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Sample records for aureus reduce linezolid

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

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    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.

  2. 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...

  3. 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

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

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    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.

  5. 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)

  6. 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)

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

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    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.

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

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    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

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

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    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.

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

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    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.

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

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    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

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

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    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.

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

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    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.

  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.

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

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    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.

  16. Linezolid and atorvastatin impact on pneumonia caused by Staphyloccocus aureus in rabbits with or without mechanical ventilation

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    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

  17. 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.

  18. Virulence-suppressing effects of linezolid on methicillin-resistant Staphylococcus aureus: possible contribution to early defervescence.

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    Yoshizawa, Sadako; Tateda, Kazuhiro; Saga, Tomoo; Ishii, Yoshikazu; Yamaguchi, Keizo

    2012-04-01

    In the present study, immunomodulatory effects of linezolid (LZD) on methicillin-resistance Staphylococcus aureus (MRSA) infections were evaluated. We have retrospectively reviewed treatment effects of LZD on 52 patients with severe MRSA infections. Sixty-four percent of the febrile patients demonstrated significant defervescence within 3 days, despite the presence of positive culture results. We speculated that this finding might be due to early anti-inflammatory effects of LZD, and to investigate this further we initiated in vivo experiments using mice MRSA pneumonia models. Mice were treated with either LZD or vancomycin (VCM) immediately after intranasal administration of MRSA. Bacterial numbers and levels of inflammatory cytokines in the lungs were determined. Although the bacterial burden in the lungs was not apparently different between the two groups, LZD but not VCM treatment significantly reduced induction of inflammatory cytokines in the lungs (P endogenous pyrogens. These data may explain at least in part early defervescence observed in LZD-treated individuals.

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

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

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    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

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

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    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

  2. 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

  3. 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.

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

    OpenAIRE

    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 an...

  5. 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

  6. Clinical Outcome with Oral Linezolid and Rifampin Following Recurrent Methicillin-Resistant Staphylococcus aureus Bacteremia Despite Prolonged Vancomycin Treatment

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    Jon-David Schwalm

    2004-01-01

    Full Text Available Drug-resistant Gram-positive bacteria, especially Staphylococcus aureus, are emerging as the predominant organisms involved in both nosocomial and community-acquired infections. Since the 1980s, vancomycin has been the first-line antibiotic used to treat methicillin-resistant S aureus. However, allergy and intolerance to vancomycin, the increasing number of vancomycin clinical failures and the existence of vancomycin intermediate-susceptible isolates of S aureus suggest that new antibiotics are needed. This paper reports the only known case of a successful clinical outcome with long term oral linezolid and rifampin therapy in the management of recurrent and persistent methicillin-resistant S aureus bacteremia with metastatic infections despite prolonged vancomycin use. More than two years since the initiation of linezolid and rifampin, the study patient has been clinically well with no evidence of adverse drug reactions including cytopenia and hepatic toxicities. Physicians must be aware of the novel developments in antibiotic therapy to treat drug-resistant bacterial infections.

  7. 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

  8. 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

  9. Cost Comparison of Linezolid Versus Vancomycin for Treatment of Complicated Skin and Skin-Structure Infection Caused by Methicillin-Resistant Staphylococcus aureus in Quebec

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    Martine Pettigrew

    2012-01-01

    Full Text Available BACKGROUND: In Canada, complicated skin and skin-structure infection (cSSSI caused by methicillin-resistant Staphylococcus aureus (MRSA is usually treated with antibiotics in hospital, with a follow-up course at home for stable patients. The cost implications of using intravenous and oral linezolid instead of intravenous vancomycin in Canadian clinical practice have not been examined.

  10. In Vivo Assessment of Phage and Linezolid Based Implant Coatings for Treatment of Methicillin Resistant S. aureus (MRSA Mediated Orthopaedic Device Related Infections.

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    Sandeep Kaur

    Full Text Available Staphylococcus comprises up to two-thirds of all pathogens in orthopaedic implant infections with two species respectively Staphylococcus aureus and Staphylococcus epidermidis, being the predominate etiological agents isolated. Further, with the emergence of methicillin-resistant S. aureus (MRSA, treatment of S. aureus implant infections has become more difficult, thus representing a devastating complication. Use of local delivery system consisting of S.aureus specific phage along with linezolid (incorporated in biopolymer allowing gradual release of the two agents at the implant site represents a new, still unexplored treatment option (against orthopaedic implant infections that has been studied in an animal model of prosthetic joint infection. Naked wire, hydroxypropyl methylcellulose (HPMC coated wire and phage and /or linezolid coated K-wire were surgically implanted into the intra-medullary canal of mouse femur bone of respective groups followed by inoculation of S.aureus ATCC 43300(MRSA. Mice implanted with K-wire coated with both the agents i.e phage as well as linezolid (dual coated wires showed maximum reduction in bacterial adherence, associated inflammation of the joint as well as faster resumption of locomotion and motor function of the limb. Also, all the coating treatments showed no emergence of resistant mutants. Use of dual coated implants incorporating lytic phage (capable of self-multiplication as well as linezolid presents an attractive and aggressive early approach in preventing as well as treating implant associated infections caused by methicillin resistant S. aureus strains as assessed in a murine model of experimental joint infection.

  11. 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.

  12. 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.

  13. An economic model to compare linezolid and vancomycin for the treatment of confirmed methicillin-resistant Staphylococcus aureus nosocomial pneumonia in Germany

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    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

  14. Co-therapy using lytic bacteriophage and linezolid: effective treatment in eliminating methicillin resistant Staphylococcus aureus (MRSA from diabetic foot infections.

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    Sanjay Chhibber

    Full Text Available BACKGROUND: Staphylococcus aureus remains the predominant pathogen in diabetic foot infections and prevalence of methicillin resistant S.aureus (MRSA strains further complicates the situation. The incidence of MRSA in infected foot ulcers is 15-30% and there is an alarming trend for its increase in many countries. Diabetes acts as an immunosuppressive state decreasing the overall immune functioning of body and to worsen the situation, wounds inflicted with drug resistant strains represent a morbid combination in diabetic patients. Foot infections caused by MRSA are associated with an increased risk of amputations, increased hospital stay, increased expenses and higher infection-related mortality. Hence, newer, safer and effective treatment strategies are required for treating MRSA mediated diabetic foot infections. The present study focuses on the use of lytic bacteriophage in combination with linezolid as an effective treatment strategy against foot infection in diabetic population. METHODOLOGY: Acute hindpaw infection with S.aureus ATCC 43300 was established in alloxan induced diabetic BALB/c mice. Therapeutic efficacy of a well characterized broad host range lytic bacteriophage, MR-10 was evaluated alone as well as in combination with linezolid in resolving the course of hindpaw foot infection in diabetic mice. The process of wound healing was also investigated. RESULTS AND CONCLUSIONS: A single administration of phage exhibited efficacy similar to linezolid in resolving the course of hindpaw infection in diabetic animals. However, combination therapy using both the agents was much more effective in arresting the entire infection process (bacterial load, lesion score, foot myeloperoxidase activity and histopathological analysis. The entire process of tissue healing was also hastened. Use of combined agents has been known to decrease the frequency of emergence of resistant mutants, hence this approach can serve as an effective strategy in

  15. Efficacy of linezolid compared to vancomycin in an experimental model of pneumonia induced by methicillin-resistant Staphylococcus aureus in ventilated pigs.

    Science.gov (United States)

    Martinez-Olondris, Pilar; Rigol, Montserrat; Soy, Dolors; Guerrero, Laura; Agusti, Carlos; Quera, Maria Angels; Li Bassi, Gianluigi; Esperatti, Mariano; Luque, Nestor; Liapikou, Manto; Filella, Xavier; Marco, Francesc; de la Bellacasa, Jordi Puig; Torres, Antoni

    2012-01-01

    To assess the efficacy of linezolid compared with vancomycin in an experimental model of pneumonia induced by methicillin-resistant Staphylococcus aureus (MRSA) in ventilated pigs. Forty pigs (30 kg) were intubated and challenged via bronchoscopy with a suspension of 106 colony forming units of MRSA into every lobe. Afterwards, pigs were ventilated up to 96 hours. Twelve hours after bacterial inoculation, the animals were randomized into 4 groups of treatment: group 1, control; group 2, vancomycin twice daily; group 3, continuous infusion of vancomycin; and group 4, linezolid. Clinical and laboratory parameters were monitored throughout the study. Bacterial cultures of bronchoalveolar lavage fluid and lung tissue samples were performed at the end of the study. Measurements of histopathology derangements of lung samples and studies of intrapulmonary drug penetration were performed. A total of 34 animals completed the study. No differences in clinical and laboratory parameters were observed. The percentage of bronchoalveolar lavage fluid and lung tissue samples with positive cultures for MRSA in controls and groups 2, 3, and 4 was respectively 75%, 11%, 11%, and 0% (p pneumonia in 95%, 69%, 58%, and 57% and signs of severe pneumonia in 48%, 29%, 22%, and 0% of controls and groups 2, 3, and 4, respectively (p treatments. In this animal model of MRSA pneumonia, linezolid showed a better efficacy than vancomycin showed because of a better pharmacokinetics/pharmacodynamics index.

  16. 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.

  17. Efficacy of linezolid, teicoplanin, and vancomycin in prevention of an experimental polytetrafluoroethylene graft infection model caused by methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Mese, Bulent; Bozoglan, Orhan; Elveren, Serdal; Eroglu, Erdinc; Gul, Mustafa; Celik, Ahmet; Ciralik, Harun; Yildirimdemir, Halil Ibrahim; Yasim, Alptekin

    2015-03-27

    The aim of this study was to evaluate the effectiveness of linezolid, teicoplanin, and vancomycin in prevention of prosthetic vascular graft infections in a vascular graft infection model. Fifty rats were divided into 5 groups. A polytetrafluoroethylene graft was implanted on the back of each rat. Methicillin-resistant Staphylococcus aureus (MRSA) strain was inoculated into all rats except Group 1. Group 2 was not given any treatment, Group 3 received linezolid, Group 4 received vancomycin, and Group 5 received teicoplanin. The grafts were removed for microbiological and histological examinations on the 7th day. In addition, C-reactive protein and prealbumin levels and leukocyte counts in obtained blood specimens were determined. Group 1 did not have infection. Group 2 had bacteria 5.7 × 10(4) CFU/cm(2). Group 3 and Group 4 had less bacterial growth. Group 5 had no bacterial growth. The number of bacteria was significantly higher in Group 2 than in the other experimental groups and the control group (pprevention of prosthetic vascular graft infections.

  18. Retrospective Analysis of Clinical and Cost Outcomes Associated with Methicillin-Resistant Staphylococcus aureus Complicated Skin and Skin Structure Infections Treated with Daptomycin, Vancomycin, or Linezolid

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    Bradley M. Wright

    2011-01-01

    Full Text Available Objective. The objective of this analysis was to compare clinical and cost outcomes associated with patients who had suspected or documented methicillin-resistant Staphylococcus aureus (MRSA infections treated with daptomycin, vancomycin, or linezolid in complicated skin and skin structure infections (cSSSIs. Design. This was a retrospective analysis conducted from February to June of 2007. Appropriate data was collected, collated, and subsequently evaluated with the purpose of quantifying length of stay, antibiotic therapy duration, clinical cure rates, adverse drug events, and cost of hospitalization. Results. All 82 patients included in the analysis experienced clinical cure. The duration of antibiotic therapy was similar among the three groups yet the length of hospitalization was slightly shorter in the daptomycin group. Conclusions. The incidence of resistant staphylococcal infections is increasing; therefore, judicious use of MRSA active agents is paramount. Future studies are necessary to determine if MRSA treatment options can be stratified based on the severity of the infectious process.

  19. Vancomycin, linezolid and daptomycin susceptibility pattern among clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA from Sub- Himalyan Center

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    Afzal Husain

    2018-01-01

    CONCLUSION: MIC creep was observed with vancomycin. Although linezolid MIC was within the susceptible zone, more than 40% strains showing MIC 3 μg/ml may herald the future development of either resistant or heteroresistant. Daptomycin showed good sensitivity against MRSA isolates. Therefore, it could be considered as an alternative agent for the treatment of infections caused by MRSA. However, it should be reserved where this class has a clear therapeutic advantage over other anti-MRSA drugs.

  20. 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

  1. Comparison of vancomycin and linezolid in patients with peripheral vascular disease and/or diabetes in an observational European study of complicated skin and soft-tissue infections due to methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Eckmann, C; Nathwani, D; Lawson, W; Corman, S; Solem, C; Stephens, J; Macahilig, C; Li, J; Charbonneau, C; Baillon-Plot, N; Haider, S

    2015-09-01

    Suboptimal antibiotic penetration into soft tissues can occur in patients with poor circulation due to peripheral vascular disease (PVD) or diabetes. We conducted a real-world analysis of antibiotic treatment, hospital resource use and clinical outcomes in patients with PVD and/or diabetes receiving linezolid or vancomycin for the treatment of methicillin-resistant Staphylococcus aureus complicated skin and soft-tissue infections (MRSA cSSTIs) across Europe. This subgroup analysis evaluated data obtained from a retrospective, observational medical chart review study that captured patient data from 12 European countries. Data were obtained from the medical records of patients ≥ 18 years of age, hospitalized with an MRSA cSSTI between 1 July 2010 and 30 June 2011 and discharged alive by 31 July 2011. Hospital length of stay and length of treatment were compared between the treatment groups using inverse probability of treatment weights to adjust for clinical and demographic differences. A total of 485 patients had PVD or diabetes and received treatment with either vancomycin (n = 258) or linezolid (n = 227). After adjustment, patients treated with linezolid compared with vancomycin respectively had significantly shorter hospital stays (17.9 ± 13.6 vs. 22.6 ± 13.6 days; p linezolid and vancomycin groups, respectively (p linezolid compared with vancomycin. Copyright © 2015. Published by Elsevier Ltd.

  2. Clinical outcomes of linezolid and vancomycin in patients with nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus stratified by baseline renal function: a retrospective, cohort analysis.

    Science.gov (United States)

    Liu, Ping; Capitano, Blair; Stein, Amy; El-Solh, Ali A

    2017-05-22

    The primary objective of this study is to assess whether baseline renal function impacts treatment outcomes of linezolid and vancomycin (with a dose-optimized regimen) for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. We conducted a retrospective cohort analysis of data generated from a prospective, randomized, controlled clinical trial (NCT 00084266). The analysis included 405 patients with culture-proven MRSA pneumonia. Baseline renal function was stratified based on creatinine clearance. Clinical and microbiological success rates and presence of nephrotoxicity were assessed at the end of treatment (EOT) and end of study (EOS). Multivariate logistic regression analyses of baseline patient characteristics, including treatment, were performed to identify independent predictors of efficacy. Vancomycin concentrations were analyzed using a nonlinear mixed-effects modeling approach. The relationships between vancomycin exposures, pharmacokinetic-pharmacodynamic index (trough concentration, area under the curve over a 24-h interval [AUC 0-24 ], and AUC 0-24 /MIC) and efficacy/nephrotoxicity were assessed in MRSA pneumonia patients using univariate logistic regression or Cox proportional hazards regression analysis approach. After controlling for use of vasoactive agents, choice of antibiotic therapy and bacteremia, baseline renal function was not correlated with clinical and microbiological successes in MRSA pneumonia at either end of treatment or at end of study for both treatment groups. No positive association was identified between vancomycin exposures and efficacy in these patients. Higher vancomycin exposures were correlated with an increased risk of nephrotoxicity (e.g., hazards ratio [95% confidence interval] for a 5 μg/ml increase in trough concentration: 1.42 [1.10, 1.82]). In non-dialysis patients, baseline renal function did not impact the differences in efficacy or nephrotoxicity with treatment of linezolid versus vancomycin in MRSA

  3. The effect of diabetes mellitus on outcomes of patients with nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus: data from a prospective double-blind clinical trial comparing treatment with linezolid versus vancomycin.

    Science.gov (United States)

    Equils, Ozlem; da Costa, Christopher; Wible, Michele; Lipsky, Benjamin A

    2016-09-06

    The presence of diabetes mellitus increases the risk of several severe infections, but data on its effect on treatment outcomes in patients with nosocomial pneumonia (NP) caused by methicillin-resistant Staphylococcus aureus (MRSA) are limited. We retrospectively analyzed data from a double-blind, randomized, multi-center, international clinical trial of culture-confirmed MRSA NP that compared treatment with linezolid to vancomycin. Specifically, we evaluated the clinical and microbiologic outcomes of patients with and without diabetes in the modified intent to treat population at end-of-treatment (EOT) and end-of-study (EOS, 7-30 days post-EOT). Among 448 enrolled patients 183 (40.8 %) had diabetes mellitus, 87 (47.5 %) of whom received linezolid and 96 (52.5 %) vancomycin. Baseline demographic and clinical characteristics were similar for the two treatment groups. Clinical success rates at EOS were 57.6 % with linezolid and 39.3 % with vancomycin, while microbiological success rates were 58.9 % with linezolid and 41.1 % with vancomycin. Among diabetic patients, rates of mortality and study drug-related adverse effects were similar between the treatment groups. Overall day 28 mortality rates were higher among diabetic patients compared to non-diabetic patients (23.5 vs 14.7 %, respectively: RD = 8.8 %, 95 % CI [1.4, 16.3]). Among diabetic patients with MRSA NP, treatment with linezolid, compared to vancomycin, was associated with higher clinical and microbiologic success rates, and comparable adverse event rates. NCT00084266 .

  4. A randomized, double-blind, comparative study to assess the safety and efficacy of topical retapamulin ointment 1% versus oral linezolid in the treatment of secondarily infected traumatic lesions and impetigo due to methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Tanus, Tonny; Scangarella-Oman, Nicole E; Dalessandro, Marybeth; Li, Gang; Breton, John J; Tomayko, John F

    2014-12-01

    To evaluate the clinical and bacteriological efficacy of topical retapamulin ointment 1% versus oral linezolid in the treatment of patients with secondarily infected traumatic lesions (SITLs; excluding abscesses) or impetigo due to methicillin-resistant Staphylococcus aureus (MRSA). A randomized, double-blind, double-dummy, multicenter, comparative study (NCT00852540). Patients recruited from 36 study centers in the United States. Patients 2 months or older with SITL (including secondarily infected lacerations or sutured wounds) or impetigo (bullous and nonbullous) suitable for treatment with a topical antibiotic, with a total Skin Infection Rating Scale score of 8 or greater, including a pus/exudate score of 3 or greater. Patients received retapamulin ointment 1% (plus oral placebo), twice daily for 5 days or oral linezolid (plus placebo ointment) 2 or 3 times daily for 10 days. Primary end point: clinical response (success/failure) at follow-up in patients with MRSA at baseline (per-protocol population). Secondary efficacy end points: clinical and microbiologic response and outcome at follow-up and end of therapy; therapeutic response at follow-up. The majority of patients had SITL (70.4% [188/267] and 66.4% [91/137] in the retapamulin and linezolid groups, respectively; intent-to-treat clinical population). Clinical success rate at follow-up was significantly lower in the retapamulin versus the linezolid group (63.9% [39/61] vs 90.6% [29/32], respectively; difference in success rate -26.7%; 95% CI, -45.7 to -7.7). Clinical success rate at follow-up in the per-protocol MRSA population was significantly lower in the retapamulin versus the linezolid group. It could not be determined whether this was related to study design, bacterial virulence, or retapamulin activity.

  5. 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)

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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....

  12. 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.

  13. 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

  14. 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.

  15. Effect of subinhibitory concentrations of chlorogenic acid on reducing the virulence factor production by Staphylococcus aureus.

    Science.gov (United States)

    Li, Guanghui; Qiao, Mingyu; Guo, Yan; Wang, Xin; Xu, Yunfeng; Xia, Xiaodong

    2014-09-01

    Chlorogenic acid (CA) has been reported to inhibit several pathogens, but the influence of subinhibitory concentrations of CA on virulence expression of pathogens has not been fully elucidated. The aim of this study was to explore the effect of CA on the virulence factor production of Staphylococcus aureus. The minimum inhibitory concentration (MIC) of CA against S. aureus was determined using a broth microdilution method. Hemolysin assays, coagulase titer assays, adherence to solid-phase fibrinogen assays, Western blot, and real-time reverse transcriptase-polymerase chain reaction were performed to evaluate the effect of subinhibitory concentrations of CA on the virulence factors of S. aureus. MIC of CA against S. aureus ATCC29213 was found to be 2.56 mg/mL. At subinhibitory concentrations, CA significantly inhibited the hemolysis and dose-dependently decreased coagulase titer. Reduced binding to fibrinogen and decreased production of SEA were observed with treatment of CA at concentrations ranging from 1/16MIC to 1/2MIC. CA markedly inhibited the expression of hla, sea, and agr genes in S. aureus. These data demonstrate that the virulence expression of S. aureus could be reduced by CA and suggest that CA could be potentially developed as a supplemental strategy to control S. aureus infection and to prevent staphylococcal food poisoning.

  16. 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.

  17. Emergence in Asian Countries of Staphylococcus aureus with Reduced Susceptibility to Vancomycin

    Science.gov (United States)

    Song, Jae-Hoon; Hiramatsu, Keiichi; Suh, Ji Yoeun; Ko, Kwan Soo; Ito, Teruyo; Kapi, Maria; Kiem, Sungmin; Kim, Yeon-Sook; Oh, Won Sup; Peck, Kyong Ran; Lee, Nam Yong

    2004-01-01

    To investigate the prevalence of Staphylococcus aureus with reduced susceptibility to vancomycin among methicillin-resistant S. aureus (MRSA) strains in Asian countries, a total of 1,357 clinical isolates of MRSA collected from 12 Asian countries were screened by using brain heart infusion agar plates containing 4 mg of vancomycin per liter. The presence of strains that were heterointermediately resistant to vancomycin (hVISA) was confirmed by population analysis. Of 347 (25.6%) MRSA isolates that grew on the screening agar plates, 58 isolates (4.3%) were hVISA. hVISA strains were found in India, South Korea, Japan, the Philippines, Singapore, Thailand, and Vietnam. However, neither vancomycin-intermediate S. aureus nor vancomycin-resistant S. aureus isolates were found among MRSA isolates from Asian countries in this survey. PMID:15561884

  18. 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.

  19. Norlichexanthone Reduces Virulence Gene Expression and Biofilm Formation in Staphylococcus aureus

    DEFF Research Database (Denmark)

    Baldry, Mara; Nielsen, Anita; Bojer, Martin S.

    2016-01-01

    Staphylococcus aureus is a serious human pathogen and antibiotic resistant, community-associated strains, such as the methicillin resistant S. aureus (MRSA) strain USA300, continue to spread. To avoid resistance, anti-virulence therapy has been proposed where toxicity is targeted rather than...... viability. Previously we have shown that norlichexanthone, a small non-reduced tricyclic polyketide produced by fungi and lichens, reduces expression of hla encoding α-hemolysin as well as the regulatory RNAIII of the agr quorum sensing system in S. aureus 8325-4. The aim of the present study was to further...... SaeRS system. Our data show that norlichexanthone treatment reduces expression of key virulence factors in CA-MRSA strain USA300 via AgrA binding and represses biofilm formation....

  20. 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

  1. Subinhibitory quinupristin/dalfopristin attenuates virulence of Staphylococcus aureus.

    Science.gov (United States)

    Koszczol, Carmen; Bernardo, Katussevani; Krönke, Martin; Krut, Oleg

    2006-09-01

    The semi-synthetic streptogramin quinupristin/dalfopristin antibiotic exerts potent bactericidal activity against Staphylococcus aureus. We investigated whether, like other bactericidal antibiotics used at subinhibitory concentrations, quinupristin/dalfopristin enhances release of toxins by Gram-positive cocci. The activity of quinupristin/dalfopristin on exotoxin release by S. aureus was investigated by 2D SDS-PAGE combined with MALDI-TOF/MS analysis and by western blotting. We show that quinupristin/dalfopristin at subinhibitory concentrations reduces the release of S. aureus factors that induce tumour necrosis factor secretion in macrophages. Furthermore, quinupristin/dalfopristin but not linezolid attenuated S. aureus-mediated killing of infected host cells. When added to S. aureus cultures at different stages of bacterial growth, quinupristin/dalfopristin reduced in a dose-dependent manner the release of specific virulence factors (e.g. autolysin, protein A, alpha- and beta-haemolysins, lipases). In contrast, other presumably non-toxic exoproteins remained unchanged. The results of the present study suggest that subinhibitory quinupristin/dalfopristin inhibits virulence factor release by S. aureus, which might be especially helpful for the treatment of S. aureus infections, where both bactericidal as well as anti-toxin activity may be advantageous.

  2. 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

  3. Eugenol reduces the expression of virulence-related exoproteins in Staphylococcus aureus.

    Science.gov (United States)

    Qiu, Jiazhang; Feng, Haihua; Lu, Jing; Xiang, Hua; Wang, Dacheng; Dong, Jing; Wang, Jianfeng; Wang, Xiaoliang; Liu, Juxiong; Deng, Xuming

    2010-09-01

    Eugenol, an essential oil component in plants, has been demonstrated to possess activity against both gram-positive and gram-negative bacteria. This study examined the influence that subinhibitory concentrations of eugenol may have on the expression of the major exotoxins produced by Staphylococcus aureus. The results from a tumor necrosis factor (TNF) release assay and a hemolysin assay indicated that S. aureus cultured with graded subinhibitory concentrations of eugenol (16 to 128 microg/ml) dose dependently decreased the TNF-inducing and hemolytic activities of culture supernatants. Western blot analysis showed that eugenol significantly reduced the production of staphylococcal enterotoxin A (SEA), SEB, and toxic shock syndrome toxin 1 (the key exotoxins to induce TNF release), as well as the expression of alpha-hemolysin (the major hemolysin to cause hemolysis). In addition, this suppression was also evaluated at the transcriptional level via real-time reverse transcription (RT)-PCR analysis. The transcriptional analysis indicated that 128 microg/ml of eugenol remarkably repressed the transcription of the S. aureus sea, seb, tst, and hla genes. According to these results, eugenol has the potential to be rationally applied on food products as a novel food antimicrobial agent both to inhibit the growth of bacteria and to suppress the production of exotoxins by S. aureus.

  4. 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...

  5. 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.

  6. 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

  7. Proteases in Escherichia coli and Staphylococcus aureus confer reduced susceptibility to lactoferricin B.

    Science.gov (United States)

    Ulvatne, Hilde; Haukland, Hanne Husom; Samuelsen, Ørjan; Krämer, Manuela; Vorland, Lars H

    2002-10-01

    Lactoferricin B is a cationic antimicrobial peptide derived from the N-terminal part of bovine lactoferrin. The effect of bacterial proteases on the antibacterial activity of lactoferricin B towards Escherichia coli and Staphylococcus aureus was investigated using various protease inhibitors and protease-deficient E. coli mutants. Sodium-EDTA, a metalloprotease inhibitor, was the most efficient inhibitors in both species, but combinations of sodium-EDTA with other types of protease inhibitor gave a synergic effect. The results indicate that several groups of proteases are involved in resistance to lactoferricin B in both E. coli and S. aureus. We also report that genetic inactivation of the heat shock-induced serine protease DegP increased the susceptibility to lactoferricin B in E. coli, suggesting that this protease, at least, is involved in reduced susceptibility to lactoferricin B.

  8. 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.

  9. Linezolid has unique immunomodulatory effects in post-influenza community acquired MRSA pneumonia.

    Directory of Open Access Journals (Sweden)

    Urvashi Bhan

    Full Text Available Post influenza pneumonia is a leading cause of mortality and morbidity, with mortality rates approaching 60% when bacterial infections are secondary to multi-drug resistant (MDR pathogens. Staphylococcus aureus, in particular community acquired MRSA (cMRSA, has emerged as a leading cause of post influenza pneumonia.Linezolid (LZD prevents acute lung injury in murine model of post influenza bacterial pneumonia.Mice were infected with HINI strain of influenza and then challenged with cMRSA at day 7, treated with antibiotics (LZD or Vanco or vehicle 6 hours post bacterial challenge and lungs and bronchoalveolar lavage fluid (BAL harvested at 24 hours for bacterial clearance, inflammatory cell influx, cytokine/chemokine analysis and assessment of lung injury.Mice treated with LZD or Vanco had lower bacterial burden in the lung and no systemic dissemination, as compared to the control (no antibiotic group at 24 hours post bacterial challenge. As compared to animals receiving Vanco, LZD group had significantly lower numbers of neutrophils in the BAL (9×10(3 vs. 2.3×10(4, p < 0.01, which was associated with reduced levels of chemotactic chemokines and inflammatory cytokines KC, MIP-2, IFN-γ, TNF-α and IL-1β in the BAL. Interestingly, LZD treatment also protected mice from lung injury, as assessed by albumin concentration in the BAL post treatment with H1N1 and cMRSA when compared to vanco treatment. Moreover, treatment with LZD was associated with significantly lower levels of PVL toxin in lungs.Linezolid has unique immunomodulatory effects on host inflammatory response and lung injury in a murine model of post-viral cMRSA pneumonia.

  10. Serotonin syndrome in an orthopaedic patient secondary to linezolid therapy for MRSA infection.

    LENUS (Irish Health Repository)

    McClean, M

    2012-01-31

    A 67-year-old patient was admitted for incision and drainage of a recurrent methicillin-resistant Staphylococcus aureus (MRSA) hip abscess. Linezolid therapy was initiated postoperatively. Within 48 h the patient developed confusion, agitation, hypertension and acute renal failure. Citalopram was stopped and resolution of symptoms occurred within 48 h of discontinuing the offending agent. The symptoms observed in our patient were consistent with the Sternbach criteria for serotonin syndrome.

  11. 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.

  12. 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.

  13. Global transcriptional response of methicillin-resistant Staphylococcus aureus to thioridazine

    DEFF Research Database (Denmark)

    Bonde, Mette; Jacobsen, Kirstine; Kolmos, Hans Jørn

    Few drugs are available against methicillin-resistant S. aureus (MRSA), and decreased susceptibility among staphylococci to newly introduced agents such as linezolid, daptomycin, and tigecycline has been observed [1-3]. Consequently, new treatment strategies are urgently needed. Thioridazine...

  14. Reducing Staphylococcus aureus biofilm formation on stainless steel 316L using functionalized self-assembled monolayers.

    Science.gov (United States)

    Kruszewski, Kristen M; Nistico, Laura; Longwell, Mark J; Hynes, Matthew J; Maurer, Joshua A; Hall-Stoodley, Luanne; Gawalt, Ellen S

    2013-05-01

    Stainless steel 316L (SS316L) is a common material used in orthopedic implants. Bacterial colonization of the surface and subsequent biofilm development can lead to refractory infection of the implant. Since the greatest risk of infection occurs perioperatively, strategies that reduce bacterial adhesion during this time are important. As a strategy to limit bacterial adhesion and biofilm formation on SS316L, self-assembled monolayers (SAMs) were used to modify the SS316L surface. SAMs with long alkyl chains terminated with hydrophobic (-CH3) or hydrophilic (oligoethylene glycol) tail groups were used to form coatings and in an orthogonal approach, SAMs were used to immobilize gentamicin or vancomycin on SS316L for the first time to form an "active" antimicrobial coating to inhibit early biofilm development. Modified SS316L surfaces were characterized using surface infrared spectroscopy, contact angles, MALDI-TOF mass spectrometry and atomic force microscopy. The ability of SAM-modified SS316L to retard biofilm development by Staphylococcus aureus was functionally tested using confocal scanning laser microscopy with COMSTAT image analysis, scanning electron microscopy and colony forming unit analysis. Neither hydrophobic nor hydrophilic SAMs reduced biofilm development. However, gentamicin-linked and vancomycin-linked SAMs significantly reduced S. aureus biofilm formation for up to 24 and 48 h, respectively. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Capsaicin, a novel inhibitor of the NorA efflux pump, reduces the intracellular invasion of Staphylococcus aureus.

    Science.gov (United States)

    Kalia, Nitin Pal; Mahajan, Priya; Mehra, Rukmankesh; Nargotra, Amit; Sharma, Jai Parkash; Koul, Surrinder; Khan, Inshad Ali

    2012-10-01

    To delineate the role of capsaicin (8-methyl-N-vanillyl-6-nonenamide) as an inhibitor of the NorA efflux pump and its impact on invasion of macrophages by Staphylococcus aureus. Capsaicin in combination with ciprofloxacin was tested for activity against S. aureus SA-1199B (NorA overproducing), SA-1199 (wild-type) and SA-K1758 (norA knockout). The role of NorA in the intracellular invasion of S. aureus and the ability of capsaicin to inhibit this invasion was established in J774 macrophage cell lines. The three-dimensional structure of NorA was predicted using an in silico approach and docking studies of capsaicin were performed. Capsaicin significantly reduced the MIC of ciprofloxacin for S. aureus SA-1199 and SA-1199B. Furthermore, capsaicin also extended the post-antibiotic effect of ciprofloxacin by 1.1 h at MIC concentration. There was a decrease in mutation prevention concentration of ciprofloxacin when combined with capsaicin. Inhibition of ethidium bromide efflux by NorA-overproducing S. aureus SA-1199B confirmed the role of capsaicin as a NorA efflux pump inhibitor (EPI). The most significant finding of this study was the ability of capsaicin to reduce the intracellular invasion of S. aureus SA-1199B (NorA overproducing) in J774 macrophage cell lines by 2 log(10). This study, for the first time, has shown that capsaicin, a novel EPI, not only inhibits the NorA efflux pump of S. aureus but also reduces the invasiveness of S. aureus, thereby reducing its virulence.

