggests that valvulopathies secondary to repeated lead manipulation can be clinically significant factors in morbidity

  10. Different extracts of Zingiber officinale decrease Enterococcus faecalis infection in Galleria mellonella.

    Science.gov (United States)

    Maekawa, Lilian Eiko; Rossoni, Rodnei Dennis; Barbosa, Júnia Oliveira; Jorge, Antonio Olavo Cardoso; Junqueira, Juliana Campos; Valera, Marcia Carneiro

    2015-01-01

    Dried, fresh and glycolic extracts of Zingiber officinale were obtained to evaluate the action against G. mellonella survival assay against Enterococcus faecalis infection. Eighty larvae were divided into: 1) E. faecalis suspension (control); 2) E. faecalis + fresh extract of Z. officinale (FEO); 3) E. faecalis + dried extract of Z. officinale (DEO); 4) E. faecalis + glycolic extract of Z. officinale (GEO); 5) Phosphate buffered saline (PBS). For control group, a 5 μL inoculum of standardized suspension (107 cells/mL) of E. faecalis (ATCC 29212) was injected into the last left proleg of each larva. For the treatment groups, after E. faecalis inoculation, the extracts were also injected, but into the last right proleg. The larvae were stored at 37 °C and the number of dead larvae was recorded daily for 168 h (7 days) to analyze the survival curve. The larvae were considered dead when they did not show any movement after touching. E. faecalis infection led to the death of 85% of the larvae after 168 h. Notwithstanding, in treatment groups with association of extracts, there was an increase in the survival rates of 50% (GEO), 61% (FEO) and 66% (DEO) of the larvae. In all treatment groups, the larvae exhibited a survival increase with statistically significant difference in relation to control group (p=0.0029). There were no statistically significant differences among treatment groups with different extracts (p=0.3859). It may be concluded that the tested extracts showed antimicrobial activity against E. faecalis infection by increasing the survival of Galleria mellonella larvae.

  11. Cardiac imaging in infectious endocarditis

    DEFF Research Database (Denmark)

    Bruun, Niels Eske; Habib, Gilbert; Thuny, Franck

    2014-01-01

    Infectious endocarditis remains both a diagnostic and a treatment challenge. A positive outcome depends on a rapid diagnosis, accurate risk stratification, and a thorough follow-up. Imaging plays a key role in each of these steps and echocardiography remains the cornerstone of the methods in use....... The technique of both transthoracic echocardiography and transoesophageal echocardiography has been markedly improved across the last decades and most recently three-dimensional real-time echocardiography has been introduced in the management of endocarditis patients. Echocardiography depicts structural changes...... with conventional CT (SPECT/CT). Of these methods, (18)F-FDG PET-CT carries the best promise for a future role in endocarditis. But there are distinct limitations with both SPECT/CT and (18)F-FDG PET-CT which should not be neglected. MRI and spiral CT are methods primarily used in the search for extra cardial...

  12. Influence of Streptococcus mutans on Enterococcus faecalis Biofilm Formation

    NARCIS (Netherlands)

    Deng, Dong Mei; Hoogenkamp, Michel A.; Exterkate, Rob A. M.; Jiang, Lei Meng; van der Sluis, Lucas W. M.; ten Cate, Jacob M.; Crielaard, Wim

    Introduction: An important virulence factor of Enterococcus faecalis is its ability to form biofilms. Most studies on biofilm formation have been carried out by using E. faecalis monocultures. Given the polymicrobial nature of root canal infections, it is important to understand biofilm formation of

  13. Activity of vancomycin, linezolid, and daptomycin against staphylococci and enterococci isolated in 5 Greek hospitals during a 5-year period (2008-2012).

    Science.gov (United States)

    Papadimitriou-Olivgeris, Matthaios; Kolonitsiou, Fevronia; Zerva, Loukia; Lebessi, Evangelia; Koutsia, Chryssa; Drougka, Eleanna; Sarrou, Styliani; Giormezis, Nikolaos; Vourli, Sofia; Doudoulakakis, Anastassios; Konsolakis, Christos; Marangos, Markos; Anastassiou, Evangelos D; Petinaki, Efthimia; Spiliopoulou, Iris

    2015-12-01

    The tendency of vancomycin, linezolid, and daptomycin MICs was investigated among 6920 staphylococci and enterococci during a 5-year period. Antimicrobial consumption was determined. Decrease of vancomycin MIC was detected associated with reduction in consumption. Linezolid and daptomycin remained active. An upward trend of linezolid MIC for methicillin-resistant staphylococci was observed. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Blue light-mediated inactivation of Enterococcus faecalis in vitro.

    Science.gov (United States)

    Pileggi, Giorgio; Wataha, John C; Girard, Myriam; Grad, Iwona; Schrenzel, Jacques; Lange, Norbert; Bouillaguet, Serge

    2013-05-01

    In dentistry, residual infection remains a major cause of failure after endodontic treatment; many of these infections involve Enterococcus faecalis. In the current study, we explored the possibility that blue light activated photosensitizers could be used, in principle, to inactivate this microbe as an adjunct disinfection strategy for endodontic therapy. Three blue light absorbing photosensitizers, eosin-Y, rose bengal, and curcumin, were tested on E. faecalis grown in planktonic suspensions or biofilms. Photosensitizers were incubated for 30 min with bacteria then exposed to blue light (450-500 nm) for 240 s. Sodium hypochlorite (3%) was used as a control. After 48 h, the viability of E. faecalis was estimated by measuring colony-forming units post-exposure vs. untreated controls (CFU/mL). Blue light irradiation alone did not alter E. faecalis viability. For planktonic cultures, blue light activated eosin-Y (5 μM), rose bengal (1 μM), or curcumin (5 μM) significantly (pcurcumin of 100, 10, and 10 μM respectively, completely suppressed E. faecalis viability (p<0.05). Although the current results are limited to an in vitro model, they support further exploration of blue light activated antimicrobials as an adjunct therapy in endodontic treatment. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Porcine models of non-bacterial thrombotic endocarditis (NBTE) and infective endocarditis (IE) caused by Staphylococcus aureus: a preliminary study.

    Science.gov (United States)

    Christiansen, Johanna G; Jensen, Henrik E; Johansen, Louise K; Kochl, Janne; Koch, Jørgen; Aalbaek, Bent; Nielsen, Ole L; Leifsson, Páll S

    2013-05-01

    Non-bacterial thrombotic endocarditis (NBTE) and, in particular, infective endocarditis (IE), are serious and potentially life-threatening diseases. An increasingly important agent of human IE is Staphylococcus aureus, which typically causes an acute endocarditis with high mortality. The study aim was to evaluate the pig as a model for non-bacterial as well as S. aureus-associated endocarditis, as these models would have several advantages compared to other laboratory animal models. Fourteen animals underwent surgery with placement of a plastic catheter in the left side of the heart. Six of the pigs did not receive a bacterial inoculation and were used to study the development of NBTE. The remaining eight pigs were inoculated intravenously once or twice with S. aureus, 10(5)-10(7) cfu/kg body weight. Two bacterial strains were used: S54F9 (porcine) and NCTC8325-4 (human). Clinical examination, echocardiography and bacterial blood cultures were used to diagnose and monitor the development of endocarditis. Animals were euthanized at between two and 15 days after catheter placement, and tissue samples were collected for bacteriology and histopathology. Pigs inoculated with 10(7) cfu/kg of S. aureus strain S54F9 developed clinical, echocardiographic and pathologic signs of IE. All other pigs, except one, developed NBTE. Serial blood cultures withdrawn after inoculation were positive in animals with IE, and negative in all other animals. S. aureus endocarditis was successfully induced in pigs with an indwelling cardiac catheter after intravenous inoculation of 10(7) cfu/kg of S. aureus strain S54F9. The model simulates typical pathological, clinical and diagnostic features seen in the human disease. Furthermore, NBTE was induced in all but one of the pigs without IE. Thus, the pig model can be used in future studies of the pathogenesis, diagnosis and therapy of NBTE and S. aureus endocarditis.

  16. Endocarditis infecciosa de válvula pulmonar nativa

    Directory of Open Access Journals (Sweden)

    Franco Romaní R

    2007-04-01

    Full Text Available La endocarditis infecciosa en válvulas derechas es predominantemente en la válvula tricuspídea, mientras la válvula pulmonar es excepcionalmente afectada (menos de 1,5%, por lo que son pocos los casos reportados en la literatura mundial. Las manifestaciones clínicas de endocarditis en válvula pulmonar no son las clásicas de endocarditis infecciosa, como son los síntomas de embolismo séptico pulmonar. La endocarditis aislada de válvula pulmonar nativa es inusual en personas que no consumen drogas intravenosas. Se presenta el caso de un paciente varón con diabetes mellitus tipo 2 y sin otro factor predisponente.

  17. Challenges in Infective Endocarditis.

    Science.gov (United States)

    Cahill, Thomas J; Baddour, Larry M; Habib, Gilbert; Hoen, Bruno; Salaun, Erwan; Pettersson, Gosta B; Schäfers, Hans Joachim; Prendergast, Bernard D

    2017-01-24

    Infective endocarditis is defined by a focus of infection within the heart and is a feared disease across the field of cardiology. It is frequently acquired in the health care setting, and more than one-half of cases now occur in patients without known heart disease. Despite optimal care, mortality approaches 30% at 1 year. The challenges posed by infective endocarditis are significant. It is heterogeneous in etiology, clinical manifestations, and course. Staphylococcus aureus, which has become the predominant causative organism in the developed world, leads to an aggressive form of the disease, often in vulnerable or elderly patient populations. There is a lack of research infrastructure and funding, with few randomized controlled trials to guide practice. Longstanding controversies such as the timing of surgery or the role of antibiotic prophylaxis have not been resolved. The present article reviews the challenges posed by infective endocarditis and outlines current and future strategies to limit its impact. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  18. Clinical Risk Factors for Infective Endocarditis in Staphylococcus aureus Bacteremia.

    Science.gov (United States)

    Salvador, Vincent Bryan D; Chapagain, Bikash; Joshi, Astha; Brennessel, Debra J

    2017-02-01

    Crucial to the management of staphylococcal bacteremia is an accurate evaluation of associated endocarditis, which has both therapeutic and prognostic implications. Because the clinical presentation of endocarditis can be nonspecific, the judicious use of echocardiography is important in distinguishing patients at high risk of developing endocarditis. In the presence of high-risk clinical features, an early transesophageal echocardiogram is warranted without prior transthoracic echocardiography. The purpose of this study was to investigate the clinical risk factors for staphylococcal infective endocarditis that might warrant earlier transesophageal echocardiography and to describe the incidence of endocarditis in cases of methicillin-resistant and methicillin-sensitive Staphylococcus aureus bacteremia. A retrospective case-control study was conducted by means of chart review of 91 patients consecutively admitted to a community hospital from January 2009 through January 2013. Clinical risk factors of patients with staphylococcal bacteremia were compared with risk factors of patients who had definite diagnoses of infective endocarditis. There were 69 patients with bacteremia alone (76%) and 22 patients with endocarditis (24%), as verified by echocardiography. Univariate analysis showed that diabetes mellitus ( P =0.024), the presence of an automatic implantable cardioverter-defibrillator/pacemaker ( P =0.006) or a prosthetic heart valve ( P =0.003), and recent hospitalization ( P =0.048) were significantly associated with developing infective endocarditis in patients with S. aureus bacteremia. The incidence of methicillin-resistant and methicillin-sensitive S. aureus bacteremia was similar in the bacteremia and infective-endocarditis groups ( P =0.437). In conclusion, identified high-risk clinical factors in the presence of bacteremia can suggest infective endocarditis. Early evaluation with transesophageal echocardiography might well be warranted.

  19. Linezolid and Tiamulin Cross-Resistance in Staphylococcus aureus Mediated by Point Mutations in the Peptidyl Transferase Center ▿

    Science.gov (United States)

    Miller, Keith; Dunsmore, Colin J.; Fishwick, Colin W. G.; Chopra, Ian

    2008-01-01

    Oxazolidinone and pleuromutilin antibiotics are currently used in the treatment of staphylococcal infections. Although both antibiotics inhibit protein synthesis and have overlapping binding regions on 23S rRNA, the potential for cross-resistance between the two classes through target site mutations has not been thoroughly examined. Mutants of Staphylococcus aureus resistant to linezolid were selected and found to exhibit cross-resistance to tiamulin, a member of the pleuromutilin class of antibiotics. However, resistance was unidirectional because mutants of S. aureus selected for resistance to tiamulin did not exhibit cross-resistance to linezolid. This contrasts with the recently described PhLOPSA phenotype, which confers resistance to both oxazolidinones and pleuromutilins. The genotypes responsible for the phenotypes we observed were examined. Selection with tiamulin resulted in recovery of mutants with changes in the single-copy rplC gene (Gly155Arg, Ser158Leu, or Arg149Ser), whereas selection with linezolid led to recovery of mutants with changes (G2576U in 23S rRNA) in all five copies of the multicopy operon rrn. In contrast, cross-resistance to linezolid was exhibited by tiamulin-resistant mutants generated in a single-copy rrn knockout strains of Escherichia coli, illustrating that the copy number of 23S rRNA is the limiting factor in the selection of 23S rRNA tiamulin-resistant mutants. The interactions of linezolid and tiamulin with the ribosome were modeled to seek explanations for resistance to both classes in the 23S rRNA mutants and the lack of cross-resistance between tiamulin and linezolid following mutation in rplC. PMID:18180348

  20. Diagnostic value of echocardiography in infective endocarditis

    International Nuclear Information System (INIS)

    Luo Yinli; Ni Xianda; Hu Yuanping; Liu Jingyun; Yang Weiyu

    2010-01-01

    Objective: To investigate the feature and value of echocardiography for diagnosing infective endocarditis. Methods: The shape, size, echogenicity, distribution of vegetations and valvular injury of the heart were observed in 30 patients with infective endocarditis. Results: The vegetations were located in the aortic valves (10 cases), bicuspid valves (5), tricuspid valve (1), pulmonary valve (2), main pulmonary artery with patent ductus arteriosus (2), and right ventricle with ventricular septal defect (2). The size of vegetation ranged from 2 to 27 mm and the echogenicity of vegetations was low to high. The location, size, shape and amount of vegetations observed on echocardiography correlated well with the operative findings. Echocardiography also demonstrated underlying heart disease and abnormal hemodynamics induced by infective endocarditis. Conclusion: Echocardiography can determine the location, size, shape, amount of vegetation and concomitant cardiac disease in patients with infective endocarditis. It play an important role in treatment and prognosis. (authors)

  1. Whole genome analysis of linezolid resistance in Streptococcus pneumoniae reveals resistance and compensatory mutations

    Directory of Open Access Journals (Sweden)

    Légaré Danielle

    2011-10-01

    Full Text Available Abstract Background Several mutations were present in the genome of Streptococcus pneumoniae linezolid-resistant strains but the role of several of these mutations had not been experimentally tested. To analyze the role of these mutations, we reconstituted resistance by serial whole genome transformation of a novel resistant isolate into two strains with sensitive background. We sequenced the parent mutant and two independent transformants exhibiting similar minimum inhibitory concentration to linezolid. Results Comparative genomic analyses revealed that transformants acquired G2576T transversions in every gene copy of 23S rRNA and that the number of altered copies correlated with the level of linezolid resistance and cross-resistance to florfenicol and chloramphenicol. One of the transformants also acquired a mutation present in the parent mutant leading to the overexpression of an ABC transporter (spr1021. The acquisition of these mutations conferred a fitness cost however, which was further enhanced by the acquisition of a mutation in a RNA methyltransferase implicated in resistance. Interestingly, the fitness of the transformants could be restored in part by the acquisition of altered copies of the L3 and L16 ribosomal proteins and by mutations leading to the overexpression of the spr1887 ABC transporter that were present in the original linezolid-resistant mutant. Conclusions Our results demonstrate the usefulness of whole genome approaches at detecting major determinants of resistance as well as compensatory mutations that alleviate the fitness cost associated with resistance.

  2. Antibiotics for the prophylaxis of bacterial endocarditis in dentistry.

    Science.gov (United States)

    Glenny, Anne-Marie; Oliver, Richard; Roberts, Graham J; Hooper, Lee; Worthington, Helen V

    2013-10-09

    Infective endocarditis is a severe infection arising in the lining of the chambers of the heart with a high mortality rate.Many dental procedures cause bacteraemia and it was believed that this may lead to bacterial endocarditis (BE) in a few people. Guidelines in many countries have recommended that prior to invasive dental procedures antibiotics are administered to people at high risk of endocarditis. However, recent guidance by the National Institute for Health and Care Excellence (NICE) in England and Wales has recommended that antibiotics are not required. To determine whether prophylactic antibiotic administration, compared to no such administration or placebo, before invasive dental procedures in people at risk or at high risk of bacterial endocarditis influences mortality, serious illness or the incidence of endocarditis. The following electronic databases were searched: the Cochrane Oral Health Group's Trials Register (to 21 January 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 12), MEDLINE via OVID (1946 to 21 January 2013) and EMBASE via OVID (1980 to 21 January 2013). We searched for ongoing trials in the US National Institutes of Health Trials Register (http://clinicaltrials.gov) and the metaRegister of Controlled Trials (http://www.controlled-trials.com/mrct/). No restrictions were placed on the language or date of publication when searching the electronic databases. Due to the low incidence of BE it was anticipated that few if any trials would be located. For this reason, cohort and case-control studies were included where suitably matched control or comparison groups had been studied. The intervention was the administration of antibiotic, compared to no such administration, before a dental procedure in people with an increased risk of BE. Cohort studies would need to follow those individuals at increased risk and assess outcomes following any invasive dental procedures, grouping by whether

  3. Listeria Endocarditis: A Diagnostic Challenge

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    Wilhelmina J. A. R. M. Valckx MD

    2017-04-01

    Full Text Available A 74-year-old hemodialysis patient with a history of an atrial septum defect closure, coronary bypass surgery, and a St. Jude aortic prosthetic valve was diagnosed with pneumonia and volume overload. Blood cultures were positive for Listeria monocytogenes, and amoxicillin was given for 2 weeks. Immediately after discontinuation of amoxicillin, fever relapsed. Transthoracic and transesophageal echocardiography showed no sign of endocarditis. Given the fever relapse and 3 positive minor Duke criteria, an 18F-FDG PET-CT scan (18F-fluorodeoxyglucose-positron emission tomography-computed tomography scan was performed. This scan showed activity at the aortic root, proximal ascending aorta, and inferior wall of the heart, making Listeria monocytogenes endocarditis a likely explanation. Amoxicillin was given for 6 weeks with good clinical result. Diagnosing a life-threatening Listeria monocytogenes endocarditis can be challenging and an 18F-FDG PET-CT scan can be helpful.

  4. A 1 year retrospective audit of quality indicators of clinical pharmacological advice for personalized linezolid dosing: one stone for two birds?

    Science.gov (United States)

    Pea, Federico; Cojutti, Piergiorgio; Dose, Lucia; Baraldo, Massimo

    2016-02-01

    This study explored the clinical and economic impact of clinical pharmacological advice (CPA) (based on therapeutic drug monitoring [TDM] results, and on patients' characteristics and co-medications) on personalized linezolid therapy in a tertiary care hospital. A 1 year retrospective analysis of quality indicators of CPA (clinicians' adherence rate to CPA, pre-post rate of linezolid trough concentrations within the desired range and cost balance analysis) was conducted. Five hundred and forty-four CPAs were provided to clinicians during 2014 for personalizing linezolid therapy in 168 patients. Clinicians' adherence to CPAs was very high (94.7%). The pre-post rate of linezolid Cmin distribution showed a favourable impact of CPA on patient care (pre-post ratio of Cmin within the desired range + 23.4%, pre, 51.2% vs. post, 74.6%). Overall, linezolid dosage was mainly reduced (56.9% of cases), whereas dose augmentation was needed only in a minority of cases (7.7%). Cost balance analysis showed that overall 1258 standard doses of linezolid (unitary dose 600 mg) were spared for treating 168 patients with a personalized dosage for a median duration of 11 days (range 3-128 days) with a cost saving of 60038.05 €. Active computerized advice elaborated by the clinical pharmacologist on the basis of TDM results and of patient's pathophysiological data and co-medications may be cost-effective for personalizing linezolid treatment. © 2015 The British Pharmacological Society.

  5. Bacteriophage Mediated Killing of Staphylococcus aureus In Vitro on Orthopaedic K Wires in Presence of Linezolid Prevents Implant Colonization

    Science.gov (United States)

    Kaur, Sandeep; Harjai, Kusum; Chhibber, Sanjay

    2014-01-01

    Background Infections of bone and joint tissues following arthroplasty surgeries remain a major challenge in orthopaedic settings. Methicillin resistant Staphylococcus aureus (MRSA) is recognised as an established pathogen in such infections. Combination therapy using linezolid and bacteriophage impregnated in biopolymer was investigated in the present study as an alternative strategy to prevent MRSA colonisation on the orthopaedic implant surface. Methodology Coating of stainless steel orthopaedic grade K-wires was achieved using hydroxypropylmethlycellulose (HPMC) mixed with phage alone, linezolid alone and phage and linezolid together. The potential of these agents to inhibit adhesion of S.aureus (MRSA) 43300 on K-wires was assessed. Coated and naked wires were analysed by scanning electron microscopy (SEM) and fluorescent staining. Result Significant reduction in bacterial adhesion was achieved on phage/linezolid wires in comparison to naked as well as HPMC coated wires. However, maximum reduction in bacterial adherence (∼4 log cycles) was observed on the wires coated with phage-linezolid combination. The frequency of emergence of resistant mutants was also negligible in presence of both the agents. Conclusion This study provides evidence to confirm that local delivery system employing linezolid (a potent protein synthesis inhibitor) along with a broad spectrum lytic bacteriophage (capable of self-multiplication) is able to attack the adhered as well as surrounding bacteria present near the implant site. Unlike other antibiotic based therapies, this combination has the potential to significantly restrict the emergence of resistant mutants, thus paving the way for effective treatment of MRSA associated infection of medical implants. PMID:24594764

  6. [Mitral valve endocarditis after Turkish "Festival of Sacrifice"].

    Science.gov (United States)

    Blaich, A; Fasel, D; Kaech, C; Frei, R

    2011-09-01

    Erysipelothrix rhusiopathiae is the causative agent of swine erysipelas. Systemic infections caused by E. rhusiopathiae are rare, but often (90%) associated with endocarditis. In about 60% of cases endocarditis develops on normal heart valves, and despite appropriate antibiotic therapy about one-third of the patients requires valve replacement. We report the case of a housewife, who developed a mitral valve endocarditis due to E. rhusiopathiae after preparing meat for the Turkish "Festival of Sacrifice".

  7. Enterococcal Infective Endocarditis following Periodontal Disease in Dogs

    OpenAIRE

    Semedo-Lemsaddek, Teresa; Tavares, Marta; S?o Braz, Berta; Tavares, Lu?s; Oliveira, Manuela

    2016-01-01

    In humans, one of the major factors associated with infective endocarditis (IE) is the concurrent presence of periodontal disease (PD). However, in veterinary medicine, the relevance of PD in the evolution of dogs' endocarditis remains poorly understood. In order to try to establish a correlation between mouth-associated Enterococcus spp. and infective endocarditis in dogs, the present study evaluated the presence and diversity of enterococci in the gum and heart of dogs with PD. Samples were...

  8. Effects of sarang semut (Myrmecodia Pendens Merr. & Perry extracts on Enterococcus faecalis sensitivity

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    Cut Soraya

    2016-12-01

    Full Text Available Background: Enterococcus faecalis (E. faecalis is a gram positive oral pathogen that reported at the main agent infection of endodontic treatment. Its activities are influenced by the virulence factors facilitating the interaction process between agents with host cells. Like aggregation substance, cytolysin, extracellular superoxide, gelatinase, hyaluronidase, sex pheromones, and surface adhesions molecules. Plant extracts are reported as the material antibacterial as well as E. faecalis in pathogenesis of endodontic infections. Purpose: Purpose of this study was to analyse of sarang semut extracts (Myrmecodia Pendens Merr. & Perry towards sensitivity of E. faecalis. Method: This research used the methanol extract of sarang semut, E. faecalis ATCC 29212, and fosfomycin also chlorhexidine as the positive controls. Whereas, Bradford protein method was measured the concentration of the surface protein of E. faecalis and active component of the sarang semut extract. Result: Generally, the sarang semut extract possessed low sensitivity toward E. faecalis (≤ 13 mm, but on the concentrations of 100 µg/ml and 75 µg/ml better than inhibition of other concentrations, round 10.6-11.6 (mm. Specifically, on 100 µg/ml has indicator the minimal bactericidal concentration (MBC on E. faecalis. Whereas minimal inhibition concentration (MIC on the concentration of 3,125 µg/ml. Conclusion: Based on MBC and MIC assay, the extract of sarang semut has potential effects to adherence growth of E. faecalis, mainly on the highest concentration 100 µg/ml also MIC on 3,125 µg/ ml.

  9. Effectiveness and safety of imipenem/clavulanate and linezolid to treat multidrug and extensively drug-resistant tuberculosis at a referral hospital in Brazil

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    M.A. Arbex

    2016-11-01

    Full Text Available Evidence on effectiveness, safety, and tolerability of imipenem/clavulanate (IC and linezolid containing regimens to treat multidrug-resistant (MDR- and extensively drug-resistant tuberculosis (XDR-TB is scarce. The aim of this observational study is to evaluate the therapeutic contribution of IC and linezolid to manage MDR/XDR-TB cases at the reference centre of São Paulo state, Brazil. Twelve patients (9 males, 1 HIV positive in antiretroviral treatment, 4 MDR, 8 XDR were treated with IC, 11 of them within linezolid-containing regimens. They all were previously treated with treatment failure, for a median (IQR, interquartile range of 4.5 (2–6.5 times, having a severe resistance pattern (median number of resistances: 7 (5–8 and being sputum smear and culture positive. IC and linezolid were prescribed at the dose of 1000 mg/day and 600 mg/day, respectively. The overall exposure was (median (IQR 419 (375.5–658 days for IC and 678 (392–720 days for linezolid. All of them converted their sputum (time to sputum conversion; 60 (37.5–90 days and culture (75 (60–135 days, and 7 were cured while 5 are still on treatment with a gradually improving clinical picture.While no adverse events were reported for IC, 2 minor side effects, only, were attributed to linezolid (17%; in both cases the drug was re-started without further problems. Our study suggests that IC and linezolid-containing regimens can be used safely and with satisfactory outcomes in reference centres to treat MDR/XDR-TB patients. Keywords: MDR-TB, XDR-TB, Imipenem, Linezolid, Effectiveness, Safety, Tolerability

  10. Buwchitin: a ruminal peptide with antimicrobial potential against Enterococcus faecalis

    Science.gov (United States)

    Oyama, Linda B.; Crochet, Jean-Adrien; Edwards, Joan E.; Girdwood, Susan E.; Cookson, Alan R.; Fernandez-Fuentes, Narcis; Hilpert, Kai; Golyshin, Peter N.; Golyshina, Olga V.; Privé, Florence; Hess, Matthias; Mantovani, Hilario C.; Creevey, Christopher J.; Huws, Sharon A.

    2017-07-01

    Antimicrobial peptides (AMPs) are gaining popularity as alternatives for treatment of bacterial infections and recent advances in omics technologies provide new platforms for AMP discovery. We sought to determine the antibacterial activity of a novel antimicrobial peptide, buwchitin, against Enterococcus faecalis. Buwchitin was identified from a rumen bacterial metagenome library, cloned, expressed and purified. The antimicrobial activity of the recombinant peptide was assessed using a broth microdilution susceptibility assay to determine the peptide's killing kinetics against selected bacterial strains. The killing mechanism of buwchitin was investigated further by monitoring its ability to cause membrane depolarization (diSC3(5) method) and morphological changes in E. faecalis cells. Transmission electron micrographs of buwchitin treated E. faecalis cells showed intact outer membranes with blebbing, but no major damaging effects and cell morphology changes. Buwchitin had negligible cytotoxicity against defibrinated sheep erythrocytes. Although no significant membrane leakage and depolarization was observed, buwchitin at minimum inhibitory concentration (MIC) was bacteriostatic against E. faecalis cells and inhibited growth in vitro by 70% when compared to untreated cells. These findings suggest that buwchitin, a rumen derived peptide, has potential for antimicrobial activity against E. faecalis.

  11. Buwchitin: A Ruminal Peptide with Antimicrobial Potential against Enterococcus faecalis

    Directory of Open Access Journals (Sweden)

    Linda B. Oyama

    2017-07-01

    Full Text Available Antimicrobial peptides (AMPs are gaining popularity as alternatives for treatment of bacterial infections and recent advances in omics technologies provide new platforms for AMP discovery. We sought to determine the antibacterial activity of a novel antimicrobial peptide, buwchitin, against Enterococcus faecalis. Buwchitin was identified from a rumen bacterial metagenome library, cloned, expressed and purified. The antimicrobial activity of the recombinant peptide was assessed using a broth microdilution susceptibility assay to determine the peptide's killing kinetics against selected bacterial strains. The killing mechanism of buwchitin was investigated further by monitoring its ability to cause membrane depolarization (diSC3(5 method and morphological changes in E. faecalis cells. Transmission electron micrographs of buwchitin treated E. faecalis cells showed intact outer membranes with blebbing, but no major damaging effects and cell morphology changes. Buwchitin had negligible cytotoxicity against defibrinated sheep erythrocytes. Although no significant membrane leakage and depolarization was observed, buwchitin at minimum inhibitory concentration (MIC was bacteriostatic against E. faecalis cells and inhibited growth in vitro by 70% when compared to untreated cells. These findings suggest that buwchitin, a rumen derived peptide, has potential for antimicrobial activity against E. faecalis.

  12. Healthcare-Associated Infective Endocarditis: a Case Series in a Referral Hospital from 2006 to 2011

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    Oslan Francischetto

    2014-10-01

    Full Text Available Background: Healthcare-associated infective endocarditis (HCA-IE, a severe complication of medical care, shows a growing incidence in literature. Objective: To evaluate epidemiology, etiology, risk factors for acquisition, complications, surgical treatment, and outcome of HCA-IE. Methods: Observational prospective case series study (2006-2011 in a public hospital in Rio de Janeiro. Results: Fifty-three patients with HCA-IE from a total of 151 cases of infective endocarditis (IE were included. There were 26 (49% males (mean age of 47 ± 18.7 years, 27 (51% females (mean age of 42 ± 20.1 years. IE was acute in 37 (70% cases and subacute in 16 (30% cases. The mitral valve was affected in 19 (36% patients and the aortic valve in 12 (36%; prosthetic valves were affected in 23 (43% patients and native valves in 30 (57%. Deep intravenous access was used in 43 (81% cases. Negative blood cultures were observed in 11 (21% patients, Enterococcus faecalis in 10 (19%, Staphylococcus aureus in 9 (17%, and Candida sp. in 7 (13%. Fever was present in 49 (92% patients, splenomegaly in 12 (23%, new regurgitation murmur in 31 (58%, and elevated C-reactive protein in 44/53 (83%. Echocardiograms showed major criteria in 46 (87% patients, and 34 (64% patients were submitted to cardiac surgery. Overall mortality was 17/53 (32%. Conclusion: In Brazil HCA-IE affected young subjects. Patients with prosthetic and native valves were affected in a similar proportion, and non-cardiac surgery was an infrequent predisposing factor, whereas intravenous access was a common one. S. aureus was significantly frequent in native valve HCA-IE, and overall mortality was high.

  13. Healthcare-Associated Infective Endocarditis: a Case Series in a Referral Hospital from 2006 to 2011

    Science.gov (United States)

    Francischetto, Oslan; da Silva, Luciana Almenara Pereira; Senna, Katia Marie Simões e; Vasques, Marcia Regina; Barbosa, Giovanna Ferraiuoli; Weksler, Clara; Ramos, Rosana Grandelle; Golebiovski, Wilma Felix; Lamas, Cristiane da Cruz

    2014-01-01

    Background Healthcare-associated infective endocarditis (HCA-IE), a severe complication of medical care, shows a growing incidence in literature. Objective To evaluate epidemiology, etiology, risk factors for acquisition, complications, surgical treatment, and outcome of HCA-IE. Methods Observational prospective case series study (2006-2011) in a public hospital in Rio de Janeiro. Results Fifty-three patients with HCA-IE from a total of 151 cases of infective endocarditis (IE) were included. There were 26 (49%) males (mean age of 47 ± 18.7 years), 27 (51%) females (mean age of 42 ± 20.1 years). IE was acute in 37 (70%) cases and subacute in 16 (30%) cases. The mitral valve was affected in 19 (36%) patients and the aortic valve in 12 (36%); prosthetic valves were affected in 23 (43%) patients and native valves in 30 (57%). Deep intravenous access was used in 43 (81%) cases. Negative blood cultures were observed in 11 (21%) patients, Enterococcus faecalis in 10 (19%), Staphylococcus aureus in 9 (17%), and Candida sp. in 7 (13%). Fever was present in 49 (92%) patients, splenomegaly in 12 (23%), new regurgitation murmur in 31 (58%), and elevated C-reactive protein in 44/53 (83%). Echocardiograms showed major criteria in 46 (87%) patients, and 34 (64%) patients were submitted to cardiac surgery. Overall mortality was 17/53 (32%). Conclusion In Brazil HCA-IE affected young subjects. Patients with prosthetic and native valves were affected in a similar proportion, and non-cardiac surgery was an infrequent predisposing factor, whereas intravenous access was a common one. S. aureus was significantly frequent in native valve HCA-IE, and overall mortality was high. PMID:25352503

  14. Novel Inhibitors of Staphyloxanthin Virulence Factor in Comparison with Linezolid and Vancomycin versus Methicillin-Resistant, Linezolid-Resistant, and Vancomycin-Intermediate Staphylococcus aureus Infections in Vivo.

    Science.gov (United States)

    Ni, Shuaishuai; Wei, Hanwen; Li, Baoli; Chen, Feifei; Liu, Yifu; Chen, Wenhua; Xu, Yixiang; Qiu, Xiaoxia; Li, Xiaokang; Lu, Yanli; Liu, Wenwen; Hu, Linhao; Lin, Dazheng; Wang, Manjiong; Zheng, Xinyu; Mao, Fei; Zhu, Jin; Lan, Lefu; Li, Jian

    2017-10-12

    Our previous work ( Wang et al. J. Med. Chem. 2016 , 59 , 4831 - 4848 ) revealed that effective benzocycloalkane-derived staphyloxanthin inhibitors against methicillin-resistant Staphylococcus aureus (S. aureus) infections were accompanied by poor water solubility and high hERG inhibition and dosages (preadministration). In this study, 92 chroman and coumaran derivatives as novel inhibitors have been addressed for overcoming deficiencies above. Derivatives 69 and 105 displayed excellent pigment inhibitory activities and low hERG inhibition, along with improvement of solubility by salt type selection. The broad and significantly potent antibacterial spectra of 69 and 105 were displayed first with normal administration in the livers and hearts in mice against pigmented S. aureus Newman, Mu50 (vancomycin-intermediate S. aureus), and NRS271 (linezolid-resistant S. aureus), compared with linezolid and vancomycin. In summary, both 69 and 105 have the potential to be developed as good antibacterial candidates targeting virulence factors.

  15. Subacute bacterial endocarditis (SBE due to Streptococcus gordonii

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    Raffaella Battista

    2009-12-01

    Full Text Available Endocarditis is an inflammatory state of the endothelium that promotes thrombus formation and tissue damage on the surface of heart valves. Recent studies have reported endocarditis mortality rates ranging from 12% to 46% (2008. The Streptococcus gordonii is a normal inhabitant of the human oral cavity. It is a component of the microbial communities responsible of plaque formation, associated with dental caries and also regarded as the main causative agent in the development of subacute bacterial endocarditis (SBE.

  16. Experimental Bacterial Endocarditis in the Opossum (Didelphis virginiana)

    Science.gov (United States)

    Sherwood, B. F.; Rowlands, D. T.; Vakilzadeh, J.; LeMay, J. C.

    1971-01-01

    It was possible to induce bacterial endocarditis in opossums with single intravenous injections of Streptococcus viridans or Staphylococcus aureus. Fiftyeight percent of those animals given Streptococcus viridans developed bacterial endocarditis in which most of the lesions were on the left side of the heart. The experimentally induced streptococcal disease was similar to that which may occur spontaneously in opossums, both with respect to the distribution and structure of the vegetations. Single injections of Staphylococcus aureus resulted in endocarditis in 100% of the test animals. These lesions differed from those due to streptococci by having a relatively high frequency of right- as well as left-sided valvular disease and by being somewhat smaller than those due to streptococci.Endocarditis could not be successfully induced with injection of three different fungi. PMID:5133514

  17. Brucella Endocarditis Caused By Brucella Melitensis

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    Suzan Saçar

    2008-01-01

    Full Text Available Brucellosis is a zoonotic disease endemically seen in Turkey, which occurs with various clinical findings. It can lead to complications affecting many systems. Endocarditis is an infrequent, but serious complication of brucellosis.The aim of this case presentation is to remind that endocarditis can be a complication of brucellosis and if is undiagnosed or misdiagnosed, progresses fatal in a high rate.

  18. Trends in Infective Endocarditis in California and New York State, 1998-2013.

    Science.gov (United States)

    Toyoda, Nana; Chikwe, Joanna; Itagaki, Shinobu; Gelijns, Annetine C; Adams, David H; Egorova, Natalia N

    2017-04-25

    Prophylaxis and treatment guidelines for infective endocarditis have changed substantially over the past decade. In the United States, few population-based studies have explored the contemporary epidemiology and outcomes of endocarditis. To quantify trends in the incidence and etiologies of infective endocarditis in the United States. Retrospective population epidemiology study of patients hospitalized with a first episode of endocarditis identified from mandatory state databases in California and New York State between January 1, 1998, and December 31, 2013. Infective endocarditis. Outcomes were crude and standardized incidence of endocarditis and trends in patient characteristics and disease etiology. Trends in acquisition mode, organism, and mortality were analyzed. Among 75 829 patients with first episodes of endocarditis (mean [SD] age, 62.3 [18.9] years; 59.1% male), the standardized annual incidence was stable between 7.6 (95% CI, 7.4 to 7.9) and 7.8 (95% CI, 7.6 to 8.0) cases per 100 000 persons (annual percentage change [APC], -0.06%; 95% CI, -0.3% to 0.2%; P = .59). From 1998 through 2013, the proportion of patients with native-valve endocarditis decreased (from 74.5% to 68.4%; APC, -0.7%; 95% CI, -0.9% to -0.5%; P endocarditis increased (from 12.0% to 13.8%; APC, 1.3%; 95% CI, 0.8% to 1.7%; P endocarditis increased (from 1.3% to 4.1%; APC, 8.8%; 95% CI, 7.8% to 9.9%; P endocarditis decreased (from 17.7% to 15.3%; APC, -1.0%; 95% CI, -1.4% to -0.7%; P endocarditis increased (from 32.1% to 35.9%; APC, 0.8%; 95% CI, 0.5% to 1.1%; P endocarditis did not increase (unadjusted: APC, -0.1%; 95% CI, -0.8% to 0.6%; P = .77; adjusted: APC, -1.3%; 95% CI, -1.8% to -0.7%; P endocarditis was stable from 1998 through 2013, with changes in patient characteristics and etiology over this time.

  19. Association Between Transcatheter Aortic Valve Replacement and Subsequent Infective Endocarditis and In-Hospital Death

    DEFF Research Database (Denmark)

    Regueiro, Ander; Linke, Axel; Latib, Azeem

    2016-01-01

    IMPORTANCE: Limited data exist on clinical characteristics and outcomes of patients who had infective endocarditis after undergoing transcatheter aortic valve replacement (TAVR). OBJECTIVE: To determine the associated factors, clinical characteristics, and outcomes of patients who had infective...... endocarditis after TAVR. DESIGN, SETTING, AND PARTICIPANTS: The Infectious Endocarditis after TAVR International Registry included patients with definite infective endocarditis after TAVR from 47 centers from Europe, North America, and South America between June 2005 and October 2015. EXPOSURE: Transcatheter...... aortic valve replacement for incidence of infective endocarditis and infective endocarditis for in-hospital mortality. MAIN OUTCOMES AND MEASURES: Infective endocarditis and in-hospital mortality after infective endocarditis. RESULTS: A total of 250 cases of infective endocarditis occurred in 20...

  20. Autoimmune Disease with Cardiac Valves Involvement: Libman-Sacks Endocarditis.

    Science.gov (United States)

    Ginanjar, Eka; Yulianto, Yulianto

    2017-04-01

    This case study aim to evaluate the response of steroid treatment for autoimmune endocarditis. Valvular heart disease is relatively rising in both congenital and acquired cases, but the autoimmune endocarditis remains rare. In this case, a 34 year old woman with clinical manifestation resembling systemic lupus erythematosus (SLE) is diagnosed with Libman-sacks Endocarditis. After six months of steroid treatment, her clinical manifestations and heart structure improved.

  1. Comparison of in vitro efficacy of linezolid and vancomycin by determining their minimum inhibitory concentrations against methicillin resistant Staphylococcus aureus (MRSA)

    International Nuclear Information System (INIS)

    Kaleem, F.; Usman, J.; Hassan, A.

    2011-01-01

    Objectives: To compare the in vitro activities of vancomycin and linezolid against methicillin resistant Staphyloccus aureus in our set up to help in formulating a better empirical treatment and reduce the emergence of vancomycin resistant Staphylococcus aureus. Methods: The study was conducted over a period of 6 months(July 1, 2009 - Dec 1, 2009). Fifty Methicillin resistant Staphylococcus aureus isolated from the clinical isolates of Military Hospital Rawalpindi were subjected to the determination of Minimum inhibitory concentrations of linezolid and vancomycin using E-strips. Results: All the isolated organisms were uniformly susceptible to both the antibiotics. Vancomycin showed higher minimum inhibitory concentrations (MICs) as compared to linezolid MICs. Conclusion: This study suggests that linezolid and vancomycin have similar in vitro efficacy for methicillin resistant Staphyloccus aureus infections. (author)

  2. Classic Peripheral Signs of Subacute Bacterial Endocarditis

    Directory of Open Access Journals (Sweden)

    Yooyoung Chong

    2016-10-01

    Full Text Available A 50-year-old female patient with visual disturbances was referred for further evaluation of a heart murmur. Fundoscopy revealed a Roth spot in both eyes. A physical examination showed peripheral signs of infective endocarditis, including Osler nodes, Janeway lesions, and splinter hemorrhages. Our preoperative diagnosis was subacute bacterial endocarditis with severe aortic regurgitation. The patient underwent aortic valve replacement and was treated with intravenous antibiotics for 6 weeks postoperatively. The patient made a remarkable recovery and was discharged without complications. We report this case of subacute endocarditis with all 4 classic peripheral signs in a patient who presented with visual disturbance.

  3. Classic Peripheral Signs of Subacute Bacterial Endocarditis

    Science.gov (United States)

    Chong, Yooyoung; Han, Sung Joon; Rhee, Youn Ju; Kang, Shin Kwang; Yu, Jae Hyeon; Na, Myung Hoon

    2016-01-01

    A 50-year-old female patient with visual disturbances was referred for further evaluation of a heart murmur. Fundoscopy revealed a Roth spot in both eyes. A physical examination showed peripheral signs of infective endocarditis, including Osler nodes, Janeway lesions, and splinter hemorrhages. Our preoperative diagnosis was subacute bacterial endocarditis with severe aortic regurgitation. The patient underwent aortic valve replacement and was treated with intravenous antibiotics for 6 weeks postoperatively. The patient made a remarkable recovery and was discharged without complications. We report this case of subacute endocarditis with all 4 classic peripheral signs in a patient who presented with visual disturbance. PMID:27734006

  4. Genes Important for Catalase Activity in Enterococcus faecalis

    Science.gov (United States)

    Baureder, Michael; Hederstedt, Lars

    2012-01-01

    Little in general is known about how heme proteins are assembled from their constituents in cells. The Gram-positive bacterium Enterococcus faecalis cannot synthesize heme and does not depend on it for growth. However, when supplied with heme in the growth medium the cells can synthesize two heme proteins; catalase (KatA) and cytochrome bd (CydAB). To identify novel factors important for catalase biogenesis libraries of E. faecalis gene insertion mutants were generated using two different types of transposons. The libraries of mutants were screened for clones deficient in catalase activity using a colony zymogram staining procedure. Analysis of obtained clones identified, in addition to katA (encoding the catalase enzyme protein), nine genes distributed over five different chromosomal loci. No factors with a dedicated essential role in catalase biogenesis or heme trafficking were revealed, but the results indicate the RNA degradosome (srmB, rnjA), an ABC-type oligopeptide transporter (oppBC), a two-component signal transducer (etaR), and NADH peroxidase (npr) as being important for expression of catalase activity in E. faecalis. It is demonstrated that catalase biogenesis in E. faecalis is independent of the CydABCD proteins and that a conserved proline residue in the N-terminal region of KatA is important for catalase assembly. PMID:22590595

  5. Plasmid mediated enhancement of uv resistance in Streptococcus faecalis

    International Nuclear Information System (INIS)

    Miehl, R.; Miller, M.; Yasbin, R.E.