  16. Reduced adhesion of Staphylococcus aureus to ZnO/PVC nanocomposites

    Directory of Open Access Journals (Sweden)

    Geilich BM

    2013-03-01

    Full Text Available Benjamin M Geilich,1 Thomas J Webster21Program in Bioengineering, 2Department of Chemical Engineering, College of Engineering, Northeastern University, Boston, MA, USAAbstract: In hospitals and clinics worldwide, medical device surfaces have become a rapidly growing source of nosocomial infections. In particular, patients requiring mechanical ventilation (and, thus, intubation with an endotracheal tube for extended lengths of time are faced with a high probability of contracting ventilator-associated pneumonia. Once inserted into the body, the endotracheal tube provides a surface to which bacteria can adhere and form a biofilm (a robust, sticky matrix that provides protection against the host immune system and antibiotic treatment. Adding to the severity of this problem is the spread of bacterial genetic tolerance to antibiotics, in part demonstrated by the recent and significant increase in the prevalence of methicillin-resistant Staphylococcus aureus. To combat these trends, different techniques in biomaterial design must be explored. Recent research has shown that nanomaterials (materials with at least one dimension less than 100 nm may have the potential to prevent or disrupt bacterial processes that lead to infections. In this study, polyvinyl chloride (PVC taken from a conventional endotracheal tube was embedded with varying concentrations of zinc oxide (ZnO nanoparticles. S. aureus biofilms were then grown on these nanocomposite surfaces during a 24-hour culture. Following this, biofilms were removed from the surfaces and the number of colony forming units present was assessed. Bacterial proliferation on the samples embedded with the highest concentration of ZnO nanoparticles was 87% less when compared to the control, indicating that this technique is effective at reducing biofilm formation on PVC surfaces without the use of antibiotics.Keywords: nanomaterials, endotracheal tube, biofilm, zinc oxide, nanoparticles, Staphylococcus aureus

  17. Reducing Staphylococcus aureus biofilm formation on stainless steel 316L using functionalized self-assembled monolayers

    International Nuclear Information System (INIS)

    Kruszewski, Kristen M.; Nistico, Laura; Longwell, Mark J.; Hynes, Matthew J.; Maurer, Joshua A.; Hall-Stoodley, Luanne; Gawalt, Ellen S.

    2013-01-01

    Stainless steel 316L (SS316L) is a common material used in orthopedic implants. Bacterial colonization of the surface and subsequent biofilm development can lead to refractory infection of the implant. Since the greatest risk of infection occurs perioperatively, strategies that reduce bacterial adhesion during this time are important. As a strategy to limit bacterial adhesion and biofilm formation on SS316L, self-assembled monolayers (SAMs) were used to modify the SS316L surface. SAMs with long alkyl chains terminated with hydrophobic (− CH 3 ) or hydrophilic (oligoethylene glycol) tail groups were used to form coatings and in an orthogonal approach, SAMs were used to immobilize gentamicin or vancomycin on SS316L for the first time to form an “active” antimicrobial coating to inhibit early biofilm development. Modified SS316L surfaces were characterized using surface infrared spectroscopy, contact angles, MALDI-TOF mass spectrometry and atomic force microscopy. The ability of SAM-modified SS316L to retard biofilm development by Staphylococcus aureus was functionally tested using confocal scanning laser microscopy with COMSTAT image analysis, scanning electron microscopy and colony forming unit analysis. Neither hydrophobic nor hydrophilic SAMs reduced biofilm development. However, gentamicin-linked and vancomycin-linked SAMs significantly reduced S. aureus biofilm formation for up to 24 and 48 h, respectively. - Highlights: ► SS316L was modified with glycol terminated SAMs in order to reduce biofilm growth. ► Antibiotics gentamicin and vancomycin were immobilized on SS316L via SAMs. ► Only the antibiotic modifications reduced biofilm development on SS316L

  18. Reducing Staphylococcus aureus biofilm formation on stainless steel 316L using functionalized self-assembled monolayers

    Energy Technology Data Exchange (ETDEWEB)

    Kruszewski, Kristen M., E-mail: kruszewskik@duq.edu [Duquesne University, Department of Chemistry and Biochemistry, 600 Forbes Avenue, Pittsburgh, PA 15282 (United States); Nistico, Laura, E-mail: lnistico@wpahs.org [Allegheny General Hospital, Center for Genomic Sciences, Allegheny-Singer Research Institute, 320 East North Avenue, 11th floor, South Tower, Pittsburgh, PA 15212 (United States); Longwell, Mark J., E-mail: mlongwel@wpahs.org [Allegheny General Hospital, Center for Genomic Sciences, Allegheny-Singer Research Institute, 320 East North Avenue, 11th floor, South Tower, Pittsburgh, PA 15212 (United States); Hynes, Matthew J., E-mail: mjhynes@go.wustl.edu [Washington University in St. Louis, Department of Chemistry, One Brookings Drive, St. Louis, MO 63130 (United States); Maurer, Joshua A., E-mail: maurer@wustl.edu [Washington University in St. Louis, Department of Chemistry, One Brookings Drive, St. Louis, MO 63130 (United States); Hall-Stoodley, Luanne, E-mail: L.Hall-Stoodley@soton.ac.uk [Southampton Wellcome Trust Clinical Research Facility/NIHR Respiratory BRU, University of Southampton Faculty of Medicine, Southampton General Hospital, Tremona Road, Southampton, Hampshire SO16 6YD (United Kingdom); Gawalt, Ellen S., E-mail: gawalte@duq.edu [Duquesne University, Department of Chemistry and Biochemistry, McGowan Institute for Regenerative Medicine, 600 Forbes Avenue, Pittsburgh, PA 15282 (United States)

    2013-05-01

    Stainless steel 316L (SS316L) is a common material used in orthopedic implants. Bacterial colonization of the surface and subsequent biofilm development can lead to refractory infection of the implant. Since the greatest risk of infection occurs perioperatively, strategies that reduce bacterial adhesion during this time are important. As a strategy to limit bacterial adhesion and biofilm formation on SS316L, self-assembled monolayers (SAMs) were used to modify the SS316L surface. SAMs with long alkyl chains terminated with hydrophobic (− CH{sub 3}) or hydrophilic (oligoethylene glycol) tail groups were used to form coatings and in an orthogonal approach, SAMs were used to immobilize gentamicin or vancomycin on SS316L for the first time to form an “active” antimicrobial coating to inhibit early biofilm development. Modified SS316L surfaces were characterized using surface infrared spectroscopy, contact angles, MALDI-TOF mass spectrometry and atomic force microscopy. The ability of SAM-modified SS316L to retard biofilm development by Staphylococcus aureus was functionally tested using confocal scanning laser microscopy with COMSTAT image analysis, scanning electron microscopy and colony forming unit analysis. Neither hydrophobic nor hydrophilic SAMs reduced biofilm development. However, gentamicin-linked and vancomycin-linked SAMs significantly reduced S. aureus biofilm formation for up to 24 and 48 h, respectively. - Highlights: ► SS316L was modified with glycol terminated SAMs in order to reduce biofilm growth. ► Antibiotics gentamicin and vancomycin were immobilized on SS316L via SAMs. ► Only the antibiotic modifications reduced biofilm development on SS316L.

  19. 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.

  20. 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.

  1. 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.

  2. Methicillin-resistant Staphylococcus aureus in North-east Croatia

    Directory of Open Access Journals (Sweden)

    Tajana Pastuović

    2015-05-01

    Full Text Available Objective. The aim of this 5-year study was to determine the frequency and antibiotic susceptibility of methicillin-resistant Staphylococcus aureus (MRSA-related infections at Osijek Clinical Hospital. Materials and methods. A total of 1987 staphylococci-infected clinical isolates were collected and analysed at the Microbiology Department of the Public Health Institute of Osijek-Baranja County. Results. Between 2008 and 2012, the average rate of MRSA-related infections in staphylococci-infected patients was 27.4%. The proportion of MRSArelated infections on all Staphylococcus aureus (S. aureus isolates from clinical specimens showed a decreasing trend, from 32.6% in 2008 to 25.5% in 2012. MRSA-related infections were mostly detected in wound swabs (50.6% and aspirates (28.8% of patients hospitalized in the surgical (49.8% and intensive care units (27.9%. MRSA-related infection showed an increase compared to S. aureus-infections in samples of wounds and aspirates in 2011 and 2012 (57.9%/34.9% and 35.2%/16.3%, respectively. The majority of strains of MRSA-related infections were resistant to several antibiotics, including erythromycin and clindamycin, where susceptibility were less than 10%. All MRSA isolates were susceptible to vancomycin, teicoplanin and linezolid. Therefore, antibiotic therapies for MRSA infections include vancomycin, teicoplanin and linezolid, but microbiological diagnostics need to be performed in order to know when the use of glycopeptides and oxazolidinones is indicated. Conclusion. Our results suggest that appropriate prevention measures, combined with the more rational use of antibiotics are crucial to reduce the spread of MRSA-related infection in healthcare settings. Further monitoring is necessary of the incidence and antibiotic susceptibility of MRSA-related infections in our community.

  3. Linezolid

    Science.gov (United States)

    ... beer, Chianti, and other red wines; alcohol-free beer; cheeses (especially strong, aged, or processed varieties); sauerkraut; yogurt; raisins; bananas; sour cream; pickled herring; liver (especially chicken liver); dried ...

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Combined use of Bacteriophage K and a novel Bacteriophage to reduce Staphylococcus aureus biofilm formation

    DEFF Research Database (Denmark)

    Alves, D.R.; Gaudion, A.; Bean, J.E.

    2014-01-01

    Biofilms are major causes of impairment of wound healing and patient morbidity. One of the most common and aggressive wound pathogens is Staphylococcus aureus, displaying a large repertoire of virulence factors and commonly reduced susceptibility to antibiotics, such as the spread of methicillin-...

  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. 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. 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...

  12. 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.

  13. Molecular characterization of vancomycin-intermediate Staphylococcus aureus isolates from Tehran

    Directory of Open Access Journals (Sweden)

    Shahin Najar-Peerayeh

    2016-09-01

    Full Text Available Objective: To determine the prevalence and some genetic characteristics of clinical isolates of Staphylococcus aureus (S. aureus with reduced susceptibility to vancomycin. Methods: A total of 414 isolates of S. aureus were collected from clinical specimens from hospitals in Tehran. Vancomycin-intermediate S. aureus (VISA was determined by brain heart infusion agar containing 4 μg/mL vancomycin screening plate and confirmed via E-test. VISA isolates were analysed for vanA, vanB, mecA, staphylococcal cassette chromosome mec types, surface protein A (Spa types and agr specific groups. Results: Brain heart infusion agar containing 4 μg/mL vancomycin screening tests revealed that 17.14% (n = 71 of S. aureus isolates were VISA phenotype. Ten of the 71 isolates were confirmed by E-test method (minimal inhibitory concentration was 4 to 8 μg/mL. All VISA isolates were susceptible to linezolid and 6 isolates (60% were methicillin-resistant S. aureus. Five isolates belonged to agr Group II, 4 belonged to agr Group I and 1 belonged to agr Group III. Spa type t030, and staphylococcal cassette chromosome mec Type III were dominant among VISA isolates. Conclusions: This study provides further evidence of the global dissemination of VISA isolates and emphasizes to vancomycin susceptibility testing prior to antibiotic therapy.

  14. Frequency of Reduced Vancomycin Susceptibility among Clinical Staphylococcus aureus Isolated in Ahvaz Iran

    Directory of Open Access Journals (Sweden)

    Mojtaba Moosavian

    2015-11-01

    Full Text Available Introduction:   One   of   the   most   important   agents   in   hospital-acquired   infections   is Staphylococcus aureus. Treatment of methicillin-resistant S. aureus (MRSA infections with decreased susceptibility to vancomycin has recently been more difficult. The aim of this study was to evaluate the possible presence of vancomycin intermediate S. aureus (VISA and vancomycin- resistant S. aureus (VRSA and also to determine the frequency of MRSA in clinical specimens.Methods: In this study, 195 S. aureus isolates were collected from the patients were examined. All of the isolates were identified using standard biochemical tests.  Susceptibility of S. aureus isolates against 10 antibiotics was detected by disk diffusion method and was followed by E-test and vancomycin screen agar methods. Minimum inhibitory concentration (MIC of vancomycin was determined according to the CLSI guidelines.  Also, detection of mecA gene was performed by PCR and finally, the results were compared.Results: All of the isolates were susceptible to vancomycin (i.e. MIC range of vancomycin was between 0.25-2 µg/ml. Out of 195 S. aureus isolates, 99 isolates (50.8% were resistant to methicillin, and mecA gene was detected in 96 isolates. These results also showed that the highest and lowest resistance rate of isolates was to penicillin (96.9% and chloramphenicol (0%, respectively.Conclusion: Our findings showed that vancomycin can still be used as a valuable drug for treatment of S. aureus infections in our region. However, periodic evaluation of vancomycin MIC of S. aureus isolates is critical for monitoring MRSA and preventing the spread of VISA or VRSA among patients.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. MEDI4893* Promotes Survival and Extends the Antibiotic Treatment Window in a Staphylococcus aureus Immunocompromised Pneumonia Model.

    Science.gov (United States)

    Hua, L; Cohen, T S; Shi, Y; Datta, V; Hilliard, J J; Tkaczyk, C; Suzich, J; Stover, C K; Sellman, B R

    2015-08-01

    Immunocompromised individuals are at increased risk of Staphylococcus aureus pneumonia. Neutralization of alpha-toxin (AT) with the monoclonal antibody (MAb) MEDI4893* protects normal mice from S. aureus pneumonia; however, the effects of the MAb in immunocompromised mice have not been reported. In this study, passive immunization with MEDI4893* increased survival rates and reduced bacterial numbers in the lungs in an immunocompromised murine S. aureus pneumonia model. Lungs from infected mice exhibited alveolar epithelial damage, protein leakage, and bacterial overgrowth, whereas lungs from mice passively immunized with MEDI4893* retained a healthy architecture, with an intact epithelial barrier. Adjunctive therapy or prophylaxis with a subtherapeutic MEDI4893* dose combined with subtherapeutic doses of vancomycin or linezolid improved survival rates, compared with the monotherapies. Furthermore, coadministration of MEDI4893* with vancomycin or linezolid extended the antibiotic treatment window. These data suggest that MAb-mediated neutralization of AT holds promise in strategies for prevention and adjunctive therapy among immunocompromised patients. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  20. 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

  1. Adjunctive rifampicin to reduce early mortality from Staphylococcus aureus bacteraemia (ARREST: study protocol for a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Thwaites Guy

    2012-12-01

    Full Text Available Abstract Background Staphylococcus aureus bacteraemia is a common and serious infection, with an associated mortality of ~25%. Once in the blood, S. aureus can disseminate to infect almost any organ, but bones, joints and heart valves are most frequently affected. Despite the infection’s severity, the evidence guiding optimal antibiotic therapy is weak: fewer than 1,500 patients have been included in 16 randomised controlled trials investigating S. aureus bacteraemia treatment. It is uncertain which antibiotics are most effective, their route of administration and duration, and whether antibiotic combinations are better than single agents. We hypothesise that adjunctive rifampicin, given in combination with a standard first-line antibiotic, will enhance killing of S. aureus early in the treatment course, sterilise infected foci and blood faster, and thereby reduce the risk of dissemination, metastatic infection and death. Our aim is to determine whether adjunctive rifampicin reduces all-cause mortality within 14 days and bacteriological failure or death within 12 weeks from randomisation. Methods We will perform a parallel group, randomised (1:1, blinded, placebo-controlled trial in NHS hospitals across the UK. Adults (≥18 years with S. aureus (meticillin-susceptible or resistant grown from at least one blood culture who have received ≤96 h of active antibiotic therapy for the current infection and do not have contraindications to the use of rifampicin will be eligible for inclusion. Participants will be randomised to adjunctive rifampicin (600-900mg/day; orally or intravenously or placebo for the first 14 days of therapy in combination with standard single-agent antibiotic therapy. The co-primary outcome measures will be all-cause mortality up to 14 days from randomisation and bacteriological failure/death (all-cause up to 12 weeks from randomisation. 940 patients will be recruited, providing >80% power to detect 45% and 30% reductions in

  2. Adjunctive rifampicin to reduce early mortality from Staphylococcus aureus bacteraemia (ARREST): study protocol for a randomised controlled trial.

    Science.gov (United States)

    Thwaites, Guy; Auckland, Cressida; Barlow, Gavin; Cunningham, Richard; Davies, Gerry; Edgeworth, Jonathan; Greig, Julia; Hopkins, Susan; Jeyaratnam, Dakshika; Jenkins, Neil; Llewelyn, Martin; Meisner, Sarah; Nsutebu, Emmanuel; Planche, Tim; Read, Robert C; Scarborough, Matthew; Soares, Marta; Tilley, Robert; Török, M Estée; Williams, John; Wilson, Peter; Wyllie, Sarah; Walker, A Sarah

    2012-12-18

    Staphylococcus aureus bacteraemia is a common and serious infection, with an associated mortality of ~25%. Once in the blood, S. aureus can disseminate to infect almost any organ, but bones, joints and heart valves are most frequently affected. Despite the infection's severity, the evidence guiding optimal antibiotic therapy is weak: fewer than 1,500 patients have been included in 16 randomised controlled trials investigating S. aureus bacteraemia treatment. It is uncertain which antibiotics are most effective, their route of administration and duration, and whether antibiotic combinations are better than single agents. We hypothesise that adjunctive rifampicin, given in combination with a standard first-line antibiotic, will enhance killing of S. aureus early in the treatment course, sterilise infected foci and blood faster, and thereby reduce the risk of dissemination, metastatic infection and death. Our aim is to determine whether adjunctive rifampicin reduces all-cause mortality within 14 days and bacteriological failure or death within 12 weeks from randomisation. We will perform a parallel group, randomised (1:1), blinded, placebo-controlled trial in NHS hospitals across the UK. Adults (≥ 18 years) with S. aureus (meticillin-susceptible or resistant) grown from at least one blood culture who have received ≤ 96 h of active antibiotic therapy for the current infection and do not have contraindications to the use of rifampicin will be eligible for inclusion. Participants will be randomised to adjunctive rifampicin (600-900 mg/day; orally or intravenously) or placebo for the first 14 days of therapy in combination with standard single-agent antibiotic therapy. The co-primary outcome measures will be all-cause mortality up to 14 days from randomisation and bacteriological failure/death (all-cause) up to 12 weeks from randomisation. 940 patients will be recruited, providing >80% power to detect 45% and 30% reductions in the two co-primary endpoints of death by

  3. Inhibition of the ATP Synthase Eliminates the Intrinsic Resistance of Staphylococcus aureus towards Polymyxins

    DEFF Research Database (Denmark)

    Vestergaard, Martin; Nøhr-Meldgaard, Katrine; Bojer, Martin Saxtorph

    2017-01-01

    , linezolid, daptomycin, and oxacillin were unchanged. ATP synthase activity is known to be inhibited by oligomycin A, and the presence of this compound increased polymyxin B-mediated killing of S. aureus Our results demonstrate that the ATP synthase contributes to intrinsic resistance of S. aureus towards...

  4. Femtosecond laser surface texturing of titanium as a method to reduce the adhesion of Staphylococcus aureus and biofilm formation

    Energy Technology Data Exchange (ETDEWEB)

    Cunha, Alexandre [Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais 1, 1049-001 Lisboa (Portugal); Bordeaux University, Institute of Chemistry & Biology of Membranes & Nanoobjects (CBMN UMR 5248, CNRS), European Institute of Chemistry and Biology, 2 Rue Robert Escarpit, 33607 Pessac (France); Elie, Anne-Marie [Bordeaux University, CBMN UMR 5248, CNRS, Bordeaux Science Agro, 1 Rue du G. de Gaulle, 33170 Gradignan (France); Plawinski, Laurent [Bordeaux University, Institute of Chemistry & Biology of Membranes & Nanoobjects (CBMN UMR 5248, CNRS), European Institute of Chemistry and Biology, 2 Rue Robert Escarpit, 33607 Pessac (France); Serro, Ana Paula [Instituto Superior Técnico, Universidade de Lisboa, CQE-Centro de Química Estrutural, Av. Rovisco Pais 1, 1049-001 Lisbon (Portugal); Botelho do Rego, Ana Maria [Instituto Superior Técnico, Universidade de Lisboa, CQFM-Centro de Química-Física Molecular and Institute of Nanoscience and Nanotechnology - IN, Av. Rovisco Pais 1, 1049-001 Lisbon (Portugal); Almeida, Amélia [Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais 1, 1049-001 Lisboa (Portugal); Urdaci, Maria C. [Bordeaux University, CBMN UMR 5248, CNRS, Bordeaux Science Agro, 1 Rue du G. de Gaulle, 33170 Gradignan (France); Durrieu, Marie-Christine [Bordeaux University, Institute of Chemistry & Biology of Membranes & Nanoobjects (CBMN UMR 5248, CNRS), European Institute of Chemistry and Biology, 2 Rue Robert Escarpit, 33607 Pessac (France); Vilar, Rui, E-mail: rui.vilar@tecnico.ulisboa.pt [Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais 1, 1049-001 Lisboa (Portugal)

    2016-01-01

    Graphical abstract: - Highlights: • The short-term adhesion of Staphylococcus aureus onto femtosecond laser textured surfaces of titanium was investigated. • The laser textured surfaces consist of laser-induced periodic surface structures (LIPSS) and nanopillars. • The laser treatment enhances the hydrophilicity and the surface free energy of the material. • The laser treatment reduces significantly the adhesion of S. aureus and biofilm formation. • Femtosecond laser surface texturing of titanium is a simple and promising method for endowing dental and orthopedic implants with antibacterial properties. - Abstract: The aim of the present work was to investigate the possibility of using femtosecond laser surface texturing as a method to reduce the colonization of Grade 2 Titanium alloy surfaces by Staphylococcus aureus and the subsequent formation of biofilm. The laser treatments were carried out with a Yb:KYW chirped-pulse-regenerative amplification laser system with a central wavelength of 1030 nm and a pulse duration of 500 fs. Two types of surface textures, consisting of laser-induced periodic surface structures (LIPSS) and nanopillars, were produced. The topography, chemical composition and phase constitution of these surfaces were investigated by atomic force microscopy, scanning electron microscopy, X-ray photoelectron spectroscopy, micro-Raman spectroscopy, and X-ray diffraction. Surface wettability was assessed by the sessile drop method using water and diiodomethane as testing liquids. The response of S. aureus put into contact with the laser treated surfaces in controlled conditions was investigated by epifluorescence microscopy and scanning electron microscopy 48 h after cell seeding. The results achieved show that the laser treatment reduces significantly the bacterial adhesion to the surface as well as biofilm formation as compared to a reference polished surfaces and suggest that femtosecond laser texturing is a simple and promising method

  5. 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.

  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. Viable adhered Staphylococcus aureus highly reduced on novel antimicrobial sutures using chlorhexidine and octenidine to avoid surgical site infection (SSI)

    Science.gov (United States)

    Schneider, Jochen; Harrasser, Norbert; Tübel, Jutta; Mühlhofer, Heinrich; Pförringer, Dominik; von Deimling, Constantin; Foehr, Peter; Kiefel, Barbara; Krämer, Christina; Stemberger, Axel; Schieker, Matthias

    2018-01-01

    coated sutures with higher roughness for palmitate coatings and sustaining integrity of coated sutures. Adherent S. aureus were found via SEM on all types of investigated sutures. The novel antimicrobial sutures showed significantly less viable adhered S. aureus bacteria (up to 6.1 log) compared to Vicryl® Plus (0.5 log). Within 11 μg/cm drug-containing sutures, octenidine-palmitate (OL11) showed the highest number of viable adhered S. aureus (0.5 log), similar to Vicryl® Plus. Chlorhexidine-laurate (CL11) showed the lowest number of S. aureus on sutures (1.7 log), a 1.2 log greater reduction. In addition, planktonic S. aureus in suspensions were highly inhibited by CL11 (0.9 log) represents a 0.6 log greater reduction compared to Vicryl® Plus (0.3 log). Conclusions Novel antimicrobial sutures can potentially limit surgical site infections caused by multiple pathogenic bacterial species. Therefore, a potential inhibition of multispecies biofilm formation is assumed. In detail tested with S. aureus, the chlorhexidine-laurate coating (CL11) best meets the medical requirements for a fast bacterial eradication. This suture coating shows the lowest survival rate of adhering as well as planktonic bacteria, a high drug release during the first–clinically most relevant– 48 hours, as well as biocompatibility. Thus, CL11 coatings should be recommended for prophylactic antimicrobial sutures as an optimal surgical supplement to reduce wound infections. However, animal and clinical investigations are important to prove safety and efficacy for future applications. PMID:29315313

  8. 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.

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

    Science.gov (United States)

    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.

  10. Clonal spread of Staphylococcus aureus with reduced susceptibility to oxacillin in a dermatological hospital unit

    DEFF Research Database (Denmark)

    Thomsen, Marianne Kragh; Rasmussen, Mads; Fuursted, Kurt

    2006-01-01

    transmission routes in order to intervene and prevent further spread. Clonality of the isolates was confirmed by pulsed field gel electrophoresis. Several breaches in infection control procedures were revealed suggesting both direct and indirect transmission between patients. Defective skin barriers, high...... carrier rates of S. aureus in dermatological patients and high consumption rates of dicloxacillin in the department might facilitate transmission. Following improvement of the general infection control measures, and after reassessment of the antibiotic policy in the department, the outbreak has......In November 2000, we became aware of isolates of Staphylococcus aureus with borderline resistance to oxacillin (BORSA) from patients in the Department of Dermatology, Aarhus University Hospital. The objective was to describe the isolates phenotypically and genotypically and to assess possible...

  11. Pharmacokinetics of linezolid during continuous hemodiafiltration: A case report.

    Science.gov (United States)

    Yamashina, Takuya; Tsuruyama, Moeko; Odawara, Miki; Tsuruta, Minako; Miyata, Hirochika; Kozono, Aki; Tsuji, Yasuhiro; Miyoshi, Takanori; Kawamata, Yosei; Hiraki, Yoichi

    2017-10-01

    The pharmacokinetics of linezolid clearance (CL LZD ) during continuous hemodiafiltration (CHDF) has not been comprehensively analyzed. Here, we examined CL LZD by CHDF in a patient with septic shock and disseminated intravascular coagulation due to methicillin-resistant Staphylococcus aureus. The extraction ratio of LZD by CHDF was 22.6%, and the protein-binding rate was 17.9% ± 7.7%. In addition, it was determined that the calculated total body clearance of LZD was 30.2 mL/min, plasma elimination half-life was 8.66 h, and the CL LZD by the dialyzer used for CHDF was 23.0 mL/min. From the obtained pharmacokinetics, the CL LZD of patients continuing CHDF was estimated to be approximately half of the reported CL LZD for healthy subjects. In addition, the LZD concentration of the sepsis patient who underwent CHDF remained higher than the minimum inhibitory concentration and was similar to the LZD concentrations reported in normal renal function patients. Although further studies are warranted, when LZD is administered to patients treated with CHDF, the present findings suggest that dose regulation is not required. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  12. 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.

  13. Label-free, electrochemical detection of methicillin-resistant staphylococcus aureus DNA with reduced graphene oxide-modified electrodes

    KAUST Repository

    Wang, Zhijuan

    2011-05-01

    Reduced graphene oxide (rGO)-modified glassy carbon electrode is used to detect the methicillin-resistant Staphylococcus aureus (MRSA) DNA by using electrochemical impedance spectroscopy. Our experiments confirm that ssDNA, before and after hybridization with target DNA, are successfully anchored on the rGO surface. After the probe DNA, pre-adsorbed on rGO electrode, hybridizes with target DNA, the measured impedance increases dramatically. It provides a new method to detect DNA with high sensitivity (10-13M, i.e., 100 fM) and selectivity. © 2011 Elsevier B.V.

  14. Electronic hand hygiene monitoring as a tool for reducing health care-associated methicillin-resistant Staphylococcus aureus infection.

    Science.gov (United States)

    Kelly, J William; Blackhurst, Dawn; McAtee, Wendy; Steed, Connie

    2016-08-01

    Electronic monitoring of hand hygiene compliance using the World Health Organization's My 5 Moments for Hand Hygiene is a new innovation that has not yet been shown to reduce hospital infections. We analyzed existing data from 23 inpatient units over a 33-month period and found a significant correlation between unit-specific improvements in electronic monitoring compliance and reductions in methicillin-resistant Staphylococcus aureus infection rates (r = -0.37, P < .001). Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  15. 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.

  16. Femtosecond laser surface texturing of titanium as a method to reduce the adhesion of Staphylococcus aureus and biofilm formation

    Science.gov (United States)

    Cunha, Alexandre; Elie, Anne-Marie; Plawinski, Laurent; Serro, Ana Paula; Botelho do Rego, Ana Maria; Almeida, Amélia; Urdaci, Maria C.; Durrieu, Marie-Christine; Vilar, Rui

    2016-01-01

    The aim of the present work was to investigate the possibility of using femtosecond laser surface texturing as a method to reduce the colonization of Grade 2 Titanium alloy surfaces by Staphylococcus aureus and the subsequent formation of biofilm. The laser treatments were carried out with a Yb:KYW chirped-pulse-regenerative amplification laser system with a central wavelength of 1030 nm and a pulse duration of 500 fs. Two types of surface textures, consisting of laser-induced periodic surface structures (LIPSS) and nanopillars, were produced. The topography, chemical composition and phase constitution of these surfaces were investigated by atomic force microscopy, scanning electron microscopy, X-ray photoelectron spectroscopy, micro-Raman spectroscopy, and X-ray diffraction. Surface wettability was assessed by the sessile drop method using water and diiodomethane as testing liquids. The response of S. aureus put into contact with the laser treated surfaces in controlled conditions was investigated by epifluorescence microscopy and scanning electron microscopy 48 h after cell seeding. The results achieved show that the laser treatment reduces significantly the bacterial adhesion to the surface as well as biofilm formation as compared to a reference polished surfaces and suggest that femtosecond laser texturing is a simple and promising method for endowing dental and orthopedic titanium implants with antibacterial properties, reducing the risk of implant-associated infections without requiring immobilized antibacterial substances, nanoparticles or coatings.

  17. Linezolid som behandling af infektiøs endokarditis

    DEFF Research Database (Denmark)

    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...

  18. 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

  19. Enterotoxigenicity and Antimicrobial Resistance of Staphylococcus aureus Isolated from Retail Food in China

    Science.gov (United States)

    Wang, Wei; Baloch, Zulqarnain; Jiang, Tao; Zhang, Cunshan; Peng, Zixin; Li, Fengqin; Fanning, Séamus; Ma, Aiguo; Xu, Jin

    2017-01-01

    Staphylococcus aureus is one of the most common causes of zoonotic agent in the world, which are attributable to the contamination of food with enterotoxins. In this study, a total of 1,150 S. aureus isolates were cultured from 27,000 retail foods items from 203 cities of 24 provinces in China in 2015 and were test for antimicrobial susceptibility. Additionally, the role of the genes responsible for the staphylococcal enterotoxins (SEA to SEE), methicillin resistance (mecA) and the toxigenic capabilities were also assessed. The results showed that 4.3% retail foods were contaminated with S. aureus, and 7.9% retail foods isolates were mecA positive. Some 97.6% of S. aureus isolates were resistant to at least one antimicrobial compound, and 57.5% of these were multi drug resistant (MDR). Resistance to penicillin (83.7%, 963/1,150), was common, followed by linezolid (67.7%, 778/1,150) and erythromycin (52.1%, 599/1,150). The isolates cultured from raw meats showed high levels of resistant to tetracycline (42.8%), ciprofloxacin (17.4%), and chloramphenicol (12.0%) and expressed a MDR phenotype (62.4%). A total of 29.7% S. aureus isolates harbored the classical SEs genes (sea, seb, sec, and sed). The sea and seb genes were the most frequent SEs genes detected. Of note, 22% of the SEs genes positive S. aureus harbored two or three SEs genes, and 16 isolates were confirmed with the capacity to simultaneously produce two or three enterotoxin types. Moreover, nearly 50% of the MRSA isolates were positive for at least one SE gene in this study. Therefore, it is important to monitor the antimicrobial susceptibility and enterotoxigenicity of MDR S. aureus and MRSA in the food chain and to use these data to develop food safety measures, designed to reduce the contamination and transmission of this bacterium. PMID:29209290

  20. 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.

  1. Reducing Staphylococcus aureus growth on Ti alloy nanostructured surfaces through the addition of Sn.

    Science.gov (United States)

    Verissimo, Nathália C; Geilich, Benjamin M; Oliveira, Haroldo G; Caram, Rubens; Webster, Thomas J

    2015-12-01

    β-type Ti alloys containing Nb are exciting materials for numerous orthopedic and dental applications due to their exceptional mechanical properties. To improve their cytocompatibility properties (such as increasing bone growth and decreasing infection), the surfaces of such materials can be optimized by adding elements and/or nanotexturing through anodization. Because of the increasing prevalence of orthopedic implant infections, the objective of this in vitro study was to add Sn and create unique nanoscale surface features on β-type Ti alloys. Nanotubes and nanofeatures on Ti-35Nb and Ti-35Nb-4Sn alloys were created by anodization in a HF-based electrolyte and then heat treated in a furnace to promote amorphous structures and phases such as anatase, a mixture of anatase-rutile, and rutile. Samples were characterized by SEM, which indicated different morphologies dependent on the oxide content and method of modification. XPS experiments identified the oxide content which resulted in a phase transformation in the oxide layer formed onto Ti-35Nb and Ti-35Nb-4Sn alloys. Most importantly, regardless of the resulting nanostructures (nanotubes or nanofeatures) and crystalline phase, this study showed for the first time that adding Sn to β-type Ti alloys strongly decreased the adhesion of Staphylococcus aureus (S. aureus; a bacteria which commonly infects orthopedic implants leading to their failure). Thus, this study demonstrated that β-type Ti alloys with Nb and Sn have great promise to improve numerous orthopedic applications where infection may be a concern. © 2015 Wiley Periodicals, Inc.

  2. Insertional inactivation of Eap in Staphylococcus aureus strain Newman confers reduced staphylococcal binding to fibroblasts.