    1980-01-01

    A 38.5-Mdal plasmid of Streptococcus faecalis subdp. zymogenes has been shown to enhance survival following uv irradiation. In addition, the presence of this plasmid increases the mutation frequencies following uv irradiation and enhanced W-reactivation. The data presented indicate that S. faecalis has an inducible error-prone repair system and that the plasmid enhances these repair functions

  6. Dentigenous infectious foci ? a risk factor of infective endocarditis

    OpenAIRE

    Wisniewska-Spychala, Beata; Sokalski, Jerzy; Grajek, Stefan; Jemielity, Marek; Trojnarska, Olga; Choroszy-Kr?l, Irena; S?jka, Anna; Maksymiuk, Tomasz

    2012-01-01

    Summary Background Dentigenous, infectious foci are frequently associated with the development of various diseases. The role of such foci in the evolution of endocarditis still remains unclear. This article presents the concluding results of an interdisciplinary study verifying the influence of dentigenous, infectious foci on the development of infective endocarditis. Material/Methods The study subjects were 60 adult patients with history of infective endocarditis and coexistent acquired hear...

  7. In vitro evaluation of the effect of linezolid and levofloxacin on Bacillus anthracis toxin production, spore formation and cell growth.

    Science.gov (United States)

    Head, Breanne M; Alfa, Michelle; Sitar, Daniel S; Rubinstein, Ethan; Meyers, Adrienne F A

    2017-02-01

    Owing to its ability to form spores and toxins, Bacillus anthracis is considered a bioterror agent. Although current therapeutic strategies can be effective, treatment does not prevent sporulation and toxin production. To quantify the combined effect of a protein synthesis inhibitor and a bactericidal agent on B. anthracis toxin production, sporulation and cell growth. Susceptibility and synergy titrations were conducted on B. anthracis Sterne and 03-0191 strains using linezolid and levofloxacin. The effect of antibiotic exposure on cell viability was evaluated using a continuous medium replacement model. In vitro static models were used to study the effect of linezolid and levofloxacin on sporulation and toxin production. Spores were quantified using the heat shock method. Toxin was quantified via commercial ELISA. Synergy titrations indicated that the combination was synergistic or indifferent; however, in all models antagonism was observed. In the spore model, linezolid resulted in the lowest sporulation rates, while combination therapy resulted in the highest. In the toxin model, linezolid prevented toxin production altogether. This study advances our understanding of the effects of combination therapy on B. anthracis infection. Used alone, linezolid therapy abolishes toxin production and reduces sporulation. These results suggest that studies using a step-wise approach using linezolid initially to stop sporulation and toxin production followed by levofloxacin to rapidly kill vegetative B. anthracis can be recommended. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Sensibilidad antimicrobiana in vitro en aislamientos de Enterococcus faecalis y Enterococcus faecium obtenidos de pacientes hospitalizados

    Directory of Open Access Journals (Sweden)

    Manuel Medell

    2014-04-01

    Full Text Available Introducción. Actualmente se considera a Enterococcus spp. como uno de los agentes de infección hospitalaria más importantes, siendo su resistencia a los antibióticos un problema importante en los centros de salud. Objetivos. Caracterizar la resistencia antimicrobiana en 50 cepas de Enterococcus spp. aisladas de muestras clínicas de pacientes hospitalizados. Materiales y métodos. Se llevó a cabo un estudio de tipo descriptivo observacional de corte transversal en 50 aislamientos clínicos de estas especies microbianas. Se trabajó un aislamiento por paciente. La identificación y la sensibilidad a los antibióticos se realizaron por métodos automatizados y convencionales. El análisis fenotípico de los mecanismos de resistencia a glucopéptidos se hizo según las recomendaciones de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. Resultados. De 50 aislamientos, 30 (60,0 % y 20 (40,0 % pertenecían a las especies de Enterococcus faecalis y Enterococcus faecium, respectivamente. La resistencia global expresada por este género fue de 38/50 (76,0 % para ampicilina; 33/50 (66,0 % para gentamicina de alto nivel; 34/50 (68,0 % para estreptomicina de alto nivel; 26/50 (52,0 % para ciprofloxacina; 4/50 (8,0 % para linezolid; 17/50 (34,0 % para teicoplanina; 25/50 (50,0 % para vancomicina; 31/50 (62,0 % para minociclina; 34/50 (68,0 % para tetraciclina y 9/50 (18,0 % para nitrofurantoina. Frente a los glucopéptidos, 25/50 (50,0 % y 10/50 (20,0 % de los aislamientos presentaron los mecanismos Van A y Van B, respectivamente. Conclusiones. Podemos concluir que la mayoría de las veces, las cepas aisladas en el Hospital Hermanos Ameijeiras mostraron porcentajes de resistencia por encima de lo reportado en la literatura científica consultada. El alto porcentaje de cepas con resistencia a la vancomicina podría influir en la aparición de otros gérmenes Gram positivos con resistencia a este fármaco. Se reporta por

  9. Efficacy, safety and tolerability of linezolid containing regimens in treating MDR-TB and XDR-TB : systematic review and meta-analysis

    NARCIS (Netherlands)

    Sotgiu, Giovanni; Centis, Rosella; D'Ambrosio, Lia; Alffenaar, Jan-William C.; Anger, Holly A.; Caminero, Jose A.; Castiglia, Paolo; De Lorenzo, Saverio; Ferrara, Giovanni; Koh, Won-Jung; Schecter, Giesela F.; Shim, Tae S.; Singla, Rupak; Skrahina, Alena; Spanevello, Antonio; Udwadia, Zarir F.; Villar, Miquel; Zampogna, Elisabetta; Zellweger, Jean-Pierre; Zumla, Alimuddin; Migliori, Giovanni Battista

    2012-01-01

    Linezolid is used off-label to treat multidrug-resistant tuberculosis (MDR-TB) in absence of systematic evidence. We performed a systematic review and meta-analysis on efficacy, safety and tolerability of linezolid-containing regimes based on individual data analysis. 12 studies (11 countries from

  10. Nonclinical and Pharmacokinetic Assessments To Evaluate the Potential of Tedizolid and Linezolid To Affect Mitochondrial Function

    Science.gov (United States)

    McKee, Edward E.; Das, Debaditya; Hosako, Hiromi; Fiedler-Kelly, Jill; Passarell, Julie; Radovsky, Ann; Prokocimer, Philippe

    2014-01-01

    Prolonged treatment with the oxazolidinone linezolid is associated with myelosuppression, lactic acidosis, and neuropathies, toxicities likely caused by impairment of mitochondrial protein synthesis (MPS). To evaluate the potential of the novel oxazolidinone tedizolid to cause similar side effects, nonclinical and pharmacokinetic assessments were conducted. In isolated rat heart mitochondria, tedizolid inhibited MPS more potently than did linezolid (average [± standard error of the mean] 50% inhibitory concentration [IC50] for MPS of 0.31 ± 0.02 μM versus 6.4 ± 1.2 μM). However, a rigorous 9-month rat study comparing placebo and high-dose tedizolid (resulting in steady-state area under the plasma concentration-time curve values about 8-fold greater than those with the standard therapeutic dose in humans) showed no evidence of neuropathy. Additional studies explored why prolonged, high-dose tedizolid did not cause these mitochondriopathic side effects despite potent MPS inhibition by tedizolid. Murine macrophage (J774) cell fractionation studies found no evidence of a stable association of tedizolid with eukaryotic mitochondria. Monte Carlo simulations based on population pharmacokinetic models showed that over the course of a dosing interval using standard therapeutic doses, free plasma concentrations fell below the respective MPS IC50 in 84% of tedizolid-treated patients (for a median duration of 7.94 h) and 38% of linezolid-treated patients (for a median duration of 0 h). Therapeutic doses of tedizolid, but not linezolid, may therefore allow for mitochondrial recovery during antibacterial therapy. The overall results suggest that tedizolid has less potential to cause myelosuppression and neuropathy than that of linezolid during prolonged treatment courses. This, however, remains a hypothesis that must be confirmed in clinical studies. PMID:25331703

  11. Tratamiento con caspofungina de endocarditis por Candida tropicalis resistente a fluconazol Treatment with caspofungin of Candida tropicalis endocarditis resistant to fluconazol

    Directory of Open Access Journals (Sweden)

    Marcelo del Castillo

    2004-04-01

    Full Text Available Las endocarditis causadas por hongos, (Candida en particular, requieren tratamiento médico-quirúrgico, siendo la anfotericina B la droga de elección. Caspofungina es una equinocandina con gran actividad sobre Candida y Aspergillus. Se presenta un paciente con una endocarditis por Candida tropicalis resistente a fluconazol tratado con caspofungina bajo un esquema de salvataje, luego de haber presentado efectos adversos por anfotericina B. El paciente tuvo respuesta microbiológica.Fungal endocarditis, in particular due to Candida species, requires medical and surgical treatment and amphotericin B is the drug of choice. Caspofungin is an echinocandin very effective against Candida and Aspergillus. We present a patient with Candida tropicalis endocarditis, fluconazol resistant, treated with caspofungin, on a compassional basis as a result of adverse effects with amphotericin B. The patient had a microbiological response.

  12. Effectiveness and safety of imipenem/clavulanate and linezolid to treat multidrug and extensively drug-resistant tuberculosis at a referral hospital in Brazil.

    Science.gov (United States)

    Arbex, M A; Bonini, E H; Kawakame Pirolla, G; D'Ambrosio, L; Centis, R; Migliori, G B

    Evidence on effectiveness, safety, and tolerability of imipenem/clavulanate (IC) and linezolid containing regimens to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) is scarce. The aim of this observational study is to evaluate the therapeutic contribution of IC and linezolid to manage MDR/XDR-TB cases at the reference centre of São Paulo state, Brazil. Twelve patients (9 males, 1 HIV positive in antiretroviral treatment, 4 MDR, 8 XDR) were treated with IC, 11 of them within linezolid-containing regimens. They all were previously treated with treatment failure, for a median (IQR, interquartile range) of 4.5 (2-6.5) times, having a severe resistance pattern (median number of resistances: 7 (5-8)) and being sputum smear and culture positive. IC and linezolid were prescribed at the dose of 1000mg/day and 600mg/day, respectively. The overall exposure was (median (IQR)) 419 (375.5-658) days for IC and 678 (392-720) days for linezolid. All of them converted their sputum (time to sputum conversion; 60 (37.5-90) days) and culture (75 (60-135) days), and 7 were cured while 5 are still on treatment with a gradually improving clinical picture. While no adverse events were reported for IC, 2 minor side effects, only, were attributed to linezolid (17%); in both cases the drug was re-started without further problems. Our study suggests that IC and linezolid-containing regimens can be used safely and with satisfactory outcomes in reference centres to treat MDR/XDR-TB patients. Copyright © 2016 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.

  13. A Case Series and Review of Bacillus Cereus Endocarditis from India.

    Science.gov (United States)

    Gopinathan, Anusha; Kumar, Anil; Sen, Amitabh C; Sudha, Srisruthy; Varma, Praveen; Gs, Sunil; Eapen, Malini; Dinesh, Kavitha R

    2018-01-01

    Bacillus cereus is a gram positive bacilli found commonly in the soil and environment. It is a bacteria rarely associated with endocarditis. Intravenous drug abuse, presence of valvular defects, pacemakers, immunodeficiency are some of the known risk factors for B.cereus endocarditis. We present here a case series of two patients with B.cereus endocarditis along with a review of the literature. This is the first report of B.cereus endocarditis from India to the best of our knowledge.

  14. Polymicrobial infective endocarditis caused by Neisseria sicca and Haemophilus parainfluenzae

    Directory of Open Access Journals (Sweden)

    Nikoloz Koshkelashvili

    2016-01-01

    Full Text Available Infective endocarditis is a common clinical problem in industrialized countries. Risk factors include abnormal cardiac valves, a history of endocarditis, intracardiac devices, prosthetic valves and intravenous drug use. We report a case of polymicrobial infective endocarditis in a 33 year-old female with a history chronic heroin use caused by Neisseria sicca and Haemophilus parainfluenzae. We believe the patient was exposed to these microbes by cleansing her skin with saliva prior to injection. Pairing a detailed history with the consideration of atypical agents is crucial in the proper diagnosis and management of endocarditis in patients with high-risk injection behaviors.

  15. [Infective endocarditis : Update on prophylaxis, diagnosis, and treatment].

    Science.gov (United States)

    Dietz, S; Lemm, H; Janusch, M; Buerke, M

    2016-05-01

    The diagnosis of infective endocarditis is often delayed in clinical practice. Timely diagnosis and rapid antibiotic treatment is important. Higher age of patients, new risk factors, and increasing use of intravascular prosthetic materials resulted in changes in microbial spectrum. Nowadays, nonspecific symptoms, critically ill patients, and immunocompromised patients require a high level of diagnostic expertise.The new guidelines from the European Society of Cardiology provide various diagnostic algorithms and recommendations for antibiotic treatment. The new guidelines also recommend the formation of an endocarditis team with various medical disciplines, including a cardiac surgeon, to improve treatment because in half of all endocarditis patients, antibiotic therapy alone does not result in successful management of the infection. If complications occur, early surgical treatment should be performed.In this overview, diagnostic strategies and therapeutic approaches for the treatment of infectious endocarditis according to the current guidelines and aspects of surgical treatment are provided.

  16. Enterococcus faecalis phosphomevalonate kinase

    Science.gov (United States)

    Doun, Stephanie S.; Burgner, John W.; Briggs, Scott D.; Rodwell, Victor W.

    2005-01-01

    The six enzymes of the mevalonate pathway of isopentenyl diphosphate biosynthesis represent potential for addressing a pressing human health concern, the development of antibiotics against resistant strains of the Gram-positive streptococci. We previously characterized the first four of the mevalonate pathway enzymes of Enterococcus faecalis, and here characterize the fifth, phosphomevalonate kinase (E.C. 2.7.4.2). E. faecalis genomic DNA and the polymerase chain reaction were used to clone DNA thought to encode phosphomevalonate kinase into pET28b(+). Double-stranded DNA sequencing verified the sequence of the recombinant gene. The encoded N-terminal hexahistidine-tagged protein was expressed in Escherichia coli with induction by isopropylthiogalactoside and purified by Ni++ affinity chromatography, yield 20 mg protein per liter. Analysis of the purified protein by MALDI-TOF mass spectrometry established it as E. faecalis phosphomevalonate kinase. Analytical ultracentrifugation revealed that the kinase exists in solution primarily as a dimer. Assay for phosphomevalonate kinase activity used pyruvate kinase and lactate dehydrogenase to couple the formation of ADP to the oxidation of NADH. Optimal activity occurred at pH 8.0 and at 37°C. The activation energy was ~5.6 kcal/mol. Activity with Mn++, the preferred cation, was optimal at about 4 mM. Relative rates using different phosphoryl donors were 100 (ATP), 3.6 (GTP), 1.6 (TTP), and 0.4 (CTP). Km values were 0.17 mM for ATP and 0.19 mM for (R,S)-5-phosphomevalonate. The specific activity of the purified enzyme was 3.9 μmol substrate converted per minute per milligram protein. Applications to an immobilized enzyme bioreactor and to drug screening and design are discussed. PMID:15802646

  17. Ribosomal protein L3 mutations are associated with cfr-mediated linezolid resistance in clinical isolates of Staphylococcus cohnii.

    Science.gov (United States)

    Xu, Hongtao; Tian, Rui; Li, Yanming; Chen, Dongke; Liu, Yalin; Hu, Yunjian; Xiao, Fei

    2015-06-01

    From June, 2012 to November, 2013 five linezolid-resistant Staphylococcus cohnii isolates were identified in our hospital in Beijing, China. The investigation of the resistance mechanisms confirmed that the cfr-carrying plasmids were the main cause of linezolid resistance in those clinical isolates. Moreover, all the five isolates had ribosomal protein L3 mutations, which had different coordinate effect on cfr-mediated linezolid resistance directly through the substitution of serine 158 by phenylalanine or tyrosine in L3 protein. In this study, two types of plasmids (p432, p438) (Accession No. KM114207) were found, which share high sequence identity with previously reported cfr-carrying pRM01 and pMHZ plasmids originated from northern and southern China, showing wide regional dissemination in China. The stability of linezolid resistance was studied by passaging single colonies serially on antibiotic-free blood medium, which showed that the susceptible derivatives emerged until the passages 39-42 with the elimination of cfr-carrying plasmid. Thus the high stability of this plasmid may pose a risk for the transmission among patients or even cause an outbreak in clinical settings.

  18. Clinical and microbiological findings of infective endocarditis.

    Science.gov (United States)

    Cancan Gursul, Nur; Vardar, Ilknur; Demirdal, Tuna; Gursul, Erdal; Ural, Serap; Yesil, Murat

    2016-05-31

    Infective endocarditis (IE) is an infection that develops on the endothelial surface of the heart. Endocarditis is a major problem for the clinicians despite of the developments in diagnostic, surgical, and medical treatment methods. In this study, we aimed to evaluate symptoms, laboratory findings, treatment options, and clinical endpoint of the patients who were diagnosed with IE in a tertiary healthcare organization according to the literature data. Between January 2006 and March 2013, 80 IE patients who were diagnosed and treated in accordance with modified Duke criteria were enrolled in the study. Demographic features, symptoms, and laboratory and echocardiographic findings were recorded after reviewing the patient files. The mean age of the patients was 51.3 ± 16.0, and IE was more common in men (n = 56; 70%). Of 41 patients who had positive blood cultures, 20 patients had Staphylococcus spp. (48.7%) and 8 patients had Streptococcus spp. (19.5%). Brucella spp. was isolated from 5 patients (12.2%). While 48.7% (n = 39) of the patients had cardiac complications, 22 patients (27.5%) had embolic complication. Hospital mortality was observed in 20 patients (15%). In our patients, endocarditis was seen at a young age, and staphylococci were the most frequently isolated microorganism from blood culture. There were more patients with Brucella endocarditis compared to the general population. Complications are frequently seen in the course of endocarditis, and they cause problems for the clinicians during follow ups due to the high mortality rate of IE.

  19. Case report

    African Journals Online (AJOL)

    abp

    2014-01-23

    Jan 23, 2014 ... Linezolid is the only member of synthetic oxyzolidone family and is active in-vitro against resistant Gram positive cocci such as vancomycin resistant Enterococcus faecalis and Enterococcus faecium and methicilin resistant Staphylococcus aureus [9,10]. The approval was declared in our country in 2005.

  20. Peripheral neuropathy in a diabetic child treated with linezolid for multidrug-resistant tuberculosis: a case report and review of the literature.

    Science.gov (United States)

    Swaminathan, Aravind; du Cros, Philipp; Seddon, James A; Mirgayosieva, Shamsiya; Asladdin, Rajabov; Dusmatova, Zulfiya

    2017-06-12

    Extensively drug-resistant (XDR) tuberculosis (TB) and multidrug resistant (MDR)-TB with additional resistance to injectable agents or fluoroquinolones are challenging to treat due to lack of available, effective drugs. Linezolid is one of the few drugs that has shown promise in treating these conditions. Long-term linezolid use is associated with toxicities such as peripheral and optic neuropathies. Diabetes mellitus (DM), especially when uncontrolled, can also result in peripheral neuropathy. The global burden of DM is increasing, and DM has been associated with a three-fold increased risk of developing TB disease. TB and DM can be a challenging combination to treat. DM can inhibit the host immune response to tuberculosis infection; and TB and some anti-TB drugs can worsen glycaemic control. A child experiencing neuropathy that is a possible complication of both DM and linezolid used to treat TB has not been reported previously. We report peripheral neuropathy in a 15-year-old boy with type 1 DM, diagnosed with MDR-TB and additional resistance to injectable TB medications. The boy was treated with a linezolid-based regimen, but after 8 months developed peripheral neuropathy. It was unclear whether the neuropathy was caused by the DM or the linezolid therapy. He had clinical improvement following cessation of linezolid and was declared cured following 21 months of treatment. Following completion of treatment, nerve conduction studies demonstrated significant improvement in neuropathy. To the best of our knowledge, this is the first case of peripheral neuropathy reported in a diabetic child on long-term linezolid therapy for tuberculosis. This case study underlines the importance of stringent follow-up for side effects of linezolid, especially when associated with co-morbidity such as DM that increases the chances of adverse effects. The presence of both DM and TB should alert a physician to strive for optimal glycaemic control to minimize the risk of

  1. A validated stability-indicating LC method for the separation of enantiomer and potential impurities of Linezolid using polar organic mode

    Directory of Open Access Journals (Sweden)

    T. Satyanarayana Raju

    2012-08-01

    Full Text Available Although a number of methods are available for evaluating Linezolid and its possible impurities, a common method for separation if its potential impurities, degradants and enantiomer in a single method with good efficiency remain unavailable. With the objective of developing an advanced method with shorter runtimes, a simple, precise, accurate stability-indicating LC method was developed for the determination of purity of Linezolid drug substance and drug products in bulk samples and pharmaceutical dosage forms in the presence of its impurities and degradation products. This method is capable of separating all the related substances of Linezolid along with the chiral impurity. This method can also be used for the estimation of assay of Linezolid in drug substance as well as in drug product. The method was developed using Chiralpak IA (250 mm×4.6 mm, 5 μm column. A mixture of acetonitrile, ethanol, n-butyl amine and trifluoro acetic acid in 96:4:0.10:0.16 (v/v/v/v ratio was used as a mobile phase. The eluted compounds were monitored at 254 nm. Linezolid was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal and photolytic degradation. The degradation products were well resolved from main peak and its impurities, proving the stability-indicating power of the method. The developed method was validated as per International Conference on Harmonization (ICH guidelines with respect to specificity, limit of detection, limit of quantification, precision, linearity, accuracy, robustness and system suitability. Keywords: HPLC, Linezolid, Validation, Polar organic mode, Stability-indicating

  2. Isolated pulmonic valve endocarditis presenting as neck pain

    Directory of Open Access Journals (Sweden)

    Aditya Goud

    2015-12-01

    Full Text Available We discuss a unique case of a 52-year-old man with no history of intravenous drug use or dental procedures who presented with neck pain, 2 weeks of fevers, chills, night sweats, cough, and dyspnea found to have isolated pulmonic valve (PV endocarditis. The patient did not have an associated murmur, which is commonly seen in right-sided infectious endocarditis. A transthoracic echocardiogram showed a thickened PV leaflet, with subsequent transesophageal echocardiogram showing a PV mass. Speciation of blood cultures revealed Streptococcus oralis. In right-sided infective endocarditis, usually the tricuspid valve is involved; however, in our case the tricuspid valve was free of any mass or vegetation. The patient did meet Duke criteria and was thus started on long-term intravenous antibiotics for infectious endocarditis. The patient's symptoms quickly improved with antibiotics. A careful history and evaluating the patient's risk factors are key in earlier detection of infective endocarditis (IE. Because of early detection and a high index of suspicion, the patient had no further complications and did not require any surgery. In conclusion, clinical suspicion of right-sided IE should be high in patients who present with persistent fevers and pulmonary symptoms in order to reduce the risk of complications, and to improve outcomes.

  3. Comparison of the Effectiveness and Safety of Linezolid and Daptomycin in Vancomycin-Resistant Enterococcal Bloodstream Infection: A National Cohort Study of Veterans Affairs Patients.

    Science.gov (United States)

    Britt, Nicholas S; Potter, Emily M; Patel, Nimish; Steed, Molly E

    2015-09-15

    Vancomycin-resistant Enterococcus bloodstream infections (VRE-BSIs) are becoming increasingly common. Linezolid and daptomycin are the primary treatment options for VRE-BSI, but optimal treatment is unclear. This was a national retrospective cohort study comparing linezolid and daptomycin for the treatment of VRE-BSI among Veterans Affairs Medical Center patients admitted during 2004-2013. The primary outcome was treatment failure, defined as a composite of (1) 30-day all-cause mortality; (2) microbiologic failure; and (3) 60-day VRE-BSI recurrence. Poisson regression was conducted to determine if antimicrobial treatment was independently associated with clinical outcomes. A total of 644 patients were included (linezolid, n = 319; daptomycin, n = 325). Overall, treatment failure was 60.9% (n = 392/644), and 30-day all-cause mortality was 38.2% (n = 246/644). Linezolid was associated with a significantly higher risk of treatment failure compared with daptomycin (risk ratio [RR], 1.37; 95% confidence interval [CI], 1.13-1.67; P = .001). After adjusting for confounding factors in Poisson regression, the relationship between linezolid use and treatment failure persisted (adjusted RR, 1.15; 95% CI, 1.02-1.30; P = .026). Linezolid was also associated with higher 30-day mortality (42.9% vs 33.5%; RR, 1.17; 95% CI, 1.04-1.32; P = .014) and microbiologic failure rates (RR, 1.10; 95% CI, 1.02-1.18; P = .011). No difference in 60-day VRE-BSI recurrence was observed between treatment groups. Treatment with linezolid for VRE-BSI resulted in significantly higher treatment failure in comparison to daptomycin. Linezolid treatment was also associated with greater 30-day all-cause mortality and microbiologic failure in this cohort. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  4. Membranous glomerulonephritis associated with enterococcal endocarditis.

    Science.gov (United States)

    Iida, H; Mizumura, Y; Uraoka, T; Takata, M; Sugimoto, T; Miwa, A; Yamagishi, T

    1985-01-01

    An autopsy case of membranous glomerulonephritis associated with enterococcal endocarditis was reported. Although enterococcal antigen was not identified in glomerular deposits, the eluate from the patient's renal tissue was shown to specifically recombine with cells of the enterococcus isolated from his own ante mortem blood. Hypocomplementemia, circulating immune complexes and antienterococcal antibodies were also observed. These findings suggest that enterococcus-related immune complexes played a role in the pathogenesis of glomerulonephritis associated with enterococcal endocarditis in this patient.

  5. Surgical Management of Multiple Valve Endocarditis Associated with Dialysis Catheter

    Directory of Open Access Journals (Sweden)

    R. Zea-Vera

    2016-01-01

    Full Text Available Endocarditis associated with dialysis catheter is a disease that must be suspected in every patient with hemodialysis who develops fever. Multiple valve disease is a severe complication of endocarditis that needs to be managed in a different way. There is very limited data for treatment and every case must be considered individually. We present a patient with this complication and describe the medical treatment and surgical management. We report the case of a 15-year-old patient with acute renal failure that develops trivalvular endocarditis after the hemodialysis catheter was placed, with multiple positive blood culture for Staphylococcus aureus. Transesophageal echocardiography was done and aortic and tricuspid valvular vegetations and mitral insufficiency were reported. Patient was successfully treated by surgery on the three valves, including aortic valve replacement. There is limited data about the appropriate treatment for multiple valvular endocarditis; it is important to consider this complication in the setting of hemodialysis patients that develop endocarditis and, despite the appropriate treatment, have a torpid evolution. In countries where endovenous drug abuse is uncommon, right sided endocarditis is commonly associated with vascular catheters. Aggressive surgical management should be the treatment of choice in these kinds of patients.

  6. Efficacy of Atmospheric Pressure Plasma as an Antibacterial Agent Against Enterococcus Faecalis in Vitro

    International Nuclear Information System (INIS)

    Cao Yingguang; Yang Ping; Lu Xinpei; Xiong Zilan; Ye Tao; Xiong Qing; Sun Ziyong

    2011-01-01

    Enterococcus faecalis (E. faecalis) is a microorganism that can survive extreme challenges in obturated root canals. The aim of this study was to evaluate the efficacy of a non-thermal atmospheric pressure plasma plume against E. faecalis in vitro. A non-thermal atmospheric pressure plasma jet device which could generate a cold plasma plume carrying a peak current of 300 mA was used. The antibacterial efficacy of this device against E. faecalis and its biofilm under different conditions was detected. The antibacterial efficacy of the plasma against E. faecalis and Staphylococcus aureus (S. aureus) was also evaluated. After plasma treatment, the average diameter of inhibition zone on S. aureus and E. faecalis was 2.62±0.26 cm and 1.06±0.30 cm, respectively (P < 0.05). The diameter was increased with prolongation of the treatment duration. The diameters of inhibition zone of the sealed Petri dishes were larger than those of the uncovered Petri dishes. There was significant difference in colony-forming units between plasma group and control group on E. faecalis biofilm (P < 0.01). The transmission electron microscopy revealed that the ultrastructural changes cytoderm of E. faecalis were observed after treatment for 2 min. It is concluded that the non-thermal atmospheric pressure plasma could serve as an effective adjunct to standard endodontic microbial treatment.

  7. Aortic root abscess resulting from endocarditis: spectrum of angiographic findings

    International Nuclear Information System (INIS)

    Miller, S.W.; Dinsmore, R.E.

    1984-01-01

    Abscesses in the aortic root are a serious complication of infective endocarditis and require accurate diagnosis for antibiotic and surgical management. Nineteen cases of endocarditis of a native valve or prosthetic valve and adjacent abscess cavities were identified with angiography. Of 6 patients with endocarditis of a native valve, 5 had bicuspid aortic valves and all had severe aortic regurgitation. Of 13 patients with endocarditis of a prosthetic aortic valve, all had paravalvular regurgitation. Fistulas were detected into the mitral anulus in 8 patients, and into the right ventricle in 3 patients. No complications from the catheterization were recorded during the 48-hour follow-up

  8. Successful Management of Prosthetic Valve Brucella Endocarditis with Antibiotherapy Alone

    Directory of Open Access Journals (Sweden)

    José Pedro Fonseca

    2018-01-01

    Full Text Available Objectives: To report a case of mechanical aortic prosthesis Brucella endocarditis successfully treated with antibiotics alone. Materials and methods: We describe a clinical case and present a review of the literature. Results: A 60-year-old female farmer with a mechanical aortic prosthetic valve presented with low back pain and fever. She was diagnosed with prosthetic valve Brucella mellitensis endocarditis and was cured with antibiotic therapy alone. Few cases of successfully treated prosthetic valve Brucella endocarditis without surgery have been reported. Conclusion: Prosthetic valve Brucella endocarditis usually requires surgical valve replacement. However, selected patients may be successfully treated with antibiotic therapy alone.

  9. Risk of Infective Endocarditis in Patients with End Stage Renal Disease

    DEFF Research Database (Denmark)

    Chaudry, Mavish S; Carlson, Nicholas; Gislason, Gunnar H

    2017-01-01

    BACKGROUND AND OBJECTIVES: Endocarditis is a serious complication in patients treated with RRT. The study aimed to examine incidence and risk factors of endocarditis in patients with ESRD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Danish National Registry on Regular Dialysis...... and Transplantation contains data on all Danish patients receiving renal replacement (hemodialysis, peritoneal dialysis, or kidney transplantation) for ESRD. Incidence of endocarditis was estimated for each RRT modality. Independent risk factors of endocarditis were identified in multivariable Cox regression models....... RESULTS: From January 1st, 1996 to December 31st, 2012, 10,612 patients (mean age 63 years, 36% female) initiated RRT (7233 hemodialysis, 3056 peritoneal dialysis, 323 pre-emptive kidney transplantation). Endocarditis developed in 267 (2.5%); of these 31 (12%) underwent valve surgery. The overall...

  10. Infective endocarditis following Melody valve implantation: comparison with a surgical cohort.

    Science.gov (United States)

    O'Donnell, Clare; Holloway, Rhonda; Tilton, Elizabeth; Stirling, John; Finucane, Kirsten; Wilson, Nigel

    2017-03-01

    Infective endocarditis has been reported post Melody percutaneous pulmonary valve implant; the incidence and risk factors, however, remain poorly defined. We identified four cases of endocarditis from our first 25 Melody implants. Our aim was to examine these cases in the context of postulated risk factors and directly compare endocarditis rates with local surgical valves. We conducted a retrospective review of patients post Melody percutaneous pulmonary valve implant in New Zealand (October, 2009-May, 2015) and also reviewed the incidence of endocarditis in New Zealand among patients who have undergone surgical pulmonary valve implants. In total, 25 patients underwent Melody implantation at a median age of 18 years. At a median follow-up of 2.9 years, most were well with low valve gradient (median 27 mmHg) and only mild regurgitation. Two patients presented with life-threatening endocarditis and obstructive vegetations at 14 and 26 months post implant, respectively. Two additional patients presented with subacute endocarditis at 5.5 years post implant. From 2009 to May, 2015, 178 surgical pulmonic bioprostheses, largely Hancock valves and homografts, were used at our institution. At a median follow-up of 2.9 years, four patients (2%) had developed endocarditis in this group compared with 4/25 (16%) in the Melody group (p=0.0089). Three surgical valves have been replaced. The Melody valve offers a good alternative to surgical conduit replacement in selected patients. Many patients have excellent outcomes in the medium term. Endocarditis, however, can occur and if associated with obstruction can be life threatening. The risk for endocarditis in the Melody group was higher in comparison with that in a contemporaneous surgical pulmonary implant cohort.

  11. Trends in Hospitalization Rates and Outcomes of Endocarditis among Medicare Beneficiaries

    Science.gov (United States)

    Bikdeli, Behnood; Wang, Yun; Kim, Nancy; Desai, Mayur M.; Quagliarello, Vincent; Krumholz, Harlan M.

    2015-01-01

    Objectives To determine the hospitalization rates and outcomes of endocarditis among older adults. Background Endocarditis is the most serious cardiovascular infection and is especially common among older adults. Little is known about recent trends for endocarditis hospitalizations and outcomes. Methods Using Medicare inpatient Standard Analytic Files, we identified all Fee-For-Service beneficiaries aged ≥65 years with a principal or secondary diagnosis of endocarditis from 1999-2010. We used Medicare Denominator Files to report hospitalizations per 100,000 person-years. Rates of 30-day and 1-year mortality were calculated using Vital Status Files. We used mixed-effects models to calculate adjusted rates of hospitalization and mortality and to compare the results before and after 2007, when the American Heart Association revised recommendations for endocarditis prophylaxis. Results Overall, 262,658 beneficiaries were hospitalized with endocarditis. The adjusted hospitalization rate increased from 1999-2005, reaching 83.5 per 100,000 person-years in 2005, and declined during 2006-2007. After 2007, the decline continued, reaching 70.6 per 100,000 person-years in 2010. Adjusted 30-day and 1-year mortality rates ranged from 14.2% to 16.5% and from 32.6% to 36.2%, respectively. There were no consistent changes in adjusted rates of 30-day and 1-year mortality after 2007. Trends in rates of hospitalization and outcomes were consistent across demographic subgroups. Adjusted rates of hospitalization and mortality declined consistently in the subgroup with principal diagnosis of endocarditis. Conclusions Our study highlights the high burden of endocarditis among older adults. We did not observe an increase in adjusted rates of hospitalization or mortality associated with endocarditis after publication of the 2007 guidelines. PMID:23994421

  12. Oral-Only Linezolid-Rifampin Is Highly Effective Compared with Other Antibiotics for Periprosthetic Joint Infection: Study of a Mouse Model.

    Science.gov (United States)

    Thompson, John M; Saini, Vikram; Ashbaugh, Alyssa G; Miller, Robert J; Ordonez, Alvaro A; Ortines, Roger V; Wang, Yu; Sterling, Robert S; Jain, Sanjay K; Miller, Lloyd S

    2017-04-19

    The medical treatment of periprosthetic joint infection (PJI) involves prolonged systemic antibiotic courses, often with suboptimal clinical outcomes including increased morbidity and health-care costs. Oral and intravenous monotherapies and combination antibiotic regimens were evaluated in a mouse model of methicillin-resistant Staphylococcus aureus (MRSA) PJI. Oral linezolid with or without oral rifampin, intravenous vancomycin with oral rifampin, intravenous daptomycin or ceftaroline with or without oral rifampin, oral doxycycline, or sham treatment were administered at human-exposure doses for 6 weeks in a mouse model of PJI. Bacterial burden was assessed by in vivo bioluminescent imaging and ex vivo counting of colony-forming units (CFUs), and reactive bone changes were evaluated with radiographs and micro-computed tomography (μCT) imaging. Oral-only linezolid-rifampin and all intravenous antibiotic-rifampin combinations resulted in no recoverable bacteria and minimized reactive bone changes. Although oral linezolid was the most effective monotherapy, all oral and intravenous antibiotic monotherapies failed to clear infection or prevent reactive bone changes. Combination antibiotic-rifampin regimens, including oral-only linezolid-rifampin and the newer ceftaroline-rifampin combinations, were highly effective and more efficacious than monotherapies when used against a preclinical MRSA PJI. This study provides important preclinical evidence to better optimize future antibiotic therapy against PJIs. In particular, the oral-only linezolid-rifampin option might reduce venous access complications and health-care costs.

  13. Acute myocardial infarction in infectious endocarditis. Report of one case

    International Nuclear Information System (INIS)

    Parietti, G; Artucio, C.; Fernandez, A; Areco, D.; Mallo, D; Lluberas, R.

    2012-01-01

    The acute myocardial infarction is a rare complication in the course of an acute endocarditis. It takes place in the first weeks infection. Although is not associated with any particular microorganism it has been associated with virulent microorganism and is common in aortic valve endocarditis insufficiency. This report is a case of a patient who suffered a myocardial infarction during a acute endocarditis of native valve

  14. Predicting the occurrence of embolic events: an analysis of 1456 episodes of infective endocarditis from the Italian Study on Endocarditis (SEI)

    Science.gov (United States)

    2014-01-01

    Background Embolic events are a major cause of morbidity and mortality in patients with infective endocarditis. We analyzed the database of the prospective cohort study SEI in order to identify factors associated with the occurrence of embolic events and to develop a scoring system for the assessment of the risk of embolism. Methods We retrospectively analyzed 1456 episodes of infective endocarditis from the multicenter study SEI. Predictors of embolism were identified. Risk factors identified at multivariate analysis as predictive of embolism in left-sided endocarditis, were used for the development of a risk score: 1 point was assigned to each risk factor (total risk score range: minimum 0 points; maximum 2 points). Three categories were defined by the score: low (0 points), intermediate (1 point), or high risk (2 points); the probability of embolic events per risk category was calculated for each day on treatment (day 0 through day 30). Results There were 499 episodes of infective endocarditis (34%) that were complicated by ≥ 1 embolic event. Most embolic events occurred early in the clinical course (first week of therapy: 15.5 episodes per 1000 patient days; second week: 3.7 episodes per 1000 patient days). In the total cohort, the factors associated with the occurrence of embolism at multivariate analysis were prosthetic valve localization (odds ratio, 1.84), right-sided endocarditis (odds ratio, 3.93), Staphylococcus aureus etiology (odds ratio, 2.23) and vegetation size ≥ 13 mm (odds ratio, 1.86). In left-sided endocarditis, Staphylococcus aureus etiology (odds ratio, 2.1) and vegetation size ≥ 13 mm (odds ratio, 2.1) were independently associated with embolic events; the 30-day cumulative incidence of embolism varied with risk score category (low risk, 12%; intermediate risk, 25%; high risk, 38%; p endocarditis, a simple scoring system, which combines etiology and vegetation size with time on antimicrobials, might contribute to a

  15. Using MALDI-TOF mass spectrometry as a rapid and accurate diagnostic tool in infective endocarditis: a case report of a patient with mitral valve infective endocarditis caused by Abiotrophia defectiva

    DEFF Research Database (Denmark)

    Holler, Jon Gitz; Pedersen, Line; Calum, Henrik

    2011-01-01

    A case of infective endocarditis caused by Abiotrophia defectiva is presented. The use of MALDI-TOF mass spectrometry as a rapid and accurate diagnostic tool in infective endocarditis is discussed.......A case of infective endocarditis caused by Abiotrophia defectiva is presented. The use of MALDI-TOF mass spectrometry as a rapid and accurate diagnostic tool in infective endocarditis is discussed....

  16. Frequency of enterococcus faecalis in saliva and root canals with treatment failure

    International Nuclear Information System (INIS)

    Khan, I.; Shan, T.; Manzoor, M.A.

    2015-01-01

    To compare the frequency of E. faecalis in the saliva and root canals of teeth associated with apical periodontitis due to endodontic treatment failure in the same patient. Study Design: Cross-sectional comparative study. Place and Duration of Study: Samples were collected from Operative Dentistry Department, AFID, while laboratory processing was done at AFIP, Rawalpindi. Study duration was one year. Patients and Methods: Fifty patients, both males and females with failed endodontic treatment were selected. Saliva and root canal samples were collected from each patient, inoculated on MacKonkey agar plate and incubated at 35-37 degree C for 48 hrs. E. faecalis colonies were identified by colony morphology, gramstain, catalase, bile asculin test, arabinose fermentation and growth in 6% NaCl nutrient broth. Results: The frequency of E. faecalis in saliva was 34% and in root canal it was 58%. Frequency between the presence of E. faecalis in root canals and saliva was found to be statistically different (p = 0.001). Conclusion: The presence of E. faecalis in root canal was not associated with their presence in saliva. (author)

  17. Frequency of enterococcus faecalis in saliva and root canals with treatment failure

    International Nuclear Information System (INIS)

    Shan, T.; Manzoor, M.A.; Hussain, W.

    2014-01-01

    To compare the frequency of E.faecalis in the saliva and root canals of teeth associated with apical periodontitis due to endodontic treatment failure Study. Design: Cross-sectional comparative. Place and Duration of Study: Samples were collected from Operative Dentistry department, AFID, while laboratory processing was done at AFIP, Rawalpindi. Duration of this study was one year. Patients and Method: Fifty patients, both males and females with failed endodontic treatment were selected. Saliva and root canal samples were collected from each patient, inoculated on MacKonkey agar plate and incubated at 35-370 C for 48 hours. E.faecalis colonies were identified by colony morphology, Gram stain, catalase, bile asculin test, arabinose fermentation and growth in 6% NaCl nutrient broth. Results: The frequency of E.faecalis in saliva was 34% and 58% in root canal samples. Frequency of the presence of E.faecalis in root canals and saliva was found to be statistically different (p=0.000). Conclusion: The presence of E.faecalis in root canal was not associated with their presence in saliva. (author)

  18. Antibacterial Effect of Diclofenac Sodium on Enterococcus faecalis

    Directory of Open Access Journals (Sweden)

    Amin Salemmilani

    2013-01-01

    Full Text Available Objective: Non-steroidal anti-inflammatory drugs (NSAIDs have shown antibacterial activity in some recent studies. The aim of this study was to evaluate the antibacterial effect of diclofenac against Enterococcus faecalis (E. faecalis as a resistant endodontic bacterium in comparison with ibuprofen, calcium hydroxide and amoxicillin.Materials and Methods: The antibacterial activity of materials was evaluated using agar diffusion test and tube dilution method. Mixtures of 400 mg/ml of materials were prepared. The bacteria were seeded on 10 Muller-Hinton agar culture plates. Thirty microliter of each test material was placed in each well punched in agar plates. After incubation, the zone of bacterial inhibition was measured. Minimum inhibitory concentration (MIC of the test materials was determined by agar dilution method. One-way Analysis of Variance (ANOVA followed by Sidak post hoc test was used to compare the mean zone of microbial growth in the groups.Results: There were significant differences between the two groups (p< 0.05. Results of the agar diffusion test showed that antibiotics (amoxicillin, gentamycin had the greatest antibacterial activity followed by NSAIDs (ibuprofen, diclofenac. Ca(OH2 failed to show antibacterial activity. Diclofenac and ibuprofen showed distinct antibacterial activity against E. faecalis in 50 µg/ml and above concentrations.Conclusion: Within the limitations of this in vitro study, it is concluded that diclofenac and ibuprofen have significantly more pronounced antibacterial activity against E. faecalis in comparison with Ca(OH2.