    Science.gov (United States)

    Hussain, Muzaffar; Haggar, Axana; Heilmann, Christine; Peters, Georg; Flock, Jan-Ingmar; Herrmann, Mathias

    2002-06-01

    To initiate invasive infection, Staphylococcus aureus must adhere to host substrates, such as the extracellular matrix or eukaryotic cells, by virtue of different surface proteins (adhesins). Recently, we identified a 60-kDa cell-secreted extracellular adherence protein (Eap) of S. aureus strain Newman with broad-spectrum binding characteristics (M. Palma, A. Haggar, and J. I. Flock, J. Bacteriol. 181:2840-2845, 1999), and we have molecularly confirmed Eap to be an analogue of the previously identified major histocompatibility complex class II analog protein (Map) (M. Hussain, K. Becker, C. von Eiff, G. Peter, and M. Herrmann, Clin. Diagn. Lab. Immunol. 8:1281-1286, 2001). Previous analyses of the Eap/Map function performed with purified protein did not allow dissection of its precise role in the complex situation of the staphylococcal whole cell presenting several secreted and wall-bound adhesins. Therefore, the role of Eap was investigated by constructing a stable eap::ermB deletion in strain Newman and by complementation of the mutant. Patterns of extracted cell surface proteins analyzed both by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by Western ligand assays with various adhesive matrix molecules clearly confirmed the absence of Eap in the mutant. However, binding and adhesion tests using whole staphylococcal cells demonstrated that both the parent and mutant strains bound equally well to fibronectin- and fibrinogen-coated surfaces, possibly due to their recognition by other staphylococcal adhesins. Furthermore, Eap mediated staphylococcal agglutination of both wild-type and mutant cells. In contrast, the mutant adhered to a significantly lesser extent to cultured fibroblasts (P Eap, whereas preimmune serum was not active. In conclusion, Eap may contribute to pathogenicity by promoting adhesion of whole staphylococcal cells to complex eukaryotic substrates.

  3. 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.

  4. 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.

  5. A severe infective endocarditis successfully treated with linezolid

    Directory of Open Access Journals (Sweden)

    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.

  6. Mechanisms of antibiotic resistance in Staphylococcus aureus.

    Science.gov (United States)

    Pantosti, Annalisa; Sanchini, Andrea; Monaco, Monica

    2007-06-01

    Staphylococcus aureus can exemplify better than any other human pathogen the adaptive evolution of bacteria in the antibiotic era, as it has demonstrated a unique ability to quickly respond to each new antibiotic with the development of a resistance mechanism, starting with penicillin and methicillin, until the most recent, linezolid and daptomycin. Resistance mechanisms include enzymatic inactivation of the antibiotic (penicillinase and aminoglycoside-modification enzymes), alteration of the target with decreased affinity for the antibiotic (notable examples being penicillin-binding protein 2a of methicillin-resistant S. aureus and D-Ala-D-Lac of peptidoglycan precursors of vancomycin-resistant strains), trapping of the antibiotic (for vancomycin and possibly daptomycin) and efflux pumps (fluoroquinolones and tetracycline). Complex genetic arrays (staphylococcal chromosomal cassette mec elements or the vanA operon) have been acquired by S. aureus through horizontal gene transfer, while resistance to other antibiotics, including some of the most recent ones (e.g., fluoroquinolones, linezolid and daptomycin) have developed through spontaneous mutations and positive selection. Detection of the resistance mechanisms and their genetic basis is an important support to antibiotic susceptibility surveillance in S. aureus.

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

    Science.gov (United States)

    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.

  8. Decolonization of Staphylococcus aureus in patients with atopic dermatitis: a reason for increasing resistance to antibiotics?

    Directory of Open Access Journals (Sweden)

    Izabela Błażewicz

    2017-12-01

    Full Text Available Introduction : Exacerbation of atopic dermatitis can be associated with bacterial infection. The skin of patients is colonized with Staphylococcus aureus in 90% of cases. An attempt has been made to demonstrate that eradication significantly reduces the severity of the disease. Studies indicate the efficacy of topical antibiotics, topical corticosteroids and calcineurin inhibitors. Due to increasing resistance to drugs and the defective antimicrobial peptide profile, decolonization is virtually impossible. Aim : To determine the prevalence of S. aureus colonization among patients with atopic dermatitis and to assess antimicrobial susceptibility of isolated strains to antibiotics, especially fusidic acid and mupirocin. Material and methods : One hundred patients with atopic dermatitis and 50 healthy subjects were microbiologically assessed for the carriage of S. aureus . Antimicrobial susceptibility tests were performed using the broth-microdilution method for antibiotics: ampicillin, ciprofloxacin, daptomycin, erythromycin, fusidic acid, linezolid, lincomycin, mupirocin, tetracycline and vancomycin. Results : Staphylococcus aureus strains were isolated from the majority of our patients, either from the skin (71% or the anterior nares (67%. In the present study, 10% of isolations represented methicillin-resistant S. aureus (MRSA. Antibiotics exhibited diverse activities against clinical isolates of S. aureus . Among those tested, the highest rates of resistance were shown for ampicillin – 58.5%, lincomycin – 37.5% and erythromycin – 31.0%. Enhanced resistance levels were expressed to mupirocin (17.5% and fusidic acid (15.5%. Conclusions : According to the increasing rate of resistance and quick recolonization after discontinuation of the treatment, chronic use of topical antibiotics is not recommended and should be limited to exacerbation of atopic dermatitis with clinical signs of bacterial infection.

  9. Antibacterial susceptibility patterns and cross-resistance of methicillin resistant and sensitive Staphyloccus aureus isolated from the hospitalized patients in Shiraz, Iran

    Directory of Open Access Journals (Sweden)

    Aziz Japoni

    2010-10-01

    Full Text Available Nosocomial infections caused by methicillin-resistant staphylococci (MRSA pose a serious problem in many countries. This study aimed to determine the antibacterial susceptibility patterns of methicillin sensitive and resistant Staphylococcus aureus isolates from the hospitalized patients. Totally 356 isolates of Staphylococcus aureus (S. aureus including 200, 137 and 19 corresponding to MSSA, MRSA, and intermediate MRSA strains, respectively were isolated. Antibacterial susceptibility patterns of the isolates to 14 antibiotics were examined using Kirby-Bauer method. MICs of 15 antibiotics to 156 MRSA isolates were determined by E test method. Cross-resistances of MRSA isolates (137+19 to the other tested antibiotics were also determined. S.aureus with high frequencies were isolated from the blood, sputum and deep wound samples. All of 200 MSSA isolates were sensitive to oxacillin, vancomycin, tecoplanin, rifampin, linezolid, quinupristin/dalfopristin, mupirocin and fusidic acid. A gradient of reduced susceptibility of MSSA to cephalexin, co-trimoxazole, ciprofloxacin, clindamycin, tetracycline, erythromycin and gentamicin were evident. MRSA isolates were sensitive to vancomycin, tecoplanin, linezolid, quinupristin/dalfopristin, mupirocin and fusidic acid, while reduced susceptibility of them to rifampin, co-trimoxazole, clindamycin, cephalexin, tetracycline, ciprofloxacin, erythromycin and gentamicin were observed. MRSA isolates exhibited a high range of cross-resistance to the eight tested antibiotics. Overall, co-trimoxazole, ciprofloxacin, clindamycin, tetracycline, erythromycin and gentamicin showed low activity against MSSA and MRSA isolates which may indicate they are not suitable to be used in clinical practices. To preserve the effectiveness of antibiotics, rational prescription and concomitant application of preventive measures against the spread of MRSA are recommended.

  10. 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.

  11. 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.

  12. 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.

  13. Silver-Containing Hydroxyapatite Coating Reduces Biofilm Formation by Methicillin-Resistant Staphylococcus aureus In Vitro and In Vivo

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    Masaya Ueno

    2016-01-01

    Full Text Available Biofilm-producing bacteria are the principal causes of infections associated with orthopaedic implants. We previously reported that silver-containing hydroxyapatite (Ag-HA coatings exhibit high antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA. In the present study, we evaluated the effects of Ag-HA coating of implant surfaces on biofilm formation. Titanium disks (14-mm diameter, 1-mm thickness, one surface of which was coated with HA or 0.5%–3.0% Ag-HA with a thermal spraying technique, were used. In vitro, the disks were inoculated with an MRSA suspension containing 4×105 CFU and incubated for 1-2 weeks. In vivo, MRSA-inoculated HA and 3% Ag-HA disks (8.8–10.0 × 108 CFU were implanted subcutaneously on the back of rats for 1–7 days. All disks were subsequently stained with a biofilm dye and observed under a fluorescence microscope, and biofilm coverage rates (BCRs were calculated. The BCRs on the Ag-HA coating were significantly lower than those on the HA coating at all time points in vitro (p<0.05. Similar results were observed in vivo (p<0.001 without argyria. Ag-HA coating reduced biofilm formation by MRSA in vitro and in vivo; therefore, Ag-HA coating might be effective for reducing implant-associated infections.

  14. 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

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    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.

  15. 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.

  16. Norlichexanthone Reduces Virulence Gene Expression and Biofilm Formation in Staphylococcus aureus

    DEFF Research Database (Denmark)

    Baldry, Mara; Nielsen, Anita; Bojer, Martin S.

    2016-01-01

    characterise the mode of action of norlichexanthone and its effect on biofilm formation. We find that norlichexanthone reduces expression of both hla and RNAIII also in strain USA300. Structurally, norlichexanthone resembles ω-hydroxyemodin that recently was shown to bind the agr two component response......-hydroxyemodin however, norlichexanthone reduces staphylococcal biofilm formation. Transcriptomic analysis revealed that genes regulated by the SaeRS two-component system are repressed by norlichexanthone when compared to untreated cells, an effect that was mitigated in strain Newman carrying a partially constitutive...... SaeRS system. Our data show that norlichexanthone treatment reduces expression of key virulence factors in CA-MRSA strain USA300 via AgrA binding and represses biofilm formation....

  17. Multiple paths towards reduced membrane potential and concomitant reduction in aminoglycoside susceptibility in staphylococcus aureus

    DEFF Research Database (Denmark)

    Vestergaard, Martin; Nøhr-Meldgaard, Katrine; Ingmer, Hanne

    2018-01-01

    susceptibility to gentamicin. 9 mutants were confirmed by E-test to display between 2 and 16-fold reduced susceptibility to this antibiotic. All of the identified genes were associated with the electron transport chain and energy metabolism. Four mutant strains (menD, hemB, aroC and SAUSA300_0355) conferred...

  18. Effectiveness of a Glycylcycline Antibiotic for Reducing the Pathogenicity of Superantigen-Producing Methicillin-Resistant Staphylococcus aureus in Burn Wounds.

    Science.gov (United States)

    Nosanov, Lauren B; Jo, Daniel Y; Randad, Pranay R; Moffatt, Lauren T; Carney, Bonnie C; Ortiz, Rachel T; Shupp, Jeffrey W

    2017-01-01

    Objective : Burn-injured patients are highly susceptible to infectious complications, which are often associated with increased morbidity and mortality. Rates of antibiotic resistance have increased, and resistant species such as methicillin-resistant Staphylococcus aureus provide additional challenges in the form of virulence factors. Proteins can disrupt local healing, leading to systemic immune disruption. To optimize outcomes, treatments that reduce pathogenicity must be identified. This study aims to compare a glycylcycline antibiotic-tigecycline-with clindamycin for effectiveness in treating superantigenic methicillin-resistant Staphylococcus aureus in burn wounds. Methods : Sprague-Dawley rats received paired 2 × 2-cm burn wounds, which were subsequently inoculated with known virulence factor-producing methicillin-resistant Staphylococcus aureus or media alone on postinjury day 1. Infected animals received twice-daily tigecycline (high or low dose), twice-daily clindamycin (high or low dose), or saline alone (positive controls). Daily sampling and imaging assessments were performed. Results : Bacterial counts and toxin levels were reduced significantly in antibiotic-treated groups relative to positive controls ( P study supports the use of tigecycline in the treatment of methicillin-resistant Staphylococcus aureus -infected burn wounds. While both protein synthesis inhibitors are effective, tigecycline appears to be superior in controlling toxin levels, enabling better wound healing.

  19. Molecular characterization and antimicrobial susceptibility of nasal Staphylococcus aureus isolates from a Chinese medical college campus.

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    Jimei Du

    Full Text Available Staphylococcus aureus colonization and infection occur more commonly among persons living or working in crowded conditions, but characterization of S. aureus colonization within medical communities in China is lacking. A total of 144 (15.4%, 144/935 S. aureus isolates, including 28 (3.0%, 28/935 MRSA isolates, were recovered from the nares of 935 healthy human volunteers residing on a Chinese medical college campus. All S. aureus isolates were susceptible to vancomycin, quinupristin/dalfopristin and linezolid but the majority were resistant to penicillin (96.5%, ampicillin/sulbactam (83.3% and trimethoprim/sulfamethoxazole (93.1%. 82%, (23/28 of the MRSA isolates and 66% (77/116 of the MSSA isolates were resistant to multiple antibiotics, and 3 MRSA isolates were resistant to mupirocin--an agent commonly used for nasal decolonization. 16 different sequence types (STs, as well as SCCmec genes II, III, IVd, and V, were represented among MRSA isolates. We also identified, for the first time, two novel STs (ST1778 and ST1779 and 5 novel spa types for MRSA. MRSA isolates were distributed in different sporadic clones, and ST59-MRSA-VId- t437 was found within 3 MRSA isolates. Moreover, one isolate with multidrug resistance belonging to ST398-MRSA-V- t571 associated with animal infections was identified, and 3 isolates distributed in three different clones harbored PVL genes. Collectively, these data indicate a high prevalence of nasal MRSA carriage and molecular heterogeneity of S. aureus isolates among persons residing on a Chinese medical college campus. Identification of epidemic MRSA clones associated with community infection supports the need for more effective infection control measures to reduce nasal carriage and prevent dissemination of MRSA to hospitalized patients and health care workers in this community.

  20. [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.

  1. 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...

  2. Occurrence of vancomycin-resistant Staphylococcus aureus in the oral cavity of patients with dental caries.

    Science.gov (United States)

    Vellappally, Sajith; Divakar, Darshan Devang; Al Kheraif, Abdulaziz Abdullah; Ramakrishnaiah, Ravikumar; Alqahtani, Amer; Dalati, M H N; Anil, Sukumaran; Khan, Aftab Ahmed; Harikrishna Varma, P R

    2017-09-01

    Oral streptococci are the major group of microbes isolated from oral microflora. They represent frequent pathogens of infective endocarditis (IE), and it is assumed that in most of the cases oral streptococci are acquired via mucosa layer of oral cavity. Staphylococcus aureus is also frequently isolated from IE as it accounts for 20%-30% of all cases. Vancomycin has been the most reliable therapeutic agent against infections caused by methicillin-resistant S. aureus (MRSA). The main objective of this study was to examine the occurrence of S. aureus species in dental caries specimens. Antimicrobial susceptibility testing of S. aureus to four antibiotics namely vancomycin, linezolid, teicoplanin, and daptomycin was performed. Detection of vancomycin resistance was conducted using polymerase chain reaction. Among the tested 150 strains, 98 were MRSA and of that 54 were vancomycin sensitive and 27 were resistant. All 98 MRSA strains were positive for mecA and 36 yielded pvl, whereas 13 carried vanA and only 2 were positive for vanB. Majority of the isolates showed sensitivity toward daptomycin and linezolid. Strains of S. aureus exhibiting decreased susceptibility to different antibiotics like vancomycin, daptomycin, and linezolid severely compromise the therapeutic alternatives and require a considerable amount of time, public awareness, and integrative health-care strategies to prevent the emergence of resistance to these compounds.

  3. 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.

  4. 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.

  5. Costo-efectividad de linezolid comparado con vancomicina en el manejo de la neumonía asociada a ventilación mecánica en Colombia

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    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.

  6. 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.

  7. Subinhibitory concentrations of thymol reduce enterotoxins A and B and alpha-hemolysin production in Staphylococcus aureus isolates.

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    Jiazhang Qiu

    Full Text Available BACKGROUND: Targeting bacterial virulence factors is now gaining interest as an alternative strategy to develop new types of anti-infective agents. It has been shown that thymol, when used at low concentrations, can inhibit the TSST-1 secretion in Staphylococcus aureus. However, there are no data on the effect of thymol on the production of other exotoxins (e.g., alpha-hemolysin and enterotoxins by S. aureus. METHODOLOGY/PRINCIPAL FINDINGS: Secretion of alpha-hemolysin, SEA and SEB in both methicillin-sensitive and methicillin-resistant S. aureus isolates cultured with graded subinhibitory concentrations of thymol was detected by immunoblot analysis. Hemolysin and tumor necrosis factor (TNF release assays were performed to elucidate the biological relevance of changes in alpha-hemolysin, SEA and SEB secretion induced by thymol. In addition, the influence of thymol on the transcription of hla, sea, and seb (the genes encoding alpha-hemolysin, SEA and SEB, respectively was analyzed by quantitative RT-PCR. Thymol inhibited transcription of hla, sea and seb in S. aureus, resulting in a reduction of alpha-hemolysin, SEA and SEB secretion and, thus, a reduction in hemolytic and TNF-inducing activities. CONCLUSIONS/SIGNIFICANCE: Subinhibitory concentrations of thymol decreased the production of alpha-hemolysin, SEA and SEB in both MSSA and MRSA in a dose-dependent manner. These data suggest that thymol may be useful for the treatment of S. aureus infections when used in combination with beta-lactams and glycopeptide antibiotics, which induce expression of alpha-hemolysin and enterotoxins at subinhibitory concentrations. Furthermore, the structure of thymol may potentially be used as a basic structure for development of drugs aimed against these bacterial virulence factors.

  8. 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

  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. Genome-wide identification of antimicrobial intrinsic resistance determinants in Staphylococcus aureus

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    Martin Vestergaard

    2016-12-01

    Full Text Available The emergence of antimicrobial resistance severely threatens our ability to treat bacterial infections. While acquired resistance has received considerable attention, relatively little is known of intrinsic resistance that allows bacteria to naturally withstand antimicrobials. Gene products that confer intrinsic resistance to antimicrobial agents may be explored for alternative antimicrobial therapies, by potentiating the efficacy of existing antimicrobials. In this study, we identified the intrinsic resistome to a broad spectrum of antimicrobials in the human pathogen, Staphylococcus aureus. We screened the Nebraska Transposon Mutant Library of 1920 single-gene inactivations in S. aureus strain JE2, for increased susceptibility to the anti-staphylococcal antimicrobials (ciprofloxacin, oxacillin, linezolid, fosfomycin, daptomycin, mupirocin, vancomycin and gentamicin. 68 mutants were confirmed by E-test to display at least two-fold increased susceptibility to one or more antimicrobial agents. The majority of the identified genes have not previously been associated with antimicrobial susceptibility in S. aureus. For example, inactivation of genes encoding for subunits of the ATP synthase, atpA, atpB, atpG and atpH, reduced the minimum inhibitory concentration (MIC of gentamicin 16-fold. To elucidate the potential of the screen, we examined treatment efficacy in the Galleria mellonella infection model. Gentamicin efficacy was significantly improved, when treating larvae infected with the atpA mutant compared to wild type cells with gentamicin at a clinically relevant concentration. Our results demonstrate that many gene products contribute to the intrinsic antimicrobial resistance of S. aureus. Knowledge of these intrinsic resistance determinants provides alternative targets for compounds that may potentiate the efficacy of existing antimicrobial agents against this important pathogen.

  11. Antibiotic Resistance Pattern of Staphylococcus aureus Strains Isolated from Personnel of Jahrom Hospitals in 2012

    Directory of Open Access Journals (Sweden)

    S Saadat

    2014-01-01

    Undo edits Methods: In this cross - sectional study, 397 of the anterior nasal samples of medical personnel and hospital services were collected by swab. The identification of S.aureus was determined by biochemical tests and microbiology, and the antibiotic resistances of isolates were determined by disk diffusion method for 13 antibiotics. In this method, the inhibition zone for methicillin-resistant strains was ≤ 10 mm the minimum inhibitory concentrations (MIC against antibiotic vancomycin, ticoplanin, linezolid and synercid were determined by E-test method. Results: In the present study, 11.3% of personals carried S. aureus in the nose. Among them, 90% were health care workers and 10% were health service workers. The most sensitivity was observed resistance to Ciprofloxacin, rifampin, linezolid and synercid (91.1%, but the lowest sensitivity was to penicillin (4.7%. of 9 MRSA strains, 1 strain was resistance to vancomycin and 2 strains were resistant to teicoplanin and linezolid. Conclusion: Because of S. aureus strains isolated from hospital staffs were resistant to most common antibiotics, identification and treatment of health care and health service workers can prevent nosocomial infections. Key words: Staphylococcu aureus carriers, hospital personnel, antibiotic resistance.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. [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.

  20. 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

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

    Science.gov (United States)

    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.

  2. 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.

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

    Science.gov (United States)

    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.

  4. 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

  5. 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...

  6. 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...

  7. 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.

  8. Gloves, gowns and masks for reducing the transmission of meticillin-resistant Staphylococcus aureus (MRSA) in the hospital setting.

    Science.gov (United States)

    López-Alcalde, Jesús; Mateos-Mazón, Marta; Guevara, Marcela; Conterno, Lucieni O; Solà, Ivan; Cabir Nunes, Sheila; Bonfill Cosp, Xavier

    2015-07-16

    Meticillin-resistant Staphylococcus aureus (MRSA; also known as methicillin-resistant S aureus) is a common hospital-acquired pathogen that increases morbidity, mortality, and healthcare costs. Its control continues to be an unresolved issue in many hospitals worldwide. The evidence base for the effects of the use of gloves, gowns or masks as control measures for MRSA is unclear. To assess the effectiveness of wearing gloves, a gown or a mask when contact is anticipated with a hospitalised patient colonised or infected with MRSA, or with the patient's immediate environment. We searched the Specialised Registers of three Cochrane Groups (Wounds Group on 5 June 2015; Effective Practice and Organisation of Care (EPOC) Group on 9 July 2013; and Infectious Diseases Group on 5 January 2009); CENTRAL (The Cochrane Library 2015, Issue 6); DARE, HTA, NHS EED, and the Methodology Register (The Cochrane Library 2015, Issue 6); MEDLINE and MEDLINE In-Process & Other Non-Indexed Citations (1946 to June week 1 2015); EMBASE (1974 to 4 June 2015); Web of Science (WOS) Core Collection (from inception to 7 June 2015); CINAHL (1982 to 5 June 2015); British Nursing Index (1985 to 6 July 2010); and ProQuest Dissertations & Theses Database (1639 to 11 June 2015). We also searched three trials registers (on 6 June 2015), references list of articles, and conference proceedings. We finally contacted relevant individuals for additional studies. Studies assessing the effects on MRSA transmission of the use of gloves, gowns or masks by any person in the hospital setting when contact is anticipated with a hospitalised patient colonised or infected with MRSA, or with the patient's immediate environment. We did not assess adverse effects or economic issues associated with these interventions.We considered any comparator to be eligible. With regard to study design, only randomised controlled trials (clustered or not) and the following non-randomised experimental studies were eligible: quasi

  9. Implementation of an industrial systems-engineering approach to reduce the incidence of methicillin-resistant Staphylococcus aureus infection.

    Science.gov (United States)

    Muder, Robert R; Cunningham, Candace; McCray, Ellesha; Squier, Cheryl; Perreiah, Peter; Jain, Rajiv; Sinkowitz-Cochran, Ronda L; Jernigan, John A

    2008-08-01

    To measure the effectiveness of an industrial systems-engineering approach to a methicillin-resistant Staphylococcus aureus (MRSA) prevention program. Before-after intervention study. An intensive care unit (ICU) and a surgical unit that was not an ICU in the Pittsburgh Veterans Administration hospital. All patients admitted to the study units. We implemented an MRSA infection control program that consisted of the following 4 elements: (1) the use of standard precautions for all patient contact, with emphasis on hand hygiene; (2) the use of contact precautions for interactions with patients known to be infected or colonized with MRSA; (3) the use of active surveillance cultures to identify patients who were asymptomatically colonized with MRSA; and (4) use of an industrial systems-engineering approach, the Toyota Production System, to facilitate consistent and reliable adherence to the infection control program. The rate of healthcare-associated MRSA infection in the surgical unit decreased from 1.56 infections per 1,000 patient-days in the 2 years before the intervention to 0.63 infections per 1,000 patient-days in the 4 years after the intervention (a 60% reduction; P = .003). The rate of healthcare-associated MRSA infection in the ICU decreased from 5.45 infections per 1,000 patient-days in the 2 years before to the intervention to 1.35 infections per 1,000 patient-days in the 3 years after the intervention (a 75% reduction; P = .001). The combined estimate for reduction in the incidence of infection after the intervention in the 2 units was 68% (95% confidence interval, 50%-79%; P systems-engineering approach can be adapted to facilitate consistent and reliable adherence to MRSA infection prevention practices in healthcare facilities.

  10. 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

  11. 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.

  12. 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.

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

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    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

  14. 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

  15. Development, Optimization, and Validation of a Microplate Bioassay for Relative Potency Determination of Linezolid Using a Design Space Concept, and its Measurement Uncertainty.

    Science.gov (United States)

    Saviano, Alessandro Morais; Francisco, Fabiane Lacerda; Ostronoff, Celina Silva; Lourenço, Felipe Rebello

    2015-01-01

    The aim of this study was to develop, optimize, and validate a microplate bioassay for relative potency determination of linezolid in pharmaceutical samples using quality-by-design and design space approaches. In addition, a procedure is described for estimating relative potency uncertainty based on microbiological response variability. The influence of culture media composition was studied using a factorial design and a central composite design was adopted to study the influence of inoculum proportion and triphenyltetrazolium chloride in microbial growth. The microplate bioassay was optimized regarding the responses of low, medium, and high doses of linezolid, negative and positive controls, and the slope, intercept, and correlation coefficient of dose-response curves. According to optimization results, design space ranges were established using: (a) low (1.0 μg/mL), medium (2.0 μg/mL), and high (4.0 μg/mL) doses of pharmaceutical samples and linezolid chemical reference substance; (b) Staphylococcus aureus ATCC 653 in an inoculum proportion of 10%; (c) antibiotic No. 3 culture medium pH 7.0±0.1; (d) 6 h incubation at 37.0±0.1ºC; and (e) addition of 50 μL of 0.5% (w/v) triphenyltetrazolium chloride solution. The microplate bioassay was linear (r2=0.992), specific, precise (repeatability RSD=2.3% and intermediate precision RSD=4.3%), accurate (mean recovery=101.4%), and robust. The overall measurement uncertainty was reasonable considering the increased variability inherent in microbiological response. Final uncertainty was comparable with those obtained with other microbiological assays, as well as chemical methods.

  16. 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

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

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    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

  18. The Role of Antibiotics in Modulating Virulence in Staphylococcus aureus.

    Science.gov (United States)

    Hodille, Elisabeth; Rose, Warren; Diep, Binh An; Goutelle, Sylvain; Lina, Gerard; Dumitrescu, Oana

    2017-10-01

    Staphylococcus aureus is often involved in severe infections, in which the effects of bacterial virulence factors have great importance. Antistaphylococcal regimens should take into account the different effects of antibacterial agents on the expression of virulence factors and on the host's immune response. A PubMed literature search was performed to select relevant articles on the effects of antibiotics on staphylococcal toxin production and on the host immune response. Information was sorted according to the methods used for data acquisition (bacterial strains, growth models, and antibiotic concentrations) and the assays used for readout generation. The reported mechanisms underlying S. aureus virulence modulation by antibiotics were reviewed. The relevance of in vitro observations is discussed in relation to animal model data and to clinical evidence extracted from case reports and recommendations on the management of toxin-related staphylococcal diseases. Most in vitro data point to a decreased level of virulence expression upon treatment with ribosomally active antibiotics (linezolid and clindamycin), while cell wall-active antibiotics (beta-lactams) mainly increase exotoxin production. In vivo studies confirmed the suppressive effect of clindamycin and linezolid on virulence expression, supporting their utilization as a valuable management strategy to improve patient outcomes in cases of toxin-associated staphylococcal disease. Copyright © 2017 American Society for Microbiology.

  19. Staphylococcus aureus: methicillin-susceptible S. aureus to methicillin-resistant S. aureus and vancomycin-resistant S. aureus.

    Science.gov (United States)

    Rehm, Susan J; Tice, Alan

    2010-09-15

    The evolution of methicillin-resistant and vancomycin-resistant Staphylococcus aureus has demanded serious review of antimicrobial use and development of new agents and revised approaches to prevent and overcome drug resistance. Depending on local conditions and patient risk factors, empirical therapy of suspected S. aureus infection may require coverage of drug-resistant organisms with newer agents and novel antibiotic combinations. The question of treatment with inappropriate antibiotics raises grave concerns with regard to methicillin-resistant S. aureus selection, overgrowth, and increased virulence. Several strategies to reduce the nosocomial burden of resistance are suggested, including shortened hospital stays and outpatient parenteral antimicrobial therapy of the most serious infections.

  20. Novel bacterial metabolite merochlorin A demonstrates in vitro activity against multi-drug resistant methicillin-resistant Staphylococcus aureus.

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    George Sakoulas

    Full Text Available We evaluated the in vitro activity of a merochlorin A, a novel compound with a unique carbon skeleton, against a spectrum of clinically relevant bacterial pathogens and against previously characterized clinical and laboratory Staphylococcus aureus isolates with resistance to numerous antibiotics.Merochlorin A was isolated and purified from a marine-derived actinomycete strain CNH189. Susceptibility testing for merochlorin A was performed against previously characterized human pathogens using broth microdilution and agar dilution methods. Cytotoxicity was assayed in tissue culture assays at 24 and 72 hours against human HeLa and mouse sarcoma L929 cell lines.The structure of as new antibiotic, merochlorin A, was assigned by comprehensive spectroscopic analysis. Merochlorin A demonstrated in vitro activity against Gram-positive bacteria, including Clostridium dificile, but not against Gram negative bacteria. In S. aureus, susceptibility was not affected by ribosomal mutations conferring linezolid resistance, mutations in dlt or mprF conferring resistance to daptomycin, accessory gene regulator knockout mutations, or the development of the vancomycin-intermediate resistant phenotype. Merochlorin A demonstrated rapid bactericidal activity against MRSA. Activity was lost in the presence of 20% serum.The unique meroterpenoid, merochlorin A demonstrated excellent in vitro activity against S. aureus and C. dificile and did not show cross-resistance to contemporary antibiotics against Gram positive organisms. The activity was, however, markedly reduced in 20% human serum. Future directions for this compound may include evaluation for topical use, coating biomedical devices, or the pursuit of chemically modified derivatives of this compound that retain activity in the presence of serum.

  1. Direct analysis of bacterial viability in endotracheal tube biofilm from a pig model of methicillin-resistant Staphylococcus aureus pneumonia following antimicrobial therapy.

    Science.gov (United States)

    Fernández-Barat, Laia; Li Bassi, Gianluigi; Ferrer, Miquel; Bosch, Anna; Calvo, Maria; Vila, Jordi; Gabarrús, Albert; Martínez-Olondris, Pilar; Rigol, Montse; Esperatti, Mariano; Luque, Néstor; Torres, Antoni

    2012-07-01

    Confocal laser scanning microscopy (CLSM) helps to observe the biofilms formed in the endotracheal tube (ETT) of ventilated subjects and to determine its structure and bacterial viability using specific dyes. We compared the effect of three different treatments (placebo, linezolid, and vancomycin) on the bacterial biofilm viability captured by CLSM. Eight pigs with pneumonia induced by methicillin-resistant Staphylococcus aureus (MRSA) were ventilated up to 96 h and treated with linezolid, vancomycin, or placebo (controls). ETT images were microscopically examined after staining with the live/dead(®) BacLight(™) Kit (Invitrogen, Barcelona, Spain) with a confocal laser scanning microscope. We analyzed 127 images obtained by CLSM. The median ratio of live/dead bacteria was 0.51, 0.74, and 1 for the linezolid, vancomycin, and control groups, respectively (P = 0.002 for the three groups); this ratio was significantly lower for the linezolid group, compared with the control group (P = 0.001). Images showed bacterial biofilm attached and non-attached to the ETT surface but growing within secretions accumulated inside ETT. Systemic treatment with linezolid is associated with a higher proportion of dead bacteria in the ETT biofilm of animals with MRSA pneumonia. Biofilm clusters not necessarily attach to the ETT surface. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  2. 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.

  3. 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.

  4. Mild Staphylococcus aureus Skin Infection Improves the Course of Subsequent Endogenous S. aureus Bacteremia in Mice.

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    Sanne van den Berg

    Full Text Available Staphylococcus aureus carriers with S. aureus bacteremia may have a reduced mortality risk compared to non-carriers. A role for the immune system is suggested. Here, we study in mice the effect of mild S. aureus skin infection prior to endogenous or exogenous S. aureus bacteremia, and evaluate protection in relation to anti-staphylococcal antibody levels. Skin infections once or twice by a clinical S. aureus isolate (isolate P or S. aureus strain 8325-4 were induced in mice free of S. aureus and anti-staphylococcal antibodies. Five weeks later, immunoglobulin G (IgG levels in blood against 25 S. aureus antigens were determined, and LD50 or LD100 bacteremia caused by S. aureus isolate P was induced. S. aureus skin infections led to elevated levels of anti-staphylococcal IgG in blood. One skin infection improved the course of subsequent severe endogenous bacteremia only. A second skin infection further improved animal survival rate, which was associated with increased pre-bacteremia IgG levels against Efb, IsaA, LukD, LukE, Nuc, PrsA and WTA. In conclusion, S. aureus isolate P skin infection in mice reduces the severity of subsequent endogenous S. aureus bacteremia only. Although cellular immune effects cannot be rules out, anti-staphylococcal IgG against specified antigens may contribute to this effect.

  5. The Use of Linezolid in Children with Malignant Solid Tumors

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    H.I. Klymniuk

    2015-09-01

    Full Text Available In recent decades, in the treatment of cancer there has been achieved a significant success not only by the introduction of cancer treatment protocol, but mostly due to the planned combination concomitant treatment of infectious complications. The need for antimicrobial agents against resistant Gram-positive bacteria, such as methicillin-resistant staphylococci, penicillin-resistant pneumococci, vancomycin-resistant enterococci, has significantly increased. In the department of pediatric oncology of the National cancer institute (Kyiv, linezolid preparations were used in children with infection of soft tissues and bones, febrile neutropenia and for the treatment of severe cases of sepsis. Experience of Linelid® use in the department of pediatric oncology of the National cancer institute indicates its effectiveness, safety and good tolerance in children with malignant solid tumors.