  19. Fungal prosthetic valve endocarditis with mycotic aneurysm: Case report.

    Science.gov (United States)

    Brandão, Mariana; Almeida, Jorge; Ferraz, Rita; Santos, Lurdes; Pinho, Paulo; Casanova, Jorge

    2016-09-01

    Fungal prosthetic valve endocarditis is an extremely severe form of infective endocarditis, with poor prognosis and high mortality despite treatment. Candida albicans is the most common etiological agent for this rare but increasingly frequent condition. We present a case of fungal prosthetic valve endocarditis due to C. albicans following aortic and pulmonary valve replacement in a 38-year-old woman with a history of surgically corrected tetralogy of Fallot, prior infective endocarditis and acute renal failure with need for catheter-based hemodialysis. Antifungal therapy with liposomal amphotericin B was initiated prior to cardiac surgery, in which the bioprostheses were replaced by homografts, providing greater resistance to recurrent infection. During hospitalization, a mycotic aneurysm was diagnosed following an episode of acute arterial ischemia, requiring two vascular surgical interventions. Despite the complications, the patient's outcome was good and she was discharged on suppressive antifungal therapy with oral fluconazole for at least a year. The reported case illustrates multiple risk factors for fungal endocarditis, as well as complications and predictors of poor prognosis, demonstrating its complexity. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. cfr-mediated linezolid-resistant clinical isolates of methicillin-resistant coagulase-negative staphylococci from China.

    Science.gov (United States)

    Song, Yunjia; Lv, Yuan; Cui, Lanqing; Li, Yun; Ke, Qian; Zhao, Yixuan

    2017-03-01

    Three linezolid-resistant coagulase-negative staphylococci (LR-CoNS), including two Staphylococcus cohnii and one Staphylococcus capitis, were isolated from 1104 clinical staphylococcal isolates across China in 2013-2014. Antibiotic susceptibilities of the bacteria were determined by the agar dilution method. PCR and DNA sequencing were performed to determine the potential molecular mechanism of linezolid resistance. The two linezolid-resistant S. cohnii isolates were subjected to pulsed-field gel electrophoresis (PFGE) to investigate their genetic relatedness. Primer walking, S1 nuclease PFGE and Southern blot hybridisation were conducted to ascertain the location and environment of the cfr gene. All three isolates were positive for the cfr gene. Amino acid mutations S158F and S158Y in the ribosomal protein L3 were identified in S. cohnii 13B289 and 13L105, respectively, both of which also had an additional substitution (D159Y) in L3. PFGE indicated that the two S. cohnii isolates belonged to diverse clonal strains. S1 nuclease PFGE and Southern blotting experiments indicated that the cfr gene of the three isolates resided on plasmids of similar size (ca. 35.4kb). The cfr-harbouring segments of S. capitis 13G350 and S. cohnii 13L105 were identical to plasmid pSS-01 reported previously. The cfr-carrying fragment of S. cohnii 13B289 was indistinguishable from the formerly described plasmid pSS-02. In conclusion, the presence of the cfr gene located on a plasmid was the main mechanism contributing to resistance to linezolid in the three staphylococcal isolates. Hence, timely detection and judicious use of antibiotics are essential to prevent further transmission of this resistance mechanism. Copyright © 2016 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

  1. Observed Antagonistic Effect of Linezolid on Daptomycin or Vancomycin Activity against Biofilm-Forming Methicillin-Resistant Staphylococcus aureus in an In Vitro Pharmacodynamic Model

    Science.gov (United States)

    Luther, Megan K.

    2015-01-01

    Pharmacodynamic activity in antibiotic combinations of daptomycin, vancomycin, and linezolid was investigated in a 48-h in vitro pharmacodynamic model. Using human-simulated free drug concentrations, activity against clinical biofilm-forming methicillin-resistant Staphylococcus aureus isolates was evaluated. Linezolid antagonized vancomycin activity at 24 and 48 h. Linezolid antagonized daptomycin at 24 and 48 h depending on dose and strain. Adding daptomycin increased vancomycin activity at 48 h (P < 0.03). These results may be strain dependent and require further clinical investigation. PMID:26369963

  2. Candida infective endocarditis

    NARCIS (Netherlands)

    Baddley, J. W.; Benjamin, D. K.; Patel, M.; Miró, J.; Athan, E.; Barsic, B.; Bouza, E.; Clara, L.; Elliott, T.; Kanafani, Z.; Klein, J.; Lerakis, S.; Levine, D.; Spelman, D.; Rubinstein, E.; Tornos, P.; Morris, A. J.; Pappas, P.; Fowler, V. G.; Chu, V. H.; Cabell, C.; DraGordon, David; Devi, Uma; Spelman, Denis; van der Meer, Jan T. M.; Kauffman, Carol; Bradley, Suzanne; Armstrong, William; Giannitsioti, Efthymia; Giamarellou, Helen; Lerakis, Stamatios; del Rio, Ana; Moreno, Asuncio; Mestres, Carlos A.; Pare, Carlos; Garcia de la Maria, Cristina; de Lazzario, Elisa; Marco, Francesc; Gatell, Jose M.; Miro, Jose M.; Almela, Manel; Azqueta, Manuel; Jimenez-Exposito, Maria Jesus; de Benito, Natividad; Perez, Noel; Almirante, Benito; Fernandez-Hidalgo, Nuria; de Vera, Pablo Rodriguez; Tornos, Pilar; Falco, Vicente

    2008-01-01

    Candida infective endocarditis (IE) is uncommon but often fatal. Most epidemiologic data are derived from small case series or case reports. This study was conducted to explore the epidemiology, treatment patterns, and outcomes of patients with Candida IE. We compared 33 Candida IE cases to 2,716

  3. Prophylaxis of endocarditis

    NARCIS (Netherlands)

    van der Meer, J. T. M.

    2002-01-01

    For a long time it has been known that bacteraemias caused by medical or dental procedures may cause endocarditis in patients with specific types of congenital or acquired heart disease. In the 1940s it was thought that the administration of antibiotics before such procedures would prevent

  4. Treatment of MRSA pneumonia: Clinical and economic comparison of linezolid vs. vancomycin – a retrospective analysis of medical charts and re-imbursement data of real-life patient populations

    Directory of Open Access Journals (Sweden)

    Wilke, Michael H.

    2017-01-01

    Full Text Available Objectives: To supplement the data collected in randomized clinical trials, the present study in patients with methicillin resistant (MRSA pneumonia was conducted to explore the clinical effectiveness of linezolid and vancomycin in a routine clinical setting. Further, the overall costs of the patients' stay in the intensive care unit (ICU were compared.Methods: This was a retrospective analysis of medical and reimbursement data of adult patients who were treated for MRSA pneumonia with linezolid or vancomycin. Since the subjects were not randomly assigned to treatments, propensity score adjustment was applied to reduce a potential selection bias.Results: In total, 226 patients were included; 95 received linezolid and 131 received vancomycin as initial therapy for MRSA pneumonia. Switches to another antibiotic were observed in 4 patients (4.2% receiving linezolid and in 23 patients (17.6% receiving vancomycin (logistic regression analysis; odds ratio linezolid/vancomycin: 0.183; 95% confidence interval [CI]: 0.052–0.647; p<0.01. All-cause in-hospital mortality was also lower in patients receiving linezolid (22 patients [23.2%] vs. 54 patients [41.2%] (logistic regression analysis; odds ratio linezolid/vancomycin: 0.351; 95% CI: 0.184–0.671; p<0.01. The analysis of the total costs of stay in ICU did not reveal any major differences between the two treatment groups (cost ratio linezolid/vancomycin: 1.29; 95% CI: 0.84–1.98; p=0.24.Conclusions: These findings confirm in a routine clinical setting that linezolid is a valuable therapeutic alternative to vancomycin for the treatment of MRSA pneumonia. However, prospective studies in real-life patient populations are warranted.

  5. Aspergillus niger endocarditis in an immunocompetent patient: an unusual course

    Science.gov (United States)

    Kreiss, Y.; Vered, Z.; Keller, N.; Kochva, I.; Sidi, Y.; Gur, H.

    2000-01-01

    Aspergillus is an opportunistic nosocomial fungus generally associated with a high mortality rate. A niger has been rarely associated with infection, and most cases have occurred in patients who have recently undergone heart surgery or in immunocompromised patients. We present a case of an immunocompetent patient with A niger endocarditis which illustrates the difficulties in diagnosis and the possible insidious course of fungal endocarditis.


Keywords: endocarditis; Aspergillus niger; transoesophageal echocardiography PMID:10644391

  6. Front-Loaded Linezolid Regimens Result in Increased Killing and Suppression of the Accessory Gene Regulator System of Staphylococcus aureus

    Science.gov (United States)

    Brown, Tanya; Parasrampuria, Ridhi; Brazeau, Daniel A.; Forrest, Alan; Kelchlin, Pamela A.; Holden, Patricia N.; Peloquin, Charles A.; Hanna, Debra; Bulitta, Jurgen B.

    2012-01-01

    Front loading is a strategy used to optimize the pharmacodynamic profile of an antibiotic through the administration of high doses early in therapy for a short duration. Our aims were to evaluate the impact of front loading of linezolid regimens on bacterial killing and suppression of resistance and on RNAIII, the effector molecule of the accessory gene regulator system (encoded by agr) in methicillin-resistant Staphylococcus aureus (MRSA). Time-killing experiments over 48 h were utilized for linezolid against four strains of MRSA: USA100, USA300, USA400, and ATCC 29213. A hollow-fiber infection model simulated traditional and front-loaded human therapeutic regimens of linezolid versus USA300 at 106 CFU/ml over 240 h. Over 48 h in time-kill experiments, linezolid displayed bacteriostatic activity, with reductions of >1 log10 CFU/ml for all strains. Front-loaded regimens that were administered over 5 days, 1,200 mg every 12 h (q12h) (total, 10 doses) and 2,400 mg q12h (total, 10 doses) followed by 300 mg q12h thereafter, resulted in sustained bactericidal activity, with reductions of the area under the CFU curve of −6.15 and −6.03, respectively, reaching undetectable limits at the 10-day study endpoint. All regimens displayed a reduction in RNAIII relative expression at 24 h and 240 h compared with that of the growth control. Monte Carlo simulations predicted a linezolid are promising and may be of utility in severe MRSA infections, where early aggressive therapy is necessary. PMID:22526313

  7. Infective endocarditis in patients on haemodialysis - possible strategies for prevention.

    Science.gov (United States)

    Oun, Hadi A; Price, Andrew J; Traynor, Jamie P

    2016-05-01

    Infective endocarditis is an important cause of morbidity and mortality in patients receiving haemodialysis for established renal failure. We carried out a prospective audit of patients developing infective endocarditis in a single renal unit. From 1 January 2000 to 31 December 2013, we collected data on all cases of endocarditis occurring in patients receiving haemodialysis at Monklands Hospital, Airdrie. Twenty-nine patients developed endocarditis during our audit period. Twenty-three (79.3%) of the patients had pre-existing cardiac valve abnormalities such as regurgitation or calcification. Staphylococcus aureus was the most common microorganism cultured from the blood of 22 patients (75.9%). MRSA bacteraemia was identified in eight of these patients and all eight patients died during that first presentation. Different strategies were introduced within the unit during the audit period aiming to reduce the rate of bacteraemia. Since 2011, a successful strategy has been introduced under the auspices of the Scottish Patient Safety Programme. This led to our Staph aureus bacteraemia rate related to non-tunnelled venous catheters going from an average of 15 days between episodes to having had no episodes between 2 December 2011 and the end of the study period (760 days). This also appears to have had a positive impact on reducing the rate of endocarditis. Infective endocarditis remains a devastating consequence of bacteraemia in patients receiving haemodialysis. An effective strategy aimed at reducing the rate of bacteraemia appears to have a similar effect on the rate of endocarditis. © The Author(s) 2016.

  8. Infective endocarditis following percutaneous pulmonary valve replacement

    DEFF Research Database (Denmark)

    Cheung, Gary; Vejlstrup, Niels; Ihlemann, Nikolaj

    2013-01-01

    Infective endocarditis (IE) following percutaneous pulmonary valve replacement (PPVR) with the Melody valve is rarely reported. Furthermore, there are challenges in this diagnosis; especially echocardiographic evidence of vegetation within the prosthesis may be difficult.......Infective endocarditis (IE) following percutaneous pulmonary valve replacement (PPVR) with the Melody valve is rarely reported. Furthermore, there are challenges in this diagnosis; especially echocardiographic evidence of vegetation within the prosthesis may be difficult....

  9. Resistance to linezolid in Staphylococcus spp. clinical isolates associated with ribosomal binding site modifications: novel mutation in domain V of 23S rRNA.

    Science.gov (United States)

    Musumeci, Rosario; Calaresu, Enrico; Gerosa, Jolanda; Oggioni, Davide; Bramati, Simone; Morelli, Patrizia; Mura, Ida; Piana, Andrea; Are, Bianca Maria; Cocuzza, Clementina Elvezia

    2016-10-01

    Linezolid is the main representative of the oxazolidinones, introduced in 2000 in clinical practice to treat severe Gram-positive infections. This compound inhibits protein synthesis by binding to the peptidyl transferase centre of the 50S bacterial ribosomal subunit. The aim of this study was to characterize 12 clinical strains of linezolid-resistant Staphylococcus spp. isolated in Northern Italy. All isolates of Staphylococcus spp. studied showed a multi-antibiotic resistance phenotype. In particular, all isolates showed the presence of the mecA gene associated with SSCmec types IVa, V or I. Mutations in domain V of 23S rRNA were shown to be the most prevalent mechanism of linezolid resistance: among these a new C2551T mutation was found in S. aureus, whilst the G2576T mutation was shown to be the most prevalent overall. Moreover, three S. epidermidis isolates were shown to have linezolid resistance associated only with alterations in both L3 and L4 ribosomal proteins. No strain was shown to harbor the previously described cfr gene. These results have shown how the clinical use of linezolid in Northern Italy has resulted in the selection of multiple antibiotic-resistant clinical isolates of Staphylococcus spp., with linezolid resistance in these strains being associated with mutations in 23S rRNA or ribosomal proteins L3 and L4.

  10. Infective Endocarditis With Paravalvular Extension: 35-Year Experience.

    Science.gov (United States)

    Rouzé, Simon; Flécher, Erwan; Revest, Matthieu; Anselmi, Amedeo; Aymami, Marie; Roisné, Antoine; Guihaire, Julien; Verhoye, Jean Philippe

    2016-08-01

    We investigated our surgical strategy and clinical results in patients from active infective endocarditis (AIE) complicated by paravalvular involvement to determine the risk factors of early and late death and reoperation. From October 1979 to December 2014, 955 patients underwent operations for AIE; among them 207 had AIE with paravalvular extension. The patients were a mean age of 59.9 ± 15.4 years, and 162 (78%) were male. Of these patients, 137 (66%) had isolated aortic valve endocarditis, and 138 (67%) had native valve endocarditis. Follow-up was 99% complete. The operative mortality of the cohort was 16% (n = 34). Abnormal communication, mechanical valve implantation, and renal failure were independent predictors of 30-day death. Survival at 1, 5, 10, and 15 years was 90.3% ± 2.3%, 62.4% ± 3.7%, 49.3% ± 4.1%, and 37.9% ± 4.4%, respectively. Streptococcus endocarditis (all species), complex annular repair, and preoperative heart failure were independent predictors of long-term death. A reoperation was required in 29 patients (14%). Streptococcus pneumoniae endocarditis was the only independent predictor of early reoperation (within 30 days after the operation or during the same hospitalization). Freedom from reoperation at 1, 5, 10, and 15 years was 91.9% ± 2.2%, 89.6% ± 2.6%, 89.6% ± 2.6%, and 87.0% ± 3.5%, respectively. Independent predictors of late reoperation were urgent/emergency operation, prosthetic valve endocarditis, and complex annular repair. AIE complicated by paravalvular involvement remains a surgical challenge. Valve replacement (particularly using bioprosthesis) associated with ad hoc reconstruction seems to be a reliable option and showed very encouraging results in this context. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  11. Infective endocarditis: a consumptive disease among the elderly

    Directory of Open Access Journals (Sweden)

    Vilma Takayasu

    2011-12-01

    Full Text Available The clinical presentation of infective endocarditis varies according to theetiologic agent and the host. In elderly individuals, infective endocarditis canbe difficult to diagnose and poses a challenge for the physician. The course ofsubacute infective endocarditis is indolent, and the onset of cardiac structurallesion is slow and gradual. In elderly patients, anemia and weight loss areoccasionally the only or the most striking symptoms. In such cases, the clinicalreasoning process leads to a hypothesis of wasting syndrome or neoplasticdisease, especially when there is no fever. We report the case of an elderlypatient who had mitral insufficiency due to degenerative valve disease andpresented with bacterial endocarditis due to Streptococcus mitis. The patientwas not treated, because the diagnosis was not established in a timely manner.It is of note that the patient presented with marked weight loss and no fever.The autopsy revealed impairment of the mitral valve and left atrium due toendocarditis, as well as lung involvement due to chronic inhalation of smokefrom biomass burning, such as that produced by wood-burning stoves.

  12. Enterococcal Infective Endocarditis following Periodontal Disease in Dogs.

    Directory of Open Access Journals (Sweden)

    Teresa Semedo-Lemsaddek

    Full Text Available In humans, one of the major factors associated with infective endocarditis (IE is the concurrent presence of periodontal disease (PD. However, in veterinary medicine, the relevance of PD in the evolution of dogs' endocarditis remains poorly understood. In order to try to establish a correlation between mouth-associated Enterococcus spp. and infective endocarditis in dogs, the present study evaluated the presence and diversity of enterococci in the gum and heart of dogs with PD. Samples were collected during necropsy of 32 dogs with PD and visually diagnosed with IE, which died of natural causes or euthanasia. Enterococci were isolated, identified and further characterized by Pulsed-Field Gel Electrophoresis (PFGE; susceptibility to antimicrobial agents and pathogenicity potential was also evaluated. In seven sampled animals, PFGE-patterns, resistance and virulence profiles were found to be identical between mouth and heart enterococci obtained from the same dog, allowing the establishment of an association between enterococcal periodontal disease and endocarditis in dogs. These findings represent a crucial step towards understanding the pathogenesis of PD-driven IE, and constitute a major progress in veterinary medicine.

  13. Enterococcal Infective Endocarditis following Periodontal Disease in Dogs.

    Science.gov (United States)

    Semedo-Lemsaddek, Teresa; Tavares, Marta; São Braz, Berta; Tavares, Luís; Oliveira, Manuela

    2016-01-01

    In humans, one of the major factors associated with infective endocarditis (IE) is the concurrent presence of periodontal disease (PD). However, in veterinary medicine, the relevance of PD in the evolution of dogs' endocarditis remains poorly understood. In order to try to establish a correlation between mouth-associated Enterococcus spp. and infective endocarditis in dogs, the present study evaluated the presence and diversity of enterococci in the gum and heart of dogs with PD. Samples were collected during necropsy of 32 dogs with PD and visually diagnosed with IE, which died of natural causes or euthanasia. Enterococci were isolated, identified and further characterized by Pulsed-Field Gel Electrophoresis (PFGE); susceptibility to antimicrobial agents and pathogenicity potential was also evaluated. In seven sampled animals, PFGE-patterns, resistance and virulence profiles were found to be identical between mouth and heart enterococci obtained from the same dog, allowing the establishment of an association between enterococcal periodontal disease and endocarditis in dogs. These findings represent a crucial step towards understanding the pathogenesis of PD-driven IE, and constitute a major progress in veterinary medicine.

  14. Streptococcus sanguinis isolate displaying a phenotype with cross-resistance to several rRNA-targeting agents.

    Science.gov (United States)

    Mendes, Rodrigo E; Deshpande, Lalitagauri M; Kim, Jihye; Myers, Debra S; Ross, James E; Jones, Ronald N

    2013-08-01

    This study describes a clinical case of a 71-year-old male with a history of ischemic cardiomyopathy after left ventricular assist device (LVAD) endocarditis caused by methicillin-resistant Staphylococcus epidermidis (MRSE) and a rare linezolid-resistant Streptococcus sanguinis strain (MIC, 32 μg/ml). The patient received courses of several antimicrobial agents, including linezolid for 79 days. The S. sanguinis strain had mutations in the 23S rRNA (T2211C, T2406C, G2576T, C2610T) and an amino acid substitution (N56D) in L22 and exhibited cross-resistance to ribosome-targeting agents.

  15. Linezolid-resistant clinical isolates of meticillin-resistant coagulase-negative staphylococci and Enterococcus faecium from China.

    Science.gov (United States)

    Cai, Jia Chang; Hu, Yan Yan; Zhang, Rong; Zhou, Hong Wei; Chen, Gong-Xiang

    2012-11-01

    Seventeen meticillin-resistant coagulase-negative staphylococci (MRCoNS), including ten Staphylococcus capitis, four Staphylococcus cohnii, two Staphylococcus haemolyticus and one Staphylococcus sciuri, and an Enterococcus faecium isolate with various levels of linezolid resistance were isolated from intensive care units in a Chinese hospital. PFGE indicated that the four S. cohnii isolates belonged to a clonal strain, and that nine of the S. capitis isolates were indistinguishable (clone A1) and the other one was closely related (clone A2). A G2576T mutation was identified in domain V of the 23S rRNA gene in the E. faecium isolate. Besides the G2576T mutation, a novel C2104T mutation was detected in the nine clone A1 S. capitis isolates. The cfr gene was detected in all the staphylococci except an S. sciuri isolate, whose 23S rRNA gene contained the G2576T mutation. There was a clonal dissemination of linezolid-resistant MRCoNS in intensive care units of our hospital, and this is the first report, to our knowledge, of linezolid-resistant staphylococci and enterococci in China.

  16. Endodontic sealers: Intratubular penetration and permeability to Enterococcus faecalis

    Directory of Open Access Journals (Sweden)

    Bortolini Maria Cecilia

    2010-01-01

    Full Text Available Aim : Evaluate in vitro the intratubular penetration and permeability of endodontic sealers in teeth contaminated with Enterococcus faecalis. Materials and Methods : Human canines were filled with AHPlus ® , Endo CPM-sealer ® or EndoRez ® sealers. To evaluate permeability, the coronary portion of each tooth was contaminated with E. faecalis, then the apical portion was immersed in brain heart infusion (BHI broth, and medium turbidity was observed for thirty days. Scanning electron microscope (SEM was used to evaluate the intratubular penetration of each sealer at the cervical, middle, and apical thirds of the tooth. Results : Only one tooth from the Endo CPM-sealer ® group presented broth contamination. EndoRez ® showed increased intratubular penetration compared to AHPlus ® and Endo CPM-sealer ® . Conclusions : Endo CPM-sealer ® showed greater permeability to E. faecalis and EndoRez ® showed increased intratubular penetration.

  17. Endocarditis due to nutritionally deficient streptococci: therapeutic dilemma

    Directory of Open Access Journals (Sweden)

    Erica Escarcega

    2017-07-01

    Full Text Available Subacute endocarditis often presents with an indolent course. A potentially lethal form generated by infection with Abiotrophia defectiva may be easily overlooked early in its presentation. This report discusses the case of an 18-year-old male discovered to have severe endocarditis after presenting to the emergency department with the chief complaint of foot pain.

  18. Infectious endocarditis caused by Escherichia coli

    DEFF Research Database (Denmark)

    Lauridsen, Trine Kiilerich; Arpi, Magnus; Fritz-Hansen, Thomas

    2011-01-01

    Although Escherichia coli is among the most common causes of Gram-negative bacteraemia, infectious endocarditis (IE) due to this pathogen is rare. A 67-y-old male without a previous medical history presented with a new mitral regurgitation murmur and persisting E. coli bacteraemia in spite of broad......-spectrum intravenous antibiotics. Transthoracic and transoesophageal echocardiography revealed a severe mitral endocarditis. E. coli DNA was identified from the mitral valve and the vegetation, and no other pathogen was found. The case was further complicated by spondylodiscitis and bilateral endophthalmitis. Extra...

  19. Survival and activity of Streptococcus faecalis and escherichia coli in tropical freshwater

    International Nuclear Information System (INIS)

    Muniz, I; Toranzos, G.A.; Jimenez, L.; Hazen, T.C.

    1989-01-01

    The survival of Streptococcus faecalis and Escherichia coli was studied in situ in a tropical rain forest watershed using membrane diffusion chambers. Densities were determined by acridine orange direct count and Coulter Counter. Population activity was determined by microautoradiography, cell respiration, and by nucleic acid composition. Densities of S. faecalis and E. coli decreased less than 1 log unit after 105 hours as measured by direct count methods. Activity as measured by respiration, acridine orange activity, and microautoradiography indicated that both bacteria remained moderately active during the entire study. After 12 hours, E. coli was more active than S. faecalis as measured by nucleic acid composition. In this tropical rain forest watershed, E. coli and S. faecalis survived and remained active for more than 5 days; consequently, both would seem to be unsuitable as indicators of recent fecal contamination in tropical waters

  20. Antistaphylococcal activity of DX-619 alone and in combination with vancomycin, teicoplanin, and linezolid assessed by time-kill synergy testing.

    Science.gov (United States)

    Credito, Kim; Lin, Genrong; Appelbaum, Peter C

    2007-04-01

    Time-kill synergy studies testing in vitro activity of DX-619 alone and with added vancomycin, teicoplanin, or linezolid against 101 Staphylococcus aureus strains showed synergy between DX-619 and teicoplanin at 12 to 24 h in 72 strains and between DX-619 and vancomycin in 28 strains. No synergy was found with linezolid, and no antagonism was observed with any combination.

  1. CRISPR-Cas and Restriction-Modification Act Additively against Conjugative Antibiotic Resistance Plasmid Transfer in Enterococcus faecalis.

    Science.gov (United States)

    Price, Valerie J; Huo, Wenwen; Sharifi, Ardalan; Palmer, Kelli L

    2016-01-01

    Enterococcus faecalis is an opportunistic pathogen and a leading cause of nosocomial infections. Conjugative pheromone-responsive plasmids are narrow-host-range mobile genetic elements (MGEs) that are rapid disseminators of antibiotic resistance in the faecalis species. Clustered regularly interspaced short palindromic repeat (CRISPR)-Cas and restriction-modification confer acquired and innate immunity, respectively, against MGE acquisition in bacteria. Most multidrug-resistant E. faecalis isolates lack CRISPR-Cas and possess an orphan locus lacking cas genes, CRISPR2, that is of unknown function. Little is known about restriction-modification defense in E. faecalis. Here, we explore the hypothesis that multidrug-resistant E. faecalis strains are immunocompromised. We assessed MGE acquisition by E. faecalis T11, a strain closely related to the multidrug-resistant hospital isolate V583 but which lacks the ~620 kb of horizontally acquired genome content that characterizes V583. T11 possesses the E. faecalis CRISPR3-cas locus and a predicted restriction-modification system, neither of which occurs in V583. We demonstrate that CRISPR-Cas and restriction-modification together confer a 4-log reduction in acquisition of the pheromone-responsive plasmid pAM714 in biofilm matings. Additionally, we show that the orphan CRISPR2 locus is functional for genome defense against another pheromone-responsive plasmid, pCF10, only in the presence of cas9 derived from the E. faecalis CRISPR1-cas locus, which most multidrug-resistant E. faecalis isolates lack. Overall, our work demonstrated that the loss of only two loci led to a dramatic reduction in genome defense against a clinically relevant MGE, highlighting the critical importance of the E. faecalis accessory genome in modulating horizontal gene transfer. Our results rationalize the development of antimicrobial strategies that capitalize upon the immunocompromised status of multidrug-resistant E. faecalis. IMPORTANCE

  2. Brucella endocarditis – A series of five case reports

    Directory of Open Access Journals (Sweden)

    I. Tammi Raju

    2013-01-01

    Full Text Available Endocarditis due to brucellosis is considered a rare occurrence involving native, congenital and prosthetic valves. The diagnosis needs high degree of suspicion in culture negative endocarditis especially in those with history of exposure to farm animals. A positive culture in a susceptible patient confirms the diagnosis with 91% sensitivity. An early diagnosis and prompt treatment with appropriate antibiotics can restore the valve structural integrity with minimal damage. Here we present a series of five cases of culture proven Brucella endocarditis (four native valves, one prosthetic valve and this report discusses the diagnostic and management issues involved.

  3. Phage therapy against Enterococcus faecalis in dental root canals

    Directory of Open Access Journals (Sweden)

    Leron Khalifa

    2016-09-01

    Full Text Available Antibiotic resistance is an ever-growing problem faced by all major sectors of health care, including dentistry. Recurrent infections related to multidrug-resistant bacteria such as methicillin-resistant Staphylococcus aureus, carbapenem-resistant Enterobacteriaceae, and vancomycin-resistant enterococci (VRE in hospitals are untreatable and question the effectiveness of notable drugs. Two major reasons for these recurrent infections are acquired antibiotic resistance genes and biofilm formation. None of the traditionally known effective techniques have been able to efficiently resolve these issues. Hence, development of a highly effective antibacterial practice has become inevitable. One example of a hard-to-eradicate pathogen in dentistry is Enterococcus faecalis, which is one of the most common threats observed in recurrent root canal treatment failures, of which the most problematic to treat are its biofilm-forming VRE strains. An effective response against such infections could be the use of bacteriophages (phages. Phage therapy was found to be highly effective against biofilm and multidrug-resistant bacteria and has other advantages like ease of isolation and possibilities for genetic manipulations. The potential of phage therapy in dentistry, in particular against E. faecalis biofilms in root canals, is almost unexplored. Here we review the efforts to develop phage therapy against biofilms. We also focus on the phages isolated against E. faecalis and discuss the possibility of using phages against E. faecalis biofilm in root canals.

  4. Complete Atrioventricular Block Complicating Mitral Infective Endocarditis Caused by Streptococcus Agalactiae

    OpenAIRE

    Arai, Masaru; Nagashima, Koichi; Kato, Mahoto; Akutsu, Naotaka; Hayase, Misa; Ogura, Kanako; Iwasawa, Yukino; Aizawa, Yoshihiro; Saito, Yuki; Okumura, Yasuo; Nishimaki, Haruna; Masuda, Shinobu; Hirayama, Atsushi

    2016-01-01

    Patient: Male, 74 Final Diagnosis: Infective endocarditis Symptoms: Apetite loss ? fever Medication: ? Clinical Procedure: Transesophageal echocardiography Specialty: Cardiology Objective: Rare co-existance of disease or pathology Background: Infective endocarditis (IE) involving the mitral valve can but rarely lead to complete atrioventricular block (CAVB). Case Report: A 74-year-old man with a history of infective endocarditis caused by Streptococcus gordonii (S. gordonii) presented to our ...

  5. The Changing “Face” of Endocarditis in Kentucky: A Rise in Tricuspid Cases

    Science.gov (United States)

    Seratnahaei, Arash; Leung, Steve W.; Charnigo, Richard J.; Cummings, Matthew S.; Sorrell, Vincent L.; Smith, Mikel D.

    2015-01-01

    Background Advancements in medical technology and increased life expectancy have been described as contributing to the evolution of endocarditis. We sought to determine whether there has been a change in the incidence, demographics, microbiology, complications, and outcomes of infective endocarditis over a ten-year time span. Methods We screened 28,420 transthoracic and transesophageal echocardiogram reports performed at our center for the following indications: fever, masses, emboli (including stroke), sepsis, bacteremia, and endocarditis in two time periods: 1999 through 2000 and 2009 through 2010. Data were collected from diagnosed endocarditis cases. Results Overall, 143 cases of infective endocarditis were analyzed (48 in 1999-2000 and 95 in 2009-2010). The endocarditis incidence per number of admissions remained nearly constant at 0.113% for 1999-2000 and 0.148% for 2009-2010 (p = 0.153). However, tricuspid valve involvement increased markedly from 6% to 36% (p endocarditis at our center has not changed and mortality remains high, but the “face of endocarditis” in Kentucky has evolved with an increased incidence of tricuspid valve involvement, valvular complications, and embolic events. PMID:24769025

  6. A validated stability-indicating LC method for the separation of enantiomer and potential impurities of Linezolid using polar organic mode.

    Science.gov (United States)

    Satyanarayana Raju, T; Vishweshwari Kutty, O; Ganesh, V; Yadagiri Swamy, P

    2012-08-01

    Although a number of methods are available for evaluating Linezolid and its possible impurities, a common method for separation if its potential impurities, degradants and enantiomer in a single method with good efficiency remain unavailable. With the objective of developing an advanced method with shorter runtimes, a simple, precise, accurate stability-indicating LC method was developed for the determination of purity of Linezolid drug substance and drug products in bulk samples and pharmaceutical dosage forms in the presence of its impurities and degradation products. This method is capable of separating all the related substances of Linezolid along with the chiral impurity. This method can also be used for the estimation of assay of Linezolid in drug substance as well as in drug product. The method was developed using Chiralpak IA (250 mm×4.6 mm, 5 μm) column. A mixture of acetonitrile, ethanol, n-butyl amine and trifluoro acetic acid in 96:4:0.10:0.16 (v/v/v/v) ratio was used as a mobile phase. The eluted compounds were monitored at 254 nm. Linezolid was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal and photolytic degradation. The degradation products were well resolved from main peak and its impurities, proving the stability-indicating power of the method. The developed method was validated as per International Conference on Harmonization (ICH) guidelines with respect to specificity, limit of detection, limit of quantification, precision, linearity, accuracy, robustness and system suitability.

  7. Bacterial endocarditis due to eikenella corrodens: A case report

    Directory of Open Access Journals (Sweden)

    Mahapatra A

    2003-01-01

    Full Text Available Of all the causes of bacterial endocarditis, HACEK group consisting of Haemophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella Kingae are rare causative agents. We report a case of bacterial endocarditis by E. corrodens, which is one of the members of the HACEK group.

  8. Success of linezolid therapy for postneurosurgical ventriculitis due to vancomycin-resistant Enterococcus faecium: case report and literature review

    Institute of Scientific and Technical Information of China (English)

    JiaJi Qiu; Jie Tang; DeLing Li

    2016-01-01

    Background:Vancomycin-resistant Enterococcus faecium ventriculitis is one of the most severe events in postneurosurgical intracranial infections.There are no guidelines recommending an appropriate treatment before.Case presentation:This case presents a successful linezolid treatment for post-neurosurgical vancomycin-resistant Enterococcus faecium ventriculitis of a 24-year-old man in the department of neurosurgery,Beijing Tiantan Hospital.Conclusions:Linezolid should be considered as one of the important methods for the treatment of postneurosurgical intracranial infections caused by vancomycin-resistant Enterococcus.

  9. Applicability of a Single Time Point Strategy for the Prediction of Area Under the Concentration Curve of Linezolid in Patients

    DEFF Research Database (Denmark)

    Srinivas, Nuggehally R; Syed, Muzeeb

    2016-01-01

    Background and Objectives: Linezolid, a oxazolidinone, was the first in class to be approved for the treatment of bacterial infections arising from both susceptible and resistant strains of Gram-positive bacteria. Since overt exposure of linezolid may precipitate serious toxicity issues......, therapeutic drug monitoring (TDM) may be required in certain situations, especially in patients who are prescribed other co-medications. Methods: Using appropriate oral pharmacokinetic data (single dose and steady state) for linezolid, both maximum plasma drug concentration (Cmax) versus area under the plasma...... concentration–time curve (AUC) and minimum plasma drug concentration (Cmin) versus AUC relationship was established by linear regression models. The predictions of the AUC values were performed using published mean/median Cmax or Cmin data and appropriate regression lines. The quotient of observed and predicted...

  10. Diagnostic value of imaging in infective endocarditis: a systematic review.

    Science.gov (United States)

    Gomes, Anna; Glaudemans, Andor W J M; Touw, Daan J; van Melle, Joost P; Willems, Tineke P; Maass, Alexander H; Natour, Ehsan; Prakken, Niek H J; Borra, Ronald J H; van Geel, Peter Paul; Slart, Riemer H J A; van Assen, Sander; Sinha, Bhanu

    2017-01-01

    Sensitivity and specificity of the modified Duke criteria for native valve endocarditis are both suboptimal, at approximately 80%. Diagnostic accuracy for intracardiac prosthetic material-related infection is even lower. Non-invasive imaging modalities could potentially improve diagnosis of infective endocarditis; however, their diagnostic value is unclear. We did a systematic literature review to critically appraise the evidence for the diagnostic performance of these imaging modalities, according to PRISMA and GRADE criteria. We searched PubMed, Embase, and Cochrane databases. 31 studies were included that presented original data on the performance of electrocardiogram (ECG)-gated multidetector CT angiography (MDCTA), ECG-gated MRI, 18 F-fluorodeoxyglucose ( 18 F-FDG) PET/CT, and leucocyte scintigraphy in diagnosis of native valve endocarditis, intracardiac prosthetic material-related infection, and extracardiac foci in adults. We consistently found positive albeit weak evidence for the diagnostic benefit of 18 F-FDG PET/CT and MDCTA. We conclude that additional imaging techniques should be considered if infective endocarditis is suspected. We propose an evidence-based diagnostic work-up for infective endocarditis including these non-invasive techniques. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Bartonella Species, an Emerging Cause of Blood-Culture-Negative Endocarditis.

    Science.gov (United States)

    Okaro, Udoka; Addisu, Anteneh; Casanas, Beata; Anderson, Burt

    2017-07-01

    Since the reclassification of the genus Bartonella in 1993, the number of species has grown from 1 to 45 currently designated members. Likewise, the association of different Bartonella species with human disease continues to grow, as does the range of clinical presentations associated with these bacteria. Among these, blood-culture-negative endocarditis stands out as a common, often undiagnosed, clinical presentation of infection with several different Bartonella species. The limitations of laboratory tests resulting in this underdiagnosis of Bartonella endocarditis are discussed. The varied clinical picture of Bartonella infection and a review of clinical aspects of endocarditis caused by Bartonella are presented. We also summarize the current knowledge of the molecular basis of Bartonella pathogenesis, focusing on surface adhesins in the two Bartonella species that most commonly cause endocarditis, B. henselae and B. quintana . We discuss evidence that surface adhesins are important factors for autoaggregation and biofilm formation by Bartonella species. Finally, we propose that biofilm formation is a critical step in the formation of vegetative masses during Bartonella -mediated endocarditis and represents a potential reservoir for persistence by these bacteria. Copyright © 2017 American Society for Microbiology.

  12. Brain magnetic resonance findings in infective endocarditis with neurological complications

    International Nuclear Information System (INIS)

    Azuma, Asako; O'uchi, Toshihiro; Toyoda, Keiko

    2009-01-01

    Diagnosing infective endocarditis and its complications can be difficult because of the nonspecific symptoms. We reviewed findings of intracranial abnormalities on magnetic resonance imaging (MRI) in 14 patients with neurological complications and herein discuss the overall intracranial MRI findings. We retrospectively reviewed patients with infective endocarditis from August 2004 to August 2006. Brain MRI, the causative bacteria, and abnormal neurological symptoms were reviewed for 14 patients with neurological complications. Of the 14 patients, 13 showed intracranial abnormalities on MRI. Embolization was seen in 10 patients, hemorrhage in 3, abscess formation in 3, and encephalitis in 2. Hyperintense lesions with a central hypointense area on T2-weighted and/or T2*-weighted imaging (Bull's-eye-like lesion) were seen in four patients. A combination of these intracranial abnormalities was observed in 6 patients. The MRI findings associated with infective endocarditis are wide-ranging: embolization, hemorrhage, meningitis, cerebritis, abscess, the bull's-eye-like lesion. Clinicians should consider the possibility of infective endocarditis in patients with unknown fever and neurological abnormality. Brain MRI should be promptly performed for those patients, and T2*-weighted imaging is recommended for an early diagnosis of infective endocarditis. (author)

  13. Infective Endocarditis in Children — New Approach in Antimicrobial Prophylaxis

    Directory of Open Access Journals (Sweden)

    Togănel Rodica

    2016-06-01

    Full Text Available Infective endocarditis (IE is an infection of the endocardium and/or heart valves with the formation of a thrombus and secondary damage of the involved tissue, with significant mortality and severe complications. The prevention of bacterial endocarditis is of great controversy. Antimicrobial prophylaxis is usable in the prevention of endocarditis by killing bacteria before or after their extension to the damaged endocardium. No human studies offer strong evidence to support the efficacy of antibiotic prophylaxis so far, thus it could be potentially dangerous. Therefore, the European Society of Cardiology (ESC may need to reconsider and update the previous guidelines with the proposal of reducing the prophylactic approach of IE. The 2015 Task Force recommends prophylaxis for highest risk patients undergoing highest risk procedures, focused on prevention rather than prophylaxis of IE, especially in nosocomial endocarditis.

  14. Sinus of Valsalva Pseudoaneurysm as a Sequela to Infective Endocarditis.

    Science.gov (United States)

    Lee, Chin C; Siegel, Robert J

    2016-02-01

    Pseudoaneurysm is an uncommon sequela of infective endocarditis. We treated a 44-year-old man who had an active case of group B streptococcal infective endocarditis of the aortic valve despite no evidence of valvular dysfunction or vegetation on his initial transesophageal echocardiogram. After completing 6 weeks of intravenous antibiotic therapy, the patient developed a sinus of Valsalva pseudoaneurysm and severe aortic regurgitation caused by partial detachment of the left coronary cusp. We used a pericardial patch to close the pseudoaneurysm and repair the coronary cusp. This case shows the importance of routine clinical follow-up evaluation in infective endocarditis, even after completion of antibiotic therapy. Late sequelae associated with infective endocarditis or its therapy include recurrent infection, heart failure caused by valvular dysfunction (albeit delayed), and antibiotic toxicity such as aminoglycoside-induced nephropathy and vestibular toxicity.

  15. Nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus treated with linezolid or vancomycin: A secondary economic analysis of resource use from a Spanish perspective.

    Science.gov (United States)

    Rello, J; Nieto, M; Solé-Violán, J; Wan, Y; Gao, X; Solem, C T; De Salas-Cansado, M; Mesa, F; Charbonneau, C; Chastre, J

    2016-11-01

    Adopting a unique Spanish perspective, this study aims to assess healthcare resource utilization (HCRU) and the costs of treating nosocomial pneumonia (NP) produced by methicillin-resistant Staphylococcus aureus (MRSA) in hospitalized adults using linezolid or vancomycin. An evaluation is also made of the renal failure rate and related economic outcomes between study groups. An economic post hoc evaluation of a randomized, double-blind, multicenter phase 4 study was carried out. Nosocomial pneumonia due to MRSA in hospitalized adults. The modified intent to treat (mITT) population comprised 224 linezolid- and 224 vancomycin-treated patients. Costs and HCRU were evaluated between patients administered either linezolid or vancomycin, and between patients who developed renal failure and those who did not. Analysis of HCRU outcomes and costs. Total costs were similar between the linezolid- (€17,782±€9,615) and vancomycin-treated patients (€17,423±€9,460) (P=.69). The renal failure rate was significantly lower in the linezolid-treated patients (4% vs. 15%; Prenal failure (€19,626±€10,840 vs. €17,388±€9,369; P=.14). Among the patients who developed renal failure, HCRU (days on mechanical ventilation: 13.2±10.7 vs. 7.6±3.6 days; P=.21; ICU stay: 14.4±10.5 vs. 9.9±6.6 days; P=.30; hospital stay: 19.5±9.5 vs. 16.1±11.0 days; P=.26) and cost (€17,219±€8,792 vs. €20,263±€11,350; P=.51) tended to be lower in the linezolid- vs. vancomycin-treated patients. There were no statistically significant differences in costs per patient-day between cohorts after correcting for mortality (€1000 vs. €1,010; P=.98). From a Spanish perspective, there were no statistically significant differences in total costs between the linezolid and vancomycin pneumonia cohorts. The drug cost corresponding to linezolid was partially offset by fewer renal failure adverse events. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

  16. Emergence of methicillin-resistant coagulase-negative staphylococci resistant to linezolid with rRNA gene C2190T and G2603T mutations.

    Science.gov (United States)

    Cidral, Thiago André; Carvalho, Maria Cícera; Figueiredo, Agnes Marie Sá; de Melo, Maria Celeste Nunes

    2015-10-01

    The aim of this article were to determinate the mechanism of linezolid resistance in coagulase-negative methicillin-resistant staphylococci from hospitals in the northeast of Brazil. We identified the isolates using VITEK(®) 2 and MALDI-TOF. Susceptibility to antibiotics was measured by the disk-diffusion method and by Etest(®) . Extraction of the whole genome DNA was performed, followed by screening of all the strains for the presence of mecA and cfr genes. The domain V region of 23S rRNA gene was sequenced and then aligned with a linezolid-susceptible reference strain. Pulsed-field gel electrophoresis (PFGE) macro-restriction analysis was performed. Three linezolid-resistant Staphylococcus hominis and two linezolid-resistant Staphylococcus epidermidis strains were analyzed. The isolates showed two point mutations in the V region of the 23S rRNA gene (C2190T and G2603T). We did not detect the cfr gene in any isolate by PCR. The S. hominis showed the same pulsotype, while the S. epidermidis did not present any genetic relation to each other. In conclusion, this study revealed three S. hominis and two S. epidermidis strains with resistance to linezolid due to a double mutation (C2190T and G2603T) in the domain V of the 23S rRNA gene. For the first time, the mutation of C2190T in S. epidermidis is described. This study also revealed the clonal spread of a S. hominis pulsotype between three public hospitals in the city of Natal, Brazil. These findings highlight the importance of continued vigilance of linezolid resistance in staphylococci. © 2015 APMIS. Published by John Wiley & Sons Ltd.

  17. Superantigens Are Critical for Staphylococcus aureus Infective Endocarditis, Sepsis, and Acute Kidney Injury

    Science.gov (United States)

    Salgado-Pabón, Wilmara; Breshears, Laura; Spaulding, Adam R.; Merriman, Joseph A.; Stach, Christopher S.; Horswill, Alexander R.; Peterson, Marnie L.; Schlievert, Patrick M.

    2013-01-01

    ABSTRACT Infective endocarditis and kidney infections are serious complications of Staphylococcus aureus sepsis. We investigated the role of superantigens (SAgs) in the development of lethal sepsis, infective endocarditis, and kidney infections. SAgs cause toxic shock syndrome, but it is unclear if SAgs contribute to infective endocarditis and kidney infections secondary to sepsis. We show in the methicillin-resistant S. aureus strain MW2 that lethal sepsis, infective endocarditis, and kidney infections in rabbits are critically dependent on high-level SAgs. In contrast, the isogenic strain lacking staphylococcal enterotoxin C (SEC), the major SAg in this strain, is attenuated in virulence, while complementation restores disease production. SAgs’ role in infective endocarditis appears to be both superantigenicity and direct endothelial cell stimulation. Maintenance of elevated blood pressure by fluid therapy significantly protects from infective endocarditis, possibly through preventing bacterial accumulation on valves and increased SAg elimination. These data should facilitate better methods to manage these serious illnesses. PMID:23963178

  18. Similar efficacy and safety of daptomycin versus linezolid for treatment of vancomycin-resistant enterococcal bloodstream infections: a meta-analysis.

    Science.gov (United States)

    Zhao, Ming; Liang, Liang; Ji, Liwei; Chen, Di; Zhang, Yatong; Zhu, Yuanchao; Patel, Khilna

    2016-09-01

    Daptomycin and linezolid are the most commonly used antibiotics for bloodstream infection caused by vancomycin-resistant enterococci (VRE-BSI). However, the best therapeutic agent to treat VRE-BSI remains to be established. In order to provide evidence for an optimal treatment decision, a systematic review and meta-analysis was performed comparing the efficacy and safety of daptomycin and linezolid for the treatment of VRE-BSI. After thorough searching of relevant studies from MEDLINE, EMBASE, Clinicaltrials.gov and international meetings up to November 2015, 11 retrospective cohort studies were finally included with a sample size of 1339 patients. Among these 11 included studies, all patients in the daptomycin group received standard or high-dose daptomycin treatment (≥6 mg/kg/day). Data were extracted and pooled risk ratios (RRs) and 95% confidence intervals (95% CIs) were calculated using a random-effects model. The meta-analysis indicated similar crude overall mortality between patients receiving daptomycin and those treated with linezolid (RR = 1.07, 95% CI 0.83-1.37). Moreover, no difference regarding clinical cure (RR = 1.11, 95% CI 0.88-1.42), microbiological cure (RR = 0.99, 95% CI 0.90-1.09) or relapse rate of VRE-BSI (RR = 1.08, 95% CI 0.76-1.52) was found between daptomycin and linezolid. Adverse event rates were not significantly different between the two groups. Currently available evidence indicates similar efficacy and safety of daptomycin and linezolid for the treatment of VRE-BSI. However, the findings in the meta-analysis are limited by heterogeneity between relatively small-scale retrospective studies and should be interpreted cautiously. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  19. Proper use of antibiotics: situation of linezolid at the intensive care unit of the Tunisian Military Hospital.

    Science.gov (United States)

    Safa, Louhichi; Afif, Neffati; Zied, Hajjej; Mehdi, Dridi; Ali, Yousfi Mohamed

    2016-01-01

    Linezolid was introduced in clinical practice in the early 2000s. It was considered to be an ideal reserve drug for treatment of vancomycin-resistant Enterococcus spp. (VRE) and vancomycin-resistant Staphylococcus aureus (VRSA). The aim of our study was to describe and evaluate the use of linezolid in clinical practice at the intensive care unit (ICU) of the Tunisian military hospital. This is a thirty-month retrospective study including patients treated with linezolid at the ICU of the Tunisian military hospital. Data collection was realized using the patients' medical files and prescriptions. A pharmacist conducted an extended medication history and checked if an advice from an infectious disease-physician and a microbiological documentation were requested. A total of 80 patients were included. Forty-one per cent of indications were outside the Marketing Authorization (MA) criteria, and were mainly sepsis and postoperative mediastinitis (32% and 4% of total prescriptions, respectively). This antibiotic was used as a first-line therapy in 58% of cases. The advice from an infectious-disease physician was requested for 33% of prescriptions. Only 20% of infections were documented microbiologically, of which 35% were caused by methicillin resistant coagulase-negative Staphylococcus. Linezolid is an interesting therapeutic alternative in case of infections due to multi-resistant bacteria and/or complex clinical situations. Therefore, its prescription must be rationalized in order to slow down the emergence of resistance to this antibiotic. The high frequency of its use outside the MA criteria shows the importance of carrying out more clinical trials to evaluate its effectiveness and safety for new indications.

  20. An agmatine-inducible system for the expression of recombinant proteins in Enterococcus faecalis.

    Science.gov (United States)

    Linares, Daniel M; Perez, Marta; Ladero, Victor; Del Rio, Beatriz; Redruello, Begoña; Martin, M Cruz; Fernandez, María; Alvarez, Miguel A

    2014-12-04

    Scientific interest in Enterococcus faecalis has increased greatly over recent decades. Some strains are involved in food fermentation and offer health benefits, whereas others are vancomycin-resistant and cause infections that are difficult to treat. The limited availability of vectors able to express cloned genes efficiently in E. faecalis has hindered biotechnological studies on the bacterium's regulatory and pathogenicity-related genes. The agmatine deiminase (AGDI) pathway of E. faecalis, involved in the conversion of agmatine into putrescine, is driven by a response inducer gene aguR. This study describes that the exposure to the induction factor (agmatine) results in the transcription of genes under the control of the aguB promoter, including the aguBDAC operon. A novel E. faecalis expression vector, named pAGEnt, combining the aguR inducer gene and the aguB promoter followed by a cloning site and a stop codon was constructed. pAGEnt was designed for the overexpression and purification of a protein fused to a 10-amino-acid His-tag at the C-terminus. The use of GFP as a reporter of gene expression in E. faecalis revealed that under induction with 60 mM agmatine, fluorescence reached 40 arbitrary units compared to 0 in uninduced cells. pAGEnt vector can be used for the overexpression of recombinant proteins under the induction of agmatine in E. faecalis, with a close correlation between agmatine concentration and fluorescence when GFP was used as reporter.

  1. Nocardia asteroides peritoneal dialysis-related peritonitis: First case in pediatrics, treated with protracted linezolid.

    Science.gov (United States)

    El-Naggari, Mohamed; El Nour, Ibtisam; Al-Nabhani, Dana; Al Muharrmi, Zakaria; Gaafar, Heba; Abdelmogheth, Anas A W

    2016-01-01

    Nocardia asteroides is a rare pathogen in peritoneal dialysis-related peritonitis. We report on a 13-year-old female with Nocardia asteroides peritonitis complicated by an intra-abdominal abscess. Linezolid was administered intravenously for 3 months and followed by oral therapy for an additional 5 months with close monitoring for adverse effects. The patient was discharged after 3 months of hospitalization on hemodialysis. The diagnosis and management of such cases can be problematic due to the slow growth and difficulty of identifying Nocardia species. The optimal duration of treatment for Nocardia peritonitis is not known. Linezolid can be used for prolonged periods in cases of trimethoprim/sulfamethoxazole-resistant cases with close monitoring for adverse effects. Copyright © 2015 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

  2. Cardiobacterium valvarum infective endocarditis and phenotypic/molecular characterization of 11 Cardiobacterium species strains

    DEFF Research Database (Denmark)

    Chen, Ming; Kemp, Michael; Bruun, Niels E

    2011-01-01

    Cardiobacterium valvarum is a newly recognized human pathogen related to infective endocarditis. Cardiobacterium species are, however, only rarely the aetiology of infective endocarditis. An infective endocarditis case is presented and, additionally, phenotypic and phylogenetic comparison...... of a further 10 collection strains, representing the two species within the genus, was performed. C. valvarum was isolated from the blood and DNA was present in valvular tissue (partial 16S rRNA gene analysis) from a 64-year-old man with infective endocarditis of the mitral valve, rupture of chordae...

  3. Francisella tularensis endocarditis: two case reports and a literature review.

    Science.gov (United States)

    Gaci, Rostane; Alauzet, Corentine; Selton-Suty, Christine; Lozniewski, Alain; Pulcini, Céline; May, Thierry; Goehringer, François

    2017-02-01

    We report the first two cases of infective endocarditis caused by Francisella tularensis in Europe (two cases have previously been reported outside Europe). We suggest clinicians should consider tularemia as a possible diagnosis in endemic regions in cases of culture-negative endocarditis.

  4. Acute Q fever and the risk of developing endocarditis.

    Science.gov (United States)

    Martín-Aspas, A; Collado-Pérez, C; Vela-Manzano, L; Fernández-Gutiérrez Del Álamo, C; Tinoco-Racero, I; Girón-González, J A

    2015-01-01

    Assess clinical and serological data as parameters indicative of a possible evolution to endocarditis after an episode of acute Q fever. Retrospective cohort study of evolution to endocarditis after an acute Q fever episode, analyzing the clinical and serological evolution and the antibiotic treatment administered. Eighty patients were recruited, 20% of whom had phase i IgG antibody levels ≥ 1:1024 in the first 3 months. Only 44% of the patients underwent antibiotherapy in the acute phase; only 2 patients underwent extended antibiotherapy. Fifteen percent of the patients underwent an echocardiogram. None of the patients had symptoms suggestive of chronic infection or progressed to endocarditis after a median follow-up of 100 months, regardless of the early increase in phase i IgG antibodies. The early increase in phase i IgG antibodies in asymptomatic patients is not associated with progression to endocarditis despite not undergoing prolonged antibiotic treatment. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  5. The value of 18F-FDG PET/CT in diagnosing infectious endocarditis

    International Nuclear Information System (INIS)

    Kouijzer, Ilse J.E.; Vos, Fidel J.; Janssen, Marcel J.R.; Dijk, Arie P.J. van; Oyen, Wim J.G.; Bleeker-Rovers, Chantal P.

    2013-01-01

    Early detection of infectious endocarditis is challenging. For diagnosing infectious endocarditis, the revised Duke criteria are the gold standard. Evidence of endocardial involvement on echocardiography is a major criterion, but sensitivity and specificity of echocardiography are not optimal. Here we investigated the utility of 18 F-fluorodeoxyglucose (FDG) positron emission tomography and computed tomography (PET/CT) to diagnose infectious endocarditis in patients with gram-positive bacteraemia. Seventy-two patients with gram-positive bacteraemia were prospectively included. Patients with a positive blood culture growing Staphylococcus aureus, Streptococcus species or Enterococcus species were eligible when a risk factor for developing metastatic infectious foci was present. Infectious endocarditis was defined according to the revised Duke criteria. All patients underwent 18 F-FDG PET/CT and echocardiography. 18 F-FDG uptake in or around the heart valves was evaluated independently by two nuclear medicine physicians. Sensitivity for diagnosing infectious endocarditis with 18 F-FDG PET/CT was 39 % and specificity was 93 %. The positive predictive value was 64 % and negative predictive value was 82 %. The mortality rate in patients without infectious endocarditis and without increased 18 F-FDG uptake in or around the heart valves was 18 %, and in patients without infectious endocarditis but with high 18 F-FDG uptake in or around the heart valves the mortality rate was 50 % (p = 0.181). 18 F-FDG PET/CT is currently not sufficiently adequate for the diagnosis of infectious endocarditis because of its low sensitivity. Improvements such as patient preparation with low carbohydrate-fat allowed diet and technical advances in the newest PET/CT scanners may increase sensitivity in future studies. (orig.)

  6. Tropheryma whipplei tricuspid endocarditis: a case report and review of the literature.

    Science.gov (United States)

    Gabus, Vincent; Grenak-Degoumois, Zita; Jeanneret, Severin; Rakotoarimanana, Riana; Greub, Gilbert; Genné, Daniel

    2010-08-04

    The main clinical manifestations of Whipple's disease are weight loss, arthropathy, diarrhea and abdominal pain. Cardiac involvement is frequently described. However, endocarditis is rare and is not usually the initial presentation of the disease. To the best of our knowledge, this is the first reported case of a patient with Tropheryma whipplei tricuspid endocarditis without any other valve involved and not presenting signs of arthralgia and abdominal involvement. We report a case of a 50-year-old Caucasian man with tricuspid endocarditis caused by Tropheryma whipplei, showing signs of severe shock and an absence of other more classic clinical signs of Whipple's disease, such as arthralgia, abdominal pain and diarrhea. Tropheryma whipplei was documented by polymerase chain reaction of the blood and pleural fluid. The infection was treated with a combined treatment of doxycycline, hydroxychloroquine and sulfamethoxazole-trimethoprim for one year. Tropheryma whipplei infectious endocarditis should always be considered when facing a blood-culture negative endocarditis particularly in right-sided valves. Although not standardized yet, treatment of Tropheryma whipplei endocarditis should probably include a bactericidal antibiotic (such as doxycycline) and should be given over a prolonged period of time (a minimum of one year).

  7. Successful Treatment of Disseminated Bacillus Calmette-Guérin Disease in an HIV-Infected Child with a Linezolid-Containing Regimen

    Directory of Open Access Journals (Sweden)

    Srđan Roglić

    2016-01-01

    Full Text Available Upon HIV infection diagnosis, an 8-month-old boy was transferred for evaluation of worsening respiratory distress requiring mechanical ventilation. Pneumocystis jirovecii pneumonia (PCP was diagnosed; the boy also had a nonhealing ulcer at the site of vaccination with Statens Serum Institut (Danish strain Bacillus Calmette-Guérin (BCG vaccine and associated axillary lymphadenopathy. PCP treatment resulted in weaning from mechanical ventilation. Antimycobacterial treatment was immediately attempted but was discontinued because of hepatotoxicity. Over several months, he developed splenic lesions and then disseminated skin and cystic bone lesions. M. bovis was repeatedly cultured from both skin and bone lesions despite various multidrug antimycobacterial regimens which included linezolid. Eventually, treatment with a regimen of rifabutin, isoniazid, ethambutol, and linezolid led to definitive cure. Clinicians should consider a linezolid-containing regimen for treatment of severe disseminated BCG infection, especially if other drug regimens have failed. Although drug toxicity is a particular concern for young children, this patient received linezolid for 13 months without serious toxicity. This case also highlights the need for universal screening among pregnant women to prevent vertical transmission of HIV. Finally, routine immunization with BCG vaccine at birth should be questioned in countries with low and declining burden of tuberculosis.

  8. Efficacy of imipenem/cilastatin in endocarditis.

    Science.gov (United States)

    Dickinson, G; Rodriguez, K; Arcey, S; Alea, A; Greenman, R

    1985-06-07

    Imipenem, a potent new beta-lactam antibiotic, which is bactericidal against most pathogenic bacteria, and cilastatin, a dehydropeptidase inhibitor combined with imipenem to prevent the metabolism of imipenem in the kidney, were evaluated in the treatment of bacterial endocarditis. Seventeen patients, including 14 who used intravenous drugs, were treated with imipenem/cilastatin in a dose of 500 mg each infused over 30 minutes every six hours. The mean duration of treatment was 29 days with a range of 21 to 56 days. Causative bacteria were Staphylococcus aureus in 10 patients, S. aureus plus group B Streptococcus in one, viridans group Streptococcus in two, Neisseria subflava, Eikenella corrodens, and group G Streptococcus in one patient, and Staphylococcus epidermidis, Hemophilus aphrophilus, and Enterobacter aerogenes in one patient each. The minimal bactericidal concentration of imipenem against 16 of 18 isolates tested was 0.04 micrograms/ml, 1 microgram/ml against H. aphrophilus, and 0.4 micrograms/ml against E. aerogenes. The site of infection was the right side of the heart in 11 patients, the left side in five, and both sides in one. The mean number of days to defervescence was 9.7. All patients were cured, and none required cardiac surgery. Adverse effects were few and interrupted treatment occurred in only one patient who had acute dyspnea during an infusion on Day 26 of therapy. Imipenem/cilastatin appears to be a relatively safe and highly effective treatment of staphylococcal endocarditis in intravenous drug users; too few patients with endocarditis caused by other bacteria were treated to allow a firm statement about efficacy in non-staphylococcal endocarditis.

  9. Antistaphylococcal Activity of DX-619 Alone and in Combination with Vancomycin, Teicoplanin, and Linezolid Assessed by Time-Kill Synergy Testing▿ †

    Science.gov (United States)

    Credito, Kim; Lin, Genrong; Appelbaum, Peter C.

    2007-01-01

    Time-kill synergy studies testing in vitro activity of DX-619 alone and with added vancomycin, teicoplanin, or linezolid against 101 Staphylococcus aureus strains showed synergy between DX-619 and teicoplanin at 12 to 24 h in 72 strains and between DX-619 and vancomycin in 28 strains. No synergy was found with linezolid, and no antagonism was observed with any combination. PMID:17261625

  10. Multicenter assessment of the linezolid spectrum and activity using the disk diffusion and Etest methods: report of the Zyvox® Antimicrobial Potency Study in Latin America (LA-ZAPS

    Directory of Open Access Journals (Sweden)

    Ballow Charles H.

    2002-01-01

    Full Text Available Linezolid was the first clinically applied member of the new antimicrobial class called the "oxazolidinones". These agents have a powerful spectrum of activity focussed against Gram-positive organisms including strains with documented resistances to other antimicrobial classes. We conducted a multicenter surveillance (Zyvox Antimicrobial Potency Study; ZAPS trial of qualifying Gram-positive isolates from 24 medical centers in eight countries in Latin America. The activity and spectrum of linezolid was compared to numerous agents including glycopeptides, quinupristin/dalfopristin, b-lactams and fluoroquinolones when testing 2,640 strains by the standardized disk diffusion method or Etest (AB BIODISK, Solna, Sweden. The linezolid spectrum was complete against staphylococci (median zone diameter, 29 - 32 mm, as was the spectrum of vancomycin and quinupristin/dalfopristin. Among the enterococci, no linezolid resistance was detected, and the susceptibility rate was 93.1 - 96.4%. Only the vancomycin-susceptible Enterococcus faecium strains remained susceptible (92.8% to quinupristin/dalfopristin. Marked differences in the glycopeptide resistance patterns (van A versus van B were noted for the 22 isolates of VRE, thus requiring local susceptibility testing to direct therapy. Streptococcus pneumoniae and other species were very susceptible (100.0% to linezolid, MIC90 at 0.75 mug/ml. Penicillin non-susceptible rate was 27.7% and erythromycin resistance was at 17.4%. Other streptococci were also completely susceptible to linezolid (MIC90, 1 mug/ml. These results provide the initial benchmark of potency and spectrum for linezolid in Latin American medical centers. Future comparisons should recognize that the oxazolidinones possess essentially a complete spectrum coverage of the monitored staphylococci, enterococci and streptococcal isolates in 2000-2001. This positions linezolid as the widest spectrum empiric choice against multi-resistant Gram

  11. Multicenter assessment of the linezolid spectrum and activity using the disk diffusion and Etest methods: report of the Zyvox® Antimicrobial Potency Study in Latin America (LA-ZAPS

    Directory of Open Access Journals (Sweden)

    Charles H. Ballow

    Full Text Available Linezolid was the first clinically applied member of the new antimicrobial class called the "oxazolidinones". These agents have a powerful spectrum of activity focussed against Gram-positive organisms including strains with documented resistances to other antimicrobial classes. We conducted a multicenter surveillance (Zyvox Antimicrobial Potency Study; ZAPS trial of qualifying Gram-positive isolates from 24 medical centers in eight countries in Latin America. The activity and spectrum of linezolid was compared to numerous agents including glycopeptides, quinupristin/dalfopristin, b-lactams and fluoroquinolones when testing 2,640 strains by the standardized disk diffusion method or Etest (AB BIODISK, Solna, Sweden. The linezolid spectrum was complete against staphylococci (median zone diameter, 29 - 32 mm, as was the spectrum of vancomycin and quinupristin/dalfopristin. Among the enterococci, no linezolid resistance was detected, and the susceptibility rate was 93.1 - 96.4%. Only the vancomycin-susceptible Enterococcus faecium strains remained susceptible (92.8% to quinupristin/dalfopristin. Marked differences in the glycopeptide resistance patterns (van A versus van B were noted for the 22 isolates of VRE, thus requiring local susceptibility testing to direct therapy. Streptococcus pneumoniae and other species were very susceptible (100.0% to linezolid, MIC90 at 0.75 mug/ml. Penicillin non-susceptible rate was 27.7% and erythromycin resistance was at 17.4%. Other streptococci were also completely susceptible to linezolid (MIC90, 1 mug/ml. These results provide the initial benchmark of potency and spectrum for linezolid in Latin American medical centers. Future comparisons should recognize that the oxazolidinones possess essentially a complete spectrum coverage of the monitored staphylococci, enterococci and streptococcal isolates in 2000-2001. This positions linezolid as the widest spectrum empiric choice against multi-resistant Gram

  12. Efficacy of antibiotic prophylaxis for prevention of native-valve endocarditis

    NARCIS (Netherlands)

    van der Meer, J. T.; van Wijk, W.; Thompson, J.; Vandenbroucke, J. P.; Valkenburg, H. A.; Michel, M. F.

    1992-01-01

    Whether antibiotic prophylaxis can prevent bacterial endocarditis is hotly debated. In an attempt to settle this issue, we have assessed the efficacy of prophylaxis for bacterial endocarditis on native valves in a nationwide, case-control study in the Netherlands. Cases were patients with known

  13. Twenty-Year Experience in the Diagnosis and Treatment of Infective Endocarditis.

    Science.gov (United States)

    Abramczuk, Elżbieta; Stępińska, Janina; Hryniewiecki, Tomasz

    2015-01-01

    The aim of this study was to compare the etiology, clinical course, selected diagnostic methods and efficacy of the treatment used in patients with infective endocarditis (IE) in the nineteen eighties and nineties. The study group comprised 300 patients with infective endocarditis hospitalized in the Institute of Cardiology in Warsaw in the following years: from 1982 to 1987 (150 patients: 75 successive patients with IE on the prosthetic valve and 75 successive patients with IE on the native valve), as well as from 1990 to 2003 (150 patients: 75 successive patients with IE on the prosthetic valve and 75 successive patients with IE on the native valve). In the nineties, immunological symptoms, embolism formation and progressive heart failure were diagnosed decidedly more frequently. Early prosthetic valve endocarditis (PVE) (up to 60 days after operation) occurred significantly more frequently in the eighties. The quantity of negative blood cultures in PVE has not decreased, it is still observed in over 20% of cases. For 20 years the etiology of PVE has remained the same, the dominant pathogen remains Staphylococcus. The frequency of PVE caused by Streptococci has markedly reduced. In both the decades analyzed the etiology of native valve endocarditis (NVE) was similar. In the eighties Streptococcus was predominant. In successive years the number of infections caused by Staphylococci was the same as that caused by Streptococci. The incidence of early PVE decreased in the nineties. More patients were treated surgically with lesser peri-operative mortality. A lower incidence of infective endocarditis on prosthetic valves caused by streptococci may signify better prophylaxis against infective endocarditis. Infective endocarditis with sterile blood cultures continues to occur frequently.

  14. Garenoxacin treatment of experimental endocarditis caused by viridans group streptococci.

    Science.gov (United States)

    Anguita-Alonso, Paloma; Rouse, Mark S; Piper, Kerryl E; Steckelberg, James M; Patel, Robin

    2006-04-01

    The activity of garenoxacin was compared to that of levofloxacin or penicillin in a rabbit model of Streptococcus mitis group (penicillin MIC, 0.125 microg/ml) and Streptococcus sanguinis group (penicillin MIC, 0.25 microg/ml) endocarditis. Garenoxacin and levofloxacin had MICs of 0.125 and 0.5 microg/ml, respectively, for both study isolates. Rabbits with catheter-induced aortic valve endocarditis were given no treatment, penicillin at 1.2x10(6) IU/8 h intramuscularly, garenoxacin at 20 mg/kg of body weight/12 h intravenously, or levofloxacin at 40 mg/kg/12 h intravenously. For both isolates tested, garenoxacin area under the curve (AUC)/MIC and maximum concentration of drug in serum (Cmax)/MIC ratios were 368 and 91, respectively. Rabbits were sacrificed after 3 days of treatment; cardiac valve vegetations were aseptically removed and quantitatively cultured. For S. mitis group experimental endocarditis, all studied antimicrobial agents were more active than no treatment (PS. sanguinis group endocarditis, no studied antimicrobial agents were more active than no treatment. We conclude that AUC/MIC and Cmax/MIC ratios may not predict activity of some quinolones in experimental viridans group endocarditis and that garenoxacin and levofloxacin may not be ideal choices for serious infections caused by some quinolone-susceptible viridans group streptococci.

  15. Association Between Transcatheter Aortic Valve Replacement and Subsequent Infective Endocarditis and In-Hospital Death.

    Science.gov (United States)

    Regueiro, Ander; Linke, Axel; Latib, Azeem; Ihlemann, Nikolaj; Urena, Marina; Walther, Thomas; Husser, Oliver; Herrmann, Howard C; Nombela-Franco, Luis; Cheema, Asim N; Le Breton, Hervé; Stortecky, Stefan; Kapadia, Samir; Bartorelli, Antonio L; Sinning, Jan Malte; Amat-Santos, Ignacio; Munoz-Garcia, Antonio; Lerakis, Stamatios; Gutiérrez-Ibanes, Enrique; Abdel-Wahab, Mohamed; Tchetche, Didier; Testa, Luca; Eltchaninoff, Helene; Livi, Ugolino; Castillo, Juan Carlos; Jilaihawi, Hasan; Webb, John G; Barbanti, Marco; Kodali, Susheel; de Brito, Fabio S; Ribeiro, Henrique B; Miceli, Antonio; Fiorina, Claudia; Dato, Guglielmo Mario Actis; Rosato, Francesco; Serra, Vicenç; Masson, Jean-Bernard; Wijeysundera, Harindra C; Mangione, Jose A; Ferreira, Maria-Cristina; Lima, Valter C; Carvalho, Luiz A; Abizaid, Alexandre; Marino, Marcos A; Esteves, Vinicius; Andrea, Julio C M; Giannini, Francesco; Messika-Zeitoun, David; Himbert, Dominique; Kim, Won-Keun; Pellegrini, Costanza; Auffret, Vincent; Nietlispach, Fabian; Pilgrim, Thomas; Durand, Eric; Lisko, John; Makkar, Raj R; Lemos, Pedro A; Leon, Martin B; Puri, Rishi; San Roman, Alberto; Vahanian, Alec; Søndergaard, Lars; Mangner, Norman; Rodés-Cabau, Josep

    2016-09-13

    Limited data exist on clinical characteristics and outcomes of patients who had infective endocarditis after undergoing transcatheter aortic valve replacement (TAVR). To determine the associated factors, clinical characteristics, and outcomes of patients who had infective endocarditis after TAVR. The Infectious Endocarditis after TAVR International Registry included patients with definite infective endocarditis after TAVR from 47 centers from Europe, North America, and South America between June 2005 and October 2015. Transcatheter aortic valve replacement for incidence of infective endocarditis and infective endocarditis for in-hospital mortality. Infective endocarditis and in-hospital mortality after infective endocarditis. A total of 250 cases of infective endocarditis occurred in 20 006 patients after TAVR (incidence, 1.1% per person-year; 95% CI, 1.1%-1.4%; median age, 80 years; 64% men). Median time from TAVR to infective endocarditis was 5.3 months (interquartile range [IQR], 1.5-13.4 months). The characteristics associated with higher risk of progressing to infective endocarditis after TAVR was younger age (78.9 years vs 81.8 years; hazard ratio [HR], 0.97 per year; 95% CI, 0.94-0.99), male sex (62.0% vs 49.7%; HR, 1.69; 95% CI, 1.13-2.52), diabetes mellitus (41.7% vs 30.0%; HR, 1.52; 95% CI, 1.02-2.29), and moderate to severe aortic regurgitation (22.4% vs 14.7%; HR, 2.05; 95% CI, 1.28-3.28). Health care-associated infective endocarditis was present in 52.8% (95% CI, 46.6%-59.0%) of patients. Enterococci species and Staphylococcus aureus were the most frequently isolated microorganisms (24.6%; 95% CI, 19.1%-30.1% and 23.3%; 95% CI, 17.9%-28.7%, respectively). The in-hospital mortality rate was 36% (95% CI, 30.0%-41.9%; 90 deaths; 160 survivors), and surgery was performed in 14.8% (95% CI, 10.4%-19.2%) of patients during the infective endocarditis episode. In-hospital mortality was associated with a higher logistic EuroSCORE (23.1% vs 18.6%; odds ratio

  16. New intracanal formulations containing doxycycline or chlorhexidine against Enterococcus faecalis.

    Science.gov (United States)

    Silva, Ana Rita Marques da; Pinto, Shelon Cristina Souza; Santos, Elizabete Brasil dos; Santos, Fábio André dos; Farago, Paulo Vitor; Gomes, João Carlos; Pina-Vaz, Irene; Carvalho, Manuel Fontes

    2014-01-01

    The present study aims to evaluate the antimicrobial effect of two new intracanal preparations against E. faecalis. Thirty single-rooted human canine teeth were used. The crowns were removed and the roots were instrumented using a conventional technique. Three groups of ten teeth each were infected with 108 CFU/ ml of E. faecalis for 21 days. The root canals were flled with new intracanal medications containing 3% doxycycline hydrochloride (DX) or 2% chlorhexidine digluconate (CHX). Ten teeth received no medication (NM)-negative control. Microbial samples were obtained 21 days after contamination: 14 days under the effect of the intracanal medications and 7 days after replacing the medications by BHI broth. The samples were homogenized, diluted, seeded on BHI agar and incubated for 48h/36°C. The number of colony forming units (CFU/ml) was obtained and analyzed statistically. All intracanal dressings significantly reduced the number of bacterial cells in the root canal after 14 days with medication. After the period with 7 days with BHI broth, the CFU counts of E. faecalis remained at low values. However, the NM group showed a significant increase of CFU in this period to similar values of the initial contamination. 3% doxycycline hydrochloride gel and 2% CHX gel were effective to eliminate E. faecalis from the root canal system.

  17. Infective endocarditis following transcatheter aortic valve replacement-

    DEFF Research Database (Denmark)

    Loh, Poay Huan; Bundgaard, Henning; S�ndergaard, Lars

    2013-01-01

    Transcatheter aortic valve replacement (TAVR) can improve the symptoms and prognosis of patients with severe aortic stenosis who, due to a high expected operative risk, would not have otherwise been treated surgically. If these patients develop prosthetic valve endocarditis, their presentations may...... be atypical causing a delay in the diagnosis and treatment. The management is also complicated by their comorbidities, and surgical treatment may not be feasible leading to a significant morbidity and mortality. We describe a case of an 85-year-old man with TAVI prosthetic valve endocarditis successfully...

  18. Genetic diversity of Enterococcus faecalis isolated from environmental, animal and clinical sources in Malaysia

    Directory of Open Access Journals (Sweden)

    Diane S. Daniel

    2017-09-01

    Full Text Available Enterococcus faecalis ranks as one of the leading causes of nosocomial infections. A strong epidemiological link has been reported between E. faecalis inhabiting animals and environmental sources. This study investigates the genetic diversity, antibiotic resistance and virulence determinants in E. faecalis from three sources in Malaysia. A total of 250 E. faecalis isolates were obtained consisting of 120 isolates from farm animals, 100 isolates from water sources and 30 isolates from hospitalized patients. Pulse-field gel electrophoresis-typing yielded 63 pulsotypes, with high diversity observed in all sources (D = ≥0.901. No pulsotype was common to all the three sources. Each patient room had its own unique PFGE pattern which persisted after six months. Minimum inhibitory concentrations of Vancomycin, Gentamicin, Penicillin, Tetracycline, Nitrofurantoin, Levofloxacin, Ciprofloxacin and Fosfomycin were evaluated. Resistance to Tetracycline was most prevalent in isolates from farm animals (62% and water sources (49%. Water isolates (86% had a higher prevalence of the asa1 gene, which encodes for aggregation substance, whereas clinical (78% and farm animal isolates (87% had a higher prevalence of the esp gene, encoding a surface exposed protein. This study generates knowledge on the genetic diversity of E. faecalis with antibiotic resistance and virulence characteristics from various sources in Malaysia. Keywords: Antibiotic resistance, Enterococcus faecalis, Genetic diversity, Molecular typing, Virulence markers

  19. Attachment of associative diazotroph alcaligenes faecalis to rice roots

    International Nuclear Information System (INIS)

    Lin Min; Fang Xuanjun; You Chongbiao

    1993-01-01

    The process of attachment of diazotroph Alcaligenes faecalis to host plant rice was studied by using 15 N-labelled bacteria and Tn5-induced mutants. A three-step attachment mechanism of A. faecalis to rice root surface is proposed on the basis of experimental data. Adsorption is the first step. The number of adsorbed bacteria reaches maximal level after 3 h of inoculation, it consists 3.7% of the total number of bacteria inoculated. Adsorbed bacteria could be removed from rice root surface quantitatively by shaking in water. Therefore, the adsorption forces are weak. Anchoring is the second step. It begins only after 9h of inoculation and reaches a maximal level (21%) after 16 h. Anchored bacteria could not be removed by shaking. Colonization is the third step. After 20 h of inoculation. part of anchored bacteria colonizes on rice root surface tightly, and it can not be removed by vortex. At this time, the pectolytic activity of bacteria appears. Chemotaxis and exopolysaccharide (EPS) play important roles in the attachment of A. faecalis to rice root surface. EPS mutants (Exo - , Exo ++ ) showed less anchoring-capability in comparison with wild type of bacterium, but they remained the adsorption capability. While chemotaxis (Che - ) mutants are defective in adsorption, but not in anchoring. Che - , Exo - mutant lost both adsorption and anchoring capabilities. A. faecalis absorbed on all part of rice root, but the anchoring and colonization of bacteria were occurred mainly on root hairs, particularly on the joint area of main root and lateral root

  20. A 10-Year Experience of Therapeutic Drug Monitoring (TDM) of Linezolid in a Hospital-wide Population of Patients Receiving Conventional Dosing: Is there Enough Evidence for Suggesting TDM in the Majority of Patients?

    Science.gov (United States)

    Pea, Federico; Cojutti, Pier Giorgio; Baraldo, Massimo

    2017-10-01

    A retrospective study was conducted to assess our 10-year experience of therapeutic drug monitoring (TDM) of linezolid in a large patient population to establish whether conventional dosing may result in adequate drug exposure in the majority of patients. Patients included in this study underwent TDM of linezolid trough concentration (C min ) during treatment with conventional doses of 600 mg every 12 hr in the period between January 2007 and June 2016. The desired range of C min was set between 2 and 7 mg/L (underexposure, C min   7 mg/L). Multivariate logistic regression analysis investigated variables potentially correlated with linezolid C min . One thousand and forty-nine patients had 2484 linezolid C min assessed during treatment with conventional doses. Median (IQR) linezolid C min was 5.08 mg/L (2.78-8.52 mg/L). Linezolid C min was within the desired range in 50.8% of cases (1262/2484). Overexposure (n = 821; 33%) occurred much more frequently than underexposure (n = 401; 16.2%) and was severe (>20 mg/L) in 3.9% of cases (98/2484). Linezolid overexposure was significantly associated with CrCL C -G estimates ≤40 mL/min. (OR 1.463; 95% CI 1.124-1.904, p = 0.005). Linezolid underexposure was significantly associated with CrCL C -G estimates >100 mL/min. (OR 3.046; 95% CI 2.234-4.152, p Linezolid C min was not correlated linearly with CrCL C -G (R 2  = 0.061). Variability in renal function explained only partially the very wide interindividual linezolid C min variability. Our study suggests that TDM could represent a valuable approach in optimizing linezolid exposure in the majority of patients. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  1. [Aortic infective endocarditis: Value of surgery. About 48 cases].

    Science.gov (United States)

    Tribak, M; Konaté, M; Elhassani, A; Mahfoudi, L; Jaabari, I; Elkenassi, F; Boutayeb, A; Lachhab, F; Filal, J; Maghraoui, A; Bensouda, A; Marmade, L; Moughil, S

    2016-02-01

    Infective endocarditis (IE) is a serious disease whose prognosis depends on early management. Aortic location is characterized by its evolution toward myocardial failure and the high number of complications reasons for early surgery. To compare the short- and mid-terms results of surgery for aortic infective endocarditis (IE) in the active phase and the healed phase. We analyzed retrospectively the data of 48 consecutive patients operated for aortic infective endocarditis between January 2000 and January 2012. The data on operative mortality, morbidity and major cardiovascular events (mortality, recurrent endocarditis, reintervention, and stroke) were analyzed. Twenty-three patients (48%) underwent surgery during the active phase (group I), 19 on native and 4 on prosthetic valves, and 25 patients (52%) were operated during healed endocarditis (group II) only on native valve. Mean age was 39 years (12-81) with a male predominance (83%). Rheumatic valvular disease was the main etiology of underlying valvular disease in both groups (85%). The clinical feature was dominated by signs of cardiogenic shock in group I and dyspnea exertion stage III-IV NYHA in group II. Streptococcus and Staphylococcus germs were most frequently encountered. Indication for surgery was heart failure in group I, it was related to the symptoms, the severity of valvular disease and its impact on the left ventricle in group II. An aortic valve replacement with a mechanical prosthesis was performed in the majority of cases (83%). Postoperative mortality concerned only one patient in group I. Twenty-one patients (44%) were followed for a mean of 30 months (1-72). One patient in group II died following cerebral hemorrhagic stroke related to accident with vitamin K antagonist. In both groups, there was an improvement in the functional class. No recurrence of endocarditis was noted in both groups during follow-up. The prognosis of infective endocarditis of the aortic valve is severe due to the fast

  2. In vitro Assays of Staphylococcus epidermidis Characteristics and Outcome in an Endocarditis Model

    Directory of Open Access Journals (Sweden)

    Betty Herndon

    1993-01-01

    Full Text Available Objective: Staphylococcus epidermidis adherence to indwelling polymers is important in prosthetic valve endocarditis. Earlier studies have related streptococcal endocarditis to isolates with high levels of cell-associated hexoses. The objective of the present study was to determine if a relationship exists between an S epidermidis isolate assay score and production/severity of experimental endocarditis.

  3. [Antineutrophil cytoplasmic antibodies associated with infective endocarditis: Literature review].

    Science.gov (United States)

    Langlois, V; Marie, I

    2017-07-01

    Antineutrophil cytoplasmic antibodies (ANCA) associated with infective endocarditis are a rare disorder. The condition can mimic primary systemic vasculitis (i.e. granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis). Thus, a wrong diagnosis of valvular involvement related to primary systemic vasculitis can be made in patients exhibiting ANCA associated with infective endocarditis. Because treatment of both conditions is different, this wrong diagnosis will lead to dramatic consequences in these latter patients. This review reports the state of knowledge and proposes an algorithm to follow when confronted to a possible case of ANCA associated with infective endocarditis. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  4. [Aspergillus fumigatus endocarditis in a patient with a biventricular pacemaker].

    Science.gov (United States)

    Cuesta, José M; Fariñas, María C; Rodilla, Irene G; Salesa, Ricardo; de Berrazueta, José R

    2005-05-01

    Aspergillus fumigatus endocarditis is one of the rarest and severest complications in cardiological patients. We describe a patient with an intracardial pacemaker who was diagnosed as having Aspergillus fumigatus endocarditis. Postmortem examination showed a large, Aspergillus-infected thrombus encased in the right ventricle, pulmonary trunk and main pulmonary branches.

  5. Infective endocarditis prophylaxis: current practice trend among paediatric cardiologists: are we following the 2007 guidelines?

    Science.gov (United States)

    Naik, Ronak J; Patel, Neil R; Wang, Ming; Shah, Nishant C

    2016-08-01

    In 2007, the American Heart Association modified the infective endocarditis prophylaxis guidelines by limiting the use of antibiotics in patients with cardiac conditions associated with the highest risk of adverse outcomes after infective endocarditis. Our objective was to evaluate current practice for infective endocarditis prophylaxis among paediatric cardiologists. A web-based survey focussing on current practice, describing the use of antibiotics for infective endocarditis prophylaxis in various congenital and acquired heart diseases, was distributed via e-mail to paediatric cardiologists. The survey was kept anonymous and was distributed twice. Data from 253 participants were analysed. Most paediatric cardiologists discontinued infective endocarditis prophylaxis in patients with simple lesions such as small ventricular septal defect, patent ductus arteriosus, and bicuspid aortic valve without stenosis or regurgitation; however, significant disagreement persists in prescribing infective endocarditis prophylaxis in certain conditions such as rheumatic heart disease, Fontan palliation without fenestration, and the Ross procedure. Use of antibiotic prophylaxis in certain selected conditions for which infective endocarditis prophylaxis has been indicated as per the current guidelines varies from 44 to 83%. Only 44% follow the current guidelines exclusively, and 34% regularly discuss the importance of oral hygiene with their patients at risk for infective endocarditis. Significant heterogeneity still persists in recommending infective endocarditis prophylaxis for several cardiac lesions among paediatric cardiologists. More than half of the participants (56%) do not follow the current guidelines exclusively in their practice. Counselling for optimal oral health in patients at risk for infective endocarditis needs to be optimised in the current practice.