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

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    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.

  7. 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

  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. Reducing the spread of Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus on a burns unit through the intervention of an infection control bundle.

    Science.gov (United States)

    Barbut, Frédéric; Yezli, Saber; Mimoun, Maurice; Pham, Julien; Chaouat, Marc; Otter, Jonathan A

    2013-05-01

    Methicillin-resistant Staphylococcus aureus (MRSA) and Acinetobacter baumannii are major nosocomial pathogens in burns units. We investigated the impact of an infection control bundle on the incidence of nosocomial MRSA and A. baumannii in our burns unit, comparing a pre-intervention period (December 2006-August 2008) with an intervention period (September 2008-December 2009). The bundle comprised regular hydrogen peroxide vapour (HPV) disinfection of the rooms following discharge of patients colonized or infected by multidrug-resistant bacteria, pre-emptive cohort isolation of newly admitted patients before being proven culture negative, cohorting of colonized or infected patients, installation of two air disinfection systems in the corridors of the unit and improvement of material storage. We also investigated the microbiological efficacy of HPV disinfection by sampling the environment before and after HPV treatments. HPV disinfection eliminated pathogens from the environment and significantly reduced total bacterial surface counts, and total fungal air and surface counts, on both a unit and room scale. The incidence of nosocomial MRSA infection or colonization fell by 89.3% from 7.22 to 0.77 cases/1000 patient days (pcontrol bundle resulted in a significant reduction in the incidence of nosocomial MRSA and A. baumannii in our burns unit and prevented further outbreaks of these organisms. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

  10. Optimization of nebulized delivery of linezolid, daptomycin, and vancomycin aerosol

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    Zarogoulidis P

    2014-08-01

    Full Text Available Paul Zarogoulidis,1 Ioannis Kioumis,1 Sofia Lampaki,1 John Organtzis,1 Konstantinos Porpodis,1 Dionysios Spyratos,1 Georgia Pitsiou,1 Dimitris Petridis,2 Athanasia Pataka,1 Haidong Huang,3 Qiang Li,3 Lonny Yarmus,4 Wolfgang Hohenforst-Schmidt,5 Nikolaos Pezirkianidis,6 Konstantinos Zarogoulidis1 1Pulmonary Department-Oncology Unit, “G Papanikolaou” General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 2Department of Food Technology, School of Food Technology and Nutrition, Alexander Technological Educational Institute, Thessaloniki, Greece; 3Department of Respiratory Diseases, Shanghai Hospital, II Military University Hospital, Shanghai, People’s Republic of China; 4Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA; 5II Medical Department, “Coburg” Regional Hospital, Coburg, Germany; 6Surgery Department, Private Cabinet, Serres, Greece Background: At this time, several antibiotics have been investigated as possibilities for aerosol administration, but local therapy has been found to be more efficient in several diseases. Materials and methods: The drugs linezolid (Zyvox, vancomycin (Voncon, and daptomycin (Cubicin were tested with three jet nebulizers with seven different residual cups and different loadings. Moreover, three ultrasound nebulizers were again tested with these drugs, with different loadings and mouthpiece attachments. Results: When drugs are combined with particular cup designs, they significantly lower the droplet size to 1.60 and 1.80 µm, which represents the best combination of Zyvox and cup G and Cubicin and cup D, respectively. Cup design D is suggested as the most effective cup for lowering the droplet size (2.30 µm when considering a higher loading level (8 mL. Conclusion: Modification of current drugs from dry powder to solution is possible, and the residual cup design plays the most important role in droplet size production when the

  11. Immunization with intestinal microbiota-derived Staphylococcus aureus and Escherichia coli reduces bacteria-specific recolonization of the intestinal tract.

    Science.gov (United States)

    Garfias-López, Julio Adrián; Castro-Escarpuli, Graciela; Cárdenas, Pedro E; Moreno-Altamirano, María Maximina Bertha; Padierna-Olivos, Juan; Sánchez-García, F Javier

    2018-04-01

    A wide array of microorganisms colonizes distinctive anatomical regions of animals, being the intestine the one that harbors the most abundant and complex microbiota. Phylogenetic analyses indicate that it is composed mainly of bacteria, and that Bacterioidetes and Firmicutes are the most represented phyla (>90% of the total eubacteria) in mice and humans. Intestinal microbiota plays an important role in host physiology, contributing to digestion, epithelial cells metabolism, stimulation of intestinal immune responses, and protection against intestinal pathogens. Changes in its composition may affect intestinal homeostasis, a condition known as dysbiosis, which may lead to non-specific inflammation and disease. The aim of this work was to analyze the effect that a bacteria-specific systemic immune response would have on the intestinal re-colonization by that particular bacterium. Bacteria were isolated and identified from the feces of Balb/c mice, bacterial cell-free extracts were used to immunize the same mice from which bacteria came from. Concurrently with immunization, mice were subjected to a previously described antibiotic-based protocol to eliminate most of their intestinal bacteria. Serum IgG and feces IgA, specific for the immunizing bacteria were determined. After antibiotic treatment was suspended, specific bacteria were orally administered, in an attempt to specifically re-colonize the intestine. Results showed that parenteral immunization with gut-derived bacteria elicited the production of both anti-bacterial IgG and IgA, and that immunization reduces bacteria specific recolonization of the gut. These findings support the idea that the systemic immune response may, at least in part, determine the bacterial composition of the gut. Copyright © 2018. Published by Elsevier B.V.

  12. Boeravinone B, A Novel Dual Inhibitor of NorA Bacterial Efflux Pump of Staphylococcus aureus and Human P-Glycoprotein, Reduces the Biofilm Formation and Intracellular Invasion of Bacteria.

    Science.gov (United States)

    Singh, Samsher; Kalia, Nitin P; Joshi, Prashant; Kumar, Ajay; Sharma, Parduman R; Kumar, Ashok; Bharate, Sandip B; Khan, Inshad A

    2017-01-01

    This study elucidated the role of boeravinone B, a NorA multidrug efflux pump inhibitor, in biofilm inhibition. The effects of boeravinone B plus ciprofloxacin, a NorA substrate, were evaluated in NorA-overexpressing, wild-type, and knocked-out Staphylococcus aureus (SA-1199B, SA-1199, and SA-K1758, respectively). The mechanism of action was confirmed using the ethidium bromide accumulation and efflux assay. The role of boeravinone B as a human P -glycoprotein ( P -gp) inhibitor was examined in the LS-180 (colon cancer) cell line. Moreover, its role in the inhibition of biofilm formation and intracellular invasion of S. aureus in macrophages was studied. Boeravinone B reduced the minimum inhibitory concentration (MIC) of ciprofloxacin against S. aureus and its methicillin-resistant strains; the effect was stronger in SA-1199B. Furthermore, time-kill kinetics revealed that boeravinone B plus ciprofloxacin, at subinhibitory concentration (0.25 × MIC), is as equipotent as that at the MIC level. This combination also had a reduced mutation prevention concentration. Boeravinone B reduced the efflux of ethidium bromide and increased the accumulation, thus strengthening the role as a NorA inhibitor. Biofilm formation was reduced by four-eightfold of the minimal biofilm inhibitory concentration of ciprofloxacin, effectively preventing bacterial entry into macrophages. Boeravinone B effectively inhibited P -gp with half maximal inhibitory concentration (IC 50 ) of 64.85 μM. The study concluded that boeravinone B not only inhibits the NorA-mediated efflux of fluoroquinolones but also considerably inhibits the biofilm formation of S. aureus. Its P -gp inhibition activity demonstrates its potential as a bioavailability and bioefficacy enhancer.

  13. Chlorhexidine whole-body washing of patients reduces methicillin-resistant Staphylococcus aureus and has a direct effect on the distribution of the ST5-MRSA-II (New York/Japan) clone.

    Science.gov (United States)

    Velázquez-Meza, Maria Elena; Mendoza-Olazarán, Soraya; Echániz-Aviles, Gabriela; Camacho-Ortiz, Adrián; Martínez-Reséndez, Michel Fernando; Valero-Moreno, Vanessa; Garza-González, Elvira

    2017-06-01

    Methicillin-resistant Staphylococcus aureus (MRSA) colonizes the skin of hospitalized patients and is associated with high morbidity and mortality. To prevent colonization and infection by S. aureus, better disinfection practices are required. Therefore, we evaluated the effect of chlorhexidine whole-body washing on hospital-acquired S. aureus infections among intensive care unit (ICU) patients in a tertiary hospital in Mexico. The study was conducted over 18 months to evaluate the effect of 2 % chlorhexidine gluconate (CXG) whole-body washing of ICU adult patients on chlorhexidine and antibiotic resistance, biofilm production and clonal distribution of S. aureus in a tertiary care hospital. Minimum inhibitory concentrations for CXG, antibiotic susceptibility and biofilm production by S. aureus isolates were determined. Pulsed-field gel electrophoresis, multilocus sequence typing (MLST) and PCR for Panton-Valentine leucocidin (PVL) were used for molecular typing of MRSA isolates.Results/Key findings. We included 158 isolates. A reduction in antibiotic resistance in the study period was observed for clindamycin, levofloxacin, norfloxacin, oxacillin and trimethoprim/sulfamethoxazole. None of the isolates showed reduced susceptibility to CXG. Most of the isolates were non-biofilm producers (147/158). The most commonly identified clone was a descendant of the ST5-MRSA-II (New York/Japan) clone. This clone decreased during the intervention period and reappeared markedly in the post-intervention period. During the post-intervention period, two isolates were related with the clone ST8-MRSA-IV (also known as USA300). Our findings suggest that the CXG bathing favored the reduction of healthcare-associated MRSA isolates and a temporary reduction of the predominant ST5-MRSA-II (New York/Japan) clone.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. 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.

  1. Clinical response and hospital costs associated with the empirical use of vancomycin and linezolid for hospital-acquired pneumonia in a Chinese tertiary care hospital: a retrospective cohort study

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    Song Y

    2014-10-01

    a nonsignificant trend of lower risk of in-hospital mortality associated with vancomycin (odds ratio: 0.186; P=0.055. The total hospital costs associated with vancomycin had a nonsignificant trend of being lower, likely because of its significantly lower acquisition costs (median: RMB 2,880 versus RMB 8,194; P<0.001; 1 RMB =0.16 USD. Conclusion: In tertiary care hospitals in the People's Republic of China, empirical treatment of patients with HAP with vancomycin had a comparable treatment failure rate but likely had a lower in-hospital mortality rate when compared with linezolid. Vancomycin also costs significantly less for drug acquisition than linezolid when treating HAP empirically. Keywords: methicillin-resistant Staphylococcus aureus, treatment failure, mortality, antibiotics

  2. 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

  3. 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

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

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    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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 1H, 13C and 15N backbone resonance assignment of the arsenate reductase from Staphylococcus aureus in its reduced state

    NARCIS (Netherlands)

    Jacobs, D.M.; Messens, J.; Wechselberger, R.W.|info:eu-repo/dai/nl/304829005; Brosens, E.; Willem, R.; Wyns, L.; Martins, J.C.

    2001-01-01

    In S. aureus, resistance to the metal(III)oxyanions arsenite As(III)O− 2 and antimonite Sb(III)O− 2 is mediated by two proteins, ArsB and ArsR, encoded in the ars operon of plasmid pI258 (Silver, 1999). ArsR acts as the transcription repressor, which is de-repressed in the presence of intracellular

  10. Antimicrobial Resistance Profile of Planktonic and Biofilm Cells of Staphylococcus aureus and Coagulase-Negative Staphylococci

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    Adilson de Oliveira

    2016-09-01

    Full Text Available The objective of the present study was to determine the antimicrobial resistance profile of planktonic and biofilm cells of Staphylococcus aureus and coagulase-negative staphylococci (CoNS. Two hundred Staphylococcus spp. strains were studied, including 50 S. aureus and 150 CoNS strains (50 S. epidermidis, 20 S. haemolyticus, 20 S. warneri, 20 S. hominis, 20 S. lugdunensis, and 20 S. saprophyticus. Biofilm formation was investigated by adherence to polystyrene plates. Positive strains were submitted to the broth microdilution method to determine the minimum inhibitory concentration (MIC for planktonic and biofilm cells and the minimal bactericidal concentration for biofilm cells (MBCB. Forty-nine Staphylococcus spp. strains (14 S. aureus, 13 S. epidermidis, 13 S. saprophyticus, 3 S. haemolyticus, 1 S. hominis, 3 S. warneri, and 2 S. lugdunensis were biofilm producers. These isolates were evaluated regarding their resistance profile. Determination of planktonic cell MIC identified three (21.4% S. aureus strains that were resistant to oxacillin and six (42.8% that were resistant to erythromycin. Among the CoNS, 31 (88.6% strains were resistant to oxacillin, 14 (40% to erythromycin, 18 (51.4% to gentamicin, and 8 (22.8% to sulfamethoxazole/trimethoprim. None of the planktonic isolates were resistant to vancomycin or linezolid. MICs were 2-, 4-, 8-, and up to 16-fold higher for biofilm cells than for planktonic cells. This observation was more common for vancomycin and erythromycin. The MBCB ranged from 8 to >256 µg/mL for oxacillin, 128 to >128 µg/mL for vancomycin, 256 to >256 µg/mL for erythromycin and gentamicin, >64 µg/mL for linezolid, and 32/608 to >32/608 µg/mL for sulfamethoxazole/trimethoprim. The results showed considerably higher MICs for S. aureus and CoNS biofilm cells compared to planktonic cells. Analysis of MBCM confirmed that even high concentrations of vancomycin were unable to eliminate the biofilms of S. aureus and Co

  11. Antibiotic resistance and molecular epidemiology of Staphylococcus aureus in Nigeria

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    Oyedara Omotayo

    2011-05-01

    Full Text Available Abstract Background Staphylococcus aureus is an important pathogen causing a wide range of infections in the hospital and community setting. In order to have adequate information for treatment of S. aureus infections, it is crucial to understand the trends in the antibiotic-resistance patterns. In addition, the occurrence and changes in types of S. aureus, clonal identities, and their geographic spread is essential for the establishment of adequate infection control programmes. In this study, 68 S. aureus isolates obtained from clinical and non-clinical sources in Nigeria between January and April 2009 were characterized using phenotypic and molecular methods. Results All the S. aureus isolates were susceptible to teicoplanin, vancomycin, phosphomycin, fusidic acid, rifampicin, daptomycin, mupirocin, linezolid and tigecycline. Sixteen percent of the isolates were resistant to oxacillin, while 55% and 72% of isolates were resistant to tetracycline and trimethoprim/sulphamethoxazole (cotrimoxazole, respectively (Table 1. There was excellent correlation between the broth microdilution assay and detection of antibiotic resistance genes by the multiplex PCR, in the determination of S. aureus resistance to erythromycin, gentamicin, methicillin and tetracycline. A total of 28 spa types were identified in the study, and the predominant spa type among the methicillin-susceptible S. aureus (MSSA isolates was t084 (13 isolates. The t037-ST241-SCCmecIII type was the only clone identified in Maiduguri (North-East Nigeria while in South-West Nigeria, diversity among the MRSA isolates (t451-ST8-SCCmecV; t008-ST94-SCCmecIV; t002-ST5-SCCmecV; t064-ST8-SCCmecV was observed. The toxin genes seh and etd were detected in isolates affiliated with clonal complexes CC1, CC80 and sequence type ST25, respectively. The proportion of PVL-positive isolates among MSSA was high (40%. Most of the PVL-positive MSSA isolates were obtained from wound infections and associated

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

    Science.gov (United States)

    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.

  13. Passive therapy with humanized anti-staphylococcal enterotoxin B antibodies attenuates systemic inflammatory response and protects from lethal pneumonia caused by staphylococcal enterotoxin B-producing Staphylococcus aureus.

    Science.gov (United States)

    Karau, Melissa J; Tilahun, Mulualem E; Krogman, Ashton; Osborne, Barbara A; Goldsby, Richard A; David, Chella S; Mandrekar, Jayawant N; Patel, Robin; Rajagopalan, Govindarajan

    2017-10-03

    Drugs such as linezolid that inhibit bacterial protein synthesis may be beneficial in treating infections caused by toxigenic Staphylococcus aureus. As protein synthesis inhibitors have no effect on preformed toxins, neutralization of pathogenic exotoxins with anti-toxin antibodies may be beneficial in conjunction with antibacterial therapy. Herein, we evaluated the efficacy of human-mouse chimeric high-affinity neutralizing anti-staphylococcal enterotoxin B (SEB) antibodies in the treatment of experimental pneumonia caused by SEB-producing S. aureus. Since HLA class II transgenic mice mount a stronger systemic immune response following challenge with SEB and are more susceptible to SEB-induced lethal toxic shock than conventional mice strains, HLA-DR3 transgenic mice were used. Lethal pneumonia caused by SEB-producing S. aureus in HLA-DR3 transgenic mice was characterized by robust T cell activation and elevated systemic levels of several pro-inflammatory cytokines and chemokines. Prophylactic administration of a single dose of linezolid 30 min prior to the onset of infection attenuated the systemic inflammatory response and protected from mortality whereas linezolid administered 60 min after the onset of infection failed to confer significant protection. Human-mouse chimeric high-affinity neutralizing anti-SEB antibodies alone, but not polyclonal human IgG, mitigated this response and protected from death when administered immediately after initiation of infection. Further, anti-SEB antibodies as well as intact polyclonal human IgG, but not its Fab or Fc fragments, protected from lethal pneumonia when followed with linezolid therapy 60 min later. In conclusion, neutralization of superantigens with high-affinity antibodies may have beneficial effects in pneumonia.

  14. 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

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. Dehydrosqualene Desaturase as a Novel Target for Anti-Virulence Therapy against Staphylococcus aureus

    OpenAIRE

    Gao, Peng; Davies, Julian; Kao, Richard Yi Tsun

    2017-01-01

    ABSTRACT Staphylococcus aureus, especially methicillin-resistant S.?aureus (MRSA), is a life-threatening pathogen in hospital- and community-acquired infections. The golden-colored carotenoid pigment of S.?aureus, staphyloxanthin, contributes to the resistance to reactive oxygen species (ROS) and host neutrophil-based killing. Here, we describe a novel inhibitor (NP16) of S.?aureus pigment production that reduces the survival of S.?aureus under oxidative stress conditions. Carotenoid componen...

  3. 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.

  4. Vancomycin-resistant Enterococcus spp.: validation of susceptibility testing and in vitro activity of vancomycin, linezolid, tigecycline and daptomycin

    DEFF Research Database (Denmark)

    Rathe, Mathias; Kristensen, Lise; Ellermann-Eriksen, Svend

    2010-01-01

    Vancomycin-resistant enterococci (VRE) have emerged to become a significant nosocomial pathogen. However, detection may be challenging and treatment possibilities are limited. Reports of resistance to linezolide, daptomycin and tigecycline underline the need for reliable susceptibility testing wi...

  5. Molecular Characteristics of Staphylococcus aureus Causing Bovine Mastitis between 2014 and 2015.

    Science.gov (United States)

    Li, Tianming; Lu, Huiying; Wang, Xing; Gao, Qianqian; Dai, Yingxin; Shang, Jun; Li, Min

    2017-01-01

    Staphylococcus aureus is highly pathogenic and can cause diseases in both humans and domestic animals. In animal species, including ruminants, S. aureus may cause severe or sub-clinical mastitis. This study aimed to investigate the molecular profile, antimicrobial resistance, and genotype/phenotype correlation of 212 S. aureus isolates recovered from cases of bovine mastitis from 2014 to 2015 in the Shanghai and Zhejiang areas of China. Nineteen sequence types (STs) were determined by multi-locus sequence typing, while the dominant ST was ST97, followed by ST520, ST188, ST398, ST7, and ST9. Within 14 methicillin-resistant S. aureus (MRSA) isolates and 198 methicillin-susceptible S. aureus (MSSA) isolates, ST97 was the predominant MSSA clone and ST9-MRSA-SCCmecXII-spa t899 was the most common MRSA clone. The MRSA strains showed much higher rates of resistance to multiple antibiotics than did MSSA strains. Compared with other MSSA strains, MSSA ST398 was more resistant to clindamycin, erythromycin, and ciprofloxacin. No isolates were resistant to vancomycin, teicoplanin, or linezolid. The molecular profiles of the virulence genes varied in different strains. ST520 strains carried seg-sei-sem-sen-seo genes, and ST9 and ST97 harbored sdrD-sdrE genes. Virulence phenotype analysis showed diversity in different clones. Biofilm formation ability was significantly enhanced in ST188 and ST7, and red blood cell lysis capacity was relatively strong in all S. aureus strains of animal origin except ST7. Our results indicate that MSSA was the predominant S. aureus strain causing bovine mastitis in eastern regions of China. However, the presence of multidrug resistant and toxigenic MRSA clone ST9 suggests that comprehensive surveillance of S. aureus infection should be implemented in the management of animal husbandry products.

  6. 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.

  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. Improved outcome of ventilator-associated pneumonia caused by methicillin-resistant Staphylococcus aureus in a trauma population.

    Science.gov (United States)

    Gonzalez, Richard P; Rostas, Jack; Simmons, Jon D; Allen, John; Frotan, Mohammad A; Brevard, Sidney B

    2013-03-01

    The treatment of ventilator-associated pneumonia (VAP) secondary to methicillin-resistant Staphylococcus aureus (MRSA) remains controversial. We performed a review of all blunt trauma patients diagnosed with MRSA VAP from June 2005 to June 2011. VAP for the first 3 years was diagnosed by sputum aspiration and treated with vancomycin. For the last 3 years of the study period, VAP was diagnosed with bronchoalveolar lavage and treated with linezolid. MRSA VAP patients treated with vancomycin had an average hospital length of stay (LOS) of 49 days (range 9-99 days), an average intensive care unit (ICU) LOS of 43 days (range 6-98 days), and average ventilator days of 34.4 (range 3-76 days). Seventeen MRSA VAP patients treated with linezolid had an average hospital LOS of 27 days (range 11-61), an average ICU LOS of 22 days (range 10-42) days, and average ventilator days of 16.6 (range 2-42). Trauma patients who develop MRSA VAP appear to have fewer ventilator days and shorter ICU and hospital LOS when treated with linezolid. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. Detection of meca gene from methicillin resistant staphylococcus aureus isolates of north sumatera

    Science.gov (United States)

    Septiani Nasution, Gabriella; Suryanto, Dwi; Lia Kusumawati, R.

    2018-03-01

    Methicillin Resistant Staphylococcus aureus (MRSA) is a major pathogen associated with hospital-acquired infections (nosocomial infections). MRSA is a type of S. aureus resistant to the sub-group of beta-lactam antibiotics such as penicillin, cephalosporin, monobactam, and carbapenem. MRSA is resistant because of genetic changes caused by exposure to irrational antibiotic therapy. This study aimed to detect mecA gene in North Sumatra isolates of MRSA and to determine the pattern of antibiotic resistance in S.aureus isolates classified as MRSA by Vitek 2 Compact in the Central Public Hospital Haji Adam Malik, Medan. Samples were 40 isolates of S. aureus classified as MRSA obtained from clinical microbiology specimens. DNA isolation of the isolates was conducted by a method of freeze-thaw cycling. Amplification of mecA gene was done by PCR technique using specific primer for the gene. PCR products were visualized using mini-gel electrophoresis. The results showed that all MRSA isolates showed to have 533 bp band of mecA. Antibiotics test of Vitek 2 Compact showed that despite all isolates were resistant to beta-lactam antibiotics groups; the isolates showed multidrug resistant to other common antibiotics, such as aminoglycosides, macrolides, and fluoroquinolones. However, they were still sensitive to vancomycin (82.5% isolates), linezolid (97.5% isolates), and tigecycline (100% isolates).

  16. Phenotypic and genomic comparisons of highly vancomycin-resistant Staphylococcus aureus strains developed from multiple clinical MRSA strains by in vitro mutagenesis.

    Science.gov (United States)

    Ishii, Kenichi; Tabuchi, Fumiaki; Matsuo, Miki; Tatsuno, Keita; Sato, Tomoaki; Okazaki, Mitsuhiro; Hamamoto, Hiroshi; Matsumoto, Yasuhiko; Kaito, Chikara; Aoyagi, Tetsuji; Hiramatsu, Keiichi; Kaku, Mitsuo; Moriya, Kyoji; Sekimizu, Kazuhisa

    2015-11-25

    The development of vancomycin (VCM) resistance in Staphylococcus aureus threatens global health. Studies of the VCM-resistance mechanism and alternative therapeutic strategies are urgently needed. We mutagenized S. aureus laboratory strains and methicillin-resistant S. aureus (MRSA) with ethyl methanesulfonate, and isolated mutants that exhibited high resistance to VCM (minimum inhibitory concentration = 32 μg/ml). These VCM-resistant strains were sensitive to linezolid and rifampicin, and partly to arbekacin and daptomycin. Beta-lactams had synergistic effects with VCM against these mutants. VCM-resistant strains exhibited a 2-fold increase in the cell wall thickness. Several genes were commonly mutated among the highly VCM-resistant mutants. These findings suggest that MRSA has a potential to develop high VCM resistance with cell wall thickening by the accumulation of mutations.

  17. Antibiotic susceptibility pattern and the prevalence of Staphylococcus aureus isolated from skin and soft tissue in Tehran Razi skin hospital (2014-15

    Directory of Open Access Journals (Sweden)

    Zeynab Fagheei-Aghmiyuni

    2017-06-01

    Full Text Available Background: Staphylococcus aureus (S. aureus is the most common cause of skin and soft tissue infections. This study aimed to determine the prevalence of S. aureus isolated from skin and soft tissue and antibiotic susceptibility pattern among the patient hospitalized in Razi skin hospital (Tehran-Iran. Materials and Methods: This cross-sectional study was conducted on patients (n=400 with skin and soft tissue infections in Razi skin hospital. Sterilized swabs were used to collect the skin infection samples. S. aureus isolates were confirmed using biochemical tests (gram staining, catalase, coagulase, DNase test and manitol fermentation tests. Result: 51.3 %( 205 out of 400 of isolates were S. aureus. Ninety six (46.8% of isolates were methicillin and penicillin-resistant S. aureus. All of the isolates showed sensitivity to vancomycin, linezolid. 98% of the isolates were susceptible to daptomycin. One-hundred sixteen (56.6% isolates were multi- drug resistant. Conclusion: More than half of the skin and soft tissue infections were caused by S.aureus. More than 46 percent of the isolates were methicillin resistant. The highest resistance to penicillin was observed.

  18. Repurposing salicylanilide anthelmintic drugs to combat drug resistant Staphylococcus aureus.

    Science.gov (United States)

    Rajamuthiah, Rajmohan; Fuchs, Beth Burgwyn; Conery, Annie L; Kim, Wooseong; Jayamani, Elamparithi; Kwon, Bumsup; Ausubel, Frederick M; Mylonakis, Eleftherios

    2015-01-01

    Staphylococcus aureus is a Gram-positive bacterium that has become the leading cause of hospital acquired infections in the US. Repurposing Food and Drug Administration (FDA) approved drugs for antimicrobial therapy involves lower risks and costs compared to de novo development of novel antimicrobial agents. In this study, we examined the antimicrobial properties of two commercially available anthelmintic drugs. The FDA approved drug niclosamide and the veterinary drug oxyclozanide displayed strong in vivo and in vitro activity against methicillin resistant S. aureus (minimum inhibitory concentration (MIC): 0.125 and 0.5 μg/ml respectively; minimum effective concentration: ≤ 0.78 μg/ml for both drugs). The two drugs were also effective against another Gram-positive bacteria Enterococcus faecium (MIC 0.25 and 2 μg/ml respectively), but not against the Gram-negative species Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter aerogenes. The in vitro antimicrobial activity of niclosamide and oxyclozanide were determined against methicillin, vancomycin, linezolid or daptomycin resistant S. aureus clinical isolates, with MICs at 0.0625-0.5 and 0.125-2 μg/ml for niclosamide and oxyclozanide respectively. A time-kill study demonstrated that niclosamide is bacteriostatic, whereas oxyclozanide is bactericidal. Interestingly, oxyclozanide permeabilized the bacterial membrane but neither of the anthelmintic drugs exhibited demonstrable toxicity to sheep erythrocytes. Oxyclozanide was non-toxic to HepG2 human liver carcinoma cells within the range of its in vitro MICs but niclosamide displayed toxicity even at low concentrations. These data show that the salicylanilide anthelmintic drugs niclosamide and oxyclozanide are suitable candidates for mechanism of action studies and further clinical evaluation for treatment of staphylococcal infections.

  19. Characterization of methicillin-resistant Staphylococcus aureus isolates from pig carcasses in Hong Kong

    DEFF Research Database (Denmark)

    Ho, J.; O'Donoghue, M.; Guardabassi, Luca

    2012-01-01

    This study describes the isolation and characterization of methicillin-resistant Staphylococcus aureus (MRSA) from slaughtered pigs sampled from local markets in Hong Kong. The nares of 400 slaughtered pigs were cultured and MRSA isolates characterized for the presence of antibiotic-resistance de......This study describes the isolation and characterization of methicillin-resistant Staphylococcus aureus (MRSA) from slaughtered pigs sampled from local markets in Hong Kong. The nares of 400 slaughtered pigs were cultured and MRSA isolates characterized for the presence of antibiotic...... tet(M). Resistance to erythromycin (89%) and chloramphenicol (71%) was associated with the presence of erm(C), and fex(A), respectively. No strains carried cfr and there was no resistance to linezolid, although minimum inhibitory concentration (MICs) were close to the resistance break point...

  20. 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

  1. 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.

  2. 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...

  3. Infection prevention practices in adult intensive care units in a large community hospital system after implementing strategies to reduce health care-associated, methicillin-resistant Staphylococcus aureus infections.

    Science.gov (United States)

    Moody, Julia; Septimus, Edward; Hickok, Jason; Huang, Susan S; Platt, Richard; Gombosev, Adrijana; Terpstra, Leah; Avery, Taliser; Lankiewicz, Julie; Perlin, Jonathan B

    2013-02-01

    A range of strategies and approaches have been developed for preventing health care-associated infections. Understanding the variation in practices among facilities is necessary to improve compliance with existing programs and aid the implementation of new interventions. In 2009, HCA Inc administered an electronic survey to measure compliance with evidence-based infection prevention practices as well as identify variation in products or methods, such as use of special approach technology for central vascular catheters and ventilator care. Responding adult intensive care units (ICUs) were those considering participation in a clinical trial to reduce health care-associated infections. Responses from 99 ICUs in 55 hospitals indicated that many evidenced-based practices were used consistently, including methicillin-resistant Staphylococcus aureus (MRSA) screening and use of contact precautions for MRSA-positive patients. Other practices exhibited wide variability including discontinuation of precautions and use of antimicrobial technology or chlorhexidine patches for central vascular catheters. MRSA decolonization was not a predominant practice in ICUs. In this large, community-based health care system, there was substantial variation in the products and methods to reduce health care-associated infections. Despite system-wide emphasis on basic practices as a precursor to adding special approach technologies, this survey showed that these technologies were commonplace, including in facilities where improvement in basic practices was needed. Copyright © 2013 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

  4. 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.

  5. Molecular characterization of antimicrobial resistance genes against Staphylococcus aureus isolates from Trinidad and Tobago

    Directory of Open Access Journals (Sweden)

    Patrick E. Akpaka

    2017-05-01

    Full Text Available Summary: Staphylococcus aureus continues to pose major public health challenges in many areas because of antibiotic resistance problems. In the Caribbean, especially Trinidad and Tobago, the challenge is not different. This study was performed to evaluate the antimicrobial resistance gene prevalence among S. aureus isolates in Trinidad and Tobago.Standard and molecular microbiological methods, including the Microscan automated system, DNA microarray and multi locus sequence typing (MLST analysis, were performed on 309 clinical S. aureus isolates recovered from patients who were treated at three of the country's main health institutions.S. aureus exhibited susceptibilities ≥80% to eleven of the 19 antimicrobials tested against it, and these belong to the most commonly used and available antibiotics in the country. While the antibiotic to which it was most susceptible of the commonly used antibiotics was trimethoprim/sulfamethoxazole, the antibiotics to which it was least susceptible or most resistant to were ampicillin and penicillin. S. aureus isolates from the pediatric ward produced the greatest rate of susceptibility among the isolates recovered from patients admitted into hospitals, while isolates from Accident and Emergency rooms displayed the greatest susceptibilities among patients from the community.S. aureus isolates from the country did not harbor acquired resistant genes targeting clindamycin/macrolides (ermB, linezolid (cfr or vancomycin (vanA. The blaZ gene, which is the most common beta lactam (Penicillinase resistance mechanism for S. aureus, was observed in 88.7% of the methicillin susceptible S. aureus, while methicillin resistance mediated by the mec gene was present in 13.6%. Most of the resistance markers found in MRSA isolates were significantly associated with the ST239-MRSA-III strain in this study, and all isolates that belonged to the USA300 strain, which additionally encoded both the PVL gene and ACME cluster

  6. 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.

  7. Recommendations to address the difficulties encountered when determining linezolid resistance from whole genome sequencing data.

    Science.gov (United States)

    Beukers, Alicia G; Hasman, Henrik; Hegstad, Kristin; van Hal, Sebastiaan J

    2018-05-29

    Mutations associated with linezolid resistance within the V domain of 23S rRNA are annotated using an Escherichia coli numbering system. The 23S rRNA gene varies in length, nucleotide sequence and copy number between bacterial species. Consequently, this numbering system is not intuitive and can lead to confusion when locating mutation sites using whole genome sequencing data. Using the mutation G2576T as an example, we demonstrate the difficulties associated with using the E. coli numbering system. © Crown copyright 2018.