  6. Investigating the mobilome in clinically important lineages of Enterococcus faecium and Enterococcus faecalis.

    Science.gov (United States)

    Mikalsen, Theresa; Pedersen, Torunn; Willems, Rob; Coque, Teresa M; Werner, Guido; Sadowy, Ewa; van Schaik, Willem; Jensen, Lars Bogø; Sundsfjord, Arnfinn; Hegstad, Kristin

    2015-04-10

    The success of Enterococcus faecium and E. faecalis evolving as multi-resistant nosocomial pathogens is associated with their ability to acquire and share adaptive traits, including antimicrobial resistance genes encoded by mobile genetic elements (MGEs). Here, we investigate this mobilome in successful hospital associated genetic lineages, E. faecium sequence type (ST)17 (n=10) and ST78 (n=10), E. faecalis ST6 (n=10) and ST40 (n=10) by DNA microarray analyses. The hybridization patterns of 272 representative targets including plasmid backbones (n=85), transposable elements (n=85), resistance determinants (n=67), prophages (n=29) and clustered regularly interspaced short palindromic repeats (CRISPR)-cas sequences (n=6) separated the strains according to species, and for E. faecalis also according to STs. RCR-, Rep_3-, RepA_N- and Inc18-family plasmids were highly prevalent and with the exception of Rep_3, evenly distributed between the species. There was a considerable difference in the replicon profile, with rep 17/pRUM , rep 2/pRE25 , rep 14/EFNP1 and rep 20/pLG1 dominating in E. faecium and rep 9/pCF10 , rep 2/pRE25 and rep 7 in E. faecalis strains. We observed an overall high correlation between the presence and absence of genes coding for resistance towards antibiotics, metals, biocides and their corresponding MGEs as well as their phenotypic antimicrobial susceptibility pattern. Although most IS families were represented in both E. faecalis and E. faecium, specific IS elements within these families were distributed in only one species. The prevalence of IS256-, IS3-, ISL3-, IS200/IS605-, IS110-, IS982- and IS4-transposases was significantly higher in E. faecium than E. faecalis, and that of IS110-, IS982- and IS1182-transposases in E. faecalis ST6 compared to ST40. Notably, the transposases of IS981, ISEfm1 and IS1678 that have only been reported in few enterococcal isolates were well represented in the E. faecium strains. E. faecalis ST40 strains harboured

  7. Tropheryma whipplei tricuspid endocarditis: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Greub Gilbert

    2010-08-01

    Full Text Available Abstract Introduction The main clinical manifestations of Whipple's disease are weight loss, arthropathy, diarrhea and abdominal pain. Cardiac involvement is frequently described. However, endocarditis is rare and is not usually the initial presentation of the disease. To the best of our knowledge, this is the first reported case of a patient with Tropheryma whipplei tricuspid endocarditis without any other valve involved and not presenting signs of arthralgia and abdominal involvement. Case presentation We report a case of a 50-year-old Caucasian man with tricuspid endocarditis caused by Tropheryma whipplei, showing signs of severe shock and an absence of other more classic clinical signs of Whipple's disease, such as arthralgia, abdominal pain and diarrhea. Tropheryma whipplei was documented by polymerase chain reaction of the blood and pleural fluid. The infection was treated with a combined treatment of doxycycline, hydroxychloroquine and sulfamethoxazole-trimethoprim for one year. Conclusion Tropheryma whipplei infectious endocarditis should always be considered when facing a blood-culture negative endocarditis particularly in right-sided valves. Although not standardized yet, treatment of Tropheryma whipplei endocarditis should probably include a bactericidal antibiotic (such as doxycycline and should be given over a prolonged period of time (a minimum of one year.

  8. Incidence of infective endocarditis in England, 2000-13: a secular trend, interrupted time-series analysis.

    Science.gov (United States)

    Dayer, Mark J; Jones, Simon; Prendergast, Bernard; Baddour, Larry M; Lockhart, Peter B; Thornhill, Martin H

    2015-03-28

    Antibiotic prophylaxis given before invasive dental procedures in patients at risk of developing infective endocarditis has historically been the focus of infective endocarditis prevention. Recent changes in antibiotic prophylaxis guidelines in the USA and Europe have substantially reduced the number of patients for whom antibiotic prophylaxis is recommended. In the UK, guidelines from the National Institute for Health and Clinical Excellence (NICE) recommended complete cessation of antibiotic prophylaxis for prevention of infective endocarditis in March, 2008. We aimed to investigate changes in the prescribing of antibiotic prophylaxis and the incidence of infective endocarditis since the introduction of these guidelines. We did a retrospective secular trend study, analysed as an interrupted time series, to investigate the effect of antibiotic prophylaxis versus no prophylaxis on the incidence of infective endocarditis in England. We analysed data for the prescription of antibiotic prophylaxis from Jan 1, 2004, to March 31, 2013, and hospital discharge episode statistics for patients with a primary diagnosis of infective endocarditis from Jan 1, 2000, to March 31, 2013. We compared the incidence of infective endocarditis before and after the introduction of the NICE guidelines using segmented regression analysis of the interrupted time series. Prescriptions of antibiotic prophylaxis for the prevention of infective endocarditis fell substantially after introduction of the NICE guidance (mean 10,900 prescriptions per month [Jan 1, 2004, to March 31, 2008] vs 2236 prescriptions per month [April 1, 2008, to March 31, 2013], pinfective endocarditis increased significantly above the projected historical trend, by 0·11 cases per 10 million people per month (95% CI 0·05-0·16, pinfective endocarditis was significant for both individuals at high risk of infective endocarditis and those at lower risk. Although our data do not establish a causal association, prescriptions

  9. Twenty-Year Experience in the Diagnosis and Treatment of Infective Endocarditis

    Science.gov (United States)

    2015-01-01

    Aims The aim of this study was to compare the etiology, clinical course, selected diagnostic methods and efficacy of the treatment used in patients with infective endocarditis (IE) in the nineteen eighties and nineties. Material and Methods The study group comprised 300 patients with infective endocarditis hospitalized in the Institute of Cardiology in Warsaw in the following years: from 1982 to 1987 (150 patients: 75 successive patients with IE on the prosthetic valve and 75 successive patients with IE on the native valve), as well as from 1990 to 2003 (150 patients: 75 successive patients with IE on the prosthetic valve and 75 successive patients with IE on the native valve). Results In the nineties, immunological symptoms, embolism formation and progressive heart failure were diagnosed decidedly more frequently. Early prosthetic valve endocarditis (PVE) (up to 60 days after operation) occurred significantly more frequently in the eighties. The quantity of negative blood cultures in PVE has not decreased, it is still observed in over 20% of cases. For 20 years the etiology of PVE has remained the same, the dominant pathogen remains Staphylococcus. The frequency of PVE caused by Streptococci has markedly reduced. In both the decades analyzed the etiology of native valve endocarditis (NVE) was similar. In the eighties Streptococcus was predominant. In successive years the number of infections caused by Staphylococci was the same as that caused by Streptococci. Conclusions The incidence of early PVE decreased in the nineties. More patients were treated surgically with lesser peri-operative mortality. A lower incidence of infective endocarditis on prosthetic valves caused by streptococci may signify better prophylaxis against infective endocarditis. Infective endocarditis with sterile blood cultures continues to occur frequently. PMID:26230402

  10. Tricuspid valve endocarditis caused by Eikenella corrodens

    Directory of Open Access Journals (Sweden)

    Martin Tretjak

    2015-06-01

    Full Text Available AbstractBackground. Infectious endocarditis of the tricuspid valve is rare in non-intravenous drug users and patients without central venous devices. The most frequent causative agents are staphylococci, rarely other bacteria.Methods. We describe a case of a 57-year-old patient without history of drug abuse that was admitted to our hospital because of fever with chills, dry cough, loss of appetite and wasting lasting for a few months. He had a venous ulcer on the right foot and interdigital inflammation on both feet. Eikenella corrodens was isolated from blood cultures. Transthoracic echocardiography showed a large vegetation on the anterior leaflet of tricuspid valve. CT scan oh the thorax showed probable septic emboli. The patient was treated conservatively with prolonged double antibiotic regimen. During the treatment there were no further complications.Conclusions. In our patients a rare form of tricuspid valve endocarditis was confirmed, caused by Eikenella corrodens. The possibility of infectious endocarditis should always be considered in patients with prolonged fever, especially when a possible causative agent is isolated from blood cultures.

  11. Cardiopulmonary manifestations of isolated pulmonary valve infective endocarditis demonstrated with cardiac CT.

    Science.gov (United States)

    Passen, Edward; Feng, Zekun

    2015-01-01

    Right-sided infective endocarditis involving the pulmonary valve is rare. This pictorial essay discusses the use and findings of cardiac CT combined with delayed chest CT and noncontrast chest CT of pulmonary valve endocarditis. Cardiac CT is able to show the full spectrum of right-sided endocarditis cardiopulmonary features including manifestations that cannot be demonstrated by echocardiography. Copyright © 2015 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

  12. Severe infective endocarditis in a healthy adult due to Streptococcus agalactiae.

    Science.gov (United States)

    Fujita, Hiroaki; Nakamura, Itaru; Tsukimori, Ayaka; Sato, Akihiro; Ohkusu, Kiyofumi; Matsumoto, Tetsuya

    2015-09-01

    A case of severe endocarditis, with complications of multiple infarction, meningitis, and ruptured mitral chordae tendineae, caused by Streptococcus agalactiae in a healthy man, is reported. Emergency cardiovascular surgery was performed on the day of admission. Infective endocarditis caused by S. agalactiae is very rare, particularly in a healthy adult. In addition, microbiological analysis revealed that S. agalactiae of sequence type (ST) 19, which belongs to serotype III, was present in the patient's vegetation, mitral valve, and blood culture. It was therefore concluded that the endocarditis was caused by ST19, which has been reported as a non-invasive type of S. agalactiae. This was an extremely rare case in which S. agalactiae of ST19 caused very severe endocarditis in an adult patient with no underlying disease. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Dentigenous infectious foci - a risk factor of infective endocarditis.

    Science.gov (United States)

    Wisniewska-Spychala, Beata; Sokalski, Jerzy; Grajek, Stefan; Jemielity, Marek; Trojnarska, Olga; Choroszy-Krol, Irena; Sójka, Anna; Maksymiuk, Tomasz

    2012-02-01

    Dentigenous, infectious foci are frequently associated with the development of various diseases. The role of such foci in the evolution of endocarditis still remains unclear. This article presents the concluding results of an interdisciplinary study verifying the influence of dentigenous, infectious foci on the development of infective endocarditis. The study subjects were 60 adult patients with history of infective endocarditis and coexistent acquired heart disease, along with the presence at least 2 odontogenic infectious foci (ie, 2 or more teeth with gangrenous pulp and periodontitis). The group had earlier been qualified for the procedure of heart valve replacement. Swabs of removed heart valve tissue with inflammatory lesions and blood were then examined microbiologically. Swabs of root canals and their periapical areas, of periodontal pockets, and of heart valves were also collected. Microbial flora, cultured from intradental foci, blood and heart valves, fully corresponded in 14 patients. This was accompanied in almost all cases by more advanced periodontitis (2nd degree, Scandinavian classification), irrespective of the bacterial co-occurrence mentioned. In the remaining patients, such consistency was not found. Among various dentigenous, infectious foci, the intradental foci appear to constitute a risk factor for infective endocarditis.

  14. Triple valve endocarditis by mycobacterium tuberculosis. A case report

    Directory of Open Access Journals (Sweden)

    Shaikh Quratulain

    2012-09-01

    Full Text Available Abstract Background Granulomas caused by Mycobacterium Tuberculosis have been observed at autopsy in the heart, pre-dominantly in the myocardium and endocardium, but rarely involving the coronary vessels and valvular structures. Mycobacterium tuberculosis valvular endocarditis is extremely rare, with most reports coming from autopsy series. Case presentation We report the case of a 17 year old immunocompetent girl who presented with history of fever, malaise, foot gangrene and a left sided hemiparesis. On investigation she was found to have infective endocarditis involving the aortic, mitral and tricuspid valves. She had developed a right middle cerebral artery stroke. She underwent dual valve replacement and tricuspid repair. The vegetations showed granulomatous inflammation but blood cultures and other biological specimen cultures were negative for any organisms. She was started on antituberculous treatment and anticoagulation. Conclusion This is the first reported case of triple valve endocarditis by Mycobacterium Tuberculosis in an immunocompetent host. Especially important is the fact that the right heart is involved which has been historically described in the setting of intravenous drug abuse. This implies that Tuberculosis should be considered in cases of culture negative endocarditis in endemic areas like Pakistan even in immunocompetent hosts.

  15. Native valve endocarditis due to Candida parapsilosis in an adult ...

    African Journals Online (AJOL)

    spectrum antimicrobial agents, pre-existing valvular heart disease and. HIV infection. A catheter-related portal of entry has been reported in. 80% of cases of C. parapsilosis endocarditis in one series of Candida endocarditis cases.[5] Other described risk factors include abdominal surgery, IV drug use and prosthetic heart ...

  16. Usefulness of three-dimensional echocardiography in the assessment of valvular involvement in Loeffler endocarditis.

    Science.gov (United States)

    Hernandez, Carlos M; Arisha, Mohammed J; Ahmad, Amier; Oates, Ethan; Nanda, Navin C; Nanda, Anil; Wasan, Anita; Caleti, Beda E; Bernal, Cinthia L P; Gallardo, Sergio M

    2017-07-01

    Loeffler endocarditis is a complication of hypereosinophilic syndrome resulting from eosinophilic infiltration of heart tissue. We report a case of Loeffler endocarditis in which three-dimensional transthoracic and transesophageal echocardiography provided additional information to what was found by two-dimensional transthoracic echocardiography alone. Our case illustrates the usefulness of combined two- and three-dimensional echocardiography in the assessment of Loeffler endocarditis. In addition, a summary of the features of hypereosinophilic syndrome and Loeffler endocarditis is provided in tabular form. © 2017, Wiley Periodicals, Inc.

  17. Superantigens are critical for Staphylococcus aureus Infective endocarditis, sepsis, and acute kidney injury.

    Science.gov (United States)

    Salgado-Pabón, Wilmara; Breshears, Laura; Spaulding, Adam R; Merriman, Joseph A; Stach, Christopher S; Horswill, Alexander R; Peterson, Marnie L; Schlievert, Patrick M

    2013-08-20

    Infective endocarditis and kidney infections are serious complications of Staphylococcus aureus sepsis. We investigated the role of superantigens (SAgs) in the development of lethal sepsis, infective endocarditis, and kidney infections. SAgs cause toxic shock syndrome, but it is unclear if SAgs contribute to infective endocarditis and kidney infections secondary to sepsis. We show in the methicillin-resistant S. aureus strain MW2 that lethal sepsis, infective endocarditis, and kidney infections in rabbits are critically dependent on high-level SAgs. In contrast, the isogenic strain lacking staphylococcal enterotoxin C (SEC), the major SAg in this strain, is attenuated in virulence, while complementation restores disease production. SAgs' role in infective endocarditis appears to be both superantigenicity and direct endothelial cell stimulation. Maintenance of elevated blood pressure by fluid therapy significantly protects from infective endocarditis, possibly through preventing bacterial accumulation on valves and increased SAg elimination. These data should facilitate better methods to manage these serious illnesses. The Centers for Disease Control and Prevention reported in 2007 that Staphylococcus aureus is the most significant cause of serious infectious diseases in the United States (R. M. Klevens, M. A. Morrison, J. Nadle, S. Petit, K. Gershman, et al., JAMA 298:1763-1771, 2007). Among these infections are sepsis, infective endocarditis, and acute kidney injury. Infective endocarditis occurs in 30 to 60% of patients with S. aureus bacteremia and carries a mortality rate of 40 to 50%. Over the past decades, infective endocarditis outcomes have not improved, and infection rates are steadily increasing (D. H. Bor, S. Woolhandler, R. Nardin, J. Brusch, D. U. Himmelstein, PLoS One 8:e60033, 2013). There is little understanding of the S. aureus virulence factors that are key for infective endocarditis development and kidney abscess formation. We demonstrate that

  18. The value of {sup 18}F-FDG PET/CT in diagnosing infectious endocarditis

    Energy Technology Data Exchange (ETDEWEB)

    Kouijzer, Ilse J.E. [Radboud University Nijmegen Medical Centre, Department of Internal Medicine, P.O. Box 9101, Nijmegen (Netherlands); Vos, Fidel J. [Radboud University Nijmegen Medical Centre, Department of Internal Medicine, P.O. Box 9101, Nijmegen (Netherlands); Sint Maartenskliniek, Nijmegen (Netherlands); Janssen, Marcel J.R. [Radboud University Nijmegen Medical Centre, Department of Nuclear Medicine, Nijmegen (Netherlands); Dijk, Arie P.J. van [Radboud University Nijmegen Medical Centre, Department of Cardiology, Nijmegen (Netherlands); Oyen, Wim J.G. [Radboud University Nijmegen Medical Centre, Department of Nuclear Medicine, Nijmegen (Netherlands); Radboud University Nijmegen Medical Centre, Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Nijmegen (Netherlands); Bleeker-Rovers, Chantal P. [Radboud University Nijmegen Medical Centre, Department of Internal Medicine, P.O. Box 9101, Nijmegen (Netherlands); Radboud University Nijmegen Medical Centre, Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Nijmegen (Netherlands)

    2013-07-15

    Early detection of infectious endocarditis is challenging. For diagnosing infectious endocarditis, the revised Duke criteria are the gold standard. Evidence of endocardial involvement on echocardiography is a major criterion, but sensitivity and specificity of echocardiography are not optimal. Here we investigated the utility of {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography and computed tomography (PET/CT) to diagnose infectious endocarditis in patients with gram-positive bacteraemia. Seventy-two patients with gram-positive bacteraemia were prospectively included. Patients with a positive blood culture growing Staphylococcus aureus, Streptococcus species or Enterococcus species were eligible when a risk factor for developing metastatic infectious foci was present. Infectious endocarditis was defined according to the revised Duke criteria. All patients underwent {sup 18}F-FDG PET/CT and echocardiography. {sup 18}F-FDG uptake in or around the heart valves was evaluated independently by two nuclear medicine physicians. Sensitivity for diagnosing infectious endocarditis with {sup 18}F-FDG PET/CT was 39 % and specificity was 93 %. The positive predictive value was 64 % and negative predictive value was 82 %. The mortality rate in patients without infectious endocarditis and without increased {sup 18}F-FDG uptake in or around the heart valves was 18 %, and in patients without infectious endocarditis but with high {sup 18}F-FDG uptake in or around the heart valves the mortality rate was 50 % (p = 0.181). {sup 18}F-FDG PET/CT is currently not sufficiently adequate for the diagnosis of infectious endocarditis because of its low sensitivity. Improvements such as patient preparation with low carbohydrate-fat allowed diet and technical advances in the newest PET/CT scanners may increase sensitivity in future studies. (orig.)

  19. 18F-FDG-PET/CT Angiography for the Diagnosis of Infective Endocarditis.

    Science.gov (United States)

    Roque, A; Pizzi, M N; Cuéllar-Calàbria, H; Aguadé-Bruix, S

    2017-02-01

    This article reviews the current imaging role of 18 F-fluordeoxyglucose positron emission computed tomography ( 18 F-FDG-PET/CT) combined with cardiac CT angiography (CTA) in infective endocarditis and discusses the strengths and limitations of this technique. The diagnosis of infective endocarditis affecting prosthetic valves and intracardiac devices is challenging because echocardiography and, therefore, the modified Duke criteria have well-recognized limitations in this clinical scenario. The high sensitivity of 18 F-FDG-PET/CT for the detection of infection associated with the accurate definition of structural damage by gated cardiac CTA in a combined technique (PET/CTA) has provided a significant increase in diagnostic sensitivity for the detection of IE. PET/CTA has proven to be a useful diagnostic tool in patients with suspected infective endocarditis. The additional information provided by this technique improves diagnostic performance in prosthetic valve endocarditis when it is used in combination with the Duke criteria. The findings obtained in PET/CTA studies have been included as a major criterion in the recently updated diagnostic algorithm in infective endocarditis guidelines.

  20. Comparing the cost-effectiveness of linezolid to trimethoprim/sulfamethoxazole plus rifampicin for the treatment of methicillin-resistant Staphylococcus aureus infection: a healthcare system perspective.

    Science.gov (United States)

    von Dach, E; Morel, C M; Murthy, A; Pagani, L; Macedo-Vinas, M; Olearo, F; Harbarth, S

    2017-09-01

    Few industry-independent studies have been conducted to compare the relative costs and benefits of drugs to treat methicillin-resistant Staphylococcus aureus (MRSA) infection. We performed a stochastic cost-effectiveness analysis comparing two treatment strategies-linezolid versus trimethoprim-sulfamethoxazole plus rifampicin-for the treatment of MRSA infection. We used cost and effectiveness data from a previously conducted clinical trial, complementing with other data from published literature, to compare the two regimens from a healthcare system perspective. Effectiveness was expressed in terms of quality-adjusted life-years (QALYs). Several sensitivity analyses were performed using Monte Carlo simulation, to measure the effect of potential parameter changes on the base-case model results, including potential differences related to type of infection and drug toxicity. Treatment of MRSA infection with trimethoprim-sulfamethoxazole plus rifampicin and linezolid were found to cost on average €146 and €2536, and lead to a gain of 0.916 and 0.881 QALYs, respectively. Treatment with trimethoprim-sulfamethoxazole plus rifampicin was found to be more cost-effective than linezolid in the base case and remained dominant over linezolid in most alternative scenarios, including different types of MRSA infection and potential disadvantages in terms of toxicity. With a willingness-to-pay threshold of €0, €50 000 and €200 000 per QALY gained, trimethoprim-sulfamethoxazole plus rifampicin was dominant in 100%, 96% and 85% of model iterations. A 95% discount on the current purchasing price of linezolid would be needed when it goes off-patent for it to represent better value for money compared with trimethoprim-sulfamethoxazole plus rifampicin. Combined treatment of trimethoprim-sulfamethoxazole plus rifampicin is more cost-effective than linezolid in the treatment of MRSA infection. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Role of Negative Trans-Thoracic Echocardiography in the Diagnosis of Infective Endocarditis.

    Science.gov (United States)

    Leitman, Marina; Peleg, Eli; Shmueli, Ruthie; Vered, Zvi

    2016-07-01

    The search for the presence of vegetations in patients with suspected infective endocarditis is a major indication for trans-esophageal echocardiographic (TEE) examinations. Advances in harmonic imaging and ongoing improvement in modern echocardiographic systems allow adequate quality of diagnostic images in most patients. To investigate whether TEE examinations are always necessary for the assessment of patients with suspected infective endocarditis. During 2012-2014 230 trans-thoracic echo (TTE) exams in patients with suspected infective endocarditis were performed at our center. Demographic, epidemiological, clinical and echocardiographic data were collected and analyzed, and the final clinical diagnosis and outcome were determined. Of 230 patients, 24 had definite infective endocarditis by clinical assessment. TEE examination was undertaken in 76 of the 230 patients based on the clinical decision of the attending physician. All TTE exams were classified as: (i) positive, i.e., vegetations present; (ii) clearly negative; or (iii) non-conclusive. Of the 92 with clearly negative TTE exams, 20 underwent TEE and all were negative. All clearly negative patients had native valves, adequate quality images, and in all 92 the final diagnosis was not infective endocarditis. Thus, the negative predictive value of a clearly negative TTE examination was 100%. In patients with native cardiac valves referred for evaluation for infective endocarditis, an adequate quality TTE with clearly negative examination may be sufficient for the diagnosis.

  2. Presence of Streptococcus faecalis in the White Cheese Sold in Kahramanmaraş (Turkish with English Abstract)

    OpenAIRE

    Erdoğrul, Özlem Turgay; Dığak, Metin

    2014-01-01

    In this study the presence of Streptococcus faecalis in the white cheeses made from pasteurize milk sold in Kahramanmaraş were examined. For this purpose, 22 cheese samples were taken. At the end of this study, all of the samples have Streptococcus faecalis (100%). It was concluded that the examined white cheese samples were inadequate from in reads of hygienic quality by Streptococcus faecalis.

  3. Isolation and identification of Enterococcus faecalis from necrotic root canals using multiplex PCR.

    Science.gov (United States)

    Mahmoudpour, Ali; Rahimi, Saeed; Sina, Mahmood; Soroush, Mohammad H; Shahi, Shahriar; Shahisa, Shahriar; Asl-Aminabadi, Naser

    2007-09-01

    This study was designed to survey the incidence of Enterococcus faecalis infection in symptomatic and asymptomatic root canals of necrotic teeth using PCR and to isolate the bacterium for further screening. Sixty patients categorized according to their clinical symptoms were used for sampling by insertion of paper points into the root canals and absorbing all the fluids present within them. The samples were incubated in 1.0 ml 2xYT (containing 16 g bacto tryptone, 10 g yeast extract and 5.0 g NaCl per liter) for 24 h at 37 degrees C without aeration prior to multiplex PCR analysis. To assist the isolation of E. faecalis, sub-samples were further grown in the same medium supplemented with 6.5% NaCl and back-inoculated into bile esculin. Using multiple cultivation-dependent and PCR analyses, 6 cases (10%) of E. faecalis were identified. Four isolates were obtained from asymptomatic cases of chronic apical periodontitis, and the other two were associated with phoenix abscess and acute apical abscess, respectively. No E. faecalis infection was found in 5 patients with acute apical periodontitis or in 9 with chronic suppurative periodontitis. Our results indicate that there is no significant difference in the incidence of E. faecalis between symptomatic and asymptomatic necrotic dental root canals (P > 0.05).

  4. Vitality of Enterococcus faecalis inside dentinal tubules after five root canal disinfection methods.

    Science.gov (United States)

    Vatkar, Niranjan Ashok; Hegde, Vivek; Sathe, Sucheta

    2016-01-01

    To compare the vitality of Enterococcus faecalis within dentinal tubules after subjected to five root canal disinfection methods. Dentin blocks (n = 60) were colonized with E. faecalis. After 4 weeks of incubation, the dentin blocks were divided into one control and five test groups (n = 10 each). The root canals of test groups were subjected to one of the disinfection methods, namely, normal saline (NS), sodium hypochlorite (NaOCl), chlorhexidine digluconate (CHX), neodymium-doped yttrium aluminum garnet (Nd: YAG) laser, and diode laser. The effect of disinfection methods was assessed by LIVE/DEAD BacLight stain under the confocal laser scanning microscopy to determine the "zone of dead bacteria" (ZDB). Mean values were calculated for ZDB and the difference between groups was established. Penetration of E. faecalis was seen to a depth of >1000 μm. Viable bacteria were detected with NS irrigation. NaOCl and CHX showed partial ZDB. When the root canals were disinfected with Nd: YAG and diode lasers, no viable bacteria were found. E. faecalis has the ability to colonize inside dentinal tubules to a depth of >1000 μm. In contrast to conventional irrigants, both Nd: YAG and diode lasers were effective in eliminating the vitality of E. faecalis. NS, NaOCl, and CHX showed viable bacteria remaining in dentinal tubules.

  5. Partial oral treatment of endocarditis

    DEFF Research Database (Denmark)

    Iversen, Kasper; Høst, Nis Baun; Bruun, Niels Eske

    2013-01-01

    Guidelines for the treatment of left-sided infective endocarditis (IE) recommend 4 to 6 weeks of intravenous antibiotics. Conversion from intravenous to oral antibiotics in clinically stabilized patients could reduce the side effects associated with intravenous treatment and shorten the length...

  6. Aortic allografts in treatment of aortic valve and ascending aorta prosthetic endocarditis

    Directory of Open Access Journals (Sweden)

    S.V. Spiridonov

    2017-03-01

    Full Text Available The aim – to assess short- and long-term results of aortic root replacement using aortic allografts in patients with prosthetic endocarditis. Materials and methods. Since February 2009 until June 2016 aortic valve and ascending aorta replacement using aortic allografts was performed in 26 patients with prosthetic endocarditis. In 50 % of cases at initial operation aortic valve replacement was performed, in another 50 % of cases – aortic valve and ascending aorta replacement. Echocardiography was performed 10 days, 3, 6 and 12 months, 2, 3 and 5 years after surgery. Analysis of long-term results included all cases of deaths, prosthesis-related complications and recurrence of endocarditis. Results. 30-day mortality was 23.1 %. Extracorporeal membranous oxygenation (ECMO was used only in 5 patients (19.2 %. Four patients were weaned from ECMO. We did not observe any allograft-related complications. During follow-up period there were no cases of reoperation due to structural allograft failure. Relapse of infection occurred in 1 patient (3.8 % four years after the operation and led to lethal outcome. Conclusion. Reoperations using allografts are an effective surgical treatment of prosthetic endocarditis. In majority of cases prosthetic endocarditis was caused by gram-positive cocci (Staphylococcus. In 84.6 % of cases it was associated with destruction of paravalvular structures and abscesses formation. Heart failure was a causative factor of different complications in these patients, which required ECMO in 19.2 % of patients. In 80 % of cases patients were weaned from ECMO. Allografts using for the treatment of prosthetic endocarditis is associated with high resistance to infection and with a significant rate of freedom from recurrence of endocarditis within 3 years after surgery.

  7. BRUCELLA ENDOCARDITIS IN IRANIAN PATIENTS: COMBINED MEDICAL AND SURGICAL TREATMENT

    Directory of Open Access Journals (Sweden)

    Ebrahim Nematipour

    1995-06-01

    Full Text Available Brucella endocarditis is a Tare but serious complication ofbrucellosis and is the main cause of death reuuedto thisdisease: Itis not rare in the endemic areas and aaualiy accounts for up to 8~lO% ofendocarditis infections: We report seven adult cases of brucella endocarditis in lmam-Khorneini Hospual: Contrary to previous independent reports, female patients were not rare in this study and accountedfor three out ofseven. Four patients were cared for by combined medical and surgical treatment and were recovered Three of the patients that did not receive the combined theraPl could not he saved This report confirms the necessity of prompt combined medical and surgical treatment ofbrucella endocarditis.

  8. Surgical treatment of infective endocarditis in active intravenous drug users: a justified procedure?

    Science.gov (United States)

    Weymann, Alexander; Borst, Tobias; Popov, Aron-Frederik; Sabashnikov, Anton; Bowles, Christopher; Schmack, Bastian; Veres, Gabor; Chaimow, Nicole; Simon, Andre Rüdiger; Karck, Matthias; Szabo, Gábor

    2014-03-24

    Infective endocarditis is a life threatening complication of intravenous drug abuse, which continues to be a major burden with inadequately characterised long-term outcomes. We reviewed our institutional experience of surgical treatment of infective endocarditis in active intravenous drug abusers with the aim of identifying the determinants long-term outcome of this distinct subgroup of infective endocarditis patients. A total of 451 patients underwent surgery for infective endocarditis between January 1993 and July 2013 at the University Hospital of Heidelberg. Of these patients, 20 (7 female, mean age 35 ± 7.7 years) underwent surgery for infective endocarditis with a history of active intravenous drug abuse. Mean follow-up was 2504 ± 1842 days. Staphylococcus aureus was the most common pathogen detected in preoperative blood cultures. Two patients (10%) died before postoperative day 30. Survival at 1, 5 and 10 years was 90%, 85% and 85%, respectively. Freedom from reoperation was 100%. Higher NYHA functional class, higher EuroSCORE II, HIV infection, longer operating time, postoperative fever and higher requirement for red blood cell transfusion were associated with 90-day mortality. In active intravenous drug abusers, surgical treatment for infective endocarditis should be performed as extensively as possible and be followed by an aggressive postoperative antibiotic therapy to avoid high mortality. Early surgical intervention is advisable in patients with precipitous cardiac deterioration and under conditions of staphylococcal endocarditis. However, larger studies are necessary to confirm our preliminary results.

  9. Platelet receptor polymorphisms do not influence Staphylococcus aureus–platelet interactions or infective endocarditis

    Science.gov (United States)

    Daga, Shruti; Shepherd, James G.; Callaghan, J. Garreth S.; Hung, Rachel K.Y.; Dawson, Dana K.; Padfield, Gareth J.; Hey, Shi Y.; Cartwright, Robyn A.; Newby, David E.; Fitzgerald, J. Ross

    2011-01-01

    Cardiac vegetations result from bacterium–platelet adherence, activation and aggregation, and are associated with increased morbidity and mortality in infective endocarditis. The GPIIb/IIIa and FcγRIIa platelet receptors play a central role in platelet adhesion, activation and aggregation induced by endocarditis pathogens such as Staphylococcus aureus, but the influence of known polymorphisms of these receptors on the pathogenesis of infective endocarditis is unknown. We determined the GPIIIa platelet antigen PlA1/A2 and FcγRIIa H131R genotype of healthy volunteers (n = 160) and patients with infective endocarditis (n = 40), and investigated the influence of these polymorphisms on clinical outcome in infective endocarditis and S. aureus–platelet interactions in vitro. Platelet receptor genotype did not correlate with development of infective endocarditis, vegetation characteristics on echocardiogram or the composite clinical end-point of embolism, heart failure, need for surgery or mortality (P > 0.05 for all), even though patients with the GPIIIa PlA1/A1 genotype had increased in vivo platelet activation (P = 0.001). Furthermore, neither GPIIIa PlA1/A2 nor FcγRIIa H131R genotype influenced S. aureus-induced platelet adhesion, activation or aggregation in vitro (P > 0.05). Taken together, our data suggest that the GPIIIa and FcγRIIa platelet receptor polymorphisms do not influence S. aureus–platelet interactions in vitro or the clinical course of infective endocarditis. PMID:21044892

  10. Surgical management for active infective endocarditis: a single hospital 10 years experience

    International Nuclear Information System (INIS)

    Parvizi, R.; Varshouchi, M.; Alizadeh, R.

    2007-01-01

    To examine the outcome of surgery for active infective endocarditis (IE) in a cohort of patients. One hundred sixty-four consecutive patients who underwent valve surgery for active IE (diagnosis according to Duke criteria) in Madani Heart Center, Tabriz, Iran from 1996 to 2006 were studied. The mean age of patients was 36.3+-16 years overall: 34.6+-17.5 years for native valve endocarditis and 38.6+-15.2 yrs for prosthetic valve endocarditis (p=0.169). Ninety one (55.5%) patients were men. The infected valve was native in 112 (68.7%) of patients and prosthetic in 52(31.3%). In 61 (37%) patients, no predisposing heart disease was found. The aortic valve was infected in 78 (47.6%), mitral valve in 69 (42.1%), and multiple valves in 17 (10.3%) of patients. Active culture positive endocarditis was present in 81 (49.4%) whereas 83 (50.6%) patients had culture-negative endocarditis. Staphylococcus aureus was the most common isolated microorganism. Ninety patients (54.8%) were in NYHA classes III and IV. Mechanical valves were implanted in 69 patients (42.1%) and bioprostheses in 95 (57.9%), including a homograft in 19 (11.5%). There were 16 (9%) operative deaths, but there was only 1 death in patients that underwent aortic homograft replacement. Reoperation was required in 18 (10.9%) of cases. On multivariate logistic regression analysis, Staphylococcus aureus infection (p=0.008), prosthetic valve endocarditis (p=0.01), paravalvular abscess (p=0.001) and left ventricular ejection fraction less than 40% (p=0.04) were independent predictors of in-hospital mortality. Surgery for infective endocarditis continues to be challenging and associated with high operative mortality and morbidity. Prosthetic valve endocarditis, impaired ventricular function, paravalvular abscess and Staphylococcus aureus infection adversely affect in-hospital mortality. Also we found that aortic valve replacement with an aortic homograft can be performed with acceptable in hospital mortality and

  11. An economic model to compare linezolid and vancomycin for the treatment of confirmed methicillin-resistant Staphylococcus aureus nosocomial pneumonia in Germany

    Directory of Open Access Journals (Sweden)

    Patel DA

    2014-10-01

    Full Text Available Dipen A Patel,1 Andre Michel,2 Jennifer Stephens,1 Bertram Weber,3 Christian Petrik,4 Claudie Charbonneau5 1Health Economic and Outcomes Research, Pharmerit International, Bethesda, MD, USA; 2Klinikum Hanau GmbH, Hanau, Germany; 3Health Technology Assessment and Outcomes Research, 4Anti-infectives, Pfizer, Berlin, Germany; 5Pfizer International Operations, Pfizer France, Paris, France Background: Across Europe, methicillin-resistant Staphylococcus aureus (MRSA is considered to be the primary cause of nosocomial pneumonia (NP. In Germany alone, approximately 14,000 cases of MRSA-associated NP occur annually, which may have a significant impact on health care resource use and associated economic costs. The objective of this study was to investigate the economic impact of linezolid compared with that of vancomycin in the treatment of hospitalized patients with MRSA-confirmed NP in the German health care system. Methods: A 4-week decision tree model incorporated published data and expert opinion on clinical parameters, resource use, and costs (2012 euros was constructed. The base case first-line treatment duration for patients with MRSA-confirmed NP was 10 days. Treatment success (survival, failure due to lack of efficacy, serious adverse events, and mortality were possible outcomes that could impact costs. Alternate scenarios were analyzed, such as varying treatment duration (7 or 14 days or treatment switch due to a serious adverse event/treatment failure (at day 5 or 10. Results: The model calculated total base case inpatient costs of €15,116 for linezolid and €15,239 for vancomycin. The incremental cost-effectiveness ratio favored linezolid (versus vancomycin, with marginally lower costs (by €123 and greater efficacy (+2.7% absolute difference in the proportion of patients successfully treated for MRSA NP. Approximately 85%–87% of the total treatment costs were attributed to hospital stay (primarily in the intensive care unit

  12. Neisseria meningitidis endocarditis: a case report and review of the literature.

    LENUS (Irish Health Repository)

    Ali, Mohammed

    2012-02-01

    Neisseria meningitidis is the leading cause of bacterial meningitis in children and young adults, with an overall mortality rate of up to 25%, but it is a rare cause of infective endocarditis. We present herein a case of N. meningitidis meningitis complicated with infective endocarditis.

  13. Endocarditis trombótica no bacteriana bivalvular asociada a cáncer y ecocardiograma transesofágico Bivalvular non bacterial thrombotic endocarditis associated with cancer and transesophageal echocardiography

    Directory of Open Access Journals (Sweden)

    Marcelo Zylberman

    2006-06-01

    Full Text Available La endocarditis trombótica no bacteriana es la causa más frecuente de accidente cerebrovascular isquémico en pacientes con cáncer. En estos pacientes se hallaron vegetaciones valvulares hasta en el 9% de las autopsias. Sin embargo, la afección bivalvular es poco frecuente, observándose en el 9% de las endocarditis trombóticas. Se presenta una paciente con cáncer de ovario que presentó afasia e imágenes compatibles con isquemia cerebral. El ecocardiograma transtorácico fue normal. El ecocardiograma transesofágico evidenció vegetaciones en las válvulas aórtica y mitral. Se enfatiza la importancia de sospechar endocarditis trombótica no bacteriana en enfermos con cáncer y embolismo sistémico y en la escasa frecuencia de afección bivalvular.Non bacterial thrombotic endocarditis is the most frequent cause of ischemic stroke in cancer patients. Up to 9% of autopsies of cancer patients show non infectious valvular masses. However, bivalvular involvement is not frequently occurring in 9% of non bacterial thrombotic endocarditis. We report a patient with ovarian cancer who presented aphasia. The MRI was compatible with cerebral ischemia. The transthoracic echocardiogram was normal and a transesophageal echocardiogram showed vegetations in aortic and mitral valves. We emphasize the importance of suspecting non bacterial thrombotic endocarditis in patients with cancer and systemic embolism and the low frequency of bivalvular involvement.

  14. Rifapentine-linezolid-loaded PLGA microspheres for interventional therapy of cavitary pulmonary tuberculosis: preparation and in vitro characterization.

    Science.gov (United States)

    Huang, Jieyun; Chen, Zhi; Li, Ying; Li, Li; Zhang, Guangyu

    2017-01-01

    In this study, we aimed to design controlled-release microspheres for the treatment of cavitary pulmonary tuberculosis (TB) for solving the issues of poor drug delivery and short duration maintained at effective drug concentration during bronchoscopic interventional therapy. We fabricated rifapentine-linezolid-loaded poly(lactic acid-co-glycolic acid) microspheres (RLPMs) using the oil-in-water emulsion solvent evaporation method and assessed their in vitro release as well as the bronchial mucosal retention characteristics. The microspheres are spherical in shape with a circular concave on the surface. The particle size of RLPMs was 27.38±1.28 μm. The drug loading of rifapentine and linezolid was 18.51±0.26 and 8.42%±0.24%, respectively, while the encapsulation efficiencies were 55.53±0.78 and 16.87%±0.47%, respectively (n=3). During the burst release phase of the in vitro release test, 21.37%±0.68% rifapentine was released in 3 days and 43.56%±2.54% linezolid was released in 1 day. Then, both the drugs entered the sustained release phase. Finally, the cumulative percentage release of rifapentine and linezolid in 14 days was 27.61±1.52 and 51.01%±3.31%, respectively (n=3). Bronchoscopic observation revealed that the controlled-release microspheres could slowly release the drugs and retain them on the surface of bronchial mucosa of canines for 20 days. These results indicated that the fabricated microspheres exhibited a significant sustained release effect and could effectively retain the drugs on the surface of bronchial mucosa. Therefore, this study provides a theoretical and practical foundation for the development of fabricated microspheres loaded with multiple anti-TB drugs in the bronchoscopic interventional therapy of cavity pulmonary TB.

  15. Unbound fraction of fluconazole and linezolid in human plasma as determined by ultrafiltration: Impact of membrane type.

    Science.gov (United States)

    Kratzer, Alexander; Kees, Frieder; Dorn, Christoph

    2016-12-15

    Ultrafiltration is a rapid and convenient method to determine the free concentrations of drugs in plasma. Several ultrafiltration devices based on Eppendorf cups are commercially available, but are not validated for such use by the manufacturer. Plasma pH, temperature and relative centrifugal force as well as membrane type can influence the results. In the present work, we developed an ultrafiltration method in order to determine the free concentrations of linezolid or fluconazole, both neutral and moderately lipophilic antiinfective drugs for parenteral as well as oral administration, in plasma of patients. Whereas both substances behaved relatively insensitive in human plasma regarding variations in pH (7.0-8.5), temperature (5-37°C) or relative centrifugal force (1000-10.000xg), losses of linezolid were observed with the Nanosep Omega device due to adsorption onto the polyethersulfone membrane (unbound fraction 75% at 100mg/L and 45% at 0.1mg/L, respectively). No losses were observed with Vivacon which is equipped with a membrane of regenerated cellulose. With fluconazole no differences between Nanosep and Vivacon were observed. Applying standard conditions (pH 7.4/37°C/1000xg/20min), the mean unbound fraction of linezolid in pooled plasma from healthy volunteers was 81.5±2.8% using Vivacon, that of fluconazole was 87.9±3.5% using Nanosep or 89.4±3.3% using Vivacon. The unbound fraction of linezolid was 85.4±3.7% in plasma samples from surgical patients and 92.1±6.2% in ICU patients, respectively. The unbound fraction of fluconazole was 93.9±3.3% in plasma samples from ICU patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Antibiotic modulation of the plasminogen binding ability of viridans group streptococci.

    Science.gov (United States)

    Teles, Cristina; Smith, Andrew; Lang, Sue

    2012-01-01

    The ability of viridans group streptococci to bind human plasminogen and its subsequent activation into plasmin may contribute to the pathogenesis of infective endocarditis (IE) by leading to a decreased stability of the streptococcal vegetation and facilitating dehiscence of emboli. At levels greater than or equal to their MICs, penicillin, vancomycin, and linezolid are efficacious in the treatment of streptococcal endocarditis. However, at sub-MICs, antibiotics can modulate the expression of bacterial genes, including virulence-associated genes, which can have counterproductive effects on the treatment of endocarditis. The effects of 1/8× and 1/4× MICs of penicillin, vancomycin, and linezolid on the plasminogen binding ability of IE isolates Streptococcus mitis 881/956, Streptococcus oralis 12601, and Streptococcus sanguinis 12403 were assessed phenotypically and the expression of plasminogen receptors α-enolase and glyceraldehyde 3-phosphate dehydrogenase of S. oralis 12601 when exposed to 1/4× MIC of penicillin, was analyzed through quantitative reverse transcription (qRT)-PCR. The plasminogen binding ability of S. mitis 881/956 and S. sanguinis 12403 remained unaffected by exposure to sub-MICs of all of the antibiotics tested, while that of S. oralis 12601 was significantly enhanced by all of the antibiotics tested at sub-MICs. qRT-PCR analysis of S. oralis 12601 demonstrated an upregulation of the eno and gapdh genes, indicating an overexpression of plasminogen receptors. These findings suggest that for some endocarditis isolates, the effect of antibiotic sub-MICs, in addition to a reduced antibacterial effect, may influence the clinical response to nonsurgical therapy. It remains difficult to accurately predict isolate responses to sub-MIC antimicrobials since there appears to be interspecies variation.

  17. Identification and Characterization of Linezolid-Resistant cfr-Positive Staphylococcus aureus USA300 Isolates from a New York City Medical Center

    Science.gov (United States)

    Zuill, Douglas E.; Scharn, Caitlyn R.; Deane, Jennifer; Sahm, Daniel F.; Goering, Richard V.; Jenkins, Stephen G.; Shaw, Karen J.

    2014-01-01

    The cfr gene was identified in three linezolid-resistant USA300 methicillin-resistant Staphylococcus aureus (MRSA) isolates collected over a 3-day period at a New York City medical center in 2011 as part of a routine surveillance program. Each isolate possessed a plasmid containing a pSCFS3-like cfr gene environment. Transformation of the cfr-bearing plasmids into the S. aureus ATCC 29213 background recapitulated the expected Cfr antibiogram, including resistance to linezolid, tiamulin, clindamycin, and florfenicol and susceptibility to tedizolid. PMID:25136008

  18. Outpatient treatment of acute bacterial skin and skin structure infections (ABSSSI) with tedizolid phosphate and linezolid in patients in the United States: Subgroup analysis of 2 randomized phase 3 trials.

    Science.gov (United States)

    De Anda, Carisa; Anuskiewicz, Steven; Prokocimer, Philippe; Vazquez, Jose

    2017-12-01

    Acute bacterial skin and skin structure infections (ABSSSI) are a frequent cause of hospital admissions in the United States. Safe and effective outpatient treatments may lower ABSSSI-associated health care costs by reducing unnecessary hospital admissions. Using data from 2 phase 3 trials (ESTABLISH-1, NCT01170221; ESTABLISH-2, NCT01421511), this post-hoc analysis explored the efficacy and safety of tedizolid in an outpatient setting. Subgroup analysis was performed on US outpatients (defined as patients who were not in hospital at the time of treatment initiation) with ABSSSI caused by presumed or proven gram-positive pathogens. Patients were randomly assigned to receive tedizolid phosphate 200 mg once daily for 6 days (n = 403) or linezolid 600 mg twice daily for 10 days (n = 410). The primary end point was early clinical response (48-72 hours after the start of treatment). Secondary end points included investigator-assessed clinical response at end of therapy (EOT) and post-therapy evaluation (PTE; 7-14 days after therapy). Additional assessments included the patient-reported level of pain using a visual analog scale (VAS) and the per-pathogen favorable microbiological response rate at the PTE visit. Compliance with treatment and safety outcomes was also recorded. Early clinical response was similar between treatment groups (tedizolid, 82.4%; linezolid, 79.0%), as was investigator-assessed clinical response at EOT (tedizolid, 87.1%; linezolid, 86.1%) and PTE (tedizolid, 83.1%; linezolid, 83.7%). Mean changes from baseline to days 10 to 13 in VAS scores were identical between treatment groups (tedizolid, -51.9 mm; linezolid, -51.9 mm). Microbiological eradication rates were generally similar in both treatment groups for all key pathogens. Patients in both groups had favorable response at PTE. More tedizolid-treated patients (89.3%) than linezolid-treated patients (77.3%) were compliant with treatment. The most frequently reported drug

  19. A 27-year experience with infective endocarditis in Lebanon.

    Science.gov (United States)

    El-Chakhtoura, Nadim; Yasmin, Mohamad; Kanj, Souha S; Baban, Tania; Sfeir, Jad; Kanafani, Zeina A

    Although rare, infective endocarditis (IE) continues to cause significant morbidity and mortality. Previous data from the American University of Beirut Medical Center (AUBMC) had shown predominance of streptococcal infection. As worldwide studies in developed countries show increasing trends in Staphylococcus aureus endocarditis, it becomes vital to continually inspect local data for epidemiological variations. We reviewed all IE cases between 2001 and 2014, and we performed a comparison to a historical cohort of 86 IE cases from 1987 to 2001. A total of 80 patients were diagnosed with IE between 2001 and 2014. The mean age was 61 years. The most commonly isolated organisms were streptococci (37%), compared to 51% in the previous cohort. S. aureus accounted for 11%. Only one S. aureus isolate was methicillin-resistant. In the historical cohort, 26% of cases were caused by S. aureus. Enterococci ranked behind staphylococci with 22% of total cases, while in the previous cohort, enterococcal IE was only 4%. Compared to previous data from AUBMC, the rates of streptococcal and staphylococcal endocarditis have decreased while enterococcal endocarditis has increased. This study reconfirms that in Lebanon, a developing country, we continue to have a low predominance of staphylococci as etiologic agents in IE. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. A Faropenem, Linezolid, and Moxifloxacin Regimen for Both Drug-Susceptible and Multidrug-Resistant Tuberculosis in Children: FLAME Path on the Milky Way.

    Science.gov (United States)

    Deshpande, Devyani; Srivastava, Shashikant; Nuermberger, Eric; Pasipanodya, Jotam G; Swaminathan, Soumya; Gumbo, Tawanda

    2016-11-01

     The regimen of linezolid and moxifloxacin was found to be efficacious in the hollow fiber system model of pediatric intracellular tuberculosis. However, its kill rate was slower than the standard 3-drug regimen of isoniazid, rifampin, and pyrazinamide. We wanted to examine the effect of adding a third oral agent, faropenem, to this dual combination.  We performed a series of studies in the hollow fiber system model of intracellular Mycobacterium tuberculosis, by mimicking pediatric pharmacokinetics of each antibiotic. First, we varied the percentage of time that faropenem persisted above minimum inhibitory concentration (T MIC ) on the moxifloxacin-linezolid regimen. After choosing the best faropenem exposure, we performed experiments in which we varied the moxifloxacin and linezolid doses in the triple regimen. Finally, we performed longer-duration therapy validation experiments. Bacterial burden was quantified using both colony-forming units per milliliter (CFU/mL) and time to positivity (TTP). Kill slopes were modeled using exponential regression.  TTP was a more sensitive measure of bacterial burden than CFU/mL. A faropenem T MIC > 62% was associated with steepest microbial kill slope. Regimens of standard linezolid and moxifloxacin plus faropenem T MIC > 60%, as well as higher-dose moxifloxacin, achieved slopes equivalent to those of the standard regimen based by both TTP and CFU/mL over 28 days of treatment.  We have developed an oral faropenem-linezolid-moxifloxacin (FLAME) regimen that is free of first-line drugs. The regimen could be effective against both multidrug-resistant and drug-susceptible tuberculosis in children. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

  1. Neisseria meningitidis endocarditis: A case report and review of the literature.

    LENUS (Irish Health Repository)

    Ali, Mohammed

    2011-04-08

    Abstract Neisseria meningitidis is the leading cause of bacterial meningitis in children and young adults, with an overall mortality rate of up to 25%, but it is a rare cause of infective endocarditis. We present herein a case of N. meningitidis meningitis complicated with infective endocarditis.

  2. Infective endocarditis in the U.S., 1998-2009: a nationwide study.

    Directory of Open Access Journals (Sweden)

    David H Bor

    Full Text Available BACKGROUND: Previous studies based on local case series estimated the annual incidence of endocarditis in the U.S. at about 4 per 100,000 population. Small-scale studies elsewhere have reported similar incidence rates. However, no nationally-representative population-based studies have verified these estimates. METHODS AND FINDINGS: Using the 1998-2009 Nationwide Inpatient Sample, which provides diagnoses from about 8 million U.S. hospitalizations annually, we examined endocarditis hospitalizations, bacteriology, co-morbidities, outcomes and costs. Hospital admissions for endocarditis rose from 25,511 in 1998 to 38, 976 in 2009 (12.7 per 100,000 population in 2009. The age-adjusted endocarditis admission rate increased 2.4% annually. The proportion of patients with intra-cardiac devices rose from 13.3% to 18.9%, while the share with drug use and/or HIV fell. Mortality remained stable at about 14.5%, as did cardiac valve replacement (9.6%. Other serious complications increased; 13.3% of patients in 2009 suffered a stroke or CNS infection, and 5.5% suffered myocardial infarction. Amongst cases with identified pathogens, Staphylococcus aureus was the most common, increasing from 37.6% in 1998 to 49.3% in 2009, 53.3% of which were MRSA. Streptococci were mentioned in 24.7% of cases, gram-negatives in 5.6% and Candida species in 1.0%. We detected no inflection in hospitalization rates after changes in prophylaxis recommendations in 2007. Mean age rose from 58.6 to 60.8 years; elderly patients suffered higher rates of myocardial infarction and death, but slightly lower rates of Staphylococcus aureus infections and neurologic complications. Our study relied on clinically diagnosed cases of endocarditis that may not meet strict criteria. Moreover, since some patients are discharged and readmitted during a single episode of endocarditis, our hospitalization figures probably slightly overstate the true incidence of this illness. CONCLUSIONS: Endocarditis

  3. Evaluation of Enterococcus faecalis adhesion, penetration, and method to prevent the penetration of Enterococcus faecalis into root cementum: Confocal laser scanning microscope and scanning electron microscope analysis.

    Science.gov (United States)

    Halkai, Rahul S; Hegde, Mithra N; Halkai, Kiran R

    2016-01-01

    To ascertain the role of Enterococcus faecalis in persistent infection and a possible method to prevent the penetration of E. faecalis into root cementum. One hundred and twenty human single-rooted extracted teeth divided into five groups. Group I (control): intact teeth, Group II: no apical treatment done, Group III divided into two subgroups. In Groups IIIa and IIIb, root apex treated with lactic acid of acidic and neutral pH, respectively. Group IV: apical root cementum exposed to lactic acid and roughened to mimic the apical resorption. Group V: apical treatment done same as Group IV and root-end filling done using mineral trioxide aggregate (MTA). Apical one-third of all samples immersed in E. faecalis broth for 8 weeks followed by bone morphogenetic protein and obturation and again immersed into broth for 8 weeks. Teeth split into two halves and observed under confocal laser scanning microscope and scanning electron microscope, organism identified by culture and polymerase chain reaction techniques. Adhesion and penetration was observed in Group IIIa and Group IV. Only adhesion in Group II and IIIB and no adhesion and penetration in Group I and V. Adhesion and penetration of E. faecalis into root cementum providing a long-term nidus for subsequent infection are the possible reason for persistent infection and root-end filling with MTA prevents the adhesion and penetration.

  4. Endocarditis Prophylaxis in Cardiac Patients: Knowledge among General Dental Practitioners in Tabriz

    Directory of Open Access Journals (Sweden)

    Ardeshir Lafzi

    2008-04-01

    Full Text Available

    Background and aims. Dental procedures injuring oral tissues may induce bacterial release to blood stream that can cause infective endocarditis in susceptible patients. The aim of this study was to determine the level of knowledge of general dental practitioners (GDPs in Tabriz, Northwest of Iran, regarding endocarditis prophylaxis in cardiac patients receiving dental treatments.

    Materials and methods. This was a cross-sectional, descriptive, analytical study that included 150 GDPs. All practitioners were given a self-administered questionnaire which consisted of three parts assessing their knowledge of cardiac diseases requiring prophylaxis, dental procedures requiring prophylaxis, and antibiotic regimen for endocarditis prophylaxis. Statistical analysis of data was carried out using independent t-test, one-way ANOVA and chi-square test.

    Results. The level of knowledge among GDPs in three areas of cardiac diseases requiring prophylaxis, dental procedures requiring prophylaxis, and antibiotic regimen for endocarditis prophylaxis were 63.7%, 66.8% and 47.7%, respectively. Their overall level of knowledge regarding endocarditis prophylaxis was 59%. Association of the level of knowledge with age and practice period was statistically significant (P < 0.05. However, the level of knowledge was not significantly associated with gender or university of graduation in either of three areas evaluated (P > 0.05.

    Conclusion. According to our results, the knowledge of endocarditis prophylaxis among GDPs in Tabriz was in a moderate level. Regarding the importance of endocarditis prophylaxis in susceptible patients, it should be more emphasized in the curriculum of dental schools and continuing dental education programs.

  5. Energy-producing system of the membrane potential generation in γ-irradiated Streptococcus faecalis

    International Nuclear Information System (INIS)

    Fomenko, B.S.

    1976-01-01

    γ-irradiated (20-100 krads) Str. faecalis cells exhibited increased glycolytic and ATPase activity whereas the ATP level remained unaffected by radiation. It is concluded that the radiation-induced reduction of the membrane potential in Str. faecalis, that has been earlier described, is not connected with the impairment of the energy-producing system of the potential generation

  6. Enterococcus faecalis Infection Causes Inflammation, Intracellular Oxphos-Independent ROS Production, and DNA Damage in Human Gastric Cancer Cells

    DEFF Research Database (Denmark)

    Strickertsson, Jesper A. B; Desler, Claus; Martin-Bertelsen, Tomas

    2013-01-01

    therefore wanted to study the impact of E. faecalis infection on inflammatory response, reactive oxygen species (ROS) formation, mitochondrial respiration, and mitochondrial genetic stability in gastric mucosal cells. Methods To separate the changes induced by bacteria from those of the inflammatory cells...... intracellular ROS production through a pathway independent of oxidative phosphorylation (oxphos). Furthermore, E. faecalis infection induced mitochondrial DNA instability. Following infection, genes coding for inflammatory response proteins were transcriptionally up-regulated while DNA damage repair and cell...... cycle control genes were down-regulated. Cell growth slowed down when infected with viable E. faecalis and responded in a dose dependent manner to E. faecalis lysate. Conclusions Infection by E. faecalis induced an oxphos-independent intracellular ROS response and damaged the mitochondrial genome...

  7. Costo-efectividad de linezolid comparado con vancomicina en el manejo de la neumonía asociada a ventilación mecánica en Colombia

    Directory of Open Access Journals (Sweden)

    Fabio Varón

    2014-12-01

    Full Text Available Objetivo: Estimar la costo-efectividad de linezolid versus vancomicina en el manejo de neumonía asociada a ventilación mecánica (NAV causada por Staphylococcus aureus resistente a meticilina (SARM en Colombia. Materiales y métodos: Se construyó un árbol de decisión para determinar la razón de costo-efectividad incremental de linezolid (600 mg iv/12 h comparado con vancomicina (15 mg/kg iv/12 h en el tratamiento de NAV por SARM. La perspectiva fue la del sistema de salud incluyendo solo costos directos. Todas las unidades monetarias se expresan en pesos colombianos del 2013 sin descuento (1 USD =$ 1.876,22. Se empleó un horizonte temporal de 30 días. Los resultados se midieron en proporción de pacientes curados. Los datos de eficacia y seguridad se tomaron de la literatura. Los costos de los procedimientos se obtuvieron del manual tarifario ISS del 2001, para medicamentos se utilizó el SISMED y la regulación de precios vigente. Se realizaron análisis de sensibilidad univariados y probabilísticos. Resultados: Los costos totales esperados por paciente curado fueron: $ 2.600.094 para linezolid y $ 1.992.753 para vancomicina. La proporción de pacientes curados fue: 53% con linezolid y 41%.con vancomicina. La razón de costo-efectividad de linezolid comparado con vancomicina fue $ 5.061.173 por paciente curado. Para cada alternativa, los resultados fueron sensibles a la probabilidad de éxito del tratamiento, a la probabilidad de presentar eventos adversos y al costo del tratamiento. Conclusión: En Colombia, linezolid sería una alternativa costo-efectiva en el tratamiento de NAV por SARM, para disponibilidades a pagar superiores a $ 5.061.173 por paciente curado.

  8. Prosthetic valve endocarditis after transcatheter aortic valve implantation

    DEFF Research Database (Denmark)

    Olsen, Niels Thue; De Backer, Ole; Thyregod, Hans G H

    2015-01-01

    BACKGROUND: Transcatheter aortic valve implantation (TAVI) is an advancing mode of treatment for inoperable or high-risk patients with aortic stenosis. Prosthetic valve endocarditis (PVE) after TAVI is a serious complication, but only limited data exist on its incidence, outcome, and procedural......%) were treated conservatively and 1 with surgery. Four patients (22%) died from endocarditis or complications to treatment, 2 of those (11%) during initial hospitalization for PVE. An increased risk of TAVI-PVE was seen in patients with low implanted valve position (hazard ratio, 2.8 [1.1-7.2]), moderate...

  9. Antifungal activity of caspofungin in experimental infective endocarditis caused by Candida albicans.

    Science.gov (United States)

    Victorio, Gerardo Becerra; Bourdon, Lorena Michele Brennan; Benavides, Leonel García; Huerta-Olvera, Selene G; Plascencia, Arturo; Villanueva, José; Martinez-Lopez, Erika; Hernández-Cañaveral, Iván Isidro

    2017-05-01

    Infective endocarditis is a disease characterised by heart valve lesions, which exhibit extracellular matrix proteins that act as a physical barrier to prevent the passage of antimicrobial agents. The genus Candida has acquired clinical importance given that it is increasingly being isolated from cases of nosocomial infections. To evaluate the activity of caspofungin compared to that of liposomal amphotericin B against Candida albicans in experimental infective endocarditis. Wistar rats underwent surgical intervention and infection with strains of C. albicans to develop infective endocarditis. Three groups were formed: the first group was treated with caspofungin, the second with liposomal amphotericin B, and the third received a placebo. In vitro sensitivity was first determined to further evaluate the effect of these treatments on a rat experimental model of endocarditis by semiquantitative culture of fibrinous vegetations and histological analysis. Our semiquantitative culture of growing vegetation showed massive C. albicans colonisation in rats without treatment, whereas rats treated with caspofungin showed significantly reduced colonisation, which was similar to the results obtained with liposomal amphotericin B. The antifungal activity of caspofungin is similar to that of liposomal amphotericin B in an experimental model of infective endocarditis caused by C. albicans.

  10. Rifapentine-linezolid-loaded PLGA microspheres for interventional therapy of cavitary pulmonary tuberculosis: preparation and in vitro characterization

    Directory of Open Access Journals (Sweden)

    Huang J

    2017-03-01

    Full Text Available Jieyun Huang,1,* Zhi Chen,2,* Ying Li,3 Li Li,2 Guangyu Zhang2 1The Second Clinical Medical College, Shanxi Medical University, Taiyuan, People’s Republic of China; 2Institute for Tuberculosis Research, The 309th Hospital of Chinese PLA, Beijing, People’s Republic of China; 3Department of Drug Delivery Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: In this study, we aimed to design controlled-release microspheres for the treatment of cavitary pulmonary tuberculosis (TB for solving the issues of poor drug delivery and short duration maintained at effective drug concentration during bronchoscopic interventional therapy. We fabricated rifapentine-linezolid-loaded poly(lactic acid-co-glycolic acid microspheres (RLPMs using the oil-in-water emulsion solvent evaporation method and assessed their in vitro release as well as the bronchial mucosal retention characteristics. The microspheres are spherical in shape with a circular concave on the surface. The particle size of RLPMs was 27.38±1.28 µm. The drug loading of rifapentine and linezolid was 18.51±0.26 and 8.42%±0.24%, respectively, while the encapsulation efficiencies were 55.53±0.78 and 16.87%±0.47%, respectively (n=3. During the burst release phase of the in vitro release test, 21.37%±0.68% rifapentine was released in 3 days and 43.56%±2.54% linezolid was released in 1 day. Then, both the drugs entered the sustained release phase. Finally, the cumulative percentage release of rifapentine and linezolid in 14 days was 27.61±1.52 and 51.01%±3.31%, respectively (n=3. Bronchoscopic observation revealed that the controlled-release microspheres could slowly release the drugs and retain them on the surface of bronchial mucosa of canines for 20 days. These results indicated that the fabricated microspheres exhibited

  11. Sensitivity, specificity and predictive value of blood cultures from cattle clinically suspected of bacterial endocarditis

    DEFF Research Database (Denmark)

    Houe, Hans; Eriksen, L.; Jungersen, Gregers

    1993-01-01

    This study investigated the number of blood culture-positive cattle among 215 animals clinically suspected of having bacterial endocarditis. For animals that were necropsied, the sensitivity, specificity and predictive value of the diagnosis of endocarditis were calculated on the basis...... of the isolation of the causative bacteria from blood. Furthermore, it was investigated whether the glutaraldehyde coagulation time, total leucocyte count, per cent neutrophil granulocytes, pulse rate and duration of disease could help to discriminate endocarditis from other diseases. Among 138 animals necropsied...... the sensitivity, specificity and predictive value of blood cultivation were 70.7 per cent, 93.8 per cent and 89.1 per cent, respectively. None of the other measurements could be used to discriminate between endocarditis and non-endocarditis cases....

  12. Endocarditis due to Rhodotorula mucilaginosa in a kidney transplanted patient: case report and review of medical literature

    Science.gov (United States)

    Cabral, Andrea Maria; da Siveira Rioja, Suzimar; Brito-Santos, Fabio; Peres da Silva, Juliana Ribeiro; MacDowell, Maria Luíza; Melhem, Marcia S. C.; Mattos-Guaraldi, Ana Luíza; Hirata Junior, Raphael

    2017-01-01

    Introduction. Endocarditis caused by yeasts is currently an emerging cause of infective endocarditis and, when accompanied byfever of unknown origin, is more severe since interferes with proper diagnosis and endocarditis treatment. Case presentation. The Rio de Janeiro Infective Endocarditis Study Group reports a case of infectious endocarditis (IE) with negative blood cultures in a 45-year-old white female resident in Rio de Janeiro, Brazil, previously submitted to kidney transplantation. After diagnosis and intervention, the valve culture revealed Rhodotorula mucilaginosa. The clinical aspects and overview of endocarditis caused by Rhodotorula spp. demonstrated that R. muscilaginosa have been isolated from the last IE cases from kidney transplanted patients. Conclusion. Though most of the patients (in literature) recovered well from endocarditis caused by Rhodotorula spp., physicians must be aware for diagnosis of fungemia and fungal treatment in kidney transplanted patients suffering of fever of unknown origin in the modern immunosuppressive treatment. PMID:29255609

  13. Antibacterial effects of Pluchea indica Less leaf extract on E. faecalis and Fusobacterium nucleatum (in vitro

    Directory of Open Access Journals (Sweden)

    Agni Febrina Pargaputri

    2016-06-01

    Full Text Available Background: Enterococcus. faecalis (E. faecalis and Fusobacterium nucleatum (F. nucleatum are the most common bacteria found in infected tooth root canal. Most of these bacteria often cause failure in endodontic treatments. Pluchea indica Less leaf is a species of plants that has several chemical properties. It consists of flavonoids, tannins, polyphenols, and essensial oils which have been reported as antibacterial agents. Because of its benefits, the extract of Pluchea indica Less leaves may be potentially developed as one of root canal sterilization dressing. Purpose: This study aimed to determine antibacterial activity of Pluchea indica Less leaves extract against E. faecalis and F. nucleatum bacteria. Method: Dilution method was conducted first to show Minimum Inhibitory Concentration (MIC of the extract against E. faecalis and F. nucleatum. The antibacterial activity test on Pluchea indica Less leaves extract was performed on E. faecalis and F. nucleatum bacteria using agar diffusion method. The Pluchea indica Less leaves extract used for antibacterial activity test was at a concentrations of 100%, 50%, 25%, 12.5%, and 6.25%. Thirty-five petridiscs were used and divided into five groups based on the extract concentration. Result: The results showed strong and moderate antibacterial effects of the Pluchea indica Less leaves extract on E. faecalis at the concentrations of 100% and 50%, while on F. nucleatum only at the concentration of 100% with moderate effect. Conclusion: Pluchea indica Less leaves extract has antibacterial activity against E. faecalis and F. nucleatum bacteria with strong-moderate effect.

  14. Streptococcus anginosus endocarditis and multiple liver abscesses in a splenectomised patient.

    Science.gov (United States)

    Finn, Talya; Schattner, Ami; Dubin, Ina; Cohen, Regev

    2018-04-27

    An unusual case of infective endocarditis and concurrent multiple liver abscesses both caused by Streptococcus anginosus in a splenectomised patient is reported. The microorganism is a very rare cause of endocarditis and its presentation with multiple liver abscesses is highly unusual. It was initially misdiagnosed as Streptococcus sanguinis and issues relating to the different clinical presentations of S. anginosus including the rare cases of endocarditis, the role of the patient's splenectomy and problems that may contribute to its potential laboratory misidentifications are discussed. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  15. [Study on the antibacterial activity of four kinds of nano-hydroxyapatite composites against Enterococcus faecalis].

    Science.gov (United States)

    Liu, Yi; Zhou, Rongjing; Wu, Hongkun

    2015-06-01

    This study aims to compare and determine a kind of nano-hydroxyapatite composite material with good antibacterial efficacy on Enterococcusfaecalis (E. faecalis) in vitro. We investigated the antimicrobial activity of four kinds of nano-hydroxyapatite composites, namely, silver/hydroxyapatite composite nanoparticles (Ag/nHA), yttrium/hydroxyapatite composite nanoparticles (Yi/nHA), cerium/hydroxyapatite composite nanoparticles (Ce/nHA), and hydroxyapatite nanoparticles (nHA), against E. faecalis in vitro using the agar diffusion and broth dilution method by measuring the growth inhibition zone and the minimum inhibitory concentration (MIC), respectively. The agar diffusion test results showed that Ag/nHA displayed an obvious growth inhibition zone, whereas Yi/nHA, Ce/nHA, and nHA showed no influence on E. faecalis. The MIC value of Ag/nHA was 1.0 g.L-1, and the three other materials had no effect on E.faecalis even at the high concentration of 32.0 g.L-1. Ag/nHA display a potential antimicrobial efficacy to planktonic E.faecalis. Whereas, the three other kinds of nano-hydroxyapatite composites (Yi/nHA, Ce/nHA, nHA) show no influence.

  16. Technetium-99m stannous pyrophosphate imaging of experimental infective endocarditis

    International Nuclear Information System (INIS)

    Riba, A.L.; Downs, J.; Thakur, M.L.; Gottschalk, A.; Andriole, V.T.; Zaret, B.L.

    1978-01-01

    Technetium-99m stannous pyrophosphate (/sup 99m/Tc-PYP) cardiac scintigraphy was performed in 15 rabbits with experimental Streptococcus sanguis aortic-valve infective endocarditis. The animals were imaged five to seven days after the administration of bacteria, and in each case abnormal accumulation of the tracer was visualized in the region of the aortic valve. Three types of cardiac scintigraphic patterns were demonstrated: focal, multifocal, and extensive, each correlating well with the anatomical extent of the lesion as defined by gross pathology. Tissue distribution studies demonstrated a 30 +- 5.3 (mean +- SEM) fold excess of radionuclide uptake in the infective endocarditis lesion compared with that of normal myocardium. Imaging of excised hearts from four animals showed an excellent correlation with in vivo imaging as well as gross pathology. Five animals with nonbacterial thrombotic aortic valve endocarditis demonstrated similar scintigraphic and tissue distribution results. In contrast, four normal animals failed to demonstrate abnormal /sup 99m/Tc-PYP cardiac scintigrams or tissue uptake. This study demonstrates that /sup 99m/Tc-PYP cardiac scintigraphy is a sensitive technique to detect experimental aortic valve endocarditis

  17. Infective endocarditis causing mitral valve stenosis - a rare but deadly complication: a case report.

    Science.gov (United States)

    Hart, Michael A; Shroff, Gautam R

    2017-02-17

    Infective endocarditis rarely causes mitral valve stenosis. When present, it has the potential to cause severe hemodynamic decompensation and death. There are only 15 reported cases in the literature of mitral prosthetic valve bacterial endocarditis causing stenosis by obstruction. This case is even more unusual due to the mechanism by which functional mitral stenosis occurred. We report a case of a 23-year-old white woman with a history of intravenous drug abuse who presented with acute heart failure. Transthoracic echocardiography failed to show valvular vegetation, but high clinical suspicion led to transesophageal imaging that demonstrated infiltrative prosthetic valve endocarditis causing severe mitral stenosis. Despite extensive efforts from a multidisciplinary team, she died as a result of her critical illness. The discussion of this case highlights endocarditis physiology, the notable absence of stenosis in modified Duke criteria, and the utility of transesophageal echocardiography in clinching a diagnosis. It advances our knowledge of how endocarditis manifests, and serves as a valuable lesson for clinicians treating similar patients who present with stenosis but no regurgitation on transthoracic imaging, as a decision to forego a transesophageal echocardiography could cause this serious complication of endocarditis to be missed.

  18. Efficacy and safety profile of linezolid in the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis: a systematic review and meta-analysis.

    Science.gov (United States)

    Agyeman, Akosua Adom; Ofori-Asenso, Richard

    2016-06-22

    Treatment options for drug-resistant tuberculosis are still limited. Linezolid has been recommended for treatment of patients with multidrug-resistant (MDR) or extensively-drug-resistant (XDR) tuberculosis, although uncertainties remain regarding its safety and tolerability in these circumstances. To systematically evaluate the existing evidence regarding the efficacy and tolerability of linezolid in the treatment of MDR or XDR tuberculosis. We conducted a systematic review and meta-analysis in accordance with the PRISMA guidelines. Searches were conducted in PubMed, Web of Science and EMBASE followed by direct search of abstracts in the International Journal of Tuberculosis and Lung Disease to retrieve primary studies published between January 2000 and January 2016 assessing linezolid efficacy and safety in the treatment of drug-resistant TB. We evaluated the occurrence of outcomes including culture conversion, treatment success and incidence of adverse events such as myelosuppression and neuropathy. Twenty-three (23) studies conducted in fourteen (14) countries and involving 507 patients were retrieved. Only 1 randomized controlled trial was identified and none of the identified studies involved participants from Africa. The pooled proportion for treatment success was 77.36 % (95 % CI = 71.38-82.83 %, I(2) = 37.6 %) with culture conversion rate determined as 88.45 % (95 % CI = 83.82-92.38 %, I(2) = 45.4 %). There was no strong evidence for both culture conversion (p = 0.0948) and treatment success (p = 0.0695) between linezolid daily doses ≤ 600 and > 600 mg. Only myelosuppression showed a strong statistical significance (p linezolid also showed no significance upon dose comparisons (p = 0.3213, p = 0.9050 respectively). Available evidence presents Linezolid as a viable option in the treatment of MDR/XDR TB although patients ought to be monitored closely for the incidence of major adverse events such as myelosuppression and

  19. Imaging experimental infective endocarditis with indium-111-labeled blood cellular components

    International Nuclear Information System (INIS)

    Riba, A.L.; Thakur, M.L.; Gottschalk, A.; Andriole, V.T.; Zaret, B.L.

    1979-01-01

    The capability of radionuclide imaging to detect experimental aortic valve infective endocarditis was assessed with indium-111 ( 111 In)-labeled blood cells. Sequential cardiac imaging and tissue distribution studies were obtained in 17 rabbits with infective endocarditis after administration of 111 In-platelets and in five after 111 In-polymorphonuclear leukocytes. Forty-eight to 72 hours after platelet administration, in vivo imaging demonstrated abnormal 111 In uptake in all animals in the region of the aortic valve in an anatomically distinct pattern. Images of the excised heart showed discrete cardiac uptake conforming to the in vivo image and gross pathological examination. 111 In-platelet uptake in vegetations from the 17 animals averaged 240 +- 41 times greater than that in normal myocardium and 99 +- 15 times greater uptake in blood. In contrast, 111 In-leukocyte cardiac imaging showed no abnormal aortic valve uptake 24 hours after tracer administration and the lesion myocardium activity ratio was only 5 +- 2 (3 +- 1 for lesion/blood activity). Four normal rabbits demonstrated neither positive 111 In-platelet scintigraphs nor abnormal cardiac tissue uptake. Likewise, noncellular 111 In was not concentrated to any significant extent in three animals with infective endocarditis. This study demonstrates that 111 In-platelet, but not leukocyte cardiac imaging, is a sensitive technique for detecting experimental infective endocarditis. The imaging data conform to the cellular pathology of the infective endocarditis vegetation

  20. Echocardiographic agreement in the diagnostic evaluation for infective endocarditis

    DEFF Research Database (Denmark)

    Lauridsen, Trine Kiilerich; Selton-Suty, Christine; Tong, Steven Y C

    2016-01-01

    Echocardiography is essential for the diagnosis and management of infective endocarditis (IE). However, the reproducibility for the echocardiographic assessment of variables relevant to IE is unknown. Objectives of this study were: (1) To define the reproducibility for IE echocardiographic...... variables and (2) to describe a methodology for assessing quality in an observational cohort containing site-interpreted data. IE reproducibility was assessed on a subset of echocardiograms from subjects enrolled in the International Collaboration on Endocarditis registry. Specific echocardiographic case...

  1. Actinobacillus equuli subsp. equuli associated with equine valvular endocarditis

    DEFF Research Database (Denmark)

    Aalbæk, Bent; Østergaard, Stine; Buhl, Rikke

    2007-01-01

    Microbiological and pathological data from a case of equine valvular endocarditis are reported. Limited information is available on the pathogenic potential of equine Actinobacillus species as several strains originate from apparently healthy horses. After the establishment of two subspecies within...... this species, this seems to be the first report of an etiological association between A. equuli subsp. equuli and equine endocarditis. Furthermore, new information on some phenotypical characteristics of this subspecies are reported, compared to previous findings...

  2. Oral antibiotic treatment of left-sided infectious endocarditis verified by 16S-PCR

    DEFF Research Database (Denmark)

    Bruun, Louise E; Tønder, Niels; Hansen, Thomas Fritz

    2011-01-01

    Treatment of infectious endocarditis (IE) comprises intravenously administered antibiotic medications given at high doses for 4-6 weeks--sometimes even longer. Approximately 50% of patients referred to tertiary care centres require additional surgical intervention. At present there are few papers...... describing the effects of oral antibiotic treatment in IE, and only in patients with right-sided endocarditis. In this case report we present a patient with left-sided Streptococcus endocarditis successfully treated with oral antibiotic drugs....

  3. Extracardiac manifestations of infective endocarditis and their historical descriptions.

    Science.gov (United States)

    Silverman, Mark E; Upshaw, Charles B

    2007-12-15

    In his landmark "Gulstonian Lectures on Malignant Endocarditis," published in 1885, William Osler commented, "Few diseases present greater difficulties in the way of diagnosis than malignant endocarditis, difficulties which in many cases are practically insurmountable." At that time, the fields of microbiology and blood cultures were in their infancy, and the diagnosis was made premortem in just half the patients with the condition. After Osler's report, extracardiac physical findings became essential clues to earlier diagnosis. Today, infective endocarditis is most commonly suggested from the history and often clinched by an echocardiogram and blood cultures. Although prized physical manifestations are much less frequent now, they still do occur and may be an invaluable clue that leads to earlier, more effective treatment. The investigators review these extracardiac findings along with their historical descriptions: splinter hemorrhages, emboli, Osler's nodes, Janeway and Bowman lesions of the eye, Roth spots, petechiae, and clubbing.

  4. Simultaneous determination of tedizolid and linezolid in rat plasma by ultra performance liquid chromatography tandem mass spectrometry and its application to a pharmacokinetic study.

    Science.gov (United States)

    Yu, Hua-chen; Pan, Chen-wei; Xie, Qi-peng; Zheng, Yi; Hu, Yue-zheng; Lin, Yi-mu

    2016-02-01

    A sensitive and rapid ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed to determine tedizolid and linezolid in rat plasma simultaneously. Chromatographic separation was carried out on an Acquity UPLC BEH C18 column and mass spectrometric analysis was performed using a XEVO TQD triple quadruple mass spectrometer coupled with an electrospray ionization (ESI) source in the positive ion mode. Multiple reaction monitoring (MRM) mode was used for quantification using target fragment ions m/z 371.4→343.2 for tedizolid, and m/z 338.3→56.1 for linezolid. This assay method has been fully validated in terms of selectivity, linearity, recovery and matrix effect, accuracy, precision and stability. The linearity of this method was found to be within the concentration range of 5-5000ng/mL for tedizolid, and 10-10,000ng/mL for linezolid in rat plasma, respectively. Only 3.0min was needed for an analytical run. This assay was used to support a preclinical study where multiple oral doses were administered to rats to investigate the pharmacokinetics of tedizolid and linezolid. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. [Severe infective endocarditis through the history].

    Science.gov (United States)

    Rouzé, S; Leguerrier, A; Verhoye, J P; Flécher, E

    2017-02-01

    The history of infective endocarditis (IE) is a good example of medical progress. Initially incurable, endocarditis, when diagnosed, was synonym of death. After significant diagnostic progress, thanks to Osler's contribution especially, the first surgeries and antibacterial drugs obtained very few successful cures. We had to wait until Flamming's discovery to observe frequent cures thanks to antibiotics. Surgery manages to push possibilities of cure a bit further. However, paravalvular extensions, described since the first surgical case of IE, was a real technical matter. Thus, the second half of 20th century was devoted to overcoming this surgical challenge. In this historical review, we describe the story of severe IE, especially with paravalvular involvement, by highlighting major progress - clinical and surgical, that allows its current management. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  6. Association of periodontal disease, oral procedures, and other clinical findings with bacterial endocarditis in dogs.

    Science.gov (United States)

    Peddle, Gordon D; Drobatz, Kenneth J; Harvey, Colin E; Adams, Allison; Sleeper, Meg M

    2009-01-01

    To identify risk factors potentially associated with the development of bacterial endocarditis in dogs and determine whether periodontal disease and surgical procedures (oral and nonoral) were associated with bacterial endocarditis. Retrospective case-control study. 76 dogs with (cases) and 80 dogs without (controls) bacterial endocarditis. Medical records were reviewed for information on signalment, physical examination findings, recent medical history, and results of echocardiography, clinicopathologic testing, and necropsy. None of the dogs with endocarditis had a history of undergoing any dental or oral procedure in the 3 months prior to the diagnosis of endocarditis, and no significant difference was found between groups with regard to the prevalence of oral infection. Dogs with endocarditis were significantly more likely to have undergone a nonoral surgical procedure that required general anesthesia in the preceding 3 months or to have developed a new heart murmur or a change in intensity of an existing heart murmur. Preexisting cardiac dis-ease (congenital or acquired) was not found to be a risk factor. Results did not provide any evidence of an association between bacterial endocarditis in dogs and either dental or oral surgical procedures or oral infection. Findings suggested that the routine use of prophylactic antimicrobial administration in dogs undergoing oral procedures needs to be reevaluated.

  7. Penicillin-sensitive Moraxella prosthetic endocarditis. Near disaster caused by failure to treat with penicillin.

    OpenAIRE

    Chen, W; Lee, P K; Chau, P Y

    1982-01-01

    A patient with late prosthetic endocarditis resulting from Moraxella non-liquefaciens is reported. Correct laboratory indentification is of therapeutic importance as Moraxella is often highly sensitive to penicillin. Because of suspected penicillin sensitivity, antibiotics other than penicillin were used, but failed to control the endocarditis. Prompt response occurred when penicillin was given. Penicillin remains by far the most effective antibiotic for the treatment of endocarditis, particu...

  8. Imaging endocarditis with Tc-99m-labeled antibody--an experimental study: concise communication

    Energy Technology Data Exchange (ETDEWEB)

    Wong, D.W.; Dhawan, V.K.; Tanaka, T.; Mishkin, F.S.; Reese, I.C.; Thadepalli, H.

    1982-03-01

    The sensitivity and specificity of Tc-99m-labeled antibacterial antibody (Tc-99m Ab) for detecting bacterial endocarditis were evaluated in an experimental model. Rabbit-produced antistaphylococcal antibody was extracted using Rivanol and chemically labeled with Tc-99m. This Tc-99m Ab was injected intravenously in New Zealand rabbits 24 hr after producing Staphylococcus aureus endocarditis of the aortic valve. Imaging and tissue analyses were performed on the following day. All 11 animals developed S. aureus aortic-valve vegetations and showed increased uptake of Tc-99m Ab at the aortic valve, 118 times higher than at the uninfected tricuspid valve. Although high hepatic radioactivity and anatomic uncertainties interfered with in vivo delineation of these lesions, images of the excised hearts showed all affected valves. Two rabbits inoculated with Escherichia coli did not develop endocarditis and had little uptake of Tc-99m Ab, while six rabbits with enterococcal endocarditis had no uptake of the Tc-99m Ab in their vegetations. The findings suggest potential value of Tc-99m Ab on the rapid diagnosis of endocarditis.

  9. [Primary Aspergillus endocarditis. Apropos of a case and review of the international literature].

    Science.gov (United States)

    Roux, J P; Koussa, A; Cajot, M A; Marquette, F; Goullard, L; Gosselin, B; Pol, A; Warembourg, H; Soots, G

    1992-01-01

    The authors report a case of primary aspergillus endocarditis with endophthalmitis and vertebral osteomyelitis. No underlying disease and no predisposing factors were found. Valve replacement plus combined antifungal chemotherapy proved to be effective as the patient is asymptomatic 18 months after the first symptoms. 48 cases of aspergillus endocarditis, without prior cardiac surgery have been reported in the literature. Aspergillus endocarditis was valvular or mural. Extracardiac dissemination was common but endophthalmitis and osteomyelitis were infrequent. In 11 cases, the diagnosis was made by histologic examination of embolectomy or ocular, skin biopsy tissue. All patients were febrile. Blood cultures showed no Aspergillus species. Clinical manifestations of endocarditis were described in less than fifty per cent of cases. Echocardiographic visualization of vegetations was obtained in 5 cases. Many patients experienced embolic phenomena. Mortality from Aspergillus endocarditis is extremely high (96%). Surgery is the main treatment, consisting of valve replacement. Antifungal chemotherapy should be combined. The proper duration and dosage and the combination of antifungal drugs have not been clearly defined.

  10. Imaging endocarditis with Tc-99m-labeled antibody--an experimental study: concise communication

    International Nuclear Information System (INIS)

    Wong, D.W.; Dhawan, V.K.; Tanaka, T.; Mishkin, F.S.; Reese, I.C.; Thadepalli, H.

    1982-01-01

    The sensitivity and specificity of Tc-99m-labeled antibacterial antibody (Tc-99m Ab) for detecting bacterial endocarditis were evaluated in an experimental model. Rabbit-produced antistaphylococcal antibody was extracted using Rivanol and chemically labeled with Tc-99m. This Tc-99m Ab was injected intravenously in New Zealand rabbits 24 hr after producing Staphylococcus aureus endocarditis of the aortic valve. Imaging and tissue analyses were performed on the following day. All 11 animals developed S. aureus aortic-valve vegetations and showed increased uptake of Tc-99m Ab at the aortic valve, 118 times higher than at the uninfected tricuspid valve. Although high hepatic radioactivity and anatomic uncertainties interfered with in vivo delineation of these lesions, images of the excised hearts showed all affected valves. Two rabbits inoculated with Escherichia coli did not develop endocarditis and had little uptake of Tc-99m Ab, while six rabbits with enterococcal endocarditis had no uptake of the Tc-99m Ab in their vegetations. The findings suggest potential value of Tc-99m Ab on the rapid diagnosis of endocarditis

  11. Bilateral foveal cysts secondary to Streptococcus constellatus endocarditis.

    Science.gov (United States)

    Shah, Anish N; Shah, Benoy N; Glover, Sarah; Herbert, Luke

    2013-06-01

    Infective endocarditis can be acute or subacute, depending on the virulence of the causative organism. It can also cause loss of vision by a variety of mechanisms, ranging from embolic retinal artery occlusion to endogenous endophthalmitis. We illustrate the first report of foveal cyst formation secondary to infective endocarditis. A 53-year-old man presented to his general practitioner with a variety of constitutional symptoms, but initial laboratory and imaging investigations revealed only mild normocytic anaemia, and he was discharged from further medical care. Four weeks later he developed bilateral visual loss associated with whitish lesions of the superficial retina at both foveae. These later developed into foveal cysts with disruption of the photoreceptor inner segment-outer segment junction and persistent poor visual acuity of 6/60 OU. No retinal haemorrhages or Roth spots were noted. Only after he presented with visual loss did further investigations reveal the underlying diagnosis of streptococcal endocarditis. Ophthalmologists assessing retinal pathology which presents in association with undiagnosed constitutional symptoms are advised to refer such patients promptly for thorough medical investigation, including blood culture and echocardiography where appropriate.