  8. Evaluation of the national Cleanyourhands campaign to reduce Staphylococcus aureus bacteraemia and Clostridium difficile infection in hospitals in England and Wales by improved hand hygiene: four year, prospective, ecological, interrupted time series study.

    Science.gov (United States)

    Stone, Sheldon Paul; Fuller, Christopher; Savage, Joan; Cookson, Barry; Hayward, Andrew; Cooper, Ben; Duckworth, Georgia; Michie, Susan; Murray, Miranda; Jeanes, Annette; Roberts, J; Teare, Louise; Charlett, Andre

    2012-05-03

    To evaluate the impact of the Cleanyourhands campaign on rates of hospital procurement of alcohol hand rub and soap, report trends in selected healthcare associated infections, and investigate the association between infections and procurement. Prospective, ecological, interrupted time series study from 1 July 2004 to 30 June 2008. 187 acute trusts in England and Wales. Installation of bedside alcohol hand rub, materials promoting hand hygiene and institutional engagement, regular hand hygiene audits, rolled out nationally from 1 December 2004. Quarterly (that is, every three months) rates for each trust of hospital procurement of alcohol hand rub and liquid soap; Staphylococcus aureus bacteraemia (meticillin resistant (MRSA) and meticillin sensitive (MSSA)) and Clostridium difficile infection for each trust. Associations between procurement and infection rates assessed by mixed effect Poisson regression model (which also accounted for effect of bed occupancy, hospital type, and timing of other national interventions targeting these infections). Combined procurement of soap and alcohol hand rub tripled from 21.8 to 59.8 mL per patient bed day; procurement rose in association with each phase of the campaign. Rates fell for MRSA bacteraemia (1.88 to 0.91 cases per 10,000 bed days) and C difficile infection (16.75 to 9.49 cases). MSSA bacteraemia rates did not fall. Increased procurement of soap was independently associated with reduced C difficile infection throughout the study (adjusted incidence rate ratio for 1 mL increase per patient bed day 0.993, 95% confidence interval 0.990 to 0.996; P hospital procurement of alcohol rub and soap, which the results suggest has an important role in reducing rates of some healthcare associated infections. National interventions for infection control undertaken in the context of a high profile political drive can reduce selected healthcare associated infections.

  9. Molecular characterization of antimicrobial resistance genes against Staphylococcus aureus isolates from Trinidad and Tobago.

    Science.gov (United States)

    Akpaka, Patrick E; Roberts, Rashida; Monecke, Stefan

    Staphylococcus aureus continues to pose major public health challenges in many areas because of antibiotic resistance problems. In the Caribbean, especially Trinidad and Tobago, the challenge is not different. This study was performed to evaluate the antimicrobial resistance gene prevalence among S. aureus isolates in Trinidad and Tobago. Standard and molecular microbiological methods, including the Microscan automated system, DNA microarray and multi locus sequence typing (MLST) analysis, were performed on 309 clinical S. aureus isolates recovered from patients who were treated at three of the country's main health institutions. S. aureus exhibited susceptibilities ≥80% to eleven of the 19 antimicrobials tested against it, and these belong to the most commonly used and available antibiotics in the country. While the antibiotic to which it was most susceptible of the commonly used antibiotics was trimethoprim/sulfamethoxazole, the antibiotics to which it was least susceptible or most resistant to were ampicillin and penicillin. S. aureus isolates from the pediatric ward produced the greatest rate of susceptibility among the isolates recovered from patients admitted into hospitals, while isolates from Accident and Emergency rooms displayed the greatest susceptibilities among patients from the community. S. aureus isolates from the country did not harbor acquired resistant genes targeting clindamycin/macrolides (ermB), linezolid (cfr) or vancomycin (vanA). The blaZ gene, which is the most common beta lactam (Penicillinase) resistance mechanism for S. aureus, was observed in 88.7% of the methicillin susceptible S. aureus, while methicillin resistance mediated by the mec gene was present in 13.6%. Most of the resistance markers found in MRSA isolates were significantly associated with the ST239-MRSA-III strain in this study, and all isolates that belonged to the USA300 strain, which additionally encoded both the PVL gene and ACME cluster, belonged to CC8. Several

  10. 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

  11. Clinical Validation of the Analysis of Linezolid and Clarithromycin in Oral Fluid of Patients with Multidrug-Resistant Tuberculosis

    NARCIS (Netherlands)

    Bolhuis, M. S.; van Altena, R.; van Hateren, K.; de Lange, W. C. M.; Greijdanus, B.; Uges, D. R. A.; Kosterink, J. G. W.; van der Werf, T. S.; Alffenaar, J. W. C.

    Linezolid plays an increasingly important role in the treatment of multidrug-resistant tuberculosis (MDR-TB). However, patients should be carefully monitored due to time-and dose-dependent toxicity. Clarithromycin plays a more modest role. Therapeutic drug monitoring may contribute to assessment of

  12. 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.

  13. Left-sided native valve Staphylococcus aureus endocarditis

    NARCIS (Netherlands)

    Slabbekoorn, M.; Horlings, H. M.; van der Meer, J. T. M.; Windhausen, A.; Van der Sloot, J. A. P.; Lagrand, W. K.

    2010-01-01

    Despite improved diagnostic tools and expanded treatment options, left-sided native valve endocarditis caused by Staphylococcus aureus infection remains a serious and destructive disease. The high morbidity and mortality, however, can be reduced by early recognition, correct diagnosis, and

  14. Impact of sub-inhibitory antibiotics on fibronectin-mediated host cell adhesion and invasion by Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Rasigade Jean

    2011-12-01

    Full Text Available Abstract Background Staphylococcus aureus is a well-armed pathogen prevalent in severe infections such as endocarditis and osteomyelitis. Fibronectin-binding proteins A and B, encoded by fnbA/B, are major pathogenesis determinants in these infections through their involvement in S. aureus adhesion to and invasion of host cells. Sub-minimum inhibitory concentrations (sub-MICs of antibiotics, frequently occurring in vivo because of impaired drug diffusion at the infection site, can alter S. aureus phenotype. We therefore investigated their impact on S. aureus fibronectin-mediated adhesiveness and invasiveness. Methods After in vitro challenge of S. aureus 8325-4 and clinical isolates with sub-MICs of major anti-staphylococcal agents, we explored fnbA/B transcription levels, bacterial adhesiveness to immobilised human fibronectin and human osteoblasts in culture, and bacterial invasion of human osteoblasts. Results Oxacillin, moxifloxacin and linezolid led to the development of a hyper-adhesive phenotype in the fibronectin adhesion assay that was consistent with an increase in fnbA/B transcription. Conversely, rifampin treatment decreased fibronectin binding in all strains tested without affecting fnbA/B transcription. Gentamicin and vancomycin had no impact on fibronectin binding or fnbA/B transcription levels. Only oxacillin-treated S. aureus displayed a significantly increased adhesion to cultured osteoblasts, but its invasiveness did not differ from that of untreated controls. Conclusion Our findings demonstrate that several antibiotics at sub-MICs modulate fibronectin binding in S. aureus in a drug-specific fashion. However, hyper- and hypo- adhesive phenotypes observed in controlled in vitro conditions were not fully confirmed in whole cell infection assays. The relevance of adhesion modulation during in vivo infections is thus still uncertain and requires further investigations.

  15. Staphylococcus aureus Transcriptome Architecture

    DEFF Research Database (Denmark)

    Mäder, Ulrike; Nicolas, Pierre; Depke, Maren

    2016-01-01

    Staphylococcus aureus is a major pathogen that colonizes about 20% of the human population. Intriguingly, this Gram-positive bacterium can survive and thrive under a wide range of different conditions, both inside and outside the human body. Here, we investigated the transcriptional adaptation of...

  16. Staphylococcus aureus CC398

    DEFF Research Database (Denmark)

    Price, Lance B.; Stegger, Marc; Hasman, Henrik

    2012-01-01

    Since its discovery in the early 2000s, methicillin-resistant Staphylococcus aureus (MRSA) clonal complex 398 (CC398) has become a rapidly emerging cause of human infections, most often associated with livestock exposure. We applied whole-genome sequence typing to characterize a diverse collection...... of CC398 isolates (n = 89), including MRSA and methicillin-susceptible S. aureus (MSSA) from animals and humans spanning 19 countries and four continents. We identified 4,238 single nucleotide polymorphisms (SNPs) among the 89 core genomes. Minimal homoplasy (consistency index = 0.9591) was detected...... among parsimony-informative SNPs, allowing for the generation of a highly accurate phylogenetic reconstruction of the CC398 clonal lineage. Phylogenetic analyses revealed that MSSA from humans formed the most ancestral clades. The most derived lineages were composed predominantly of livestock...

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

    Directory of Open Access Journals (Sweden)

    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

  18. Linezolid Injection

    Science.gov (United States)

    ... beer, Chianti, and other red wines; alcohol-free beer; cheeses (especially strong, aged, or processed varieties); sauerkraut; yogurt; raisins; bananas; sour cream; pickled herring; liver (especially chicken liver); dried ...

  19. Incidenza della meticillino-resistenza in Staphylococcus aureus e stafilococchi coagulasi-negativi isolati da emocolture

    Directory of Open Access Journals (Sweden)

    Alessandra Siddi

    2007-12-01

    Full Text Available Background: Staphylococci are major cause of nosocomial blood stream infections.This local surveillance study was carry out to monitor frequency of occurrence of Staphylococcus aureus and coagulase-negative staphylococci (CoNS in blood stream infections and the incidence of methicillin-resistant (MET-R strains. Materials and methods: During the period January – December 2006, 9840 blood specimens were analyzed and microrganisms from positive samples were collected. Bacterial identifications were performed according to the standard methods (Murray, 2003.We evaluated, in particular, the antibiotic-resistance phenotype of staphylococci employing disk diffusion test as suggested by the CLSI (2006. The following antimicrobial agents were tested: oxacillin, penicillin, amoxiciclin-clavulanate, cefalotin, cefamandole, imipenem, teicoplanin, linezolid, ciprofloxacin, erythromycin, clindamicin, rifampicin, trimethoprim-sulfamethoxazole, gentamicin, doxiciclin, fosfomycin. Results: The microrganisms isolated were 551: 370 Gram-positives (67%, 131 Gram-negatives (24%, 11 anaerobes (2% and 39 mycetes (7%. In particular, 121 S. epidermidis, 75 S. aureus, 42 S. haemolyticus and other 39 CoNS were analyzed: methicillin-resistance occurred in more than 80% of S.aureus strains collected from Intensive Care Units (ICU and in about 50 % of those isolated from other divisions. In CoNS the incidence of MET-R ranged from 30 to 80 %, the higher values were registered among S. epidermidis and S. haemolyticus. MET-R strains were characterized by high resistance rates even to ciprofloxacin (from 47 to 100%, erythromycin (from 70 to 100%, and in same cases to gentamicin (from 23 to 86% also. Conclusions: Staphylococci are the prevalent cause of blood stream infections.The distinctive feature of MET-R strains is their resistance not only to all b-lactam antibiotics, but also to a wide range of other antimicrobial agents. However, the glycopeptide teicoplanin remains 100

  20. 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.

  1. 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.

  2. 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.

  3. Methicillin resistant Staphylococcus aureus in Ethiopia: a meta-analysis.

    Science.gov (United States)

    Eshetie, Setegn; Tarekegn, Fentahun; Moges, Feleke; Amsalu, Anteneh; Birhan, Wubet; Huruy, Kahsay

    2016-11-21

    The burden of methicillin resistant Staphylococcus aureus is a major public health concern worldwide; however the overall epidemiology of multidrug resistant strains is neither coordinated nor harmonized, particularly in developing countries including Ethiopia. Therefore, the aim of this meta-analysis was to assess the burden of methicillin resistant Staphylococcos aureus and its antibiotic resistance pattern in Ethiopia at large. PubMed, Google Scholar, and lancet databases were searched and a total of 20 studies have been selected for meta-analysis. Six authors have independently extracts data on the prevalence of methicillin resistant Staphylococcus aureus among clinical isolates of Staphylococcus aureus. Statistical analysis was achieved by using Open meta-analyst (version 3.13) and Comprehensive meta-analysis (version 3.3) softwares. The overall prevalence of methicillin resistant Staphylococcus aureus and its antibiotic resistance pattern were pooled by using the forest plot, table and figure with 95% CI. The pooled prevalence of methicillin resistant Staphylococcus aureus was 32.5% (95% CI, 24.1 to 40.9%). Moreover, methicillin resistant Staphylococcus aureus strains were found to be highly resistant to penicillin, ampicillin, erythromycin, and amoxicillin, with a pooled resistance ratio of 99.1, 98.1, 97.2 and 97.1%, respectively. On the other hand, comparably low levels of resistance ratio were noted to vancomycin, 5.3%. The overall burden of methicillin resistant Staphylococcus aureus is considerably high, besides these strains showed extreme resistance to penicillin, ampicillin, erythromycin and amoxicillin. In principle, appropriate use of antibiotics, applying safety precautions are the key to reduce the spread of multidrug resistant strains, methicillin resistant Staphylococcus aureus in particular.

  4. Fabrification of electroreduced graphene oxide–bentonite sodium composite modified electrode and its sensing application for linezolid

    International Nuclear Information System (INIS)

    Prashanth, S.N.; Teradal, Nagappa L.; Seetharamappa, J.; Satpati, Ashis K.; Reddy, A.V.R.

    2014-01-01

    Graphene and its composites have attracted considerable attention in synthesis and electrochemical applications. In the present work, we have synthesized and characterized graphene oxide-bentonite composite (GO-BEN) and utilized it to fabricate an electrochemical sensor. For this, the solution of GO-BEN cast on glassy carbon electrode (GCE) was reduced electrochemically in phosphate buffer solution of pH 6 to obtain electrochemically reduced graphene oxide-bentonite composite (ERGO-BEN-GCE). This ERGO-BEN film was used for electrochemical investigation of an oxazolidinone class of antibiotic, linezolid (LIN) for the first time. The electrochemical sensor showed excellent enhancement and adsorptive ability towards the electrooxidation of LIN. LIN exhibited two each of oxidation and reduction peaks on ERGO-BEN film in phosphate buffer of pH 7.0. Effects of accumulation time, pH of solution and scan rate were studied and various electrochemical parameters were evaluated. The plot of pH versus E p gave a slope of 26.2 mV/pH in the pH range of 4.2-8.0 indicating the participation of two electrons and one proton in the electrode process. An adsorptive stripping differential pulse voltammetric method (AdSDPV) was developed for the determination of LIN in bulk, pharmaceutical formulations and urine samples. Adsorptive stripping linear sweep voltammetric (AdSLSV) and differential pulse voltammetric (DPV) methods were also developed and the results were compared. LIN showed linear relationship between the current density and concentration in the range of 0.25 - 31.25 μM with a LOD of 0.0337 μM in AdSDPV method; 0.5 - 31.25 μM with a LOD of 0.100 μM in DPV method and 1.25 - 37.5 μM with a LOD of 0.5461 μM in AdSLSV method respectively. The proposed AdSDPV method was observed to be simple, fast and inexpensive and hence, could be readily adopted for quality control in pharmaceutical products

  5. 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.

  6. 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.

  7. Antibiotic Resistance Profiling of Staphylococcus aureus Isolated from Clinical Specimens in a Tertiary Hospital from 2010 to 2012

    Directory of Open Access Journals (Sweden)

    Alain C. Juayang

    2014-01-01

    Full Text Available MRSA infection can affect a wide array of individuals that may lead to treatment failure. Also, the infection has the potential to spread from one area to another particularly health care facilities or communities eventually causing minor outbreaks. With this premise, the study aimed to describe MRSA infections using the hospital-based data of a tertiary hospital in Bacolod City, Philippines, from 2010 to 2012. Specifically, this study aimed to evaluate the antimicrobial resistance of S. aureus isolated from clinical specimens and to put emphasis on the prevalence of MRSA and Inducible Clindamycin Resistance. A total of 94 cases from 2010 to 2012 were diagnosed to have S. aureus infection using conventional bacteriologic methods. From these cases, 38 (40.6% were identified as MRSA and 37 (39.4% were inducible clindamycin resistant. Wounds and abscesses were considered to be the most common specimens with MRSA infections having 71.05% while blood was the least with 5.3%. For drug susceptibility, out of the 94 S. aureus cases, including MRSA, 100% were susceptible to linezolid making it the drug of choice for this study. It was then followed by tetracycline having a mean susceptibility of 95%;, while penicillin G was ineffective with 94 cases having 0% susceptibility.

  8. Methicillin-resistant Staphylococcus aureus in Zimbabwe ...

    African Journals Online (AJOL)

    Resistance was high for most widely used drugs in Zimbabwe with high sensitivity to vancomycin, linezolid and teicoplanin. Conclusion: Although there are no recent reports in the literature of the presence of MRSA in Zimbabwe, this study documented a 7.0% prevalence. Resistance to common antibiotics is high and ...

  9. Characterization of Staphylococcus aureus nasal colonization rates ...

    African Journals Online (AJOL)

    No resistance was detected to linezolid and vancomycin in all isolates. Coagulase negative staphylococci carriage was 87% in all our volunteers and was highest in the HCWs (93%). In conclusion, the study shows the need for a periodic screening of both the community and hospital personnel to adopt strategies for treating ...

  10. Staphylococcus aureus Nasal Colonization Differs among Pig Lineages and Is Associated with the Presence of Other Staphylococcal Species.

    Science.gov (United States)

    Verstappen, Koen M; Willems, Eveline; Fluit, Ad C; Duim, Birgitta; Martens, Marc; Wagenaar, Jaap A

    2017-01-01

    Staphylococcus aureus is a common colonizer in pigs, with methicillin-resistant S. aureus (MRSA) in particular being a potential health risk to humans. To reduce the exposure to humans, the colonization in pigs should be reduced. The aim of this study was to quantitatively compare the susceptibility of pig lineages for S. aureus colonization, and if the absence of S. aureus could be associated with the presence or absence of other staphylococcal species. Nasal samples ( n  = 129) were obtained from seven different pig lineages in the Netherlands, France, and Germany. S. aureus and other staphylococci were enumerated from these samples by real-time (RT)-PCR and culture. Associations were explored between the presence of S. aureus and other staphylococci. S. aureus was detected by RT-PCR on all farms and in samples from pigs of all lineages. Twenty-five percent of the pigs from lineage F (from two farms) were colonized with S. aureus , while in all other lineages it was more than 50% ( p  Staphylococcus sciuri, Staphylococcus cohnii , and Staphylococcus saprophyticus were usually not found in combination with S. aureus in these samples. (i) pigs from different genetic lineages have different susceptibilities for colonization with S. aureus . These pigs might contain a genetic factor influencing nasal colonization. (ii) Colonization of S. aureus is also associated with the absence of S. sciuri, S. cohnii , or S. saprophyticus . (iii) The farm environment seems to influence the presence of S. aureus in pigs.

  11. 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

  12. Antimicrobial resistance and prevalence of CvfB, SEK and SEQ genes among Staphylococcus aureus isolates from paediatric patients with bloodstream infections.

    Science.gov (United States)

    Liang, Bing-Shao; Huang, Yan-Mei; Chen, Yin-Shuang; Dong, Hui; Mai, Jia-Liang; Xie, Yong-Qiang; Zhong, Hua-Min; Deng, Qiu-Lian; Long, Yan; Yang, Yi-Yu; Gong, Si-Tang; Zhou, Zhen-Wen

    2017-11-01

    Staphylococcus aureus ( S. aureus ) is one of the most frequently isolated pathogens in neonatal cases of early and late-onset sepsis. Drug resistance profiles and carriage of toxin genes may affect the treatment and outcome of an infection. The present study aimed to determine the antimicrobial resistance patterns and frequencies of the toxin-associated genes conserved virulence factor B (CvfB), staphylococcal enterotoxin Q (SEQ) and staphylococcal enterotoxin K (SEK) among S. aureus isolates recovered from paediatric patients with bloodstream infections (BSIs) in Guangzhou (China). Of the 53 isolates, 43.4% were methicillin-resistant S. aureus (MRSA), and resistance rates to penicillin, erythromycin, clindamycin, trimethoprim/sulfamethoxazole, tetracycline, and ciprofloxacin of 92.5, 66.0, 62.3, 13.2, 20.8 and 1.9% were recorded, respectively. However, no resistance to nitrofurantoin, dalfopristin/quinupristin, rifampicin, gentamicin, linezolid or vancomycin was detected. Resistance to erythromycin, clindamycin and tetracycline in the MRSA group was significantly higher than that in the methicillin-susceptible S. aureus (MSSA) group. No significant differences in antimicrobial resistance patterns were noted between two age groups (≤1 year and >1 year). The proportion of S. aureus isolates positive for CvfB, SEQ and SEK was 100, 34.0 and 35.8%, respectively, with 24.5% (13/53) of strains carrying all three genes. Compared with those in MSSA isolates, the rates of SEK, SEQ and SEK + SEQ carriage among MRSA isolates were significantly higher. Correlations were identified between the carriage of SEQ, SEK and SEQ + SEK genes and MRSA (contingency coefficient 0.500, 0.416, 0.546, respectively; Pstudy clarified the characteristics of BSI-associated S. aureus and enhanced the current understanding of the pathogenicity and treatment of MRSA.

  13. Dehydrosqualene Desaturase as a Novel Target for Anti-Virulence Therapy against Staphylococcus aureus.

    Science.gov (United States)

    Gao, Peng; Davies, Julian; Kao, Richard Yi Tsun

    2017-09-05

    Staphylococcus aureus , especially methicillin-resistant S. aureus (MRSA), is a life-threatening pathogen in hospital- and community-acquired infections. The golden-colored carotenoid pigment of S. aureus , staphyloxanthin, contributes to the resistance to reactive oxygen species (ROS) and host neutrophil-based killing. Here, we describe a novel inhibitor (NP16) of S. aureus pigment production that reduces the survival of S. aureus under oxidative stress conditions. Carotenoid components analysis, enzyme inhibition, and crtN mutational studies indicated that the molecular target of NP16 is dehydrosqualene desaturase (CrtN). S. aureus treated with NP16 showed increased susceptibility to human neutrophil killing and to innate immune clearance in a mouse infection model. Our study validates CrtN as a novel druggable target in S. aureus and presents a potent and effective lead compound for the development of virulence factor-based therapy against S. aureus IMPORTANCE S. aureus staphyloxanthin contributes substantially to pathogenesis by interfering with host immune clearance mechanisms, but it has little impact on ex vivo survival of the bacterium. Agents blocking staphyloxanthin production may discourage the establishment and maintenance of bacterial infection without exerting selective pressure for antimicrobial resistance. Our newly discovered CrtN inhibitor, NP16, may offer an effective strategy for combating S. aureus infections. Copyright © 2017 Gao et al.

  14. Characterization of pig-associated methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Li, Jun; Jiang, Nansong; Ke, Yuebin; Feßler, Andrea T; Wang, Yang; Schwarz, Stefan; Wu, Congming

    2017-03-01

    Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) have been reported in various countries worldwide. However, although China is one of the biggest pig and pork producers, large-scale studies on pig-associated LA-MRSA from China are scarce. The aims of this study were to analyze 2420 non-duplicate samples collected from pigs at swine farms and slaughterhouses in different regions in China during 2014 for the prevalence of pig-associated MRSA and to determine the antimicrobial resistance pheno- and genotypes of the respective isolates. MRSA isolates were identified in 270 (11.2%) samples. The isolates were characterized by antimicrobial susceptibility testing, multilocus sequence typing (MLST), spa typing, pulsed-field gel electrophoresis (PFGE) and screening for resistance genes. All MRSA isolates belonged to the clonal complex 9 and spa type t899, but showed variable PFGE patterns. All isolates were non-susceptible to oxacillin, cefoxitin, clindamycin, chloramphenicol, florfenicol, ciprofloxacin, and valnemulin. High rates of resistance were also observed for tetracycline (99.6%), erythromycin (97.0%), quinupristin-dalfopristin (97.0%), and gentamicin (80.4%). Three linezolid-non-susceptible isolates containing the multi-resistance gene cfr and nine rifampicin-non-susceptible isolates with mutations in rpoB were detected. Resistance to β-lactams was exclusively associated with mecA, while phenicol resistance was mainly attributable to fexA, except in the three cfr-positive isolates. The pleuromutilin-lincosamide-streptogramin A resistance gene lsa(E) was identified in all MRSA isolates, and no other pleuromutilin resistance genes, except cfr in three isolates, were detected. Pigs are the most important hosts of LA-MRSA in China. Screening for pig-associated MRSA is necessary to monitor changes in epidemiology and characteristics of these important pathogens. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Prevalence of nasal portal of Staphylococcus aureus in disabled children.

    Directory of Open Access Journals (Sweden)

    Clotilde Molin

    2016-06-01

    Full Text Available Introduction: Colonization of the nasal mucosa by Staphylococcus aureus set a carrier state. Which is recognized as a potential source of infection and a high risk factor for subsequent invasive infections. The prevalence of nasal carriage of this germ in disabled children in Paraguay is not known, thus contributing to the knowledge of their frequency and evaluate the profile of sensitivity to common antimicrobials was conducted this study, from May to July 2015.  Objective: to determine the prevalence of Staphylococcus aureus nasal carriage and profile of antimicrobial resistance in disabled children. Materials and Methods: A descriptive cross-sectional study in which 80 nasal swabs of children, who attended the service laboratory of SENADIS (Secretaria Nacional por los Derechos Humanos de las Personas con Discapacidad. The identification and sensitivity of germ was accomplished by conventional testing.  Results: 80 pediatric patients, 46 boys and 34 girls. 18 isolates of Staphylococcus aureus were obtained, corresponding to a prevalence of 22,5%. Susceptibility testing indicated that 14 strains were MSSA (Methicillin – Sensitive Staphylococcus aureus and 4 RMSA ( Methicillin- resistant Staphylococcus aureus. Conclusion: The prevalence of Staphylococcus aureus in a population with its own characteristics provides valuable data for the epidemiology, reflecting the need for continued vigilance and take steps to reduce associated infections. The detection of RMAR evidences their progress; it is important to evaluate the empirical treatment to primary care.

  16. Misidentification of methicillin-resistant Staphylococcus aureus (MRSA) in hospitals in Tripoli, Libya

    Science.gov (United States)

    Ahmed, Mohamed O.; Abuzweda, Abdulbaset R.; Alghazali, Mohamed H.; Elramalli, Asma K.; Amri, Samira G.; Aghila, Ezzeddin Sh.; Abouzeed, Yousef M.

    2010-01-01

    Background Methicillin-resistant Staphylococcus aureus (MRSA) is a nosocomial (hospital-acquired) pathogen of exceptional concern. It is responsible for life-threatening infections in both the hospital and the community. Aims To determine the frequency of MRSA misidentification in hospitals in Tripoli, Libya using current testing methods. Methods One hundred and seventy S. aureus isolates previously identified as MRSA were obtained from three hospitals in Tripoli. All isolates were reidentified by culturing on mannitol salt agar, API 20 Staph System and retested for resistance to methicillin using the cefoxitin disk diffusion susceptibility test and PBP2a. D-tests and vancomycin E-tests (Van-E-tests) were also performed for vancomycin-resistant isolates. Results Of the 170 isolates examined, 86 (51%) were confirmed as MRSA (i.e. 49% were misidentified as MRSA). Fifteen (17%) of the confirmed MRSA strains exhibited inducible clindamycin resistance. Of the 86 confirmed MRSA isolates, 13 (15%) were resistant to mupirocin, 53 (62%) were resistant to ciprofloxacin, 41 (48%) were resistant to trimethoprim-sulfamethoxazole, and none were resistant to linezolid. Although disc-diffusion testing indicated that 23 (27%) of the isolates were resistant to vancomycin, none of the isolates were vancomycin-resistant by Van-E-test. Conclusions Misidentification of nosocomial S. aureus as MRSA is a serious problem in Libyan hospitals. There is an urgent need for the proper training of microbiology laboratory technicians in standard antimicrobial susceptibility procedures and the implementation of quality control programs in microbiology laboratories of Libyan hospitals. PMID:21483574

  17. Molecular and phenotypic characteristics of methicillin-resistant Staphylococcus aureus isolated from hospitalized patients.

    Science.gov (United States)

    de Oliveira, Caio Ferreira; Morey, Alexandre Tadachi; Santos, Jussevania Pereira; Gomes, Ludmila Vilela Pereira; Cardoso, Juscélio Donizete; Pinge-Filho, Phileno; Perugini, Márcia Regina Eches; Yamauchi, Lucy Megumi; Yamada-Ogatta, Sueli Fumie

    2015-07-30

    Methicillin-resistant Staphylococcus aureus (MRSA) is one of the leading causes of infections acquired in both community and hospital settings. In this study, MRSA isolated from different sources of hospitalized patients was characterized by molecular and phenotypic methods. A total of 123 S. aureus isolates were characterized according to their genetic relatedness by repetitive element sequence based-PCR (REP-PCR), in vitro antimicrobial susceptibility profile, SCCmec typing and presence of seven virulence factor-encoding genes. REP-PCR fingerprinting showed low relatedness between the isolates, and the predominance of one specific lineage or clonal group was not observed. All isolates were susceptible to teicoplanin and linezolide. All isolates were resistant to cefoxitin and penicillin, and the majority were also resistant to one or more other antimicrobials. Fifty isolates (41.7%) were intermediately resistant to vancomycin. Most isolates harbored SCCmec type II (53.7%), followed by type I (22.8%), type IV (8.1%) and type III (1.6%). All isolates harbored at least two virulence factor-encoding genes, and the prevalence was as follows: coa, 100%; icaA, 100%; hla, 13.0%; hlb, 91.1%, hld, 91.1%; lukS-PV and lukF-PV, 2.4%; and tst, 34.1%. A positive association with the presence of hla and SCCmec type II, and tst and SCCmec type I was observed. This study showed the high virulence potential of multidrug-resistant MRSA circulating in a teaching hospital. A high prevalence of MRSA showing intermediate vancomycin resistance was also observed, indicating the urgent need to improve strategies for controlling the use of antimicrobials for appropriate management of S. aureus infections.

  18. Intracellular activity of antibiotics in a model of human THP-1 macrophages infected by a Staphylococcus aureus small-colony variant strain isolated from a cystic fibrosis patient: pharmacodynamic evaluation and comparison with isogenic normal-phenotype and revertant strains.

    Science.gov (United States)

    Nguyen, Hoang Anh; Denis, Olivier; Vergison, Anne; Theunis, Anne; Tulkens, Paul M; Struelens, Marc J; Van Bambeke, Françoise

    2009-04-01

    Small-colony variant (SCV) strains of Staphylococcus aureus show reduced antibiotic susceptibility and intracellular persistence, potentially explaining therapeutic failures. The activities of oxacillin, fusidic acid, clindamycin, gentamicin, rifampin, vancomycin, linezolid, quinupristin-dalfopristin, daptomycin, tigecycline, moxifloxacin, telavancin, and oritavancin have been examined in THP-1 macrophages infected by a stable thymidine-dependent SCV strain in comparison with normal-phenotype and revertant isogenic strains isolated from the same cystic fibrosis patient. The SCV strain grew slowly extracellularly and intracellularly (1- and 0.2-log CFU increase in 24 h, respectively). In confocal and electron microscopy, SCV and the normal-phenotype bacteria remain confined in acid vacuoles. All antibiotics tested, except tigecycline, caused a net reduction in bacterial counts that was both time and concentration dependent. At an extracellular concentration corresponding to the maximum concentration in human serum (total drug), oritavancin caused a 2-log CFU reduction at 24 h; rifampin, moxifloxacin, and quinupristin-dalfopristin caused a similar reduction at 72 h; and all other antibiotics had only a static effect at 24 h and a 1-log CFU reduction at 72 h. In concentration dependence experiments, response to oritavancin was bimodal (two successive plateaus of -0.4 and -3.1 log CFU); tigecycline, moxifloxacin, and rifampin showed maximal effects of -1.1 to -1.7 log CFU; and the other antibiotics produced results of -0.6 log CFU or less. Addition of thymidine restored intracellular growth of the SCV strain but did not modify the activity of antibiotics (except quinupristin-dalfopristin). All drugs (except tigecycline and oritavancin) showed higher intracellular activity against normal or revertant phenotypes than against SCV strains. The data may help rationalizing the design of further studies with intracellular SCV strains.

  19. Emergence of methicillin-resistant coagulase-negative staphylococci resistant to linezolid with rRNA gene C2190T and G2603T mutations.

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    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.

  20. 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.

  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. 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.

  3. 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

  4. In vitro activities of ramoplanin, teicoplanin, vancomycin, linezolid, bacitracin, and four other antimicrobials against intestinal anaerobic bacteria.

    Science.gov (United States)

    Citron, D M; Merriam, C V; Tyrrell, K L; Warren, Y A; Fernandez, H; Goldstein, E J C

    2003-07-01

    By using an agar dilution method, the in vitro activities of ramoplanin, teicoplanin, vancomycin, linezolid, and five other agents were determined against 300 gram-positive and 54 gram-negative strains of intestinal anaerobes. Ramoplanin was active at Eubacterium, Actinomyces, Propionibacterium, and Peptostreptococcus spp. were inhibited by spp. were >or=256 microg/ml. Ramoplanin displays excellent activity against C. difficile and other gram-positive enteric anaerobes, including vancomycin-resistant strains; however, it has poor activity against most gram-negative anaerobes and thus potentially has a lesser effect on the ecological balance of normal fecal flora.

  5. Antimicrobial susceptibility of microorganisms isolated from sputum culture of patients with cystic fibrosis: Methicillin-resistant Staphylococcus aureus as a serious concern.

    Science.gov (United States)

    Mazloomi Nobandegani, Narges; Mahmoudi, Shima; Pourakbari, Babak; Hosseinpour Sadeghi, Reihaneh; Najafi Sani, Mehri; Farahmand, Fateme; Motamed, Farzaneh; Nabavizadeh Rafsanjani, Raheleh; Mamishi, Setareh

    2016-11-01

    Infection is a major cause of morbidity and mortality in patients with cystic fibrosis (CF). Antimicrobial resistance of the bacterial spp. particularly methicillin resistance in Staphylococcus aureus has caused a lot of attention. The aim of this study was to describe the prevalence of S. aureus, Pseudomonas aeruginosa and Burkholderia cepacia-complex as well as their antimicrobial susceptibility patterns in CF patients in an Iranian referral pediatrics Hospital. From March 2011 until February 2012, 172 samples were collected at the Children Medical Center (CMC), an Iranian referral hospital in Tehran, Iran. Sputum specimens were cultured for the following bacterial pathogens: P. aeruginosa, S. aureus, B. cepacia complex. Antimicrobial susceptibility was performed according to the Clinical Laboratory Standards Institute recommendations. In our study, 54% of the patients (n = 93) harbored at least once S. aureus, 30% (n = 52) P. aeruginosa, and 2% (n = 3) Burkholderia cepacia. In 40 patients (23%), none of these organisms was grown. An increasing colonization rate of P. aeruginosa in the second decade of life was found. In contrast, the colonization rate of S. aureus was constant in both decades of life. Methicillin resistant S. aureus (MRSA) was detected in 40 isolates (43%). Among MRSA, no resistance against vancomycin, linezolid and quinupristin/dalfopristin occurred. The susceptibility of P. aeruginosa isolates to meropenem, imipenem, doripenem, levofloxacin and polymixin B were more than 90%. The prevalence of MRSA has been rising. Since its impact on clinical outcomes, optimal prevention and treatment strategies are unclear, further studies to expand the knowledge about the infection control strategies and MRSA treatment are highly recommended. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Frequency of methicillin resistant Staphylococcus aureus in health care

    Directory of Open Access Journals (Sweden)

    Somayeh Rahimi-Alang

    2011-03-01

    Full Text Available Background: Methicillin resistant Staphylococcus aureus (MRSA is one of the most important pathogen in hospitals. Healthcare personnel are the main source of nosocomial infections and identification and control of MRSA carriers can reduce incidence of infections. The aim of this study was to determine the prevalence of MRSA and their antibiotic susceptibility profile among healthcare workers in Gorgan.Materials and Method: 333 healthcare workers were participated in this cross-sectional study in 2009. Samples were taken with sterile cotton swabs from both anterior nares and hands. Swabs were plated immediately on to the mannitol salt agar. Suspected colonies were confirmed as S. aureus by Gram staining, catalase, coagulase and DNase tests. Minimum inhibition concentration by micro dilution broth method was used to determine methicillin resistant strains. Antimicrobial susceptibility to other antibiotics was performed according to NCCLS guidelines by disc diffusion method.Result: Frequency of S.aureus and MRSA carriers among healthcare workers was 24% and 3% respectively. The highest rate of S. aureus and MRSA carriers were observed in operating room staff. Resistance to penicillin was seen in 97.5% of isolates and all strains were sensitive to vancomycin.Conclusions: Frequency of S. aureus and MRSA in healthcare workers was median and rather low respectively. Continual monitoring and control of carriers can reduce distribution of this organism and their infections

  7. In Vitro Synergy of Telavancin and Rifampin Against Enterococcus faecium Resistant to Both Linezolid and Vancomycin.

    Science.gov (United States)

    Pankey, George A; Ashcraft, Deborah S

    2013-01-01

    An emerging pathogen is Enterococcus faecium resistant to both linezolid and vancomycin (LRVRE). Antimicrobial combinations may be required for therapy and need to be evaluated. The combination of daptomycin and rifampin has demonstrated good in vitro activity against gram-positive bacteria, including E faecium. Telavancin, a newer lipoglycopeptide, has shown in vitro activity against E faecium. We evaluated the combination of telavancin and rifampin and compared the results to the combination of daptomycin and rifampin used previously on the same isolates. Twenty-four genetically unique (by pulsed-field gel electrophoresis), clinical LRVRE isolates were collected in the United States from 2001-2004. Etest minimal inhibitory concentrations (MICs) (μg/mL) were 0.064-8 for telavancin, 1-4 for daptomycin, and 0.012 to >32 for rifampin. In vitro synergy testing was performed in triplicate by an Etest MIC:MIC ratio method, and summation fractional inhibitory concentration (ΣFIC) was calculated: synergy ≤0.5; indifference >0.5-4; and antagonism >4. The Etest method showed synergy (ΣFICs of 0.1-0.5) with telavancin + rifampin in 20/24 (83%) isolates and indifference (ΣFICs of 0.6-0.8) in 4/24 (17%) isolates. Similarly, the daptomycin + rifampin combination showed synergy (ΣFICs of 0.1-0.5) in 21/24 (88%) isolates and indifference (ΣFICs of 0.6-1.0) in 3/24 (12%) isolates by the Etest method. No antagonism was found. In vitro synergy with both combinations (rifampin + telavancin or daptomycin) was 83% and 88%, respectively, by Etest against these LRVRE isolates. Although both daptomycin and telavancin in combination with rifampin showed a high incidence of synergistic activity, further in vitro synergy testing with this combination should be performed against additional E faecium isolates. In vitro synergy may or may not translate into in vivo effectiveness.

  8. Emergence and dissemination of a linezolid-resistant Staphylococcus capitis clone in Europe.

    Science.gov (United States)

    Butin, M; Martins-Simões, P; Pichon, B; Leyssene, D; Bordes-Couecou, S; Meugnier, H; Rouard, C; Lemaitre, N; Schramm, F; Kearns, A; Spiliopoulou, I; Hyyryläinen, H-L; Dumitrescu, O; Vandenesch, F; Dupieux, C; Laurent, F

    2017-04-01

    We investigated the epidemiological, clinical, microbiological and genetic characteristics of linezolid-resistant (LZR) Staphylococcus capitis isolates from French ICUs, and compared them with LZR S. capitis isolates from other European countries. All LZR isolates were subjected to antimicrobial susceptibility testing (AST) and the presence of cfr and optrA genes as well as mutations in the 23S rRNA and ribosomal proteins were investigated using specific PCR with sequencing. The genetic relationship between isolates was investigated using PFGE and WGS. Epidemiological data concerning LZR S. capitis were collected retrospectively in French microbiology laboratories. Twenty-one LZR isolates were studied: 9 from France, 11 from Greece and 1 from Finland. All were resistant to methicillin and aminoglycosides. In addition, this unusual AST profile was identified in S. capitis isolates from seven French hospitals, and represented up to 12% of the S. capitis isolates in one centre. A G2576T mutation in 23S rRNA was identified in all isolates; cfr and optrA genes were absent. All isolates belonged to the same clone on the basis of their PFGE profiles, whatever their geographical origin. WGS found at most 212 SNPs between core genomes of the LZR isolates. We identified and characterized an LZR S. capitis clone disseminated in three European countries, harbouring the same multiple resistance and a G2576T mutation in the 23S rRNA. The possible unrecognized wider distribution of this clone, belonging to a species classically regarded as a low-virulence skin colonizer, is of major concern not least because of the increasing use of oxazolidinones. © 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.

  9. Inhibition of Staphylococcus aureus invasion into bovine mammary epithelial cells by contact with live Lactobacillus casei.

    Science.gov (United States)

    Bouchard, Damien S; Rault, Lucie; Berkova, Nadia; Le Loir, Yves; Even, Sergine

    2013-02-01

    Staphylococcus aureus is a major pathogen that is responsible for mastitis in dairy herds. S. aureus mastitis is difficult to treat and prone to recurrence despite antibiotic treatment. The ability of S. aureus to invade bovine mammary epithelial cells (bMEC) is evoked to explain this chronicity. One sustainable alternative to treat or prevent mastitis is the use of lactic acid bacteria (LAB) as mammary probiotics. In this study, we tested the ability of Lactobacillus casei strains to prevent invasion of bMEC by two S. aureus bovine strains, RF122 and Newbould305, which reproducibly induce acute and moderate mastitis, respectively. L. casei strains affected adhesion and/or internalization of S. aureus in a strain-dependent manner. Interestingly, L. casei CIRM-BIA 667 reduced S. aureus Newbould305 and RF122 internalization by 60 to 80%, and this inhibition was confirmed for two other L. casei strains, including one isolated from bovine teat canal. The protective effect occurred without affecting bMEC morphology and viability. Once internalized, the fate of S. aureus was not affected by L. casei. It should be noted that L. casei was internalized at a low rate but survived in bMEC cells with a better efficiency than that of S. aureus RF122. Inhibition of S. aureus adhesion was maintained with heat-killed L. casei, whereas contact between live L. casei and S. aureus or bMEC was required to prevent S. aureus internalization. This first study of the antagonism of LAB toward S. aureus in a mammary context opens avenues for the development of novel control strategies against this major pathogen.

  10. Inhibition of Staphylococcus aureus Invasion into Bovine Mammary Epithelial Cells by Contact with Live Lactobacillus casei

    Science.gov (United States)

    Bouchard, Damien S.; Rault, Lucie; Berkova, Nadia; Le Loir, Yves

    2013-01-01

    Staphylococcus aureus is a major pathogen that is responsible for mastitis in dairy herds. S. aureus mastitis is difficult to treat and prone to recurrence despite antibiotic treatment. The ability of S. aureus to invade bovine mammary epithelial cells (bMEC) is evoked to explain this chronicity. One sustainable alternative to treat or prevent mastitis is the use of lactic acid bacteria (LAB) as mammary probiotics. In this study, we tested the ability of Lactobacillus casei strains to prevent invasion of bMEC by two S. aureus bovine strains, RF122 and Newbould305, which reproducibly induce acute and moderate mastitis, respectively. L. casei strains affected adhesion and/or internalization of S. aureus in a strain-dependent manner. Interestingly, L. casei CIRM-BIA 667 reduced S. aureus Newbould305 and RF122 internalization by 60 to 80%, and this inhibition was confirmed for two other L. casei strains, including one isolated from bovine teat canal. The protective effect occurred without affecting bMEC morphology and viability. Once internalized, the fate of S. aureus was not affected by L. casei. It should be noted that L. casei was internalized at a low rate but survived in bMEC cells with a better efficiency than that of S. aureus RF122. Inhibition of S. aureus adhesion was maintained with heat-killed L. casei, whereas contact between live L. casei and S. aureus or bMEC was required to prevent S. aureus internalization. This first study of the antagonism of LAB toward S. aureus in a mammary context opens avenues for the development of novel control strategies against this major pathogen. PMID:23183972

  11. Lysionotin attenuates Staphylococcus aureus pathogenicity by inhibiting α-toxin expression.

    Science.gov (United States)

    Teng, Zihao; Shi, Dongxue; Liu, Huanyu; Shen, Ziying; Zha, Yonghong; Li, Wenhua; Deng, Xuming; Wang, Jianfeng

    2017-09-01

    α-Toxin, one of the best known pore-forming proteins produced by Staphylococcus aureus (S. aureus), is a critical virulence factor in multiple infections. The necessity of α-toxin for S. aureus pathogenicity suggests that this toxin is an important target for the development of a potential treatment strategy. In this study, we showed that lysionotin, a natural compound, can inhibit the hemolytic activity of culture supernatants by S. aureus by reducing α-toxin expression. Using real-time PCR analysis, we showed that transcription of hla (the gene encoding α-toxin) and agr (the locus regulating hla) was significantly inhibited by lysionotin. Lactate dehydrogenase and live/dead assays indicated that lysionotin effectively protected human alveolar epithelial cells against S. aureus, and in vivo studies also demonstrated that lysionotin can protect mice from pneumonia caused by S. aureus. These findings suggest that lysionotin is an efficient inhibitor of α-toxin expression and shows significant protection against S. aureus in vitro and in vivo. This study supports a potential strategy for the treatment of S. aureus infection by inhibiting the expression of virulence factors and indicates that lysionotin may be a potential treatment for S. aureus pneumonia.

  12. Inducible clindamycin and methicillin resistant Staphylococcus aureus in a tertiary care hospital, Kathmandu, Nepal.

    Science.gov (United States)

    Adhikari, R P; Shrestha, S; Barakoti, A; Amatya, R

    2017-07-11

    Staphylococcus aureus, an important nosocomial pathogen, is frequently associated with infections in human. The management of the infections by it especially methicillin resistant ones is often difficult because methicillin resistant S. aureus is usually resistant to multiple antibiotics. Macrolide-lincosamide streptogramin B family of antibiotics is commonly used to treat such infections as an alternative to vancomycin. This study was conducted over the period of one and half year from November 2013-April 2015 in Microbiology laboratory of Nepal Medical College and Teaching Hospital, Kathmandu, Nepal to find the incidence of different phenotypes of MLS B resistance among S. aureus from clinical samples and their association with methicillin resistance. Two hundred seventy isolates of S. aureus were included in the study. Methicillin resistance was detected by cefoxitin disc diffusion method and inducible clindamycin resistance by erythromycin and clindamycin disc approximation test (D-test). Of the 270 clinical isolates of S. aureus, 25.1% (68/270) were MRSA. Erythromycin and clindamycin resistance was seen in 54.4% (147/270) and 41.8% (113/270) isolates respectively. Resistance to erythromycin and clindamycin were higher in MRSA as compared to MSSA (erythromycin-resistance: 88.2% Vs 39.1% and clindamycin-resistance: 79.4% Vs 41.8%). The overall prevalence of i MLS B and c MLS B phenotype was 11.48% (31/270) and 29.25% (79/270) respectively. Both i MLS B and c MLS B phenotypes predominated in MRSA strains. Detection rate of MRSA in our study shows the necessity to improve in healthcare practices and to formulate new policy for the control of MRSA infections. Clindamycin resistance in the form of i MLS B and c MLS B especially among MRSA emphasizes the need of D-test to be performed routinely in our set up while using clindamycin as an alternative choice to anti-staphylococcal antibiotics like vancomycin and linezolid in the treatment of staphylococcal infections.

  13. Staphylococcus aureus Nasal Colonization Differs among Pig Lineages and Is Associated with the Presence of Other Staphylococcal Species

    Directory of Open Access Journals (Sweden)

    Koen M. Verstappen

    2017-06-01

    Full Text Available Staphylococcus aureus is a common colonizer in pigs, with methicillin-resistant S. aureus (MRSA in particular being a potential health risk to humans. To reduce the exposure to humans, the colonization in pigs should be reduced. The aim of this study was to quantitatively compare the susceptibility of pig lineages for S. aureus colonization, and if the absence of S. aureus could be associated with the presence or absence of other staphylococcal species. Nasal samples (n = 129 were obtained from seven different pig lineages in the Netherlands, France, and Germany. S. aureus and other staphylococci were enumerated from these samples by real-time (RT-PCR and culture. Associations were explored between the presence of S. aureus and other staphylococci. S. aureus was detected by RT-PCR on all farms and in samples from pigs of all lineages. Twenty-five percent of the pigs from lineage F (from two farms were colonized with S. aureus, while in all other lineages it was more than 50% (p < 0.01. Moreover, in S. aureus-positive samples from pigs of lineage F smaller amounts of S. aureus were found than in other lineages. Staphylococcus sciuri, Staphylococcus cohnii, and Staphylococcus saprophyticus were usually not found in combination with S. aureus in these samples. In conclusion: (i pigs from different genetic lineages have different susceptibilities for colonization with S. aureus. These pigs might contain a genetic factor influencing nasal colonization. (ii Colonization of S. aureus is also associated with the absence of S. sciuri, S. cohnii, or S. saprophyticus. (iii The farm environment seems to influence the presence of S. aureus in pigs.

  14. Tratamento e prevenção das infecções e da colonização por Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Isabel Ribeiro

    2003-09-01

    resistant strains, the use of antibiotherapy must be optimised, laboratory methods for the detection of resistant pathogens must be enhanced and strict precautions should be taken following of the infection or colonization of patients 6−10.In this paper, we review anti-staphylococci history evolution and point out the present recommendations for the treatment and prevention of Staphylococcus aureus infections and colonization.REV PORT PNEUMOL 2003; IX (5: 395-409 Palavras-chave: Staphylococcus aureus, estafilococos meticilino-resistentes, anti-estafilocócicos, oxacillina, glicopeptídeos, vancomicina, linezolide, dalfopristina-quinopristina, Key-words: Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, anti-staphylococci, oxacillin, glycopeptide, vancomycin, linezolid, dalfopristin-quinopristin

  15. Staphylococcus aureus small colony variants in diabetic foot infections

    Directory of Open Access Journals (Sweden)

    Estrella Cervantes-García

    2015-03-01

    Full Text Available Background: Staphylococcus aureus (S. aureus is one of the major pathogens causing chronic infections. The ability of S. aureus to acquire resistance to a diverse range of antimicrobial compounds results in limited treatment options, particularly in methicillin-resistant S. aureus (MRSA. A mechanism by which S. aureus develops reduced susceptibility to antimicrobials is through the formation of small colony variants (SCVs. Infections by SCVs of S. aureus are an upcoming problem due to difficulties in laboratory diagnosis and resistance to antimicrobial therapy. Methods: A prospective study was performed on 120 patients diagnosed with both type 2 diabetes mellitus and infected diabetic foot ulcers. The study was carried out from July 2012 to December 2013 in Hospital General de Mexico. The samples were cultured in blood agar, mannitol salt agar, and MacConkey agar media, and incubated at 37°C in aerobic conditions. Results: We describe the first known cases of diabetic foot infections caused by MRSA-SCVs in patients diagnosed with type 2 diabetes mellitus and infected diabetic foot ulcers. In all of our cases, the patients had not received any form of gentamicin therapy. Conclusions: The antibiotic therapy commonly used in diabetic patients with infected diabetic foot ulcers fails in the case of MRSA-SCVs because the intracellular location protects S. aureus-SCVs from the host's defenses and also helps them resist antibiotics. The cases studied in this article add to the spectrum of persistent and relapsing infections attributed to MRSA-SCVs and emphasizes that these variants may also play a relevant role in diabetic foot infections.

  16. Curcumin Reverse Methicillin Resistance in Staphylococcus aureus

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    Su-Hyun Mun

    2014-11-01

    Full Text Available Curcumin, a natural polyphenolic flavonoid extracted from the rhizome of Curcuma longa L., was shown to possess superior potency to resensitize methicillin-resistant Staphylococcus aureus (MRSA to antibiotics. Previous studies have shown the synergistic activity of curcumin with β-lactam and quinolone antibiotics. Further, to understand the anti-MRSA mechanism of curcumin, we investigated the potentiated effect of curcumin by its interaction in diverse conditions. The mechanism of anti-MRSA action of curcumin was analyzed by the viability assay in the presence of detergents, ATPase inhibitors and peptidoglycan (PGN from S. aureus, and the PBP2a protein level was analyzed by western blotting. The morphological changes in the curcumin-treated MRSA strains were investigated by transmission electron microscopy (TEM. We analyzed increased susceptibility to MRSA isolates in the presence of curcumin. The optical densities at 600 nm (OD600 of the suspensions treated with the combinations of curcumin with triton X-100 and Tris were reduced to 63% and 59%, respectively, compared to curcumin without treatment. N,N'-dicyclohexylcarbodiimide (DCCD and sodium azide (NaN3 were reduced to 94% and 55%, respectively. When peptidoglycan (PGN from S. aureus was combined with curcumin, PGN (0–125 μg/mL gradually blocked the antibacterial activity of curcumin (125 μg/mL; however, at a concentration of 125 µg/mL PGN, it did not completely block curcumin. Curcumin has a significant effect on the protein level of PBP2a. The TEM images of MRSA showed damage of the cell wall, disruption of the cytoplasmic contents, broken cell membrane and cell lysis after the treatment of curcumin. These data indicate a remarkable antibacterial effect of curcumin, with membrane permeability enhancers and ATPase inhibitors, and curcumin did not directly bind to PGN on the cell wall. Further, the antimicrobial action of curcumin involved in the PBP2a-mediated resistance mechanism was

  17. Loading of atorvastatin and linezolid in β-cyclodextrin–conjugated cadmium selenide/silica nanoparticles: A spectroscopic study

    International Nuclear Information System (INIS)

    Antony, Eva Janet; Shibu, Abhishek; Ramasamy, Sivaraj; Paulraj, Mosae Selvakumar; Enoch, Israel V.M.V.

    2016-01-01

    The preparation of β–cyclodextrin–conjugated cadmium selenide–silica nanoparticles, the loading of two drugs viz., Atorvastatin and linezolid in the cyclodextrin cavity, and the fluorescence energy transfer between CdSe/SiO_2 nanoparticles and the drugs encapsulated in the cyclodextrin cavity are reported in this paper. IR spectroscopy, X-ray diffractometry, transmission electron microscopy, and particle size analysis by light–scattering experiment were used as the tools of characterizing the size and the crystal system of the nanoparticles. The nanoparticles fall under hexagonal system. The silica–shell containing CdSe nanoparticles were functionalized by reaction with aminoethylamino–β–cyclodextrin. Fluorescence spectra of the nanoparticles in their free and drug–encapsulated forms were studied. The FÖrster distances between the encapsulated drugs and the CdSe nanoparticles are below 3 nm. The change in the FÖrster resonance energy parameters under physiological conditions may aid in tracking the release of drugs from the cavity of the cyclodextrin. - Highlights: • CdSe/SiO_2 nanoparticles of crystallite size 15 nm are prepared. • β-Cyclodextrin is attached to the surface of the nanoparticles. • Atorvastatin and linezolid get encapsulated in the cyclodextrin cavity. • FRET efficiency between the nanoparticles and the loaded drugs are determined.

  18. Loading of atorvastatin and linezolid in β-cyclodextrin–conjugated cadmium selenide/silica nanoparticles: A spectroscopic study

    Energy Technology Data Exchange (ETDEWEB)

    Antony, Eva Janet; Shibu, Abhishek [Department of Nanosciences & Technology, Karunya University, Coimbatore 641114, Tamil Nadu (India); Ramasamy, Sivaraj; Paulraj, Mosae Selvakumar [Department of Chemistry, Karunya University, Coimbatore 641114, Tamil Nadu (India); Enoch, Israel V.M.V., E-mail: drisraelenoch@gmail.com [Department of Nanosciences & Technology, Karunya University, Coimbatore 641114, Tamil Nadu (India); Department of Chemistry, Karunya University, Coimbatore 641114, Tamil Nadu (India)

    2016-08-01

    The preparation of β–cyclodextrin–conjugated cadmium selenide–silica nanoparticles, the loading of two drugs viz., Atorvastatin and linezolid in the cyclodextrin cavity, and the fluorescence energy transfer between CdSe/SiO{sub 2} nanoparticles and the drugs encapsulated in the cyclodextrin cavity are reported in this paper. IR spectroscopy, X-ray diffractometry, transmission electron microscopy, and particle size analysis by light–scattering experiment were used as the tools of characterizing the size and the crystal system of the nanoparticles. The nanoparticles fall under hexagonal system. The silica–shell containing CdSe nanoparticles were functionalized by reaction with aminoethylamino–β–cyclodextrin. Fluorescence spectra of the nanoparticles in their free and drug–encapsulated forms were studied. The FÖrster distances between the encapsulated drugs and the CdSe nanoparticles are below 3 nm. The change in the FÖrster resonance energy parameters under physiological conditions may aid in tracking the release of drugs from the cavity of the cyclodextrin. - Highlights: • CdSe/SiO{sub 2} nanoparticles of crystallite size 15 nm are prepared. • β-Cyclodextrin is attached to the surface of the nanoparticles. • Atorvastatin and linezolid get encapsulated in the cyclodextrin cavity. • FRET efficiency between the nanoparticles and the loaded drugs are determined.

  19. Density functional theory, comparative vibrational spectroscopic studies, highest occupied molecular orbital and lowest unoccupied molecular orbital analysis of Linezolid

    Science.gov (United States)

    Rajalakshmi, K.; Gunasekaran, S.; Kumaresan, S.

    2015-06-01

    The Fourier transform infrared spectra and Fourier transform Raman spectra of Linezolid have been recorded in the regions 4,000-400 and 4,000-100 cm-1, respectively. Utilizing the observed Fourier transform infrared spectra and Fourier transform Raman spectra data, a complete vibrational assignment and analysis of the fundamental modes of the compound have been carried out. The optimum molecular geometry, harmonic vibrational frequencies, infrared intensities and Raman scattering activities, have been calculated by density functional theory with 6-31G(d,p), 6-311G(d,p) and M06-2X/6-31G(d,p) levels. The difference between the observed and scaled wavenumber values of most of the fundamentals is very small. A detailed interpretation of the infrared and Raman spectra of Linezolid is reported. Mulliken's net charges have also been calculated. Ultraviolet-visible spectrum of the title molecule has also been calculated using time-dependent density functional method. Besides, molecular electrostatic potential, highest occupied molecular orbital and lowest unoccupied molecular orbital analysis and several thermodynamic properties have been performed by the density functional theoretical method.

  20. Staphylococcus aureus nasal colonization differs among pig lineages and is associated with the presence of other staphylococcal species

    NARCIS (Netherlands)

    Verstappen, Koen M.; Willems, Eveline; Fluit, Ad C.; Duim, Birgitta; Martens, Marc; Wagenaar, Jaap A.

    2017-01-01

    Staphylococcus aureus is a common colonizer in pigs, with methicillin-resistant S. aureus (MRSA) in particular being a potential health risk to humans. To reduce the exposure to humans, the colonization in pigs should be reduced. The aim of this study was to quantitatively compare the susceptibility

  1. Staphylococcus aureus Nasal Colonization Differs among Pig Lineages and Is Associated with the Presence of Other Staphylococcal Species

    NARCIS (Netherlands)

    Verstappen, Koen M; Willems, Eveline; Fluit, Ad C; Duim, Birgitta; Martens, Marc; Wagenaar, Jaap A

    2017-01-01

    Staphylococcus aureus is a common colonizer in pigs, with methicillin-resistant S. aureus (MRSA) in particular being a potential health risk to humans. To reduce the exposure to humans, the colonization in pigs should be reduced. The aim of this study was to quantitatively compare the susceptibility

  2. Invasive Community-Acquired Methicillin-Resistant Staphylococcus aureus in a Japanese Girl with Disseminating Multiple Organ Infection: A Case Report and Review of Japanese Pediatric Cases

    Directory of Open Access Journals (Sweden)

    Ryuta Yonezawa

    2015-01-01

    Full Text Available Pediatric invasive community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA infection is very serious and occasionally fatal. This infectious disease is still a relatively rare and unfamiliar infectious disease in Japan. We report a positive outcome in a 23-month-old Japanese girl with meningitis, osteomyelitis, fasciitis, necrotizing pneumonia, urinary tract infection, and bacteremia due to CA-MRSA treated with linezolid. PCR testing of the CA-MRSA strain was positive for PVL and staphylococcal enterotoxin b and negative for ACME. SCC mec was type IVa. This case underscores the selection of effective combinations of antimicrobial agents for its treatment. We need to be aware of invasive CA-MRSA infection, which rapidly progresses with a serious clinical course, because the incidence of the disease may be increasing in Japan.

  3. Antimicrobial resistant coagulase positive Staphylococcus aureus ...

    African Journals Online (AJOL)

    ADEYEYE

    S. aureus is associated with many clinical syndromes including tenosynovitis, omphalitis, femoral head necrosis, .... Markey, 2008) where occurrence of multidrug ... Staphylococcus aureus isolates from bovine mastitis in. Denmark. Veterinary.

  4. Human factor in Staphylococcus aureus nasal carriage

    NARCIS (Netherlands)

    J.L. Nouwen (Jan); H.A.M. Boelens (Hélène); A.F. van Belkum (Alex); H.A. Verbrugh (Henri)

    2004-01-01

    textabstractPersistent nasal carriers and noncarriers of Staphylococcus aureus were inoculated with a mixture of different S. aureus strains. The majority of noncarriers and nearly all persistent carriers returned to their original carrier state after artificial inoculation. Furthermore, the

  5. Antibiotic susceptibility of Staphylococcus aureus in suppurative ...

    African Journals Online (AJOL)

    1299, p<0.05) and Methicillin resistance was confirmed by PCR. Conclusion: Staphylococcus aureus is highly prevalent and more resistant in inpatients. There is a higher risk of acquiring drug resistant staphylococcus aureus infection in ...

  6. Methicillin-resistant Staphylococcus aureus (MRSA)

    Science.gov (United States)

    Methicillin-resistant Staphylococcus aureus; Hospital-acquired MRSA (HA-MRSA); Staph - MRSA; Staphylococcal - MRSA ... Centers for Disease Control and Prevention website. Methicillin-resistant Staphylococcus aureus (MRSA). www.cdc.gov/mrsa/index.html . Updated ...

  7. Comparison of the pharmacokinetics of two dosage regimens of linezolid in multidrug-resistant and extensively drug-resistant tuberculosis patients.

    NARCIS (Netherlands)

    Alffenaar, J.W.C.; Altena, R. van; Harmelink, I.M.; Filguera, P.; Molenaar, E.; Wessels, A.M.; Soolingen, D. van; Kosterink, J.G.W.; Uges, D.R.A.; Werf, T.S. van der

    2010-01-01

    BACKGROUND AND OBJECTIVES: For the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB), potent new drugs are urgently needed. Linezolid is a promising drug, but its use is limited by adverse effects with prolonged administration of 600 mg twice daily. In

  8. 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.

  9. Comparison of the Pharmacokinetics of Two Dosage Regimens of Linezolid in Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis Patients

    NARCIS (Netherlands)

    Alffenaar, Jan-Willem C.; van Altena, Richard; Harmelink, Ilse M.; Filguera, Patricia; Molenaar, Esther; Wessels, A. Mireille A.; van Soolingen, Dick; Kosterink, Jos G. W.; Uges, Donald R. A.; van der Werf, Tjip S.

    2010-01-01

    Background and Objectives: For the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB), potent new drugs are urgently needed. Linezolid is a promising drug, but its use is limited by adverse effects with prolonged administration of 600 mg twice daily. In

  10. 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.

  11. In vitro susceptibility of methicillin-resistant Staphylococcus aureus isolates from skin and soft tissue infections to vancomycin, daptomycin, linezolid and tedizolid

    Directory of Open Access Journals (Sweden)

    Johanna Marcela Vanegas Múnera

    2017-09-01

    Conclusion: In vitro effectiveness of tedizolid was superior for isolates from skin and soft tissue infections in comparison with the other antibiotics evaluated. The above added to its less toxicity, good bioavailability, daily dose and unnecessity of dosage adjustment, make tedizolid in a promising alternative for the treatment of infections caused by MRSA.

  12. 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

  13. A Case of Childhood Lichen Aureus

    OpenAIRE

    Kim, Min Ji; Kim, Byung Yoon; Park, Kyung Chan; Youn, Sang Woong

    2009-01-01

    Lichen aureus is a rare type of chronic pigmented purpuric dermatosis. The eruptions consist of discrete or confluent golden to brownish lichenoid macules and papules, and are usually asymptomatic. Lichen aureus commonly occurs in young adults, but less frequently in children. We report the first case of multiple lichen aureus occurring in a Korean child.

  14. Decrease of Staphylococcus aureus Virulence by Helcococcus kunzii in a Caenorhabditis elegans Model.

    Science.gov (United States)

    Ngba Essebe, Christelle; Visvikis, Orane; Fines-Guyon, Marguerite; Vergne, Anne; Cattoir, Vincent; Lecoustumier, Alain; Lemichez, Emmanuel; Sotto, Albert; Lavigne, Jean-Philippe; Dunyach-Remy, Catherine

    2017-01-01

    Social bacterial interactions are considered essential in numerous infectious diseases, particularly in wounds. Foot ulcers are a common complication in diabetic patients and these ulcers become frequently infected. This infection is usually polymicrobial promoting cell-to-cell communications. Staphylococcus aureus is the most prevalent pathogen isolated. Its association with Helcococcus kunzii , commensal Gram-positive cocci, is frequently described. The aim of this study was to assess the impact of co-infection on virulence of both H. kunzii and S. aureus strains in a Caenorhabditis elegans model. To study the host response, qRT-PCRs targeting host defense genes were performed. We observed that H. kunzii strains harbored a very low (LT50: 5.7 days ± 0.4) or an absence of virulence (LT50: 6.9 days ± 0.5). In contrast, S. aureus strains (LT50: 2.9 days ± 0.4) were significantly more virulent than all H. kunzii ( P aureus strains were associated, H. kunzii significantly reduced the virulence of the S. aureus strain in nematodes (LT50 between 4.4 and 5.2 days; P aureus led to a strong induction of defense genes ( lys-5, sodh-1 , and cyp-37B1 ) while H. kunzii did not. No statistical difference of host response genes expression was observed when C. elegans were infected with either S. aureus alone or with S. aureus + H. kunzii . Moreover, two well-characterized virulence factors ( hla and agr ) present in S. aureus were down-regulated when S. aureus were co-infected with H. kunzii . This study showed that H. kunzii decreased the virulence of S. aureus without modifying directly the host defense response. Factor(s) produced by this bacterium modulating the staphylococci virulence must be investigated.

  15. Results of a multicentre randomised controlled trial of statistical process control charts and structured diagnostic tools to reduce ward-acquired meticillin-resistant Staphylococcus aureus: the CHART Project.

    Science.gov (United States)

    Curran, E; Harper, P; Loveday, H; Gilmour, H; Jones, S; Benneyan, J; Hood, J; Pratt, R

    2008-10-01

    Statistical process control (SPC) charts have previously been advocated for infection control quality improvement. To determine their effectiveness, a multicentre randomised controlled trial was undertaken to explore whether monthly SPC feedback from infection control nurses (ICNs) to healthcare workers of ward-acquired meticillin-resistant Staphylococcus aureus (WA-MRSA) colonisation or infection rates would produce any reductions in incidence. Seventy-five wards in 24 hospitals in the UK were randomised into three arms: (1) wards receiving SPC chart feedback; (2) wards receiving SPC chart feedback in conjunction with structured diagnostic tools; and (3) control wards receiving neither type of feedback. Twenty-five months of pre-intervention WA-MRSA data were compared with 24 months of post-intervention data. Statistically significant and sustained decreases in WA-MRSA rates were identified in all three arms (Pcontrol wards, but with no significant difference between the control and intervention arms (P=0.23). There were significantly more post-intervention 'out-of-control' episodes (P=0.021) in the control arm (averages of 0.60, 0.28, and 0.28 for Control, SPC and SPC+Tools wards, respectively). Participants identified SPC charts as an effective communication tool and valuable for disseminating WA-MRSA data.