  12. Echocardiography in Infective Endocarditis: State of the Art.

    Science.gov (United States)

    Afonso, Luis; Kottam, Anupama; Reddy, Vivek; Penumetcha, Anirudh

    2017-10-25

    In this review, we examine the central role of echocardiography in the diagnosis, prognosis, and management of infective endocarditis (IE). 2D transthoracic echocardiography (TTE) and transesophageal echocardiography TEE have complementary roles and are unequivocally the mainstay of diagnostic imaging in IE. The advent of 3D and multiplanar imaging have greatly enhanced the ability of the imager to evaluate cardiac structure and function. Technologic advances in 3D imaging allow for the reconstruction of realistic anatomic images that in turn have positively impacted IE-related surgical planning and intervention. CT and metabolic imaging appear to be emerging as promising ancillary diagnostic tools that could be deployed in select scenarios to circumvent some of the limitations of echocardiography. Our review summarizes the indispensable and central role of various echocardiographic modalities in the management of infective endocarditis. The complementary role of 2D TTE and TEE are discussed and areas where 3D TEE offers incremental value highlighted. An algorithm summarizing a contemporary approach to the workup of endocarditis is provided and major societal guidelines for timing of surgery are reviewed.

  13. [Infective endocarditis in intensive cardiac care unit - clinical and biochemical differences of blood-culture negative infective endocarditis].

    Science.gov (United States)

    Kaziród-Wolski, Karol; Sielski, Janusz; Ciuraszkiewicz, Katarzyna

    2017-01-23

    Diagnosis and treatment of infective endocarditis (IE) is still a challenge for physicians. Group of patients with the worst prognosis is treated in Intensive Cardiac Care Unit (ICCU). Etiologic agent can not be identified in a substantial number of patients. The aim of study is to find differences between patients with blood culture negative infective endocarditis (BCNIE) and blood culture positive infective endocarditis (BCPIE) treated in ICCU by comparing their clinical course and laboratory parameters. Retrospective analysis of 30 patients with IE hospitalized in ICCU Swietokrzyskie Cardiac Centre between 2010 and 2016. This group consist of 26 men (86,67%) and 4 women (13,3%). Mean age was 58 years ±13. Most of the cases were new disease, recurrence of the disease was observed in 2 cases (6,7%). 8 patients (26,7%) required artificial ventilation, 11 (36,7%) received inotropes and 6 (20%) vasopresors. In 14 (46,7%) cases blood cultures was negative (BCNIE), the rest of patients (16, 53,3%) was blood cultures - positive infective endocarditis (BCIE). Both of the groups were clinically similar. There were no statistically significant differences in incidence of cardiac implants, localization of bacterial vegetations, administered catecholamines, antibiotic therapy, artificial ventilation, surgical treatment, complication and in-hospital mortality. Incidence of cardiac complications in all of BCNIE cases and in 81,3% cases of BCPIE draws attention, but it is not statistically significant difference (p=0,08). There was statistically significant difference in mean BNP blood concentration (3005,17 ng/ml ±2045,2 vs 1013,42 ng/ml ±1087,6; p=0,01), but there were no statistically significant differences in rest of laboratory parameters. BCNIE group has got higher mean BNP blood concentration than BCPIE group. There were no statistically significant differences between these groups in others laboratory parameters, clinical course and administered antibiotic therapy

  14. Surface-Associated Lipoproteins Link Enterococcus faecalis Virulence to Colitogenic Activity in IL-10-Deficient Mice Independent of Their Expression Levels.

    Directory of Open Access Journals (Sweden)

    Soeren Ocvirk

    2015-06-01

    Full Text Available The commensal Enterococcus faecalis is among the most common causes of nosocomial infections. Recent findings regarding increased abundance of enterococci in the intestinal microbiota of patients with inflammatory bowel diseases and induction of colitis in IL-10-deficient (IL-10-/- mice put a new perspective on the contribution of E. faecalis to chronic intestinal inflammation. Based on the expression of virulence-related genes in the inflammatory milieu of IL-10-/- mice using RNA-sequencing analysis, we characterized the colitogenic role of two bacterial structures that substantially impact on E. faecalis virulence by different mechanisms: the enterococcal polysaccharide antigen and cell surface-associated lipoproteins. Germ-free wild type and IL-10-/- mice were monoassociated with E. faecalis wild type OG1RF or the respective isogenic mutants for 16 weeks. Intestinal tissue and mesenteric lymph nodes (MLN were collected to characterize tissue pathology, loss of intestinal barrier function, bacterial adhesion to intestinal epithelium and immune cell activation. Bone marrow-derived dendritic cells (BMDC were stimulated with bacterial lysates and E. faecalis virulence was additionally investigated in three invertebrate models. Colitogenic activity of wild type E. faecalis (OG1RF score: 7.2±1.2 in monoassociated IL-10-/- mice was partially impaired in E. faecalis lacking enterococcal polysaccharide antigen (ΔepaB score: 4.7±2.3; p<0.05 and was almost completely abrogated in E. faecalis deficient for lipoproteins (Δlgt score: 2.3±2.3; p<0.0001. Consistently both E. faecalis mutants showed significantly impaired virulence in Galleria mellonella and Caenorhabditis elegans. Loss of E-cadherin in the epithelium was shown for all bacterial strains in inflamed IL-10-/- but not wild type mice. Inactivation of epaB in E. faecalis reduced microcolony and biofilm formation in vitro, altered bacterial adhesion to intestinal epithelium of germ

  15. Neurological complications of infective endocarditis

    International Nuclear Information System (INIS)

    Khan, Sonia A.A.; Yaqub, Basim A.; Al-Deeb, Saleh M.

    1996-01-01

    We reviewed the files of 80 successive patients with native and prosthetic valve endocarditis admitted to Riyadh Armed Forces Hospital. Neurolological complications (NC) occurred in 28 (35%) patients. The valves involved were mitral in 12 (43%), aortic in eight (29%), combined mitral and aortic lesions in six (21%) and others in two (7%). The common causative organisms were Streptococci in 12 (43%), Staphylococcus aureus and Staphylococcus epidermides, both occurring in four (14%). Compared to the 52 infective endocarditis patients with no neurological complications (NNC), the NC occurred more frequently in male patients, those with aortic valve lesion, those with atrial fibrillation, those with delayed therapy and those with causative organisms being Streptococci or Staphylococci. Eleven patients died (39%), 12 (43%) recovered with motor sequelae, six (21%) had seizure disorder and five (18%) had full recovery. The frequency of neurological complications and mortality is comparable to those reported in the literature: however, the frequency was higher in our patients. (author)

  16. Enterococcus faecalis infection causes inflammation, intracellular oxphos-independent ROS production, and DNA damage in human gastric cancer cells.

    Directory of Open Access Journals (Sweden)

    Jesper A B Strickertsson

    Full Text Available BACKGROUND: Achlorhydria caused by e.g. atrophic gastritis allows for bacterial overgrowth, which induces chronic inflammation and damage to the mucosal cells of infected individuals driving gastric malignancies and cancer. Enterococcus faecalis (E. faecalis can colonize achlohydric stomachs and we therefore wanted to study the impact of E. faecalis infection on inflammatory response, reactive oxygen species (ROS formation, mitochondrial respiration, and mitochondrial genetic stability in gastric mucosal cells. METHODS: To separate the changes induced by bacteria from those of the inflammatory cells we established an in vitro E. faecalis infection model system using the gastric carcinoma cell line MKN74. Total ROS and superoxide was measured by fluorescence microscopy. Cellular oxygen consumption was characterized non-invasively using XF24 microplate based respirometry. Gene expression was examined by microarray, and response pathways were identified by Gene Set Analysis (GSA. Selected gene transcripts were verified by quantitative real-time polymerase chain reaction (qRT-PCR. Mitochondrial mutations were determined by sequencing. RESULTS: Infection of MKN74 cells with E. faecalis induced intracellular ROS production through a pathway independent of oxidative phosphorylation (oxphos. Furthermore, E. faecalis infection induced mitochondrial DNA instability. Following infection, genes coding for inflammatory response proteins were transcriptionally up-regulated while DNA damage repair and cell cycle control genes were down-regulated. Cell growth slowed down when infected with viable E. faecalis and responded in a dose dependent manner to E. faecalis lysate. CONCLUSIONS: Infection by E. faecalis induced an oxphos-independent intracellular ROS response and damaged the mitochondrial genome in gastric cell culture. Finally the bacteria induced an NF-κB inflammatory response as well as impaired DNA damage response and cell cycle control gene

  17. Risk of infective endocarditis in patients with systemic lupus erythematosus in Taiwan: a nationwide population-based study.

    Science.gov (United States)

    Chang, Y S; Chang, C C; Chen, Y H; Chen, W S; Chen, J H

    2017-10-01

    Objectives Patients with systemic lupus erythematosus are considered vulnerable to infective endocarditis and prophylactic antibiotics are recommended before an invasive dental procedure. However, the evidence is insufficient. This nationwide population-based study evaluated the risk and related factors of infective endocarditis in systemic lupus erythematosus. Methods We identified 12,102 systemic lupus erythematosus patients from the National Health Insurance research-oriented database, and compared the incidence rate of infective endocarditis with that among 48,408 non-systemic lupus erythematosus controls. A Cox multivariable proportional hazards model was employed to evaluate the risk of infective endocarditis in the systemic lupus erythematosus cohort. Results After a mean follow-up of more than six years, the systemic lupus erythematosus cohort had a significantly higher incidence rate of infective endocarditis (42.58 vs 4.32 per 100,000 person-years, incidence rate ratio = 9.86, p endocarditis in systemic lupus erythematosus patients. Conclusions A higher risk of infective endocarditis was observed in systemic lupus erythematosus patients. Risk factors for infective endocarditis in the systemic lupus erythematosus cohort included heart disease, chronic kidney disease, steroid pulse therapy within 30 days, and a recent invasive dental procedure within 30 days.

  18. Anti-fibrin antibody binding in valvular vegetations and kidney lesions during experimental endocarditis.

    Science.gov (United States)

    Yokota, M; Basi, D L; Herzberg, M C; Meyer, M W

    2001-01-01

    In Streptococcus sanguinis (sanguis) induced experimental endocarditis, we sought evidence that the development of aortic valvular vegetation depends on the availability of fibrin. Endocarditis was induced in New Zealand white rabbits by catheter placement into the left ventricle and inoculation of the bacteria. Fibrin was localized in the developing vegetation with 99mTechnetium (Tc)-labeled anti-fibrin antibody one or three days later. When rabbit anti-fibrin antibody was given intravenously on day 1, the mass of aortic valvular vegetation was significantly reduced at day 3; infusion of non-specific rabbit IgG showed no effect. The 99mTc-labeled anti-fibrin antibody also labeled kidneys that showed macroscopic subcapsular hemorrhage. To learn if the deposition of fibrin in the kidneys was a consequence of endocarditis required a comparison of farm-bred and specific pathogen-free rabbits before and after the induction of endocarditis. Before induction, the kidneys of farm-bred rabbits were labeled, but specific pathogen-free rabbits were free of labeling and signs of macroscopic hemorrhage. After 3 days of endocarditis, kidneys of 10 of 14 specific pathogen-free rabbits labeled with 99mTc-labeled anti-fibrin antibody and showed hemorrhage. Kidney lesions were suggested to be a frequent sequellae of S. sanguinis infective endocarditis. For the first time, fibrin was shown to be required for the continued development of aortic valvular vegetations.

  19. Novel Tissue Level Effects of the Staphylococcus aureus Enterotoxin Gene Cluster Are Essential for Infective Endocarditis.

    Science.gov (United States)

    Stach, Christopher S; Vu, Bao G; Merriman, Joseph A; Herrera, Alfa; Cahill, Michael P; Schlievert, Patrick M; Salgado-Pabón, Wilmara

    2016-01-01

    Superantigens are indispensable virulence factors for Staphylococcus aureus in disease causation. Superantigens stimulate massive immune cell activation, leading to toxic shock syndrome (TSS) and contributing to other illnesses. However, superantigens differ in their capacities to induce body-wide effects. For many, their production, at least as tested in vitro, is not high enough to reach the circulation, or the proteins are not efficient in crossing epithelial and endothelial barriers, thus remaining within tissues or localized on mucosal surfaces where they exert only local effects. In this study, we address the role of TSS toxin-1 (TSST-1) and most importantly the enterotoxin gene cluster (egc) in infective endocarditis and sepsis, gaining insights into the body-wide versus local effects of superantigens. We examined S. aureus TSST-1 gene (tstH) and egc deletion strains in the rabbit model of infective endocarditis and sepsis. Importantly, we also assessed the ability of commercial human intravenous immunoglobulin (IVIG) plus vancomycin to alter the course of infective endocarditis and sepsis. TSST-1 contributed to infective endocarditis vegetations and lethal sepsis, while superantigens of the egc, a cluster with uncharacterized functions in S. aureus infections, promoted vegetation formation in infective endocarditis. IVIG plus vancomycin prevented lethality and stroke development in infective endocarditis and sepsis. Our studies support the local tissue effects of egc superantigens for establishment and progression of infective endocarditis providing evidence for their role in life-threatening illnesses. In contrast, TSST-1 contributes to both infective endocarditis and lethal sepsis. IVIG may be a useful adjunct therapy for infective endocarditis and sepsis.

  20. Suboptimal Addiction Interventions for Patients Hospitalized with Injection Drug Use-Associated Infective Endocarditis.

    Science.gov (United States)

    Rosenthal, Elana S; Karchmer, Adolf W; Theisen-Toupal, Jesse; Castillo, Roger Araujo; Rowley, Chris F

    2016-05-01

    Infective endocarditis is a serious infection, often resulting from injection drug use. Inpatient treatment regularly focuses on management of infection without attention to the underlying addiction. We aimed to determine the addiction interventions done in patients hospitalized with injection drug use-associated infective endocarditis. This is a retrospective review of patients hospitalized with injection drug use-associated infective endocarditis from January, 2004 through August, 2014 at a large academic tertiary care center in Boston, Massachusetts. For the initial and subsequent admissions, data were collected regarding addiction interventions, including consultation by social work, addiction clinical nurse and psychiatry, documentation of addiction in the discharge summary plan, plan for medication-assisted treatment and naloxone provision. There were 102 patients admitted with injection drug use-associated infective endocarditis, 50 patients (49.0%) were readmitted and 28 (27.5%) patients had ongoing injection drug use at readmission. At initial admission, 86.4% of patients had social work consultation, 23.7% had addiction consultation, and 24.0% had psychiatry consultation. Addiction was mentioned in 55.9% of discharge summary plans, 7.8% of patients had a plan for medication-assisted treatment, and naloxone was never prescribed. Of 102 patients, 26 (25.5%) are deceased. The median age at death was 40.9 years (interquartile range 28.7-48.7). We found that patients hospitalized with injection drug use-associated infective endocarditis had high rates of readmission, recurrent infective endocarditis and death. Despite this, addiction interventions were suboptimal. Improved addiction interventions are imperative in the treatment of injection drug use-associated infective endocarditis. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Probiotic assessment of Enterococcus faecalis CP58 isolated from human gut.

    Science.gov (United States)

    Nueno-Palop, Carmen; Narbad, Arjan

    2011-02-28

    A total of seventy lactic acid bacteria (LAB) were isolated from the faeces of healthy humans and their identities were confirmed by sequencing of their 16S rDNA genes. Of these only 5 isolates were found to resist bile salts and indicated survival in the simulated in vitro digestion assay which reproduces the stomach and intestinal digestion indicating their tolerance to gastric enzymes and the low pH conditions. Species that showed the best resistance to these conditions were: Lactobacillus casei, Lactobacillus sp., uncultured bifidobacteria, Enterococcus faecalis and Streptococcus anginosus. These strains were investigated further to study their capacity to adhere to human intestinal Caco-2 cells. E. faecalis was the most adherent strain. Examination of the virulence determinants for this strain indicated that it was positive for efaAfs, gelE, agg, cpd, cob, ccf and cad, a profile that is similar to that of many E. faecalis isolates from food sources. The cytolysin biosynthetic genes cylA, cylB and cylM that are more associated with the clinical isolates of E. faecium were not detected in this strain. The antibiotic susceptibility tests indicated that the strain was sensitive to vancomycin, tetracycline, rifampicin and erythromycin but resistant only to kanamycin and chloramphenicol. These data suggest that the strain E. faecalis CP58 may be tested further for beneficial properties and developed as a new probiotic. Copyright © 2010 Elsevier B.V. All rights reserved.

  2. Lupus-Negative Libman-Sacks Endocarditis Complicated by Catastrophic Antiphospholipid Syndrome.

    Science.gov (United States)

    Murtaza, Ghulam; Iskandar, Joy; Humphrey, Tara; Adhikari, Sujeen; Kuruvilla, Aneesh

    2017-04-01

    Libman-Sacks endocarditis is characterized by sterile and verrucous lesions that predominantly affect the aortic and mitral valves. In most cases, patients do not have significant valvular dysfunction. However, patients with significant valvular dysfunction may present with serious complications such as cardiac failure, arrhythmias, and thromboembolic events. Recently, association of Libman-Sacks endocarditis with antiphospholipid antibody syndrome (APS) has been made. APS is most commonly defined by venous and arterial thrombosis, recurrent pregnancy loss, and thrombocytopenia. While the syndrome can be a primary syndrome, it is usually secondary to systemic lupus erythematosus. Catastrophic antiphospholipid syndrome (CAPS) can be a life-threatening presentation of APS and can occur in 1% of patients with antiphospholipid syndrome. We present a very rare case of a young female patient with lupus-negative Libman-Sacks endocarditis complicated by CAPS.

  3. Candida Infective Endocarditis: an Observational Cohort Study with a Focus on Therapy

    Science.gov (United States)

    Johnson, Melissa; Bayer, Arnold S.; Bradley, Suzanne; Giannitsioti, Efthymia; Miró, José M.; Tornos, Pilar; Tattevin, Pierre; Strahilevitz, Jacob; Spelman, Denis; Athan, Eugene; Nacinovich, Francisco; Fortes, Claudio Q.; Lamas, Cristiane; Barsic, Bruno; Fernández-Hidalgo, Nuria; Muñoz, Patricia; Chu, Vivian H.

    2015-01-01

    Candida infective endocarditis is a rare disease with a high mortality rate. Our understanding of this infection is derived from case series, case reports, and small prospective cohorts. The purpose of this study was to evaluate the clinical features and use of different antifungal treatment regimens for Candida infective endocarditis. This prospective cohort study was based on 70 cases of Candida infective endocarditis from the International Collaboration on Endocarditis (ICE)-Prospective Cohort Study and ICE-Plus databases collected between 2000 and 2010. The majority of infections were acquired nosocomially (67%). Congestive heart failure (24%), prosthetic heart valve (46%), and previous infective endocarditis (26%) were common comorbidities. Overall mortality was high, with 36% mortality in the hospital and 59% at 1 year. On univariate analysis, older age, heart failure at baseline, persistent candidemia, nosocomial acquisition, heart failure as a complication, and intracardiac abscess were associated with higher mortality. Mortality was not affected by use of surgical therapy or choice of antifungal agent. A subgroup analysis was performed on 33 patients for whom specific antifungal therapy information was available. In this subgroup, 11 patients received amphotericin B-based therapy and 14 received echinocandin-based therapy. Despite a higher percentage of older patients and nosocomial infection in the echinocandin group, mortality rates were similar between the two groups. In conclusion, Candida infective endocarditis is associated with a high mortality rate that was not impacted by choice of antifungal therapy or by adjunctive surgical intervention. Additionally, echinocandin therapy was as effective as amphotericin B-based therapy in the small subgroup analysis. PMID:25645855

  4. Triple valve infective endocarditis - a late diagnosis

    Directory of Open Access Journals (Sweden)

    Edme R. Mustafa

    2018-04-01

    Full Text Available Behcet's disease is a systemic vasculitis of unknown aetiology with cardiac involvement as well as damage to other organs. Whether the sterile valvular inflammation which occurs in this autoimmune disease predisposes to bacterial adhesion and infective endocarditis is not yet established. We present the case of a patient with Behcet disease in which transthoracic echocardiography showed mobile masses on the aortic, tricuspid, and mitral valves, leading to multivalvular infective endocarditis diagnosis, possibly in the context of valvular inflammation. The case presented in this article confirms observation of other studies, namely that ultrasonography plays an important role in the diagnosis and evaluation of rheumatic diseases and permits optimal management in daily practice.

  5. First Report of Granulicatella sp. Endocarditis in a Kidney Transplant Patient

    Directory of Open Access Journals (Sweden)

    Flávio Jota de Paula

    Full Text Available Abstract Granulicatella and Abiotrophia are genera of fastidious Gram-positive cocci commensal of the oral, genitourinary, and intestinal flora. We report the first case of infective endocarditis caused by Granulicatella sp. in a kidney transplant recipient. A 67-year-old male kidney transplant recipient was admitted to the hospital for investigation of fever, abdominal pain, and diarrhea. On physical examination, he was dehydrated. Laboratory tests identified impaired renal function (creatinine level of 15.5 mg/dl; reference, 3.0 mg/dl, metabolic acidosis, and electrolyte disturbances. Cryptosporidium sp. was identified as the cause of the diarrhea, and the infection was treated with nitazoxanide. On admission, cultures of blood, urine, and stool samples were negative. Echocardiography results were normal. Despite the antimicrobial treatment, the fever persisted. A transthoracic echocardiogram revealed infective endocarditis of the mitral valve, and Granulicatella spp. were isolated in blood cultures. Although the patient was treated with penicillin and amikacin, he evolved to septic shock of pulmonary origin and died. Infective endocarditis caused by Granulicatella sp. should be suspected in cases of culture-negative endocarditis.

  6. Lactococcus garvieae Endocarditis on a Prosthetic Biological Aortic Valve.

    Science.gov (United States)

    Tsur, A; Slutzki, T; Flusser, D

    2015-09-01

    Lactococcus garvieae (LG) endocarditis is a rare disease in humans. There are only about 16 reported cases in the world. We report a 76-year-old male patient with LG endocarditis. In depth interview with the patient revealed that 2 weeks prior to admission, he had eaten sushi containing raw fish. Unlike many of the other infections reported, which were on a native mitral valve, our patient's vegetation was on a prosthetic aortic valve. © 2014 Blackwell Verlag GmbH.

  7. Demonstration of infective endocarditis by cardiac CT and transoesophageal echocardiography: comparison with intra-operative findings.

    Science.gov (United States)

    Koo, Hyun Jung; Yang, Dong Hyun; Kang, Joon-Won; Lee, Joo Yeon; Kim, Dae-Hee; Song, Jong-Min; Kang, Duk-Hyun; Song, Jae-Kwan; Kim, Joon Bum; Jung, Sung-Ho; Choo, Suk Jung; Chung, Cheol Hyun; Lee, Jae-Won; Lim, Tae-Hwan

    2018-02-01

    We aimed to compare imaging findings of infective endocarditis between computed tomography (CT) and transoesophageal echocardiography (TEE) using surgical inspection as a reference standard. Forty-nine patients (aged 54 ± 17 years, 69% men) who underwent pre-operative CT and TEE for infective endocarditis were included. Twelve of these patients had prosthetic valve endocarditis. Imaging findings of infective endocarditis were classified as vegetation, leaflet perforation, abscess/pseudoaneurysm, and paravalvular leakage. Diagnostic performances of CT and TEE were evaluated using surgical inspection as a reference standard. Interobserver agreements for CT findings were obtained using Cohen's κ test. The detection rates of infective endocarditis per patient with CT and TEE were 93.9% (46/49) and 95.9% (47/49), respectively. In per-imaging analysis, the sensitivities of CT and TEE were not significantly different for both native and prosthetic valve infective endocarditis (sensitivity: vegetation, 100% in TEE and 90.9% in CT; leaflet perforation, 87.5% in TEE and 50.0% in CT; abscess/pseudoaneurysm, 40.0% in TEE and 60.0% in CT; paravalvular leakage, 100% in TEE and 50.0% in CT). Interobserver agreements for CT findings were substantial or excellent (0.79-0.88). Cardiac CT can accurately demonstrate infective endocarditis in pre-operative patients with a similar diagnostic accuracy to TEE. The interobserver agreements for the CT findings of infective endocarditis were excellent. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

  8. Capnocytophaga canimorsus: a rare case of conservatively treated prosthetic valve endocarditis.

    Science.gov (United States)

    Jalava-Karvinen, Päivi; Grönroos, Juha O; Tuunanen, Helena; Kemppainen, Jukka; Oksi, Jarmo; Hohenthal, Ulla

    2018-05-01

    We describe a rare case of prosthetic valve endocarditis caused by the canine bacterium Capnocytophaga canimorsus in a male aged 73 years. The diagnosis of infective endocarditis was unequivocal, as it blood cultures were positive for C. canimorsus and vegetations were detected on transesophageal echocardiography; the modified Duke criteria were fulfilled. PET-CT showed intense 18 F-FDG uptake of the prosthetic valve area. The patient was treated with antibiotics alone (no surgery), and is now on life-long suppressive antibiotic therapy. To our knowledge, this is the third reported case of prosthetic valve endocarditis caused by C. canimorsus and the first one to have been treated conservatively. © 2018 APMIS. Published by John Wiley & Sons Ltd.

  9. Inhibition of Serratia marcescens Smj-11 biofilm formation by Alcaligenes faecalis STN17 crude extract

    International Nuclear Information System (INIS)

    Lutfi, Zainal; Ahmad, Asmat; Usup, Gires

    2014-01-01

    Serratia marcescens biofilms are formed when they are bound to surfaces in aqueous environments. S. marcescens utilizes N-acylhomoserine lactone (AHL) as its quorum sensing signal molecule. The accumulation of AHL indicates the bacteria to produce matrices to form biofilms. Prodigiosin (2-methyl-3-pentyl-6-methoxyprodigiosin), which causes red pigmentation in the colonies, are also produced when the AHL reaches a certain threshold. The Alcaligenes faecalis STN17 crude extract is believed to inhibit quorum sensing in the S. marcescens Smj-11 and, thus, impedes its biofilm formation ability. A. faecalis STN17 was grown in marine broth, and ethyl acetate extraction was carried out. The crude compound of A. faecalis STN17 was diluted at high concentration (0.2-6.4 mg/mL) and was taken to confirm anti-biofilm activity through the crystal violet method in 96-wells plate. Then, the crude extract underwent purification using simple solvents partitioning test to discern the respective compounds that had the anti-biofilm activity under the crystal violet method. The crystal violet test showed that the crude did have anti-biofilm activity on S. marcescens Smj-11, but did not kill the cells. This finding signifies that the suppression of biofilm formation in S. marcescens by A. faecalis STN17 has a strong correlation. The partitioning test showed that A. faecalis STN17 crude extract has several compounds and only the compound(s) in chloroform showed activities. In conclusion, the crude extract of A. faecalis STN17 has the ability to inhibit S. marcescens Smj-11 biofilm formation

  10. Inhibition of Serratia marcescens Smj-11 biofilm formation by Alcaligenes faecalis STN17 crude extract

    Energy Technology Data Exchange (ETDEWEB)

    Lutfi, Zainal; Ahmad, Asmat [School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia (UKM), 43600 Bangi, Selangor (Malaysia); Usup, Gires [School of Environmental and Natural Resources Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia (UKM), 43600 Bangi, Selangor (Malaysia)

    2014-09-03

    Serratia marcescens biofilms are formed when they are bound to surfaces in aqueous environments. S. marcescens utilizes N-acylhomoserine lactone (AHL) as its quorum sensing signal molecule. The accumulation of AHL indicates the bacteria to produce matrices to form biofilms. Prodigiosin (2-methyl-3-pentyl-6-methoxyprodigiosin), which causes red pigmentation in the colonies, are also produced when the AHL reaches a certain threshold. The Alcaligenes faecalis STN17 crude extract is believed to inhibit quorum sensing in the S. marcescens Smj-11 and, thus, impedes its biofilm formation ability. A. faecalis STN17 was grown in marine broth, and ethyl acetate extraction was carried out. The crude compound of A. faecalis STN17 was diluted at high concentration (0.2-6.4 mg/mL) and was taken to confirm anti-biofilm activity through the crystal violet method in 96-wells plate. Then, the crude extract underwent purification using simple solvents partitioning test to discern the respective compounds that had the anti-biofilm activity under the crystal violet method. The crystal violet test showed that the crude did have anti-biofilm activity on S. marcescens Smj-11, but did not kill the cells. This finding signifies that the suppression of biofilm formation in S. marcescens by A. faecalis STN17 has a strong correlation. The partitioning test showed that A. faecalis STN17 crude extract has several compounds and only the compound(s) in chloroform showed activities. In conclusion, the crude extract of A. faecalis STN17 has the ability to inhibit S. marcescens Smj-11 biofilm formation.

  11. Pulmonary valve endocarditis associated to a septal interventricular defect and infundibular and pulmonary valve Stenosis

    International Nuclear Information System (INIS)

    Echeverri, Juan G; Diaz, Alejandro; Jaramillo, Nicolas; Gonzalez, Sergio

    2004-01-01

    Ventricular septal defects generate 10% of all adult congenital cardiopathies. 4% to 8% of patients to whom the defect has not been corrected are in risk of developing endocarditis. Pulmonary valve endocarditis is a rare event (1.5% to 2% of all endocarditis cases) and its mean etiology is intravenous drug abuse. The most frequently isolated microorganism in these cases is staphylococcus aurous. We report a case of pulmonary valve endocarditis associated with ventricular septal defect and valvular and infundibular pulmonary stenosis caused by streptococcus sp. in a patient without past medical history of drug abuse, alcoholism or previous invasive procedures

  12. Infective Endocarditis: A Review of the Past and Present, and a Look into the Future

    Directory of Open Access Journals (Sweden)

    Eric I-Hun Jeng, MD, MBA

    2017-05-01

    Full Text Available Infective endocarditis is a lethal and challenging multifaceted disease that can involve any vascularized system. We believe that multimodality imaging is invaluable to provide a comprehensive diagnosis. Our management approach to infective endocarditis adheres to a combination of the AHA, ACC, STS, and ESC guidelines. With the rapidly increasing transcatheter valve population, we expect an increased caseload of infective endocarditis. Beyond patients with hemorrhagic strokes, we advocate for early surgery if medical management has failed. Furthermore, a multidisciplinary team approach is imperative in infective endocarditis, and clear communication reduces the time to diagnosis and definitive treatment for this patient population.

  13. Characterization and Application of Enterocin RM6, a Bacteriocin from Enterococcus faecalis

    OpenAIRE

    Huang, En; Zhang, Liwen; Chung, Yoon-Kyung; Zheng, Zuoxing; Yousef, Ahmed E.

    2013-01-01

    Use of bacteriocins in food preservation has received great attention in recent years. The goal of this study is to characterize enterocin RM6 from Enterococcus faecalis OSY-RM6 and investigate its efficacy against Listeria monocytogenes in cottage cheese. Enterocin RM6 was purified from E. faecalis culture supernatant using ion exchange column, multiple C18-silica cartridges, followed by reverse-phase high-performance liquid chromatography. The molecular weight of enterocin RM6 is 7145.0823 ...

  14. Infective Endocarditis of the Aortic Valve with Anterior Mitral Valve Leaflet Aneurysm

    NARCIS (Netherlands)

    Tomsic, Anton; Li, Wilson W. L.; van Paridon, Marieke; Bindraban, Navin R.; de Mol, Bas A. J. M.

    2016-01-01

    Mitral valve leaflet aneurysm is a rare and potentially devastating complication of aortic valve endocarditis. We report the case of a 48-year-old man who had endocarditis of the native aortic valve and a concomitant aneurysm of the anterior mitral valve leaflet. Severe mitral regurgitation occurred

  15. Linezolid and atorvastatin impact on pneumonia caused by Staphyloccocus aureus in rabbits with or without mechanical ventilation

    Science.gov (United States)

    Pauchard, Laure-Anne; Blot, Mathieu; Bruyere, Rémi; Barbar, Saber-Davide; Croisier, Delphine; Piroth, Lionel

    2017-01-01

    Pneumonia may involve methicillin-resistant Staphylococcus aureus (MRSA), with elevated rates of antibiotics failure. The present study aimed to assess the effect of statins given prior to pneumonia development. Spontaneously breathing (SB) or mechanically ventilated (MV) rabbits with pneumonia received atorvastatin alone, linezolid (LNZ) alone, or a combination of both (n = 5 in each group). Spontaneously breathing and MV untreated infected animals (n = 11 in each group), as well as uninfected animals (n = 5 in each group) were used as controls. Microbiological features and inflammation were evaluated. Data are presented as medians (interquartile range). Linezolid alone tended to reduce pulmonary MRSA load in both SB and MV rabbits, but failed to prevent bacteremia (59%) in the latter. Linezolid alone dampened TNF-α lung production in both SB and MV rabbits (e.g., 2226 [789] vs. 11478 [10251] pg/g; p = 0.022). Statins alone did the same in both SB and MV animals (e.g., 2040 [133]; p = 0.016), and dampened systemic inflammation in the latter, possibly through TLR2 down-regulation within the lung. However, the combination of LNZ and statin led to an increased rate of bacteremia in MV animals up to 75%. Statins provide an anti-inflammatory effect in rabbits with MRSA pneumonia, especially in MV ones. However, dampening the systemic inflammatory response with statins could impede blood defenses against MRSA. PMID:29149185

  16. Influence of irrigation regimens on the adherence of Enterococcus faecalis to root canal dentin.

    Science.gov (United States)

    Kishen, Anil; Sum, Chee-Peng; Mathew, Shibi; Lim, Chwee-Teck

    2008-07-01

    Enterococcus faecalis is frequently associated with post-treatment endodontic infections. Because adherence of bacteria to a substrate is the earliest stage in biofilm formation, eliciting the factors that links adherence of this bacterium to dentin would help in understanding its association with treatment-failed root canals. This investigation aimed to study the effects of endodontic irrigants on the adherence of E. faecalis to dentin. The bacteria adherence assay was conducted by using fluorescence microscopy, and the adhesion force was measured by using atomic force microscopy. There were significant increases in adherence and adhesion force after irrigation of dentin with ethylenediaminetetraacetic acid (EDTA), whereas sodium hypochlorite (NaOCl) reduced it. With the use of chlorhexidine (CHX), the force of adhesion increased, but the adherence assay showed a reduction in the number of adhering bacteria. The irrigation regimen of EDTA, NaOCl, and CHX resulted in the least number of adhering E. faecalis cells. This study highlighted that chemicals that alter the physicochemical properties of dentin will influence the nature of adherence, adhesion force, and subsequent biofilm formation of E. faecalis to dentin.

  17. The diagnostic ability of echocardiography for infective endocarditis and its associated complications.

    Science.gov (United States)

    Vilacosta, Isidre; Olmos, Carmen; de Agustín, Alberto; López, Javier; Islas, Fabián; Sarriá, Cristina; Ferrera, Carlos; Ortiz-Bautista, Carlos; Sánchez-Enrique, Cristina; Vivas, David; San Román, Alberto

    2015-11-01

    Echocardiography, transthoracic and transoesophageal, plays a key role in the diagnosis and prognosis assessment of patients with infective endocarditis. It constitutes a major Duke criterion and is pivotal in treatment guiding. Seven echocardiographic findings are major criteria in the diagnosis of infective endocarditis (IE) (vegetation, abscess, pseudoaneurysm, fistulae, new dehiscence of a prosthetic valve, perforation and valve aneurysm). Echocardiography must be performed as soon as endocarditis is suspected. Transoesophageal echocardiography should be done in most cases of left-sided endocarditis to better define the anatomic lesions and to rule out local complications. Transoesophageal echocardiography is not necessary in isolated right-sided native valve IE with good quality transthoracic examination and unequivocal echocardiographic findings. Echocardiography is a very useful tool to assess the prognosis of patients with IE at any time during the course of the disease. Echocardiographic predictors of poor outcome include presence of periannular complications, prosthetic dysfunction, low left ventricular ejection fraction, pulmonary hypertension and very large vegetations.

  18. Infectious endocarditis caused by Escherichia coli

    DEFF Research Database (Denmark)

    Lauridsen, Trine Kiilerich; Arpi, Magnus; Fritz-Hansen, Thomas

    2011-01-01

    Although Escherichia coli is among the most common causes of Gram-negative bacteraemia, infectious endocarditis (IE) due to this pathogen is rare. A 67-y-old male without a previous medical history presented with a new mitral regurgitation murmur and persisting E. coli bacteraemia in spite of broad......-spectrum intravenous antibiotics. Transthoracic and transoesophageal echocardiography revealed a severe mitral endocarditis. E. coli DNA was identified from the mitral valve and the vegetation, and no other pathogen was found. The case was further complicated by spondylodiscitis and bilateral endophthalmitis. Extra......-intestinal pathogenic E. coli (ExPEC) are able to colonize tissue outside the gastrointestinal tract and contain a variety of virulence factors that may enable the pathogens to invade and induce infections in the cardiac endothelia. In these cases echocardiography as the imaging technology is of paramount importance...

  19. Infective Endocarditis in the U.S., 1998–2009: A Nationwide Study

    Science.gov (United States)

    Bor, David H.; Woolhandler, Steffie; Nardin, Rachel; Brusch, John; Himmelstein, David U.

    2013-01-01

    Background Previous studies based on local case series estimated the annual incidence of endocarditis in the U.S. at about 4 per 100,000 population. Small-scale studies elsewhere have reported similar incidence rates. However, no nationally-representative population-based studies have verified these estimates. Methods and Findings Using the 1998–2009 Nationwide Inpatient Sample, which provides diagnoses from about 8 million U.S. hospitalizations annually, we examined endocarditis hospitalizations, bacteriology, co-morbidities, outcomes and costs. Hospital admissions for endocarditis rose from 25,511 in 1998 to 38, 976 in 2009 (12.7 per 100,000 population in 2009). The age-adjusted endocarditis admission rate increased 2.4% annually. The proportion of patients with intra-cardiac devices rose from 13.3% to 18.9%, while the share with drug use and/or HIV fell. Mortality remained stable at about 14.5%, as did cardiac valve replacement (9.6%). Other serious complications increased; 13.3% of patients in 2009 suffered a stroke or CNS infection, and 5.5% suffered myocardial infarction. Amongst cases with identified pathogens, Staphylococcus aureus was the most common, increasing from 37.6% in 1998 to 49.3% in 2009, 53.3% of which were MRSA. Streptococci were mentioned in 24.7% of cases, gram-negatives in 5.6% and Candida species in 1.0%. We detected no inflection in hospitalization rates after changes in prophylaxis recommendations in 2007. Mean age rose from 58.6 to 60.8 years; elderly patients suffered higher rates of myocardial infarction and death, but slightly lower rates of Staphylococcus aureus infections and neurologic complications. Our study relied on clinically diagnosed cases of endocarditis that may not meet strict criteria. Moreover, since some patients are discharged and readmitted during a single episode of endocarditis, our hospitalization figures probably slightly overstate the true incidence of this illness. Conclusions Endocarditis is more common in

  20. Bioprosthetic Aortic Valve Endocarditis in Association with Enterococcus durans.

    Science.gov (United States)

    Fallavollita, Luca; Di Gioacchino, Lorena; Balestrini, Fabrizio

    2016-04-01

    Enterococci are common organisms associated with endocarditis, but infection by Enterococcus durans is very rare. To our knowledge, only 3 cases have been reported in the medical literature, and all 3 have involved native valves. Here we publish the first reported case (to our knowledge) of E. durans endocarditis in association with a bioprosthetic aortic valve. After the organism and its antibiotic susceptibility were identified, the 74-year-old male patient was treated successfully with teicoplanin and gentamicin, over a course of 6 weeks.

  1. High readmission rates and mental distress after infective endocarditis

    DEFF Research Database (Denmark)

    Rasmussen, Trine Bernholdt; Zwisler, Ann-Dorthe; Thygesen, Lau Caspar

    2017-01-01

    BACKGROUND: Infective endocarditis (IE) is a severe disease requiring lengthy hospitalisation. Little is known about patients' recovery after IE. The aims of this study in IE patients were; (i) to describe mortality, readmission, self-reported health and rehabilitation up to 1year post-discharge,......BACKGROUND: Infective endocarditis (IE) is a severe disease requiring lengthy hospitalisation. Little is known about patients' recovery after IE. The aims of this study in IE patients were; (i) to describe mortality, readmission, self-reported health and rehabilitation up to 1year post...

  2. Dentigenous infectious foci – a risk factor of infective endocarditis

    Science.gov (United States)

    Wisniewska-Spychala, Beata; Sokalski, Jerzy; Grajek, Stefan; Jemielity, Marek; Trojnarska, Olga; Choroszy-Król, Irena; Sójka, Anna; Maksymiuk, Tomasz

    2012-01-01

    Summary Background Dentigenous, infectious foci are frequently associated with the development of various diseases. The role of such foci in the evolution of endocarditis still remains unclear. This article presents the concluding results of an interdisciplinary study verifying the influence of dentigenous, infectious foci on the development of infective endocarditis. Material/Methods The study subjects were 60 adult patients with history of infective endocarditis and coexistent acquired heart disease, along with the presence at least 2 odontogenic infectious foci (ie, 2 or more teeth with gangrenous pulp and periodontitis). The group had earlier been qualified for the procedure of heart valve replacement. Swabs of removed heart valve tissue with inflammatory lesions and blood were then examined microbiologically. Swabs of root canals and their periapical areas, of periodontal pockets, and of heart valves were also collected. Results Microbial flora, cultured from intradental foci, blood and heart valves, fully corresponded in 14 patients. This was accompanied in almost all cases by more advanced periodontitis (2nd degree, Scandinavian classification), irrespective of the bacterial co-occurrence mentioned. In the remaining patients, such consistency was not found. Conclusions Among various dentigenous, infectious foci, the intradental foci appear to constitute a risk factor for infective endocarditis. PMID:22293883

  3. Transcriptomic and functional analysis of NaCl-induced stress in Enterococcus faecalis.

    Directory of Open Access Journals (Sweden)

    Margrete Solheim

    Full Text Available The robust physiology of Enterococcus faecalis facilitates tolerance to various stresses. We here report the transcriptional response of E. faecalis V583 to growth in the presence of 6.5% NaCl. Among the early responses observed was an immediate down-regulation of mscL, accompanied by an up-regulation of genes predicted to be involved in uptake of extracellular potassium and glycine betaine. The high NaCl concentration also induced expression of chaperons and cell envelope related traits, such as the enterococcal polysaccharide antigen (epa locus. Functional genetic analysis revealed reduced salt stress resistance in both epaB and epaE mutants. The reduced salt resistance phenotype associated with the epaB mutant was restored by complementation, hence demonstrating a role of Epa in the physiological robustness of E. faecalis. Furthermore, we demonstrate that Epa confers increased resistance towards multiple cell envelope stress-inducing factors. Accordingly, these findings delineate a potential link between the robust nature of E. faecalis and its ability to perform as a human pathogen, and provide a new perspective on the mechanisms by which Epa contributes to virulence. Notably, the high NaCl concentration also resulted in strict repression of the gelE-sprE operon and impaired gelatinase activity. We demonstrate that NaCl antagonize the GBAP-pheromone dependent induction in a concentration dependent manner.