  16. 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.

  17. 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.

  18. 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.

  19. Prevention of meticillin-resistant Staphylococcus aureus bloodstream infections in European hospitals: moving beyond policies

    NARCIS (Netherlands)

    Borg, M.A.; Hulscher, M.; Scicluna, E.A.; Richards, J.; Azanowsky, J.M.; Xuereb, D.; Huis, A. van; Moro, M.L.; Maltezou, H.C.; Frank, U.

    2014-01-01

    BACKGROUND: There is evidence that meticillin-resistant Staphylococcus aureus (MRSA) bacteraemia can be reduced with improved infection control and antibiotic stewardship. AIM: To survey infection control and antibiotic stewardship practices within European hospitals and to identify initiatives that

  20. Communications of Staphylococcus aureus and non-aureus Staphylococcus species from bovine intramammary infections and teat apex colonization.

    Science.gov (United States)

    Mahmmod, Yasser S; Klaas, Ilka Christine; Svennesen, Line; Pedersen, Karl; Ingmer, Hanne

    2018-05-16

    The role of non-aureus staphylococci (NAS) in the risk of acquisition of intramammary infections with Staphylococcus aureus is vague and still under debate. The objectives of this study were to (1) investigate the distribution patterns of NAS species from milk and teat skin in dairy herds with automatic milking systems, and (2) examine if the isolated NAS influences the expression of S. aureus virulence factors controlled by the accessory gene regulator (agr) quorum sensing system. In 8 herds, 14 to 20 cows with elevated somatic cell count were randomly selected for teat skin swabbing and aseptic quarter foremilk samples from right hind and left front quarters. Teat skin swabs were collected using the modified wet-dry method and milk samples were taken aseptically for bacterial culture. Colonies from quarters with suspicion of having NAS in milk or teat skin samples (or both) were subjected to MALDI-TOF assay for species identification. To investigate the interaction between S. aureus and NAS, 81 isolates NAS were subjected to a qualitative β-galactosidase reporter plate assay. In total, 373 NAS isolates were identified representing 105 from milk and 268 from teat skin of 284 quarters (= 142 cows). Sixteen different NAS species were identified, 15 species from teat skin and 10 species from milk. The most prevalent NAS species identified from milk were Staphylococcus epidermidis (50%), Staphylococcus haemolyticus (15%), and Staphylococcus chromogenes (11%), accounting for 76%. Meanwhile, the most prevalent NAS species from teat skin were Staphylococcus equorum (43%), S. haemolyticus (16%), and Staphylococcus cohnii (14%), accounting for 73%. Using reporter gene fusions monitoring transcriptional activity of key virulence factors and regulators, we found that out of 81 supernatants of NAS isolates, 77% reduced expression of hla, encoding a-hemolysin, 70% reduced expression of RNAIII, the key effector molecule of agr, and 61% reduced expression of spa encoding

  1. Occurrence and antimicrobial resistance of Staphylococcus aureus in bulk tank milk and milk filters

    Directory of Open Access Journals (Sweden)

    Kateřina Bogdanovičová

    2014-02-01

    . Improving the hygienic conditions of the milking environment and utensils may reduce the prevalence of S. aureus in milk. Objective of this study was monitoring of Staphylococcus aureus prevalence and determine the prevalence rate of antimicrobial resistance of S. aureus isolated from raw milk and milk filters in the Czech Republic.

  2. ESCHERICHIA COLI AND STAPHYLOCOCCUS AUREUS

    African Journals Online (AJOL)

    DR. AMINU

    ABSTRACT. The bio-effects of the ethanol extracts from the leaf and stem of Momordica charantia were studied with the view to ascertain the medical usefulness ascribed to the plant by the locals. The plant parts, stem and leaf, revealed remarkable activity against Escherichia coli and Staphlococcus aureus. The leaves ...

  3. Antimicrobial activity of Lactobacillus salivarius and Lactobacillus fermentum against Staphylococcus aureus.

    Science.gov (United States)

    Kang, Mi-Sun; Lim, Hae-Soon; Oh, Jong-Suk; Lim, You-Jin; Wuertz-Kozak, Karin; Harro, Janette M; Shirtliff, Mark E; Achermann, Yvonne

    2017-03-01

    The increasing prevalence of methicillin-resistant Staphylococcus aureus has become a major public health threat. While lactobacilli were recently found useful in combating various pathogens, limited data exist on their therapeutic potential for S. aureus infections. The aim of this study was to determine whether Lactobacillus salivarius was able to produce bactericidal activities against S. aureus and to determine whether the inhibition was due to a generalized reduction in pH or due to secreted Lactobacillus product(s). We found an 8.6-log10 reduction of planktonic and a 6.3-log10 reduction of biofilm S. aureus. In contrast, the previously described anti-staphylococcal effects of L. fermentum only caused a 4.0-log10 reduction in planktonic S. aureus cells, with no effect on biofilm S. aureus cells. Killing of S. aureus was partially pH dependent, but independent of nutrient depletion. Cell-free supernatant that was pH neutralized and heat inactivated or proteinase K treated had significantly reduced killing of L. salivarius than with pH-neutralized supernatant alone. Proteomic analysis of the L. salivarius secretome identified a total of five secreted proteins including a LysM-containing peptidoglycan binding protein and a protein peptidase M23B. These proteins may represent potential novel anti-staphylococcal agents that could be effective against S. aureus biofilms. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Dehydrosqualene Desaturase as a Novel Target for Anti-Virulence Therapy against Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Peng Gao

    2017-09-01

    Full Text Available Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA, is a life-threatening pathogen in hospital- and community-acquired infections. The golden-colored carotenoid pigment of S. aureus, staphyloxanthin, contributes to the resistance to reactive oxygen species (ROS and host neutrophil-based killing. Here, we describe a novel inhibitor (NP16 of S. aureus pigment production that reduces the survival of S. aureus under oxidative stress conditions. Carotenoid components analysis, enzyme inhibition, and crtN mutational studies indicated that the molecular target of NP16 is dehydrosqualene desaturase (CrtN. S. aureus treated with NP16 showed increased susceptibility to human neutrophil killing and to innate immune clearance in a mouse infection model. Our study validates CrtN as a novel druggable target in S. aureus and presents a potent and effective lead compound for the development of virulence factor-based therapy against S. aureus.

  5. Low Efficacy of Antibiotics Against Staphylococcus aureus Airway Colonization in Ventilated Patients.

    Science.gov (United States)

    Stulik, Lukas; Hudcova, Jana; Craven, Donald E; Nagy, Gabor; Nagy, Eszter

    2017-04-15

    Airway-colonization by Staphylococcus aureus predisposes to the development of ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP). Despite extensive antibiotic treatment of intensive care unit patients, limited data are available on the efficacy of antibiotics on bacterial airway colonization and/or prevention of infections. Therefore, microbiologic responses to antibiotic treatment were evaluated in ventilated patients. Results of semiquantitative analyses of S. aureus burden in serial endotracheal-aspirate (ETA) samples and VAT/VAP diagnosis were correlated to antibiotic treatment. Minimum inhibitory concentrations of relevant antibiotics using serially collected isolates were evaluated. Forty-eight mechanically ventilated patients who were S. aureus positive by ETA samples and treated with relevant antibiotics for at least 2 consecutive days were included in the study. Vancomycin failed to reduce methicillin-resistant S. aureus (MRSA) or methicillin-susceptible S. aureus (MSSA) burden in the airways. Oxacillin was ineffective for MSSA colonization in approximately 30% of the patients, and responders were typically coadministered additional antibiotics. Despite antibiotic exposure, 15 of the 39 patients (approximately 38%) colonized only by S. aureus and treated with appropriate antibiotic for at least 2 days still progressed to VAP. Importantly, no change in antibiotic susceptibility of S. aureus isolates was observed during treatment. Staphylococcus aureus colonization levels inversely correlated with the presence of normal respiratory flora. Antibiotic treatment is ineffective in reducing S. aureus colonization in the lower airways and preventing VAT or VAP. Staphylococcus aureus is in competition for colonization with the normal respiratory flora. To improve patient outcomes, alternatives to antibiotics are urgently needed. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of

  6. New epidemiology of Staphylococcus aureus infection in Asia.

    Science.gov (United States)

    Chen, C-J; Huang, Y-C

    2014-07-01

    Not only is Asia the most populous region in the world, but inappropriate therapy, including self-medication with over-the-counter antimicrobial agents, is a common response to infectious diseases. The high antibiotic selective pressure among the overcrowded inhabitants creates an environment that is suitable for the rapid development and efficient spread of numerous multidrug-resistant pathogens. Indeed, Asia is among the regions with the highest prevalence rates of healthcare-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) and community-associated methicillin-resistant S. aureus (CA-MRSA) in the world. Most hospitals in Asia are endemic for multidrug-resistant methicillin-resistant S. aureus (MRSA), with an estimated proportion from 28% (in Hong Kong and Indonesia) to >70% (in Korea) among all clinical S. aureus isolates in the early 2010s. Isolates with reduced susceptibility or a high level of resistance to glycopeptides have also been increasingly identified in the past few years. In contrast, the proportion of MRSA among community-associated S. aureus infections in Asian countries varies markedly, from 35%. Two pandemic HA-MRSA clones, namely multilocus sequence type (ST) 239 and ST5, are disseminated internationally in Asia, whereas the molecular epidemiology of CA-MRSA in Asia is characterized by clonal heterogeneity, similar to that in Europe. In this review, the epidemiology of S. aureus in both healthcare facilities and communities in Asia is addressed, with an emphasis on the prevalence, clonal structure and antibiotic resistant profiles of the MRSA strains. The novel MRSA strains from livestock animals have been considered to constitute a public health threat in western countries. The emerging livestock-associated MRSA strains in Asia are also included in this review. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

  7. 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).

  8. 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

  9. 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

  10. 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

    Science.gov (United States)

    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

  11. Increased Susceptibility of Humanized NSG Mice to Panton-Valentine Leukocidin and Staphylococcus aureus Skin Infection.

    Directory of Open Access Journals (Sweden)

    Ching Wen Tseng

    Full Text Available Staphylococcus aureus is a leading cause of skin and soft-tissue infections worldwide. Mice are the most commonly used animals for modeling human staphylococcal infections. However a supra-physiologic S. aureus inoculum is required to establish gross murine skin pathology. Moreover, many staphylococcal factors, including Panton-Valentine leukocidin (PVL elaborated by community-associated methicillin-resistant S. aureus (CA-MRSA, exhibit selective human tropism and cannot be adequately studied in mice. To overcome these deficiencies, we investigated S. aureus infection in non-obese diabetic (NOD/severe combined immune deficiency (SCID/IL2rγnull (NSG mice engrafted with human CD34+ umbilical cord blood cells. These "humanized" NSG mice require one to two log lower inoculum to induce consistent skin lesions compared with control mice, and exhibit larger cutaneous lesions upon infection with PVL+ versus isogenic PVL- S. aureus. Neutrophils appear important for PVL pathology as adoptive transfer of human neutrophils alone to NSG mice was sufficient to induce dermonecrosis following challenge with PVL+ S. aureus but not PVL- S. aureus. PMX53, a human C5aR inhibitor, blocked PVL-induced cellular cytotoxicity in vitro and reduced the size difference of lesions induced by the PVL+ and PVL- S. aureus, but PMX53 also reduced recruitment of neutrophils and exacerbated the infection. Overall, our findings establish humanized mice as an important translational tool for the study of S. aureus infection and provide strong evidence that PVL is a human virulence factor.

  12. Population structure of Staphylococcus aureus in China

    OpenAIRE

    Yan, Xiaomei

    2015-01-01

    The present PhD research was aimed at analysing the population structure of Staphylococcus aureus in China. Between 2000 and 2005 we found that patients from a single Chinese hospital showed increasing trends in antimicrobial resistance. Among methicillin-resistant S. aureus (MRSA), resistance against rifampicin doubled to 68%. Staphylococcal food poisoning (SFP) is frequent in China. Two predominant S. aureus lineages, ST6 and ST943, were identified causing outbreaks of SFP in Southern China...

  13. Influence of the Vaginal Microbiota on Toxic Shock Syndrome Toxin 1 Production by Staphylococcus aureus

    OpenAIRE

    MacPhee, Roderick A.; Miller, Wayne L.; Gloor, Gregory B.; McCormick, John K.; Hammond, Jo-Anne; Burton, Jeremy P.; Reid, Gregor

    2013-01-01

    Menstrual toxic shock syndrome (TSS) is a serious illness that afflicts women of premenopausal age worldwide and arises from vaginal infection by Staphylococcus aureus and concurrent production of toxic shock syndrome toxin-1 (TSST-1). Studies have illustrated the capacity of lactobacilli to reduce S. aureus virulence, including the capacity to suppress TSST-1. We hypothesized that an aberrant microbiota characteristic of pathogenic bacteria would induce the increased production of TSST-1 and...

  14. Exfoliation rate of mammary epithelial cells in milk on bovine mastitis caused by Staphylococcus aureus is associated with bacterial load.

    Science.gov (United States)

    Nagasawa, Yuya; Kiku, Yoshio; Sugawara, Kazue; Tanabe, Fuyuko; Hayashi, Tomohito

    2018-01-01

    The exfoliation rate of mammary epithelial cells (MECs) in milk is affected by physiological, breeding and environmental factors. Little is known about the relationship between the MEC exfoliation into milk and mammary-infected Staphylococcus aureus (S. aureus) load on bovine mastitis caused by S. aureus. The aim of this study was to investigate the relationship between S. aureus load and the proportion of MEC exfoliation in milk using five substantial bovine mastitis models. In 64 randomly extracted milk samples from udders at 3-21 days after S. aureus infusion, there were various samples with different numbers of S. aureus counts and somatic cell counts. No significant correlations were found between the S. aureus counts and somatic cell count (r = 0.338). In contrast, a significant correlation was noted between S. aureus counts and the proportion of cytokeratin-positive cells in the milk from the infused udders (r = 0.734, P mastitis udders caused by S. aureus may contribute to reduced milk yield. © 2017 Japanese Society of Animal Science.

  15. Clinical Determinants of Target Non-Attainment of Linezolid in Plasma and Interstitial Space Fluid: A Pooled Population Pharmacokinetic Analysis with Focus on Critically Ill Patients.

    Science.gov (United States)

    Minichmayr, Iris K; Schaeftlein, André; Kuti, Joseph L; Zeitlinger, Markus; Kloft, Charlotte

    2017-06-01

    We aimed to assess linezolid pharmacokinetics in the plasma and interstitial space fluid (ISF) of patients with sepsis, diabetic foot infections or cystic fibrosis and healthy volunteers. The impacts of joint characteristics and disease on plasma and target-site exposure were to be identified together with the benefit of dose intensification in critically ill patients. Rich plasma (n = 1598) and ISF concentrations in subcutaneous adipose (n = 1430) and muscle tissue (n = 1089) measured by microdialysis were pooled from three clinical trials with 51 individuals receiving 600 mg of intravenous and oral linezolid. All data were analysed simultaneously by a population approach also considering methodological aspects of microdialysis. The impact of covariates on the attainment of the pharmacokinetic/pharmacodynamic targets, AUC/MIC = 100 (area under the concentration-time curve/minimum inhibitory concentration) and fT >MIC  = 99 % (time that unbound concentrations exceed the MIC), was assessed by deterministic and Monte Carlo simulations. A two-compartment pharmacokinetic model with nonlinear elimination and tissue distribution factors accounting for differences between plasma and ISF concentrations adequately predicted all measurements. Clearance (CL) was highest in septic patients (11.2 L/h vs. CL Healthy /CL Cystic fibrosis /CL Diabetic  = 7.67/6.87/6.35 L/h). Penetration into subcutaneous adipose ISF was lowest in diabetic patients (-34.9 % compared with healthy volunteers). Creatinine clearance and total body weight further impacted linezolid exposure. To achieve timely efficacious therapy, front-loaded dosing and continuous infusion seemed beneficial in septic patients. Our analysis suggests that after standard linezolid doses, particularly patients with sepsis and conserved renal function are at risk of not attaining pharmacokinetic/pharmacodynamic targets and would benefit from initial dose intensification.

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

    OpenAIRE

    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...

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

    Science.gov (United States)

    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.

  18. Linezolid Is Associated with Serotonin Syndrome in a Patient Receiving Amitriptyline, and Fentanyl: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Lampros Samartzis

    2013-01-01

    Full Text Available We report a unique case of an adverse interaction between the oxazolidinone antibiotic linezolid, the tricyclic antidepressant amitriptyline and the opioid analgesic fentanyl in a 68-year-old woman with advanced ischemic peripheral arterial disease and sepsis, under empirical antibiotic treatment. We also summarize the current relevant literature as identified via PubMed, EMBASE, and PsycINFO as well as reference sections of selected articles.

  19. Population structure and antimicrobial profile of Staphylococcus aureus strains associated with bovine mastitis in China.

    Science.gov (United States)

    Zhang, Lili; Li, Yuchen; Bao, Hongduo; Wei, Ruicheng; Zhou, Yan; Zhang, Hui; Wang, Ran

    2016-08-01

    Staphylococcus aureus is a significant bacterial pathogen associated with bovine mastitis. The aim of the present study was to investigate and characterize of S. aureus strains isolated from the milk of cows suffering from mastitis in the mid-east of China. Among the 200 milk samples analyzed, 58 were positive for S. aureus, of these isolates, 11 isolates were methicillin-resistant Staphylococcus aureus (MRSA). All of the 58 S. aureus strains were classified in agr group I, while seven different sequence type (ST) patterns were identified and among them the most common was ST630 followed by ST188. All of the S. aureus isolates belonging to ST630 were resistant to more than four antimicrobials, and 22.2% of isolates belonging to ST188 were resistant to eight antimicrobials. Interestingly, while strong biofilm producers demonstrated higher resistance to multiple antimicrobials, they exhibited lower intracellular survival rates. The results of this study illustrated the distribution, antimicrobial susceptibility profiles, genotype, and the ability of biofilm production and mammary epithelial cells invasion of these S. aureus isolates. This study can provide the basis for the development of a disease prevention program in dairy farms to reduce the potential risk in both animal and human health. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Relationship and susceptibility profile of Staphylococcus aureus infection diabetic foot ulcers with Staphylococcus aureus nasal carriage.

    Science.gov (United States)

    Taha, Aza Bahadeen

    2013-03-01

    Staphylococcus aureus is the main cause of diabetic foot infection with the patient's endogenous flora as the principal source. Nasal carriage of S. aureus has been identified as an important risk factor for the acquisition of diabetic foot infections. The study assessment the associations of S. aureus with methicillin resistant S. aureus were isolation from diabetic foot infection and nasal carriage of the same patients and their antibiotic susceptibility profile. Diagnosis of S. aureus and methicillin resistant S. aureus were carried out by using standard procedures. Antibiotic sensitivity profiles were determent by breakpoint dilution method. Out of 222 S. aureus isolation, 139 (62.61%) were isolated from the diabetic foot and 83 (37.39%) from the nasal carriage. Seventy one (30.87%) of the patients were S. aureus infection diabetic foot with nasal carriage. Among diabetic foot infection and nasal carriage patients, 40.85% of S. aureus were considered as methicillin resistant S. aureus. Rifampicin (96.40%) and Levofloxacin (91.44%) were active against S. aureus. Patients at strong risk for methicillin resistant S. aureus nasal carriage and subsequent diabetic foot infection with high resistance to antibiotics. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Several Virulence Factors of Multidrug-Resistant Staphylococcus aureus Isolates From Hospitalized Patients in Tehran

    Directory of Open Access Journals (Sweden)

    Abdolmajid Ghasemian

    2015-05-01

    Full Text Available Background: Biofilm formation plays an important role in resistance of Staphylococcus aureus isolates; especially multidrug-resistant isolates are a threat to healthcare settings. Objectives: The aims of this study were to detect biofilm formation and presence of several related genes among multidrug-resistant (MDR isolates of Staphylococcus aureus. Patients and Methods: A total Of 209 S. aureus strains were isolated from patients and identified by conventional diagnostic tests. The multidrug-resistant MRSA isolates were detected by antibiotic susceptibility test. The phenotypic biofilm formation was detected by micro-titre tissue plate assay. The polymerase chain reaction (PCR was performed to detect the mecA, Staphylococcal Cassette Chromosome mec (SCCmec types, accessory gene regulatory (agr genes, the icaADBC and several genes encoding staphylococcal surface proteins including clfAB, fnbAB, fib, eno, can, ebps and bbp genes with specific primers. Results: Sixty-four (30.6% isolates were methicillin-resistant, among which thirty-six (56.2% were MDR. These isolates were resistant to amoxicillin, tetracycline, ciprofloxacin, gentamicin, erythromycin and trimethoprim-sulfamethoxazole (except to 6 isolates. All the isolates were susceptible to vancomycin and linezolid. All the MDR-MRSA harbored SCCmec type III. All the MDR- MRSA isolates were strong biofilm producers in the phenotypic test. The majority of MDR- MRSA was belonged to agrI (67%, n = 24, followed by agr II (17%, n = 6, agrIV (11%, n = 4 and agrIII (5.5%, n = 2. The frequency of icaADBC genes were 75% (n = 27, 61% (n = 22, 72% (n = 26 and 72% (n = 26, respectively. Furthermore, the prevalence of clfA, clfB, fnbA, fnbB, fib, can, eno, ebps and bbp genes was 100%, 100%, 67%, 56%, 80%, 63%, 78%, 7% and 0%, respectively. Furthermore, approximately all the MRSA was strong biofilm producers. Conclusions: Multidrug-resistant isolates produced biofilm strongly and the majority harbored most

  2. Prevalence of Staphylococcus aureus and of methicillin-resistant S. aureus clonal complexes in bulk tank milk from dairy cattle herds in Lombardy Region (Northern Italy).

    Science.gov (United States)

    Cortimiglia, C; Luini, M; Bianchini, V; Marzagalli, L; Vezzoli, F; Avisani, D; Bertoletti, M; Ianzano, A; Franco, A; Battisti, A

    2016-10-01

    Staphylococcus aureus is the most important causative agent of subclinical mastitis in cattle resulting in reduced milk production and quality. Methicillin-resistant S. aureus (MRSA) strains has a clear zoonotic relevance, especially in the case of occupational exposure. The aim of the study was to evaluate the prevalence of S. aureus and MRSA in bulk tank milk (BTM) from dairy cattle herds in the Lombardy Region (Northern Italy) and to identify the main MRSA circulating genotypes. MRSA strains were characterized by susceptibility testing, multi-locus sequence typing (MLST), spa typing and SCCmec typing. A total 844 BTM samples were analysed and S. aureus and MRSA were detected in 47·2% and 3·8% of dairy herds, respectively. MLST showed that the majority (28/32) of isolates belonged to the typical livestock-associated lineages: ST398, ST97 and ST1. Interestingly, in this study we report for the first time the new ST3211, a single locus variant of ST(CC)22, with the newly described 462 aroE allele. Our study indicates high diffusion of S. aureus mastitis and low, but not negligible, prevalence of MRSA in the considered area, suggesting the need for planning specific control programmes for bovine mastitis caused by S. aureus, especially when MRSA is implicated.

  3. Staphylococcus aureus and Community-Associated Methicillin-Resistant Staphylococcus aureus (CA-MRSA) in and Around Therapeutic Whirlpools in College Athletic Training Rooms

    Science.gov (United States)

    Kahanov, Leamor; Kim, Young Kyun; Eberman, Lindsey; Dannelly, Kathleen; Kaur, Haninder; Ramalinga, A.

    2015-01-01

    Context: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has become a leading cause of skin and soft tissue infection in the nonhospitalized community. Care of the athletes in athletic training rooms is specifically designed with equipment tailored to the health care needs of the athletes, yet recent studies indicate that CA-MRSA is still prevalent in athletic facilities and that cleaning methods may not be optimal. Objective: To investigate the prevalence of Staphylococcus aureus and CA-MRSA in and around whirlpools in the athletic training room. Design: Cross-sectional study. Setting: National Collegiate Athletic Association Division I university. Patients or Other Participants: Student-athletes (n = 109) consisting of 46 men (42%) and 63 women (58%) representing 6 sports. Main Outcome Measure(s): Presence of MRSA and Staphylococcus aureus in and around the whirlpool structures relative to sport and number of athletes using the whirlpools. Results: We identified Staphylococcus aureus in 22% (n = 52/240) of the samples and MRSA in 0.8% (n = 2/240). A statistically significant difference existed between the number of athletes using the whirlpool and the presence of Staphylococcus aureus in and around the whirlpools (F2,238 = 2.445, P = .007). However, Staphylococcus aureus was identified regardless of whether multiple athletes used a whirlpool or no athletes used a whirlpool. We did not identify a relationship between the number of athletes who used a whirlpool and Staphylococcus aureus or MRSA density (P = .134). Conclusions: Staphylococcus aureus and MRSA were identified in and around the whirlpools. Transmission of the bacteria can be reduced by following the cleaning and disinfecting protocols recommended by the Centers for Disease Control and Prevention. Athletic trainers should use disinfectants registered by the Environmental Protection Agency to sanitize all whirlpools between uses. PMID:25710853

  4. Staphylococcus aureus and community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in and around therapeutic whirlpools in college athletic training rooms.

    Science.gov (United States)

    Kahanov, Leamor; Kim, Young Kyun; Eberman, Lindsey; Dannelly, Kathleen; Kaur, Haninder; Ramalinga, A

    2015-04-01

    Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has become a leading cause of skin and soft tissue infection in the nonhospitalized community. Care of the athletes in athletic training rooms is specifically designed with equipment tailored to the health care needs of the athletes, yet recent studies indicate that CA-MRSA is still prevalent in athletic facilities and that cleaning methods may not be optimal. To investigate the prevalence of Staphylococcus aureus and CA-MRSA in and around whirlpools in the athletic training room. Cross-sectional study. National Collegiate Athletic Association Division I university. Student-athletes (n = 109) consisting of 46 men (42%) and 63 women (58%) representing 6 sports. Presence of MRSA and Staphylococcus aureus in and around the whirlpool structures relative to sport and number of athletes using the whirlpools. We identified Staphylococcus aureus in 22% (n = 52/240) of the samples and MRSA in 0.8% (n = 2/240). A statistically significant difference existed between the number of athletes using the whirlpool and the presence of Staphylococcus aureus in and around the whirlpools (F(2,238) = 2.445, P = .007). However, Staphylococcus aureus was identified regardless of whether multiple athletes used a whirlpool or no athletes used a whirlpool. We did not identify a relationship between the number of athletes who used a whirlpool and Staphylococcus aureus or MRSA density (P = .134). Staphylococcus aureus and MRSA were identified in and around the whirlpools. Transmission of the bacteria can be reduced by following the cleaning and disinfecting protocols recommended by the Centers for Disease Control and Prevention. Athletic trainers should use disinfectants registered by the Environmental Protection Agency to sanitize all whirlpools between uses.

  5. Glycerol monolaurate and dodecylglycerol effects on Staphylococcus aureus and toxic shock syndrome toxin-1 in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Ying-Chi Lin

    2009-10-01

    Full Text Available Glycerol monolaurate (GML, a 12 carbon fatty acid monoester, inhibits Staphylococcus aureus growth and exotoxin production, but is degraded by S. aureus lipase. Therefore, dodecylglycerol (DDG, a 12 carbon fatty acid monoether, was compared in vitro and in vivo to GML for its effects on S. aureus growth, exotoxin production, and stability.Antimicrobial effects of GML and DDG (0 to 500 microg/ml on 54 clinical isolates of S. aureus, including pulsed-field gel electrophoresis (PFGE types USA200, USA300, and USA400, were determined in vitro. A rabbit Wiffle ball infection model assessed GML and DDG (1 mg/ml instilled into the Wiffle ball every other day effects on S. aureus (MN8 growth (inoculum 3x10(8 CFU/ml, toxic shock syndrome toxin-1 (TSST-1 production, tumor necrosis factor-alpha (TNF-alpha concentrations and mortality over 7 days. DDG (50 and 100 microg/ml inhibited S. aureus growth in vitro more effectively than GML (p<0.01 and was stable to lipase degradation. Unlike GML, DDG inhibition of TSST-1 was dependent on S. aureus growth. GML-treated (4 of 5; 80% and DDG-treated rabbits (2 of 5; 40% survived after 7 days. Control rabbits (5 of 5; 100% succumbed by day 4. GML suppressed TNF-alpha at the infection site on day 7; however, DDG did not (<10 ng/ml versus 80 ng/ml, respectively.These data suggest that DDG was stable to S. aureus lipase and inhibited S. aureus growth at lower concentrations than GML in vitro. However, in vivo GML was more effective than DDG by reducing mortality, and suppressing TNF-alpha, S. aureus growth and exotoxin production, which may reduce toxic shock syndrome. GML is proposed as a more effective anti-staphylococcal topical anti-infective candidate than DDG, despite its potential degradation by S. aureus lipase.

  6. Effect of Linezolid on the 50% Lethal Dose and 50% Protective Dose in Treatment of Infections by Gram-Negative Pathogens in Naive and Immunosuppressed Mice and on the Efficacy of Ciprofloxacin in an Acute Murine Model of Septicemia

    Science.gov (United States)

    Marra, Andrea; Lamb, Lucinda; Medina, Ivette; George, David; Gibson, Glenn; Hardink, Joel; Rugg, Jady; Van Deusen, Jeffrey

    2012-01-01

    Murine models of infection were used to study the effect of linezolid on the virulence of Gram-negative bacteria and to assess potential pharmacodynamic interactions with ciprofloxacin in the treatment of these infections, prompted by observations from a recent clinical trial. Naive and immunosuppressed mice were challenged with Klebsiella pneumoniae 53A1109, K. pneumoniae GC6658, and Pseudomonas aeruginosa UC12120 in acute sepsis and pulmonary infection models, using different serial dilutions of these pathogens (groups of 8 animals each). Linezolid (100 mg/kg/dose) was administered orally at 0.5 and 4.0 h postchallenge in the sepsis model and at 4 h postchallenge followed by 2 days of twice-daily treatment in the pulmonary model. Further, ciprofloxacin alone and in combination with oral linezolid was investigated in the sepsis model. Survival was assessed for 4 and 10 days postchallenge in the systemic and respiratory models, respectively. The data were fitted to a nonlinear regression analysis to determine 50% lethal doses (LD50s) and 50% protective doses (PD50s). A clinically relevant, high-dose regimen of linezolid had no significant effect on LD50 in these models. This lack of effect was independent of immune status. A combination of oral ciprofloxacin with linezolid yielded lower PD50s than oral ciprofloxacin alone (ciprofloxacin in combination, 8.4 to 32.7 mg/kg; oral ciprofloxacin, 39.4 to 88.3 mg/kg). Linezolid did not improve the efficacy of subcutaneous ciprofloxacin (ciprofloxacin in combination, 2.0 to 2.4 mg/kg; subcutaneous ciprofloxacin, 2.0 to 2.8 mg/kg). In conclusion, linezolid does not seem to potentiate infections caused by Gram-negative pathogens or to interact antagonistically with ciprofloxacin. PMID:22710118

  7. Genetic and Virulent Difference Between Pigmented and Non-pigmented Staphylococcus aureus.

    Science.gov (United States)

    Zhang, Jing; Suo, Yujuan; Zhang, Daofeng; Jin, Fangning; Zhao, Hang; Shi, Chunlei

    2018-01-01

    Staphyloxanthin (STX), a golden carotenoid pigment produced by Staphylococcus aureus , is suggested to act as an important virulence factor due to its antioxidant properties. Restraining biosynthesis of STX was considered as an indicator of virulence decline in pigmented S. aureus isolates. However, it is not clear whether natural non-pigmented S. aureus isolates have less virulence than pigmented ones. In this study, it is aimed to compare the pigmented and non-pigmented S. aureus isolates to clarify the genetic and virulent differences between the two groups. Here, 132 S. aureus isolates were divided into two phenotype groups depending on the absorbance (OD 450 ) of the extracted carotenoids. Then, all isolates were subjected to spa typing and multilocus sequence typing (MLST), and then the detection of presence of 30 virulence factors and the gene integrity of crtN and crtM . Furthermore, 24 typical S. aureus isolates and 4 S. argenteus strains were selected for the murine infection assay of in vivo virulence, in which the histological observation and enumeration of CFUs were carried out. These isolates were distributed in 26 sequence types (STs) and 49 spa types. The pigmented isolates were scattered in 25 STs, while the non-pigmented isolates were more centralized, which mainly belonged to ST20 (59%) and ST25 (13%). Among the 54 non-pigmented isolates, about 20% carried intact crtN and crtM genes. The in vivo assay suggested that comparing with pigmented S. aureus , non-pigmented S. aureus and S. argenteus strains did not show a reduced virulence in murine sepsis models. Therefore, it suggested that there were no significant genetic and virulent differences between pigmented and non-pigmented S. aureus .

  8. Genetic and Virulent Difference Between Pigmented and Non-pigmented Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Jing Zhang

    2018-04-01

    Full Text Available Staphyloxanthin (STX, a golden carotenoid pigment produced by Staphylococcus aureus, is suggested to act as an important virulence factor due to its antioxidant properties. Restraining biosynthesis of STX was considered as an indicator of virulence decline in pigmented S. aureus isolates. However, it is not clear whether natural non-pigmented S. aureus isolates have less virulence than pigmented ones. In this study, it is aimed to compare the pigmented and non-pigmented S. aureus isolates to clarify the genetic and virulent differences between the two groups. Here, 132 S. aureus isolates were divided into two phenotype groups depending on the absorbance (OD450 of the extracted carotenoids. Then, all isolates were subjected to spa typing and multilocus sequence typing (MLST, and then the detection of presence of 30 virulence factors and the gene integrity of crtN and crtM. Furthermore, 24 typical S. aureus isolates and 4 S. argenteus strains were selected for the murine infection assay of in vivo virulence, in which the histological observation and enumeration of CFUs were carried out. These isolates were distributed in 26 sequence types (STs and 49 spa types. The pigmented isolates were scattered in 25 STs, while the non-pigmented isolates were more centralized, which mainly belonged to ST20 (59% and ST25 (13%. Among the 54 non-pigmented isolates, about 20% carried intact crtN and crtM genes. The in vivo assay suggested that comparing with pigmented S. aureus, non-pigmented S. aureus and S. argenteus strains did not show a reduced virulence in murine sepsis models. Therefore, it suggested that there were no significant genetic and virulent differences between pigmented and non-pigmented S. aureus.