  4. Endocarditis due to Micrococcus sedentarius incertae sedis.

    Science.gov (United States)

    Old, D C; McNeill, G P

    1979-01-01

    The clinical and bacteriological features of a case of endocarditis are described in which a Gram-positive coccus, presently designated Micrococcus sedentarius incertae sedis, was repeatedly isolated. PMID:512056

  5. Enterococcus faecalis from healthy infants modulates inflammation through MAPK signaling pathways.

    Directory of Open Access Journals (Sweden)

    Shugui Wang

    Full Text Available Colonizing commensal bacteria after birth are required for the proper development of the gastrointestinal tract. It is believed that bacterial colonization pattern in neonatal gut affects gut barrier function and immune system maturation. Studies on the development of faecal microbiota in infants showed that the neonatal gut was first colonized with enterococci followed by other microbiota such as Bifidobacterium. Other studies showed that babies who developed allergy were less often colonized with Enterococcus during the first month of life as compared to healthy infants. Many studies have been conducted to elucidate how bifidobacteria or lactobacilli, some of which are considered probiotic, regulate infant gut immunity. However, fewer studies have been focused on enterococi. In our study, we demonstrate that E. faecalis, isolated from healthy newborns, suppress inflammatory responses activated in vivo and in vitro. We found E. faecalis attenuates proinflammatory cytokine secretions, especially IL-8, through JNK and p38 signaling pathways. This finding shed light on how the first colonizer, E.faecalis, regulates inflammatory responses in the host.

  6. Candida infective endocarditis: an observational cohort study with a focus on therapy.

    Science.gov (United States)

    Arnold, Christopher J; Johnson, Melissa; Bayer, Arnold S; Bradley, Suzanne; Giannitsioti, Efthymia; Miró, José M; Tornos, Pilar; Tattevin, Pierre; Strahilevitz, Jacob; Spelman, Denis; Athan, Eugene; Nacinovich, Francisco; Fortes, Claudio Q; Lamas, Cristiane; Barsic, Bruno; Fernández-Hidalgo, Nuria; Muñoz, Patricia; Chu, Vivian H

    2015-04-01

    Candida infective endocarditis is a rare disease with a high mortality rate. Our understanding of this infection is derived from case series, case reports, and small prospective cohorts. The purpose of this study was to evaluate the clinical features and use of different antifungal treatment regimens for Candida infective endocarditis. This prospective cohort study was based on 70 cases of Candida infective endocarditis from the International Collaboration on Endocarditis (ICE)-Prospective Cohort Study and ICE-Plus databases collected between 2000 and 2010. The majority of infections were acquired nosocomially (67%). Congestive heart failure (24%), prosthetic heart valve (46%), and previous infective endocarditis (26%) were common comorbidities. Overall mortality was high, with 36% mortality in the hospital and 59% at 1 year. On univariate analysis, older age, heart failure at baseline, persistent candidemia, nosocomial acquisition, heart failure as a complication, and intracardiac abscess were associated with higher mortality. Mortality was not affected by use of surgical therapy or choice of antifungal agent. A subgroup analysis was performed on 33 patients for whom specific antifungal therapy information was available. In this subgroup, 11 patients received amphotericin B-based therapy and 14 received echinocandin-based therapy. Despite a higher percentage of older patients and nosocomial infection in the echinocandin group, mortality rates were similar between the two groups. In conclusion, Candida infective endocarditis is associated with a high mortality rate that was not impacted by choice of antifungal therapy or by adjunctive surgical intervention. Additionally, echinocandin therapy was as effective as amphotericin B-based therapy in the small subgroup analysis. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  7. A case of native valve endocarditis caused by Burkholderia cepacia without predisposing factors

    Directory of Open Access Journals (Sweden)

    Han Seong

    2011-05-01

    Full Text Available Abstract Background Infective endocarditis is rarely caused by Burkholderia cepacia. This infection is known to occur particularly in immunocompromised hosts, intravenous heroin users, and in patients with prosthetic valve replacement. Most patients with Burkholderia cepacia endocarditis usually need surgical treatment in addition to antimicrobial treatment. Case Presentation Here, we report the case of a patient who developed Burkholderia cepacia-induced native valve endocarditis with consequent cerebral involvement without any predisposing factors; she was successfully treated by antimicrobial agents only. Conclusion In this report, we also present literature review of relevant cases.

  8. Mitral endocarditis due to Rothia aeria with cerebral haemorrhage and femoral mycotic aneurysms, first French description

    Directory of Open Access Journals (Sweden)

    R. Collarino

    2016-09-01

    Full Text Available Rothia aeria is a Rothia species from the Micrococcaceae family. We report here the first French R. aeria endocarditis complicated by brain haemorrhage and femoral mycotic aneurysms. Altogether, severity and antimicrobial susceptibility should make us consider the management of R. aeria endocarditis as Staphylococcus aureus methicillin-susceptible endocarditis.

  9. Three-dimensional transesophageal echocardiography in the evaluation of aortic valve destruction by endocarditis

    NARCIS (Netherlands)

    Nemes, Attila; Lagrand, Wim K.; McGhie, Jackie S.; ten Cate, Folkert J.

    2006-01-01

    Infective endocarditis remains a serious and complex disease with significant morbidity and mortality. The aim of this study was to demonstrate the clinical usefulness of 3-dimensional transesophageal echocardiography for the spatial assessment of aortic valve endocarditis. This case showed severe

  10. Antibacterial Effect of All-in-one Self-etch Adhesives on Enterococcus faecalis

    Directory of Open Access Journals (Sweden)

    Mohammad Esmaeel Ebrahimi Chaharom

    2014-12-01

    Full Text Available Background and aims. The aim of this study was to evaluate the antibacterial activity of one-step self-etch adhesives on Enterococcus faecalis on days 1, 7 and 14 with the use of modified direct contact test. Materials and methods. The modified directcontact test was used to evaluate the antibacterial effect of Adper Easy One, Bond Force, Clearfil S3 Bond, Futurabond M, G-Bond, iBond and OptiBond All-in-one adhesives on Enterococcus faecalisafter aging the samples in phosphate-buffered saline for one, seven and fourteen days. Data were analyzed using one-way ANOVA and post hoc Tukey tests. Aging effect of each adhesive was evaluated by paired-sample test. In this study, P0.05. Conclusion. iBond exhibited the highest antibacterial effect on E. faecalis after one week. Futurabond and OptiBond All-in-one exhibited antibacterial effects against E. faecalis for one week.

  11. INFECTIVE ENDOCARDITIS IN INTRAVENOUS DRUGS ABUSED PATIENT

    Directory of Open Access Journals (Sweden)

    E. Y. Ponomareva

    2014-07-01

    Full Text Available Three-year observation of acute tricuspid infective endocarditis in intravenous drug abused patient: diagnosis, clinical features, visceral lesions, the possibility of cardiac surgery and conservative treatment, outcome.

  12. INFECTIVE ENDOCARDITIS IN INTRAVENOUS DRUGS ABUSED PATIENT

    Directory of Open Access Journals (Sweden)

    E. Y. Ponomareva

    2011-01-01

    Full Text Available Three-year observation of acute tricuspid infective endocarditis in intravenous drug abused patient: diagnosis, clinical features, visceral lesions, the possibility of cardiac surgery and conservative treatment, outcome.

  13. Extracellular dextran and DNA affect the formation of Enterococcus faecalis biofilms and their susceptibility to 2% chlorhexidine.

    Science.gov (United States)

    Li, Weilan; Liu, Hongyan; Xu, Qiong

    2012-07-01

    Enterococcus faecalis is frequently recovered from root-filled teeth with refractory apical periodontitis. The ability of E. faecalis to form a matrix-encased biofilm contributes to its pathogenicity; however, the role of extracellular dextran and DNA in biofilm formation and its effect on the susceptibility of the biofilm to chlorhexidine remains poorly understood. E. faecalis biofilms were incubated on dentin blocks. The effect of a dextran-degrading enzyme (dextranase) and DNase I on the adhesion of E. faecalis to dentin was measured using the colony-forming unit (CFU) counting method. CFU assays and confocal laser scanning microscopy were used to investigate the influence of dextranase and DNase I on the antimicrobial activity of 2% chlorhexidine. The CFU count assays indicated that the formation of biofilms by E. faecalis was reduced in cells treated with dextranase or DNase I compared with that in untreated cells (P biofilms with dextranase or DNase I effectively sensitized the biofilms to 2% chlorhexidine (P biofilms to 2% chlorhexidine. Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  14. Fungal Endocarditis Due to Aspergillus oryzae: The First Case Reported in the Literature.

    Science.gov (United States)

    Mazza, Andrea; Luciani, Nicola; Luciani, Marco; Cammertoni, Federico; Giaquinto, Alessia; Pavone, Natalia; Bruno, Piergiorgio; Massetti, Massimo

    2017-03-01

    Infective endocarditis (IE) is a severe disease with high mortality and morbidity. Prosthetic valve endocarditis is a life-threatening complication which can occur in less than 10% of patients with valve prosthesis. A fungal etiology of IE is rare and accounts for only 2-4% of all case of endocarditis, but is associated with a higher mortality and morbidity. Herein is reported the first case of fungal endocarditis of aortic valve prosthesis due to Aspergillus oryzae in a 67-year-old caucasian man who nine years previously underwent mitral and aortic valve replacement with mechanical prostheses, and tricuspid annuloplasty for acute IE due to Enterococcus spp. Seven months previously, the patient also underwent a redo cardiac procedure to replace a mitral valve prosthesis with a new mechanical device due to a leakage. Aspergillus oryzae showed impressive growth with strong and unexpected virulence in both local and systemic settings.

  15. Dried blood spot analysis for therapeutic drug monitoring of linezolid in patients with multidrug-resistant tuberculosis

    NARCIS (Netherlands)

    Vu, D H; Bolhuis, M S; Koster, R A; Greijdanus, B; de Lange, W C M; van Altena, R; Brouwers, J R B J; Uges, D R A; Alffenaar, J W C

    2012-01-01

    Linezolid is a promising antimicrobial agent for the treatment of multidrug-resistant tuberculosis (MDR-TB), but its use is limited by toxicity. Therapeutic drug monitoring (TDM) may help to minimize toxicity while adequate drug exposure is maintained. Conventional plasma sampling and monitoring

  16. Biodegradable materials for surgical management of infective endocarditis: new solution or a dead end street?

    Science.gov (United States)

    Myers, Patrick O; Cikirikcioglu, Mustafa; Kalangos, Afksendiyos

    2014-08-03

    One third of patients with infective endocarditis will require operative intervention. Given the superiority of valve repair over valve replacement in many indications other than endocarditis, there has been increasing interest and an increasing number of reports of excellent results of valve repair in acute infective endocarditis. The theoretically ideal material for valve repair in this setting is non-permanent, "vanishing" material, not at risk of seeding or colonization. The goal of this contribution is to review currently available data on biodegradable materials for valve repair in infective endocarditis. Rigorous electronic and manual literature searches were conducted to identify reports of biodegradable materials for valve repair in infective endocarditis. Articles were identified in electronic database searches of Medline, Embase and the Cochrane Library, using a predetermined search strategy. 49 manuscripts were included in the review. Prosthetic materials needed for valve repair can be summarized into annuloplasty rings to remodel the mitral or tricuspid annulus, and patch materials to replace resected valvar tissue. The commercially available biodegradable annuloplasty ring has shown interesting clinical results in a single-center experience; however further data is required for validation and longer follow-up. Unmodified extra-cellular matrix patches, such as small intestinal submucosa, have had promising initial experimental and clinical results in non-infected valve repair, although in valve repair for endocarditis has been reported in only one patient, and concerns have been raised regarding their mechanical stability in an infected field. These evolving biodegradable devices offer the potential for valve repair with degradable materials replaced with autologous tissue, which could further improve the results of valve repair for infective endocarditis. This is an evolving field with promising experimental or initial clinical results, however long

  17. Biodegradable materials for surgical management of infective endocarditis: new solution or a dead end street?

    Science.gov (United States)

    2014-01-01

    Background One third of patients with infective endocarditis will require operative intervention. Given the superiority of valve repair over valve replacement in many indications other than endocarditis, there has been increasing interest and an increasing number of reports of excellent results of valve repair in acute infective endocarditis. The theoretically ideal material for valve repair in this setting is non-permanent, “vanishing” material, not at risk of seeding or colonization. The goal of this contribution is to review currently available data on biodegradable materials for valve repair in infective endocarditis. Discussion Rigorous electronic and manual literature searches were conducted to identify reports of biodegradable materials for valve repair in infective endocarditis. Articles were identified in electronic database searches of Medline, Embase and the Cochrane Library, using a predetermined search strategy. 49 manuscripts were included in the review. Prosthetic materials needed for valve repair can be summarized into annuloplasty rings to remodel the mitral or tricuspid annulus, and patch materials to replace resected valvar tissue. The commercially available biodegradable annuloplasty ring has shown interesting clinical results in a single-center experience; however further data is required for validation and longer follow-up. Unmodified extra-cellular matrix patches, such as small intestinal submucosa, have had promising initial experimental and clinical results in non-infected valve repair, although in valve repair for endocarditis has been reported in only one patient, and concerns have been raised regarding their mechanical stability in an infected field. Summary These evolving biodegradable devices offer the potential for valve repair with degradable materials replaced with autologous tissue, which could further improve the results of valve repair for infective endocarditis. This is an evolving field with promising experimental or

  18. Asymptomatic and symptomatic embolic events in infective endocarditis: associated factors and clinical impact.

    Science.gov (United States)

    Monteiro, Thaíssa S; Correia, Marcelo G; Golebiovski, Wilma F; Barbosa, Giovanna Ianini F; Weksler, Clara; Lamas, Cristiane C

    Embolic complications of infective endocarditis are common. The impact of asymptomatic embolism is uncertain. To determine the frequency of emboli due to IE and to identify events associated with embolism. Retrospective analysis of an endocarditis database, prospectively implemented, with a post hoc study driven by analysis of data on embolic events. Data was obtained from the International Collaboration Endocarditis case report forms and additional information on embolic events and imaging reports were obtained from the medical records. Variables associated with embolism were analyzed by the statistical software R version 3.1.0. In the study period, 2006-2011, 136 episodes of definite infective endocarditis were included. The most common complication was heart failure (55.1%), followed by embolism (50%). Among the 100 medical records analyzed for emboli in left-sided infective endocarditis, 36 (36%) were found to have had asymptomatic events, 11 (11%) to the central nervous system and 28 (28%) to the spleen. Cardiac surgery was performed in 98/136 (72%). In the multivariate analysis, splenomegaly was the only associated factor for embolism to any site (pinfective endocarditis of the mitral valve (p<0.05, OR 3.5, 95% CI 1.23-10) and male gender (p<0.05, OR 3.2, 95% CI 1.04-10). Splenectomy and cardiac surgery did not impact on in-hospital mortality. Asymptomatic embolism to the central nervous system and to the spleen were frequent. Splenomegaly was consistently associated with embolic events. Copyright © 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

  19. Fungal endocarditis in paediatrics: a review of 192 cases (1971-2016).

    Science.gov (United States)

    Ganesan, Vithiya; Ponnusamy, Shunmuga Sundaram; Sundaramurthy, Raja

    2017-10-01

    The aims of this article were to review the published literature on fungal endocarditis in children and to discuss the aetiology and diagnosis, with emphasis on non-invasive methods and various treatment regimes. We systematically reviewed published cases and case series of fungal endocarditis in children. We searched the literature, including PubMed and individual references for publications of original articles, single cases, or case series of paediatric fungal endocarditis, with the following keywords: "fungal endocarditis", "neonates", "infants", "child", and "cardiac vegetation". There have been 192 documented cases of fungal endocarditis in paediatrics. The highest number of cases was reported in infants (93/192, 48%) including 60 in neonates. Of the neonatal cases, 57 were premature with a median gestational age of 27 weeks and median birth weight of 860 g. Overall, 120 yeast - fungus that grows as a single cell - infections and 43 mould - fungus that grows in multicellular filaments, hyphae - infections were reported. With increasing age, there was an increased infection rate with moulds. All the yeast infections were detected by blood culture. In cases with mould infection, diagnosis was mainly established by culture or histology of emboli or infected valves after invasive surgical procedures. There have been a few recent cases of successful early diagnosis by non-invasive methods such as blood polymerase chain reaction (PCR) for moulds. The overall mortality for paediatric fungal endocarditis was 56.25%. The most important cause of death was cardiac complications due to heart failure. Among the various treatment regimens used, none of them was significantly associated with better outcome. Non-invasive methods such as PCR tests can be used to improve the chances of detecting and identifying the aetiological agent in a timely manner. Delays in the diagnosis of these infections may result in high mortality and morbidity. No significant difference was noted

  20. In vitro activity of daptomycin against clinical isolates of Gram-positive bacteria.

    Science.gov (United States)

    Piper, Kerryl E; Steckelberg, James M; Patel, Robin

    2005-08-01

    We determined the activity of daptomycin, a recently FDA-approved antimicrobial agent, against clinical isolates of Gram-positive bacteria, including viridans group streptococci (16 Streptococcus mitis species group, 12 S. mutans species group, 9 S. anginosus species group, 8 S. sanguinis species group, 5 S. salivarius species group) from patients with infective endocarditis, 32 methicillin-resistant Staphylococcus aureus, 32 high-level penicillin-resistant Streptococcus pneumoniae, 38 vancomycin-resistant enterococci (including 1 linezolid-resistant isolate), and the following unusual Gram-positive bacteria: 3 Listeria monocytogenes, 4 Erysipelothrix rhusiopathiae, 9 Corynebacterium species, 10 Abiotrophia/Granulicatella species, 2 Rothia (Stomatococcus) mucilaginosus, and 4 Gemella morbillorum. Daptomycin minimum inhibitory concentration (MIC)(90) values for the viridans group streptococci, methicillin-resistant S. aureus, penicillin-resistant S. pneumoniae, and Enterococcus species were 0.5, 0.5, endocarditis as well as against several types of unusual Gram-positive bacteria that can cause endocarditis.

  1. Candida endocarditis: systematic literature review from 1997 to 2014 and analysis of 29 cases from the Italian Study of Endocarditis.

    Science.gov (United States)

    Giuliano, Simone; Guastalegname, Maurizio; Russo, Alessandro; Falcone, Marco; Ravasio, Veronica; Rizzi, Marco; Bassetti, Matteo; Viale, Pierluigi; Pasticci, Maria Bruna; Durante-Mangoni, Emanuele; Venditti, Mario

    2017-09-01

    Candida Endocarditis (CE) is a deadly disease. It is of paramount importance to assess risk factors for acquisition of both Candida native (NVE) and prosthetic (PVE) valve endocarditis and relate clinical features and treatment strategies with the outcome of the disease. Areas covered: We searched the literature using the Pubmed database. Cases of CE from the Italian Study on Endocarditis (SEI) were also included. Overall, 140 cases of CE were analyzed. Patients with a history of abdominal surgery and antibiotic exposure had higher probability of developing NVE than PVE. In the PVE group, time to onset of CE was significantly lower for biological prosthesis compared to mechanical prosthesis. In the whole population, greater age and longer time to diagnosis were associated with increased likelihood of death. Patients with effective anti-biofilm treatment, patients who underwent cardiac surgery and patients who were administered chronic suppressive antifungal treatment showed increased survival. For PVE, moderate active anti-biofilm and highly active anti-biofilm treatment were associated with lower mortality. Expert commentary: Both NVE and PVE could be considered biofilm-related diseases, pathogenetically characterized by Candida intestinal translocation and initial transient candidemia. Cardiac surgery, EAB treatment and chronic suppressive therapy might be crucial in increasing patient survival.

  2. Resistência antimicrobiana em Enterococcus faecalis e Enterococcus faecium isolados de carcaças de frango

    Directory of Open Access Journals (Sweden)

    Ana Claudia F. Borges de Campos

    2013-05-01

    Full Text Available O objetivo deste trabalho foi realizar o isolamento e analisar o perfil de resistência antimicrobiana de Enterococcus de carcaças de frango resfriadas e congeladas comercializadas no Distrito Federal, detectando genes de resistência antimicrobiana e identificando as espécies Enterococcus faecalis e Enterococcus faecium por reação polimerase em cadeia. Foram analisadas 100 carcaças de frangos, das quais foram isoladas 50 cepas de Enterococcus spp., sendo 42% de E. faecalis e 2% de E. faecium. O teste de susceptibilidade antimicrobiana demonstrou que todas as cepas isoladas apresentaram resistência a pelo menos um antimicrobiano, dos quais 90,47% das cepas de E. faecalis, 100% das cepas de E. Faecium e 82,14% dos Enterococcus spp. apresentaram resistência à Tetraciclina; 80,95% das cepas de E. faecalis e 35,71% das cepas de Enterococcus spp. foram resistentes à Eritromicina; 39,28% dos Enterococcus spp. e 23,80% dos E. faecalis à Ciprofloxacina e 28,57% dos E. faecalis apresentaram resistência ao Cloranfenicol. Foram detectados os genes de resistência antimicrobiana erm(B, vanC-1, aph(3'-llla, ant(6-la, vanB, vanA, aac(6'-le-aph(2''-la, erm(A e tet(M - este último mais frequente. Estes resultados sugerem sérios problemas para a Saúde Pública, uma vez que esses microrganismos podem possuir a capacidade de transmitir genes de resistência antimicrobiana para outros microrganismos presentes na microbiota intestinal de humanos e animais, podendo inviabilizar o uso destas drogas para tratamentos clínicos.

  3. Combined computed tomography and fluorodeoxyglucose positron emission tomography in the diagnosis of prosthetic valve endocarditis: a case series.

    Science.gov (United States)

    Bartoletti, Michele; Tumietto, Fabio; Fasulo, Giovanni; Giannella, Maddalena; Cristini, Francesco; Bonfiglioli, Rachele; Raumer, Luigi; Nanni, Cristina; Sanfilippo, Silvia; Di Eusanio, Marco; Scotton, Pier Giorgio; Graziosi, Maddalena; Rapezzi, Claudio; Fanti, Stefano; Viale, Pierluigi

    2014-01-13

    The diagnosis of prosthetic valve endocarditis is challenging. The gold standard for prosthetic valve endocarditis diagnosis is trans-esophageal echocardiography. However, trans-esophageal echocardiography may result in negative findings or yield images difficult to differentiate from thrombus in patients with prosthetic valve endocarditis. Combined computed tomography and fluorodeoxyglucose positron emission tomography is a potentially promising diagnostic tool for several infectious conditions and it has also been employed in patients with prosthetic valve endocarditis but data are still scant. We reviewed the charts of 6 patients with prosthetic aortic valves evaluated for suspicion of prosthetic valve endocarditis, at two different hospital, over a 3-year period. We found 3 patients with early-onset PVE cases and blood cultures yielding Pseudomonas aeruginosa, Staphylococcus epidermidis and Staphylococcus lugdunensis, respectively; and 3 late-onset cases in the remaining 3 patients with isolation in the blood of Streptococcus bovis, Candida albicans and P. aeruginosa, respectively. Initial trans-esophageal echocardiography was negative in all the patients, while fluorodeoxyglucose positron emission tomography showed images suspicious for prosthetic valve endocarditis. In 4 out of 6 patients valve replacement was done with histology confirming the prosthetic valve endocarditis diagnosis. After an adequate course of antibiotic therapy fluorodeoxyglucose positron emission tomography showed resolution of prosthetic valve endocarditis in all the patients. Our experience confirms the potential role of fluoroseoxyglucose positron emission tomography in the diagnosis and follow-up of prosthetic valve endocarditis.

  4. Rothia aeria endocarditis in a patient with a bicuspid aortic valve: case report

    Directory of Open Access Journals (Sweden)

    Antonio Carlos Nicodemo

    2014-09-01

    Full Text Available Rothia aeria is an uncommon pathogen mainly associated with endocarditis in case reports. In previous reports, endocarditis by R. aeria was complicated by central nervous system embolization. In the case we report herein, endocarditis by R. aeria was diagnosed after acute self-limited diarrhea. In addition to the common translocation of R. aeria from the oral cavity, we hypothesize the possibility of intestinal translocation. Matrix-assisted laser desorption ionization-time of flight mass spectrometry and genetic sequencing are important tools that can contribute to early and more accurate etiologic diagnosis of severe infections caused by Gram-positive rods.

  5. Histologic and bacteriologic findings in valvular endocarditis of slaughter-age pigs

    DEFF Research Database (Denmark)

    Jensen, Henrik E.; Gyllensten, Johanna; Hofman, Carolina

    2010-01-01

    Endocarditis lesions from 117 slaughter pigs were examined pathologically and etiologically in addition to 90 control hearts with cardiac valves. Lesions were located on the valves; however, the lesions had extended to the walls in 21 cases (18%). Lesions predominated on the mitral valve (59...... 10 cases of endocarditis due to S. suis and E. rhusiopathiae were disclosed. Within lesions, streptococci predominated (53%) followed by E. rhusiopathiae (30%). Distinct features of both the lesions and the shape and localization of bacterial colonies were related to streptococci and E. rhusiopathiae....... The propensity for streptococci to be localized on more than 1 valve in single hearts may be because S. suis-infected pigs tend to have been infected for a longer period compared with E. rhusiopathiae. Mineralization of endocarditis lesions was significantly associated with infection by streptococci...

  6. Nosocomial infective endocarditis in Hemodialysis

    International Nuclear Information System (INIS)

    Bhat, A.W.; Solangi, S.; Murtada, O.

    2002-01-01

    There is an increased risk of infective endocarditis catheterization usedfor Hemodialysis. We report a case of a young man who had endocarditissecondary to the use of a permanent jugular catheter for hemodialysis. Bloodcultures were repeatedly negative, but vegetations were seen on the tricuspidvalve on echocardiography. A high index of suspicion is recommended for thisserious complication. (author)

  7. Recent Surgical Results for Active Endocarditis Complicated With Perivalvular Abscess.

    Science.gov (United States)

    Yoshioka, Daisuke; Toda, Koichi; Yokoyama, Jun-Ya; Matsuura, Ryohei; Miyagawa, Shigeru; Shirakawa, Yukitoshi; Takahashi, Toshiki; Sakaguchi, Taichi; Fukuda, Hirotsugu; Sawa, Yoshiki

    2017-10-25

    Surgical treatment for endocarditis patients with a perivalvular abscess is still challenging.Methods and Results:From 2009 to 2016, 470 patients underwent surgery for active endocarditis at 11 hospitals. Of these, 226 patients underwent aortic valve surgery. We compared the clinical results of 162 patients without a perivalvular abscess, 37 patients who required patch reconstruction of the aortic annulus (PR group) and 27 who underwent aortic root replacement (ARR group). Patients with a perivalvular abscess had a greater number ofStaphylococcusspecies and prosthetic valve endocarditis, a greater level of inflammation at diagnosis and symptomatic heart failure before surgery, especially in the ARR group. Nevertheless, the duration between diagnosis and surgery was similar, because of a high prevalence of intracranial hemorrhage in the ARR group. Hospital death occurred in 13 (9%) patients without a perivalvular abscess, in 4 (12%) in the PR and in 7 (32%) in the ARR group. Postoperative inflammation and end-organ function were similar between the groups. Overall survival of patients without a perivalvular abscess and that of the PR group was similar, but was significantly worse in the ARR group (P=0.050, 0.026). Freedom from endocarditis recurrence was similar among all patients. Patients treated with patch reconstruction showed favorable clinical results. Early surgical intervention is necessary when a refractory invasive infection is suspected.

  8. In Vitro Resistance Studies with Bacteria That Exhibit Low Mutation Frequencies: Prediction of “Antimutant” Linezolid Concentrations Using a Mixed Inoculum Containing both Susceptible and Resistant Staphylococcus aureus

    Science.gov (United States)

    Golikova, Maria V.; Strukova, Elena N.; Portnoy, Yury A.; Romanov, Andrey V.; Edelstein, Mikhail V.; Zinner, Stephen H.

    2014-01-01

    Bacterial resistance studies using in vitro dynamic models are highly dependent on the starting inoculum that might or might not contain spontaneously resistant mutants (RMs). To delineate concentration-resistance relationships with linezolid-exposed Staphylococcus aureus, a mixed inoculum containing both susceptible cells and RMs was used. An RM selected after the 9th passage of the parent strain (MIC, 2 μg/ml) on antibiotic-containing media (RM9; MIC, 8 μg/ml) was chosen for the pharmacodynamic studies, because the mutant prevention concentration (MPC) of linezolid against the parent strain in the presence of RM9 at 102 (but not at 104) CFU/ml did not differ from the MPC value determined in the absence of the RMs. Five-day treatments with twice-daily linezolid doses were simulated at concentrations either between the MIC and MPC or above the MPC. S. aureus RMs (resistant to 2× and 4× MIC but not 8× and 16× MIC) were enriched at ratios of the 24-h area under the concentration-time curve (AUC24) to the MIC that provide linezolid concentrations between the MIC and MPC for 100% (AUC24/MIC, 60 h) and 86% (AUC24/MIC, 120 h) of the dosing interval. No such enrichment occurred when linezolid concentrations were above the MIC and below the MPC for a shorter time (37% of the dosing interval; AUC24/MIC, 240 h) or when concentrations were consistently above the MPC (AUC24/MIC, 480 h). These findings obtained using linezolid-susceptible staphylococci supplemented with RMs support the mutant selection window hypothesis. This method provides an option to delineate antibiotic concentration-resistance relationships with bacteria that exhibit low mutation frequencies. PMID:25451050

  9. Substitution of ethambutol with linezolid during the intensive phase of treatment of pulmonary tuberculosis: study protocol for a prospective, multicenter, randomized, open-label, phase II trial.

    Science.gov (United States)

    Lee, Ji Yeon; Kim, Deog Kyeom; Lee, Jung-Kyu; Yoon, Ho Il; Jeong, Ina; Heo, Eunyoung; Park, Young Sik; Lee, Jae Ho; Park, Sung Soo; Lee, Sang-Min; Lee, Chang-Hoon; Lee, Jinwoo; Choi, Sun Mi; Park, Jong Sun; Joh, Joon-Sung; Cho, Young-Jae; Lee, Yeon Joo; Kim, Se Joong; Hwang, Young Ran; Kim, Hyeonjeong; Ki, Jongeun; Choi, Hyungsook; Han, Jiyeon; Ahn, Heejung; Hahn, Seokyung; Yim, Jae-Joon

    2017-02-13

    Linezolid, an oxazolidinone, substantially improves treatment outcomes of multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis. We started a trial to test whether the use of linezolid instead of ethambutol could increase the rate of sputum culture conversion as of 8 weeks of treatment in patients with drug-susceptible tuberculosis. This is a phase II, multicenter, randomized study with three arms. We are enrolling patients with pulmonary tuberculosis without rifampicin resistance screened by the Xpert MTB/RIF® assay. The standard treatment arm uses isoniazid (6 months), rifampicin (6 months), pyrazinamide (2 months), and ethambutol (2 months). Experimental arm 1 uses linezolid (600 mg/day) for 4 weeks instead of ethambutol. Experimental arm 2 uses linezolid (600 mg/day) for 2 weeks instead of ethambutol. The primary outcome is the sputum culture conversion rate on liquid media after 2 months of treatment. Secondary outcomes include the sputum culture conversion rate on solid media after 2 months of treatment, time to sputum culture conversion on liquid and solid media, cure rate, and treatment success rate. The frequencies of total adverse events (AEs) and serious AEs will be described and documented. Based on an α = 0.05 level of significance, a power of 85%, a 15% difference in the culture conversion rate after 2 months between the control arm and experimental arm 1 (75% vs. 90%), a 10% default (loss to follow-up) rate, and a 10% culture failure, the required number per arm was calculated to be 143 (429 in total). This trial will reveal the effectiveness and safety of 2 or 4 weeks of use of linezolid instead of ethambutol for patients with drug-susceptible pulmonary tuberculosis. If a new regimen including linezolid shows a higher culture conversion rate by week 8, and is safe, it could be tested as a 4-month antituberculosis treatment regimen in the future. ClincalTrials.gov, NCT01994460 . Registered on 13 November 2013.

  10. Purification and characterization of enterocin 4, a bacteriocin produced by Enterococcus faecalis INIA 4.

    Science.gov (United States)

    Joosten, H M; Nunez, M; Devreese, B; Van Beeumen, J; Marugg, J D

    1996-01-01

    A simple two-step procedure was developed to obtain pure enterocin 4, a bacteriocin produced by Enterococcus faecalis INIA 4. Chemical and genetic characterization revealed that the primary structure of enterocin 4 is identical to that of peptide antibiotic AS-48 from Enterococcus faecalis S-48. In contrast to the reported inhibitory spectrum of AS-48, enterocin 4 displayed no activity against gram-negative bacteria. PMID:8900014

  11. Purification and characterization of enterocin 4, a bacteriocin produced by Enterococcus faecalis INIA 4.

    OpenAIRE

    Joosten, H M; Nunez, M; Devreese, B; Van Beeumen, J; Marugg, J D

    1996-01-01

    A simple two-step procedure was developed to obtain pure enterocin 4, a bacteriocin produced by Enterococcus faecalis INIA 4. Chemical and genetic characterization revealed that the primary structure of enterocin 4 is identical to that of peptide antibiotic AS-48 from Enterococcus faecalis S-48. In contrast to the reported inhibitory spectrum of AS-48, enterocin 4 displayed no activity against gram-negative bacteria.

  12. A Case of Loeffler's Endocarditis Associated with Churg-Strauss Syndrome

    Science.gov (United States)

    Seo, Jeong-Sook; Kim, Dae-Hee; Kang, Duk-Hyun; Song, Jae-Kwan

    2010-01-01

    Loeffler's endocarditis is generally caused by hypereosinophilic syndrome. It is a restrictive cardiomyopathy characterized with eosinophilia and eosionophilic penetration leading to the fibrous thickening of endocardium of both ventricles, apical obliteration and heart failure. We report a case of a 23-year-old male with Loeffler's endocarditis caused by Churg-Strauss syndrome. The echocardiogram showed that biventricular failure with large thrombus in left ventricle. His symptoms and typical echocardiographic findings markedly improved within 2 months after treatment for Churg-Strauss syndrome. PMID:20661332

  13. Survival and activity of Streptococcus faecalis and Escherichia coli in petroleum-contaminated tropical marine waters

    Energy Technology Data Exchange (ETDEWEB)

    Santo Domingo, J.W.; Fuentes, F.A.; Hazen, T.C. [Univ. of Puerto Rico, Rio Piedras (Puerto Rico). Microbial Ecology Lab.

    1987-12-31

    The in situ survival and activity of Streptococcus faecalis and Escherichia coli were studied using membrane diffusion chambers in tropical marine waters receiving oil refinery effluents. Protein synthesis, DNA synthesis, respiration or fermentation, INT reduced per cell, and ATP per cell were used to measure physiological activity. Cell densities decreased significantly over time at both sites for both S. faecalis and E. coli; however, no significant differences in survival pattern were observed between S. faecalis and E.coli. Differences in protein synthesis between the two were only observed at a study site which was not heavily oiled. Although fecal streptococci have been suggested as a better indicator of fecal contamination than fecal coliforms in marine waters, in this study both E. coli and S. faecalis survived and remained physiologically active for extended periods of time. These results suggest that the fecal streptococci group is not a better indicator of fecal contamination in tropical marine waters than the fecal coliform group, especially when that environment is high in long-chained hydrocarbons.

  14. Vitality of Enterococcus faecalis inside dentinal tubules after five root canal disinfection methods

    OpenAIRE

    Vatkar, Niranjan Ashok; Hegde, Vivek; Sathe, Sucheta

    2016-01-01

    Aim: To compare the vitality of Enterococcus faecalis within dentinal tubules after subjected to five root canal disinfection methods. Materials and Methods: Dentin blocks (n = 60) were colonized with E. faecalis. After 4 weeks of incubation, the dentin blocks were divided into one control and five test groups (n = 10 each). The root canals of test groups were subjected to one of the disinfection methods, namely, normal saline (NS), sodium hypochlorite (NaOCl), chlorhexidine digluconate (C...

  15. Rarity of invasiveness in right-sided infective endocarditis.

    Science.gov (United States)

    Hussain, Syed T; Shrestha, Nabin K; Witten, James; Gordon, Steven M; Houghtaling, Penny L; Tingleff, Jens; Navia, José L; Blackstone, Eugene H; Pettersson, Gösta B

    2018-01-01

    The rarity of invasiveness of right-sided infective endocarditis (IE) compared with left-sided has not been well recognized and evaluated. Thus, we compared invasiveness of right- versus left-sided IE in surgically treated patients. From January 2002 to January 2015, 1292 patients underwent surgery for active IE, 138 right-sided and 1224 left-sided. Among patients with right-sided IE, 131 had tricuspid and 7 pulmonary valve IE; 12% had prosthetic valve endocarditis. Endocarditis-related invasiveness was based on echocardiographic and operative findings. Invasive disease was rare on the right side, occurring in 1 patient (0.72%; 95% confidence interval 0.02%-4.0%); rather, it was limited to valve cusps/leaflets or was superficial. In contrast, IE was invasive in 408 of 633 patients with aortic valve (AV) IE (65%), 113 of 369 with mitral valve (MV) IE (31%), and 148 of 222 with AV and MV IE (67%). Staphylococcus aureus was a more predominant organism in right-sided than left-sided IE (right 40%, AV 19%, MV 29%), yet invasion was observed almost exclusively on the left side of the heart, which was more common and more severe with AV than MV IE and more common with prosthetic valve endocarditis than native valve IE. Rarity of right-sided invasion even when caused by S aureus suggests that invasion and development of cavities/"abscesses" in patients with IE may be driven more by chamber pressure than organism, along with other reported host-microbial interactions. The lesser invasiveness of MV compared with AV IE suggests a similar mechanism: decompression of MV annulus invasion site(s) toward the left atrium. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  16. Prognostic criteria for the development of infective endocarditis in children with heart pathology

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    Porokhnya N.G.

    2014-09-01

    Full Text Available To determine the most informative prognostic signs of infectious endocarditis development in children with heart pathology on the background of bacterial infections clinical course of 15 cases of infective endocarditis in children aged from 1 month to 17 years was performed. The comparison group consisted of 40 children aged 5 - 17 years with mitral valve prolapse. Of 19 analyzed clinical-anamnestic predictive diagnostic features for the development of infective endocarditis in children, presence of febrile fever during infusion therapy, the operated congenital heart disease, treatment in an intensive therapy unit with mechanical ventilation, intravenous infusions through a catheter lasting more than three days, a positive blood culture during the disease course, diagnostic catheterization of large vessels were of high informative value. In a positive prognosis of infective endocarditis development with a probability of 95% and more, children underwent complex of therapeutic measures with the following observation of pediatric cardio-rheumatologist.

  17. Levofloxacin-resistant-Streptococcus mitis endophthalmitis: a unique presentation of bacterial endocarditis.

    Science.gov (United States)

    Dinani, Amreen; Ktaich, Nessrine; Urban, Carl; Rubin, David

    2009-10-01

    Endogenous endophthalmitis is a rare complication of infective endocarditis and has been decreasing due to the availability of effective antibiotics. We highlight a case of endogenous endophthalmitis due to levofloxacin-resistant Streptococcus mitis presenting as infective endocarditis. Endogenous endophthalmitis should be considered as a manifestation of an underlying systemic disease, especially in patients who present with non-specific signs and symptoms with no obvious source of precipitating infection.

  18. Strawberry Extract’s Effects on Enterococcus faecalis and Porphyromonas gingivalis Biofilms in vitro

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    Armelia Sari Widyarman

    2017-09-01

    Full Text Available Background: Enterococcus faecalis (E. faecalis and Porphyromonas gingivalis (P. gingivalis are oral bacteria related to root canal infection and periodontal disease pathogenesis. Strawberries (Fragaria x ananassa fruit are rich in vitamins and minerals, have antibacterial and antioxidant effects. Objective: This study investigated the inhibition effect of strawberry extract on monospecies and multispecies E. faecalis and P. gingivalis bacteria grown as biofilms in vitro. Methods: This study used E. faecalis ATCC 29212 and P. gingivalis ATCC 33277. It analyzed the effect of strawberry extract on bacteria biofilm formation using a biofilm assay on microplate wells. Five concentrations of strawberry extracts were used (100%, 50%, 25%, 12.5%, and 6.25%, and the inhibition effect was observed after a 1h, 3h, 6h, and 24h incubation period. Biofilms without the strawberry extract were used as the negative controls, and crystal violet and safranin (0.5%w/v were used to count the biofilm mass. The biofilms grown on microplates were counted using an ELISA reader at 450 nm after 200 mL of 90% ethanol was added to attract the absorbed stain. The strawberry extract inhibition effectiveness on the biofilm formation of each bacterium tested was analyzed using one-way Anova, where p<0.05 was defined as a significant difference. Result: The strawberry extract inhibited the tested monospecies and multispecies bacteria biofilm formation. The optimal strawberry extract concentration for the inhibition of either monospecies biofilms was 100%. However, the optimal incubation time for the strawberry extract to inhibit the multispecies biofilm formation was 24h, which was the study’s biofilm maturity phase. Conclusions: The 100% strawberry extract concentration inhibited the formation of both the monospecies and multispecies E. faecalis and P. gingivalis biofilms. Future studies are needed to evaluate the potential of strawberry extract as an alternative dental

  19. Enterococcus faecalis Responds to Individual Exogenous Fatty Acids Independently of Their Degree of Saturation or Chain Length.

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    Saito, Holly E; Harp, John R; Fozo, Elizabeth M

    2018-01-01

    Enterococcus faecalis is a commensal of the human gastrointestinal tract that can persist in the external environment and is a leading cause of hospital-acquired infections. Given its diverse habitats, the organism has developed numerous strategies to survive a multitude of environmental conditions. Previous studies have demonstrated that E. faecalis will incorporate fatty acids from bile and serum into its membrane, resulting in an induced tolerance to membrane-damaging agents. To discern whether all fatty acids induce membrane stress protection, we examined how E. faecalis responded to individually supplied fatty acids. E. faecalis readily incorporated fatty acids 14 to 18 carbons in length into its membrane but poorly incorporated fatty acids shorter or longer than this length. Supplementation with saturated fatty acids tended to increase generation time and lead to altered cellular morphology in most cases. Further, exogenously supplied saturated fatty acids did not induce tolerance to the membrane-damaging antibiotic daptomycin. Supplementation with unsaturated fatty acids produced variable growth effects, with some impacting generation time and morphology. Exogenously supplied unsaturated fatty acids that are normally produced by E. faecalis and those that are found in bile or serum could restore growth in the presence of a fatty acid biosynthetic inhibitor. However, only the eukaryote-derived fatty acids oleic acid and linoleic acid provided protection from daptomycin. Thus, exogenous fatty acids do not lead to a common physiological effect on E. faecalis The organism responds uniquely to each, and only host-derived fatty acids induce membrane protection. IMPORTANCE Enterococcus faecalis is a commonly acquired hospital infectious agent with resistance to many antibiotics, including those that target its cellular membrane. We previously demonstrated that E. faecalis will incorporate fatty acids found in human fluids, like serum, into its cellular membrane

  20. Comparison between syringe irrigation and RinsEndo in reduction of Enterococcus faecalis in experimentally infected root canal

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    Sharareh Mousavi Zahed

    2015-05-01

    Full Text Available Background and Aims: To ensure root canal treatment success, endodontic microbiota should be efficiently reduced. Several irrigation devices have been recently introduced with the main objective of improving root canal disinfection.The purpose of this study was to evaluate the rinsing effect of RinsEndo system in reduction of enterococcus faecalis in comparison with conventional hand syringe in infected root canals.   Materials and Methods: 60 extracted single canal anterior teeth were infected with enterococcus faecalis and divided into 3 groups: RinsEndo system, conventional hand syringe and control group. The enterococcus faecalis colonies were counted in each group before and after rinsing. Data were analyzed using Variance and Kruskal Wallis test.   Results: The mean of enterococcus faecalis growth after rinsing was 3.50×103 in group with conventional syring rinsing, 2.04×103 in group with RinsEndo washing and 6.11×103 in control group. Reduction of enterococcus faecalis after rinsing was statistically significant in each group (P<0.001. The amount of reduction in number of colonies with RinsEndo and conventional syringe rinsing was higher in comparison with control group and this difference was significant (P<0.001. RinsEndo rinsing effect was statistically significantly higher in comparison to conventional syringe as well (P<0.001.   Conclusion: Rinsing with RinsEndo system was significantly more efficient in reduction of enterococcus faecalis from root canal in comparison with hand syringe washing.