  9. Novel structurally designed vaccine for S. aureus α-hemolysin: protection against bacteremia and pneumonia.

    Directory of Open Access Journals (Sweden)

    Rajan P Adhikari

    Full Text Available Staphylococcus aureus (S. aureus is a human pathogen associated with skin and soft tissue infections (SSTI and life threatening sepsis and pneumonia. Efforts to develop effective vaccines against S. aureus have been largely unsuccessful, in part due to the variety of virulence factors produced by this organism. S. aureus alpha-hemolysin (Hla is a pore-forming toxin expressed by most S. aureus strains and reported to play a key role in the pathogenesis of SSTI and pneumonia. Here we report a novel recombinant subunit vaccine candidate for Hla, rationally designed based on the heptameric crystal structure. This vaccine candidate, denoted AT-62aa, was tested in pneumonia and bacteremia infection models using S. aureus strain Newman and the pandemic strain USA300 (LAC. Significant protection from lethal bacteremia/sepsis and pneumonia was observed upon vaccination with AT-62aa along with a Glucopyranosyl Lipid Adjuvant-Stable Emulsion (GLA-SE that is currently in clinical trials. Passive transfer of rabbit immunoglobulin against AT-62aa (AT62-IgG protected mice against intraperitoneal and intranasal challenge with USA300 and produced significant reduction in bacterial burden in blood, spleen, kidney, and lungs. Our Hla-based vaccine is the first to be reported to reduce bacterial dissemination and to provide protection in a sepsis model of S. aureus infection. AT62-IgG and sera from vaccinated mice effectively neutralized the toxin in vitro and AT62-IgG inhibited the formation of Hla heptamers, suggesting antibody-mediated neutralization as the primary mechanism of action. This remarkable efficacy makes this Hla-based vaccine a prime candidate for inclusion in future multivalent S. aureus vaccine. Furthermore, identification of protective epitopes within AT-62aa could lead to novel immunotherapy for S. aureus infection.

  10. Dermoscopy of lichen aureus Dermatoscopia do liquen aureus

    Directory of Open Access Journals (Sweden)

    Poliana Santin Portela

    2013-04-01

    Full Text Available Lichen aureus (also called "lichen purpuricus" is an uncommon subtype of pigmented purpuric dermatosis. Clinically characterized by rust macules, papules or plaques, it is a chronic disease which more often affects young adults and is localized mainly on the lower extremities. The diagnosis is made on the basis of clinical and histopathological features. Dermoscopy findings are useful to confirm clinical diagnosis.O líquen aureus (também denominado "liquen purpuricus" é um subtipo pouco comum entre as dermatoses purpúricas pigmentadas. Clinicamente caracterizado por máculas, pápulas ou placas de coloração ferruginosa, é doença crônica, que acomete mais frequentemente adultos jovens e localiza-se principalmente nos membros inferiores. O diagnóstico pode ser feito a partir das características clínicas e histopatológicas, sendo os achados dermatoscópicos úteis para corroborar o diagnóstico clínico.

  11. [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.

  12. Resistencia de Staphylococcus aureus a los antibióticos en un hospital de la orinoquia colombiana Antimicrobial resistance of Staphylococus aureus at a hospital from the Colombian Orinoquia

    Directory of Open Access Journals (Sweden)

    Norton Pérez

    2010-09-01

    Full Text Available Introducción: El objetivo de este estudio de cohorte retrospectivo fue analizar la resistencia de Staphylococcus aureus a los antibióticos en el Hospital Departamental de Villavicencio, centro de mediana y alta complejidad, entre 2005 y 2009. Materiales y métodos: Se analizaron los resultados de los estudios microbiológicos de los pacientes con cultivo positivo para S. aureus. No se hizo ninguna intervención. La variable de estudio fue la resistencia a la meticilina y el desenlace, la resistencia a los antimicrobianos. Resultados: Se tamizaron 29.451 estudios de microbiología y se encontraron 976 aislamientos de S. aureus, los cuales se analizaron para determinar su resistencia a los antibióticos por el método de microdilución en caldo. El 49,6 % de ellos (484 fueron clasificados como resistentes a la meticilina; se encontró un mayor grado de resistencia múltiple, especialmente para gentamicina (25,0% Vs. 2,9%, ciprofloxacina (25,1% Vs.2,4%, clindamicina (29,4% Vs.4,1% y eritromicina (31,0% Vs.1,7%, y menor, para trimetoprim/sulfametoxazol (11,8% Vs.4,1%. Aunque era de esperarse que la resistencia simultánea para la vancomicina fuera muy baja, se encontraron algunas cepas intermedias y resistentes, pero este resultado no se puede analizar adecuadamente debido a que estas cepas no se remitieron a un laboratorio de referencia para pruebas de confirmación. La resistencia a la tetraciclina, aun en las cepas sensibles a la meticilina, fue alta. No se identificó ninguna cepa resistente al linezolid. No se realizaron estudios para evaluar la resistencia a la tigeciclina. Conclusiones: La resistencia de S. aureus a la meticilina es frecuente también en esta institución hospitalaria de la orinoquia colombiana. La resistencia múltiple es mayor en S. aureus resistente a la meticilina, especialmente a la gentamicina, la ciprofloxacina y la clindamicina. Cuando S. aureus es sensible a la meticilina, también se observa un alto grado de

  13. Staphylococcus aureus effect of different factors on mammary gland infection with staphylococcus aureus bacteria

    Directory of Open Access Journals (Sweden)

    Jurčevič Alen

    2004-01-01

    Full Text Available The objective of our investigation was to determine how certain factors (the environment, treatment, prevention, animal affect udder infection with Staphylococcus aureurs (S. aureus bacteria. A questionnaire investigated the effect of different factors on the frequency of infection with S. aureus bacteria. We established that prevention, treatment on the basis of results of bacteriological examinations and antibiograms, and the elimination of the negative influence of the environment, form a basis for reducing the frequency of udder infections. We verified the questionannire results with the variant analysis method and established that the effect of the environment significantly digresses from the other factors (prevention treatment and diagnosis, animal. Our results show that the breeder, with good prevention and good treatment of mastitis, often disregards the effects of the barn and the environment in which the cows are maintained. Poor barn conditions have a negative effect on cow resistance and at the same time enable the existence and multiplication of pathogenic species of bacteria. In addition to the maintenance conditions, one must not forget prevention and therapy of mammary gland inflammation, either. On the grounds of our previous investigations (Pengov et al., 2000, we recommend for the therapy of mammary gland inflammation the use of a combination of amoxicillin and clavulonic acid, and as prevention of mammary gland inflammation the use of an udder ointment.

  14. Therapy-refractory Panton Valentine Leukocidin-positive community-acquired methicillin-sensitive Staphylococcus aureus sepsis with progressive metastatic soft tissue infection: a case report

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    Schefold Joerg C

    2007-12-01

    Full Text Available Abstract We report a case of fulminant multiple organ failure including the Acute Respiratory Distress Syndrome (ARDS, haemodynamic, and renal failure due to community-acquired methicillin-sensitive Panton Valentine Leukocidin (PVL positive spa-type 284 (ST121 Staphylococcus aureus septic shock. The patient's first clinical symptom was necrotizing pneumonia. Despite organism-sensitive triple antibiotic therapy with linezolid, imipenem and clindamycin from the first day of treatment, progressive abscess formation in multiple skeletal muscles was observed. As a result, repeated surgical interventions became necessary. Due to progressive soft tissue infection, the anti-microbial therapy was changed to a combination of clindamycin and daptomycin. Continued surgical and antimicrobial therapy finally led to a stabilisation of the patients' condition. The clinical course of our patient underlines the existence of a "PVL-syndrome" which is independent of in vitro Staphylococcus aureus susceptibility. The PVL-syndrome should not only be considered in patients with soft tissue or bone infection, but also in patients with pneumonia. Such a condition, which may easily be mistaken for uncomplicated pneumonia, should be treated early, aggressively and over a long period of time in order to avoid relapsing infection.

  15. The Lytic SA Phage Demonstrate Bactericidal Activity against Mastitis Causing Staphylococcus aureus

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    Hamza Ameer

    2016-01-01

    Full Text Available Staphylococcus aureus is the major causative agent of mastitis among dairy animals as it causes intramammary gland infection. Due to antibiotic resistance and contamination of antibiotics in the milk of diseased animals; alternative therapeutic agents are required to cure mastitis. Lytic bacteriophages and their gene products can be potential therapeutic agents against bacteria as they are host specific and less harmful than antibiotics. In this study, Staphylococcus aureus were isolated from milk samples of the infected animals and identified biochemically. SA phage was isolated from sewage water showing lytic activity against Staphylococcus aureus isolates. The highest lytic activity of bacteriophages was observed at 37°C and pH 7, and the most suitable storage condition was at 4°C. SA phage efficiently reduced bacterial growth in the bacterial reduction assay. The characterization and bacterial growth reduction activity of the bacteriophages against Staphylococcus aureus signifies their underlying potential of phage therapy against mastitis.

  16. Reversible antibiotic tolerance induced in Staphylococcus aureus by concurrent drug exposure

    DEFF Research Database (Denmark)

    Haaber, Jakob Krause; Friberg, Cathrine; McCreary, Mark

    2015-01-01

    UNLABELLED: Resistance of Staphylococcus aureus to beta-lactam antibiotics has led to increasing use of the glycopeptide antibiotic vancomycin as a life-saving treatment for major S. aureus infections. Coinfection by an unrelated bacterial species may necessitate concurrent treatment with a second...... antibiotic that targets the coinfecting pathogen. While investigating factors that affect bacterial antibiotic sensitivity, we discovered that susceptibility of S. aureus to vancomycin is reduced by concurrent exposure to colistin, a cationic peptide antimicrobial employed to treat infections by Gram......-negative pathogens. We show that colistin-induced vancomycin tolerance persists only as long as the inducer is present and is accompanied by gene expression changes similar to those resulting from mutations that produce stably inherited reduction of vancomycin sensitivity (vancomycin-intermediate S. aureus [VISA...

  17. Staphylococcus aureus and healthcare-associated infections

    NARCIS (Netherlands)

    Ekkelenkamp, M.B.

    2011-01-01

    Many medical procedures breach or suppress patients’ natural defences, leaving them vulnerable to infections which would not occur in healthy humans: “healthcare-associated infections”. Healthcare-associated infections caused by the bacterium Staphylococcus aureus (S. aureus) are probably the most

  18. Population structure of Staphylococcus aureus in China

    NARCIS (Netherlands)

    Yan, Xiaomei

    2015-01-01

    The present PhD research was aimed at analysing the population structure of Staphylococcus aureus in China. Between 2000 and 2005 we found that patients from a single Chinese hospital showed increasing trends in antimicrobial resistance. Among methicillin-resistant S. aureus (MRSA), resistance

  19. METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS (MRSA ...

    African Journals Online (AJOL)

    Nosocomial infections caused by methicillin-resistant strains of Staphylococcus aureus often pose therapeutic dilemma to the clinicians because of the multi resistant nature of these strains of Staphylococcus aureus. Outbreaks of both nosocomial and community acquired infections are also frequent and difficult to control.

  20. Staphylococcus aureus and hand eczema severity

    DEFF Research Database (Denmark)

    Haslund, P; Bangsgaard, N; Jarløv, J O

    2009-01-01

    BACKGROUND: The role of bacterial infections in hand eczema (HE) remains to be assessed. OBJECTIVES: To determine the prevalence of Staphylococcus aureus in patients with HE compared with controls, and to relate presence of S. aureus, subtypes and toxin production to severity of HE. METHODS......: Bacterial swabs were taken at three different visits from the hand and nose in 50 patients with HE and 50 controls. Staphylococcus aureus was subtyped by spa typing and assigned to clonal complexes (CCs), and isolates were tested for exotoxin-producing S. aureus strains. The Hand Eczema Severity Index...... and in the nose in all cases, and between visits in 90% of cases. Ten different CC types were identified, no association with severity was found, and toxin-producing strains were not found more frequently in patients with HE than in controls. CONCLUSIONS: Staphylococcus aureus was present on hands in almost half...

  1. Transfer of Antibiotic Resistance in Staphylococcus aureus

    DEFF Research Database (Denmark)

    Haaber, Jakob; Penadés, José R; Ingmer, Hanne

    2017-01-01

    Staphylococcus aureus is a serious human pathogen with remarkable adaptive powers. Antibiotic-resistant clones rapidly emerge mainly by acquisition of antibiotic-resistance genes from other S. aureus strains or even from other genera. Transfer is mediated by a diverse complement of mobile genetic...... of plasmids that can be transferred by conjugation and the efficiency with which transduction occurs. Here, we review the main routes of antibiotic resistance gene transfer in S. aureus in the context of its biology as a human commensal and a life-threatening pathogen. Staphylococcus aureus cells...... are effective in exchanging mobile genetic elements, including antibiotic-resistance genes.During colonization or infection of host organisms, the exchange appears to be particularly effective.Bacteriophage-mediated transfer involves both transduction and autotransduction, which may enable lysogenic S. aureus...

  2. Active immunization with an octa-valent Staphylococcus aureus antigen mixture in models of S. aureus bacteremia and skin infection in mice.

    Directory of Open Access Journals (Sweden)

    Sanne van den Berg

    Full Text Available Proteomic studies with different Staphylococcus aureus isolates have shown that the cell surface-exposed and secreted proteins IsaA, LytM, Nuc, the propeptide of Atl (pro-Atl and four phenol-soluble modulins α (PSMα are invariantly produced by this pathogen. Therefore the present study was aimed at investigating whether these proteins can be used for active immunization against S. aureus infection in mouse models of bacteremia and skin infection. To this end, recombinant His-tagged fusions of IsaA, LytM, Nuc and pro-Atl were isolated from Lactococcus lactis or Escherichia coli, while the PSMα1-4 peptides were chemically synthesized. Importantly, patients colonized by S. aureus showed significant immunoglobulin G (IgG responses against all eight antigens. BALB/cBYJ mice were immunized subcutaneously with a mixture of the antigens at day one (5 μg each, and boosted twice (25 μg of each antigen with 28 days interval. This resulted in high IgG responses against all antigens although the response against pro-Atl was around one log lower compared to the other antigens. Compared to placebo-immunized mice, immunization with the octa-valent antigen mixture did not reduce the S. aureus isolate P load in blood, lungs, spleen, liver, and kidneys in a bacteremia model in which the animals were challenged for 14 days with a primary load of 3 × 10(5 CFU. Discomfort scores and animal survival rates over 14 days did not differ between immunized mice and placebo-immunized mice upon bacteremia with S. aureus USA300 (6 × 10(5 CFU. In addition, this immunization did not reduce the S. aureus isolate P load in mice with skin infection. These results show that the target antigens are immunogenic in both humans and mice, but in the used animal models do not result in protection against S. aureus infection.

  3. Reduction of nasal Staphylococcus aureus carriage in health care professionals by treatment with a nonantibiotic, alcohol-based nasal antiseptic.

    Science.gov (United States)

    Steed, Lisa L; Costello, Justin; Lohia, Shivangi; Jones, Taylor; Spannhake, Ernst W; Nguyen, Shaun

    2014-08-01

    Antibiotics used to reduce nasal colonization by Staphylococcus aureus in patients before admission are inappropriate for carriage reduction on a regular basis within a hospital community. Effective nonantibiotic alternatives for daily use in the nares will allow reduction of this bacterial source to be addressed. Our study tested the effectiveness of a nonantibiotic, alcohol-based antiseptic in reducing nasal bacterial carriage in health care professionals (HCPs) at an urban hospital center. HCPs testing positive for vestibular S aureus colonization were treated 3 times during the day with topical antiseptic or control preparations. Nasal S aureus and total bacterial colonization levels were determined before and at the end of a 10-hour workday. Seventy-eight of 387 HCPs screened (20.2%) tested positive for S aureus infection. Of 39 subjects who tested positive for S aureus infection who completed the study, 20 received antiseptic and 19 received placebo treatment. Antiseptic treatment reduced S aureus colony forming units from baseline by 99% (median) and 82% (mean) (P antiseptic was effective in reducing S aureus and total bacterial carriage, suggesting the usefulness of this approach as a safe, effective, and convenient alternative to antibiotic treatment. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

  4. Methicillin-Resistant Staphylococcus aureus Infections: A Comprehensive Review and a Plastic Surgeon's Approach to the Occult Sites.

    Science.gov (United States)

    Hunter, Cedric; Rosenfield, Lorne; Silverstein, Elena; Petrou-Zeniou, Panayiota

    2016-08-01

    Up to 20 percent of the general population is persistently colonized with Staphylococcus aureus, and 1 to 3 percent of the population is colonized with community-acquired methicillin-resistant S. aureus. Currently, the knowledge of methicillin-resistant Staphylococcus aureus carriage sites other than the nose, and their effect on surgical site infections in cosmetic surgery, is lacking. A comprehensive literature review using the PubMed database to analyze prevalence, anatomical carrier sites, current screening and decontamination protocols and guidelines, and methicillin-resistant S. aureus in cosmetic surgery was performed. The senior author's (L.R.) methicillin-resistant S. aureus infection experience and prevention protocols were also reviewed. Nasal swabs detect only 50.5 percent of methicillin-resistant S. aureus colonization, and broad screening has noted the presence of methicillin-resistant S. aureus in the ear canal and umbilicus. Decolonization protocols within the orthopedic and cardiothoracic surgery literature have reduced rates of methicillin-resistant S. aureus surgical-site infections. There are no decolonization guidelines for plastic surgeons. Since instituting their decolonization protocol, the authors have had no cases of methicillin-resistant S. aureus infection in nearly 1000 cosmetic surgery procedures. There are very limited, if any, Level I or II data regarding methicillin-resistant S. aureus screening and decolonization. As the sequelae of a surgical-site infection can be disastrous, expert opinions recommend that plastic surgeons vigorously address methicillin-resistant S. aureus colonization and infection. The authors have developed and recommend a simple decolonization protocol that includes treatment of the umbilicus, ear canal, and nares to limit surgical-site infection and improve surgical outcomes.

  5. Cfr-mediated linezolid-resistance among methicillin-resistant coagulase-negative staphylococci from infections of humans.

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    Lanqing Cui

    Full Text Available Four methicillin-resistant coagulase-negative staphylococci (MRCoNS, one Staphylococcus haemolyticus and three Staphylococcus cohnii, from infections of humans collected via the Ministry of Health National Antimicrobial Resistance Surveillance Net (Mohnarin program in China were identified as linezolid-resistant. These four isolates were negative for the 23S rRNA mutations, but positive for the gene cfr. Mutations in the gene for the ribosomal protein L3, which resulted in the amino acid exchanges Gly152Asp and Tyr158Phe, were identified in S. haemolyticus 09D279 and S. cohnii NDM113, respectively. In each isolate, the cfr gene was located on a plasmid of ca. 35.4 kb, as shown by S1 nuclease pulsed-field gel electrophoresis and Southern blotting experiments. This plasmid was indistinguishable from the previously described plasmid pSS-02 by its size, restriction pattern, and a sequenced 14-kb cfr-carrying segment. Plasmid pSS-02 was originally identified in staphylococci isolated from pigs. This is the first time that a cfr-carrying plasmid has been detected in MRCoNS obtained from intensive care patients in China. Based on the similarities to the cfr-carrying plasmid pSS-02 from porcine coagulase-negative staphylococci, a transmission of this cfr-carrying plasmid between staphylococci from pigs and humans appears to be likely.

  6. Cfr-mediated linezolid-resistance among methicillin-resistant coagulase-negative staphylococci from infections of humans.

    Science.gov (United States)

    Cui, Lanqing; Wang, Yang; Li, Yun; He, Tao; Schwarz, Stefan; Ding, Yujing; Shen, Jianzhong; Lv, Yuan

    2013-01-01

    Four methicillin-resistant coagulase-negative staphylococci (MRCoNS), one Staphylococcus haemolyticus and three Staphylococcus cohnii, from infections of humans collected via the Ministry of Health National Antimicrobial Resistance Surveillance Net (Mohnarin) program in China were identified as linezolid-resistant. These four isolates were negative for the 23S rRNA mutations, but positive for the gene cfr. Mutations in the gene for the ribosomal protein L3, which resulted in the amino acid exchanges Gly152Asp and Tyr158Phe, were identified in S. haemolyticus 09D279 and S. cohnii NDM113, respectively. In each isolate, the cfr gene was located on a plasmid of ca. 35.4 kb, as shown by S1 nuclease pulsed-field gel electrophoresis and Southern blotting experiments. This plasmid was indistinguishable from the previously described plasmid pSS-02 by its size, restriction pattern, and a sequenced 14-kb cfr-carrying segment. Plasmid pSS-02 was originally identified in staphylococci isolated from pigs. This is the first time that a cfr-carrying plasmid has been detected in MRCoNS obtained from intensive care patients in China. Based on the similarities to the cfr-carrying plasmid pSS-02 from porcine coagulase-negative staphylococci, a transmission of this cfr-carrying plasmid between staphylococci from pigs and humans appears to be likely.

  7. Determination of in vitro synergy between linezolid and other antimicrobial agents against Mycobacterium tuberculosis isolates.

    Science.gov (United States)

    Zou, Lin; Liu, Min; Wang, Yufeng; Lu, Jie; Pang, Yu

    2015-12-01

    In this study, our objective was to explore the potential in vitro synergy between linezolid (LZD) and six other anti-TB drugs in Mycobacterium tuberculosis strains, especially multidrug-resistant tuberculosis (MDR-TB) strains. Among the different combinations, the LZD-clarithromycin (CLA) combination showed the best synergism, which was observed in 85% (34/40) of 40 isolates. In addition, one (2.5%) and twenty-one (52.5%) of 40 isolates showed synergism for the LZD-levofloxcin (LEV) and LZD-moxifloxacin (MOX) combinations, respectively, and the difference in the proportion of synergy between these two combinations was significantly different (P synergy against non-MDR group seemed higher than that against MDR group in each combination, while the significant difference was only observed in the LZD-EMB combination (P = 0.046). In conclusion, our findings demonstrate that LZD shows the synergistic activity against both non-MDR and MDR M. tuberculosis strains when in combination with CLA, EMB, MOX, amikacin and clofazimine, indicating that LZD may be considered as a promising component involving the regimen for the treatment of MDR-TB. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Smart Methods for Linezolid Determination in the Presence of Alkaline and Oxidative Degradation Products Utilizing Their Overlapped Spectral Bands

    Science.gov (United States)

    Abd El-Monem Hegazy, M.; Shaaban Eissa, M.; Abd El-Sattar, O. I.; Abd El-Kawy, M. M.

    2014-09-01

    Linezolid (LIN) is considered the first available oxazolidinone antibacterial agent. It is susceptible to hydrolysis and oxidation. Five simple, accurate, sensitive and validated UV spectrophotometric methods were developed for LIN determination in the presence of its alkaline (ALK) and oxidative (OXD) degradation products in bulk powder and pharmaceutical formulation. Method A is a second derivative one (D2) in which LIN is determined at 240.9 nm. Method B is a pH-induced differential derivative one where LIN is determined using the fourth derivative (D4) of the difference spectra (ΔA) at 285.3 nm. Methods C, D, and E are manipulating ratio spectra, where C is the double divisor-ratio difference spectrophotometric one (DD-RD) in which LIN was determined by calculating the amplitude difference at 243.7 and 267.6 nm of the ratio spectra. Method D is the double divisor-first derivative of ratio spectra (DD-DD1) in which LIN was determined at 270.2 nm. Method E is a mean centering of ratio spectra one (MCR) in which LIN was determined at 318.0 nm. The developed methods have been validated according to ICH guidelines. The results were statistically compared to that of a reported HPLC method and there was no significant difference regarding both accuracy and precision.

  9. Spectrofluorimetric determination of gemifloxacin mesylate and linezolid in pharmaceutical formulations: Application of quinone-based fluorophores and enhanced native fluorescence

    Directory of Open Access Journals (Sweden)

    Moussa Bahia Abbas

    2014-03-01

    Full Text Available Quinone-based fluorophores and enhanced native fluorescence techniques were applied for a fast quantitative analysis of gemifloxacin mesylate (GEM and linezolid (LIN in pharmaceutical formulations. For this purpose, three sensitive, accurate and precise spectrofluorimetric methods were developed. GEM, as an n-electron donor, reacts with 7,7,8,8-tetracyanoquinodimethane (method A and 2,5-dichloro-3,6-dihydroxy-p-benzoquinone (method B as п-electron acceptors, forming charge transfer complexes that exhibit high fluorescence intensity at 441 and 390 nm upon excitation at 260 and 339 nm, respectively. Method C depends on measurement of enhanced native fluorescence of LIN in phosphate buffer (pH 5 at 380 nm upon excitation at 260 nm. Experimental factors affecting fluorescence intensity were optimized. Linearity was obtained over concentration ranges 50-500, 10-60 and 20-400 ng mL-1 for methods A, B and C, respectively. The developed methods were validated and successfully applied for determination of the cited drugs in tablets.

  10. Community-acquired pneumonia caused by methicillin-resistant Staphylococcus aureus in critically-ill patients: systematic review

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    Nuria Carballo

    2017-03-01

    Full Text Available Introduction: Community-acquired pneumonia (CAP is associated with high morbidity and mortality rates. Despite methicillin-resistant Staphylococcus aureus (MRSA having often been associated with nosocomial pneumonia, the condition of some MRSA CAP patients is severe enough to warrant their being admitted to ICU. Objective: The purpose of this study is to conduct a systematic review of the literature on antibiotic treatment of MRSA CAP in critically-ill patients. Material and methods: An online search was conducted for locating articles on MRSA CAP in critically ill patients. Relevant publications were identified in PUBMED, the BestPractice database, UpToDate database and the Cochrane Library for articles published in English within the December 2001 - April 2016 time frame. Results: A total of 70 articles were found to have been published, 13 (18.8% having been included and 57 (81.4% excluded. Cohort studies were predominant, having totaled 16 in number (20.7% as compared to one sole cross-sectional study (3.5%. Conclusions: The experience in the treatment of MRSA CAP in patients requiring admission to ICU is quite limited. Vancomycin or linezolid seem to be the treatments of choice for MRSA CAP, although there not be any specific recommendation in this regard. It may be useful to use alternative routes, such as administration via aerosolized antibiotics, continuous infusion or in association with other antibiotics.

  11. High MICs for Vancomycin and Daptomycin and Complicated Catheter-Related Bloodstream Infections with Methicillin-Sensitive Staphylococcus aureus

    Science.gov (United States)

    Viedma, Esther; Chaves, Fernando; Lalueza, Antonio; Fortún, Jesús; Loza, Elena; Pujol, Miquel; Ardanuy, Carmen; Morales, Isabel; de Cueto, Marina; Resino-Foz, Elena; Morales-Cartagena, Alejandra; Rico, Alicia; Romero, María P.; Orellana, María Ángeles; López-Medrano, Francisco; Fernández-Ruiz, Mario; Aguado, José María

    2016-01-01

    We investigated the prognostic role of high MICs for antistaphylococcal agents in patients with methicillin-sensitive Staphylococcus aureus catheter-related bloodstream infection (MSSA CRBSI). We prospectively reviewed 83 episodes from 5 centers in Spain during April 2011–June 2014 that had optimized clinical management and analyzed the relationship between E-test MICs for vancomycin, daptomycin, oxacillin, and linezolid and development of complicated bacteremia by using multivariate analysis. Complicated MSSA CRBSI occurred in 26 (31.3%) patients; MICs for vancomycin and daptomycin were higher in these patients (optimal cutoff values for predictive accuracy = 1.5 μg/mL and 0.5 μg/mL). High MICs for vancomycin (hazard ratio 2.4, 95% CI 1.2–5.5) and daptomycin (hazard ratio 2.4, 95% CI 1.1–5.9) were independent risk factors for development of complicated MSSA CRBSI. Our data suggest that patients with MSSA CRBSI caused by strains that have high MICs for vancomycin or daptomycin are at increased risk for complications. PMID:27192097

  12. In vitro pharmacokinetics of antimicrobial cationic peptides alone and in combination with antibiotics against methicillin resistant Staphylococcus aureus biofilms.

    Science.gov (United States)

    Dosler, Sibel; Mataraci, Emel

    2013-11-01

    Antibiotic therapy for methicillin-resistant Staphylococcus aureus (MRSA) infections is becoming more difficult in hospitals and communities because of strong biofilm-forming properties and multidrug resistance. Biofilm-associated MRSA is not affected by therapeutically achievable concentrations of antibiotics. Therefore, we investigated the in vitro pharmacokinetic activities of antimicrobial cationic peptides (AMPs; indolicidin, cecropin [1-7]-melittin A [2-9] amide [CAMA], and nisin), either alone or in combination with antibiotics (daptomycin, linezolid, teicoplanin, ciprofloxacin, and azithromycin), against standard and 2 clinically obtained MRSA biofilms. The minimum inhibitory concentrations (MIC) and minimum biofilm-eradication concentrations (MBEC) were determined by microbroth dilution technique. The time-kill curve (TKC) method was used to determine the bactericidal activities of the AMPs alone and in combination with the antibiotics against standard and clinically obtained MRSA biofilms. The MIC values of the AMPs and antibiotics ranged between 2 to 16 and 0.25 to 512 mg/L, and their MBEC values were 640 and 512 to 5120 mg/L, respectively. The TKC studies demonstrated that synergistic interactions occurred most frequently when using nisin+daptomycin/ciprofloxacin, indolicidin+teicoplanin, and CAMA+ciprofloxacin combinations. No antagonism was observed with any combination. AMPs appear to be good candidates for the treatment of MRSA biofilms, as they act as both enhancers of anti-biofilm activities and help to prevent or delay the emergence of resistance when used either alone or in combination with antibiotics. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Staphylococcus aureus resistente a vancomicina.

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    Carlos Andrés Rodríguez

    2005-12-01

    Full Text Available Objetivo. Revisar la evolución y mecanismos moleculares de la resistencia de Staphylococcus aureus a vancomicina. Fuente de los datos. Se consultó la base de datos MEDLINE y se seleccionaron artículos tipo reportes de caso, estudios bioquímicos, de microscopía electrónica y biología molecular pertinentes. Síntesis. Después de casi 40 años de eficacia ininterrumpida de la vancomicina, en 1997 se reportaron los primeros casos de fracaso terapéutico debido a cepas de Staphylococcus aureus con resistencia intermedia, denominadas VISA (concentración inhibitoria mínima, CIM, 8 a 16 ?g/ml, así como a cepas con resistencia heterogénea hVISA (CIM global = 4 ?g/ml, pero con subpoblaciones VISA, en las cuales la resistencia está mediada por engrosamiento de la pared celular y disminución de su entrecruzamiento, lo que afecta la llegada del antibiótico al blanco principal, los monómeros del peptidoglicano en la membrana plasmática. En 2002 se aisló la primera de las 3 cepas reportadas hasta la fecha con resistencia total al antibiótico, denominadas VRSA (CIM>32 ?g/ml, en las que se encontró el transposón Tn1546 proveniente de Enterococcus spp, responsable del reemplazo de la terminación D-Ala-D-Ala por D-Ala-Dlactato en los precursores de la pared celular con pérdida de la afinidad por el glicopéptido. Conclusiones. La resistencia a vancomicina es una realidad en S. aureus, mediada en el caso de VISA por alteraciones en la pared celular que atrapan el antibiótico antes de llegar al sitio de acción, y en el caso de VRSA, por transferencia desde Enterococcus spp. de genes que llevan a la modificación del blanco molecular.

  14. Prevalence and Genetic Basis of Antimicrobial Resistance in Non-aureus Staphylococci Isolated from Canadian Dairy Herds

    Science.gov (United States)

    Nobrega, Diego B.; Naushad, Sohail; Naqvi, S. Ali; Condas, Larissa A. Z.; Saini, Vineet; Kastelic, John P.; Luby, Christopher; De Buck, Jeroen; Barkema, Herman W.

    2018-01-01

    Emergence and spread of antimicrobial resistance is a major concern for the dairy industry worldwide. Objectives were to determine: (1) phenotypic and genotypic prevalence of drug-specific resistance for 25 species of non-aureus staphylococci, and (2) associations between presence of resistance determinants and antimicrobial resistance. Broth micro-dilution was used to determine resistance profiles for 1,702 isolates from 89 dairy herds. Additionally, 405 isolates were sequenced to screen for resistance determinants. Antimicrobial resistance was clearly species-dependent. Resistance to quinupristin/dalfopristin was common in Staphylococcus gallinarum (prevalence of 98%), whereas S. cohnii and S. arlettae were frequently resistant to erythromycin (prevalence of 63 and 100%, respectively). Prevalence of resistance was 10% against β-lactams and tetracyclines. In contrast, resistance to antimicrobials critically important for human medicine, namely vancomycin, fluoroquinolones, linezolid and daptomycin, was uncommon (< 1%). Genes encoding multidrug-resistance efflux pumps and resistance-associated residues in deducted amino acid sequences of the folP gene were the most frequent mechanisms of resistance, regardless of species. The estimated prevalence of the mecA gene was 17% for S. epidermidis. Several genes, including blaZ, mecA, fexA, erm, mphC, msrA, and tet were associated with drug-specific resistance, whereas other elements were not. There were specific residues in gyrB for all isolates of species intrinsically resistant to novobiocin. This study provided consensus protein sequences of key elements previously associated with resistance for 25 species of non-aureus staphylococci from dairy cattle. These results will be important for evaluating effects of interventions in antimicrobial use in Canadian dairy herds. PMID:29503642

  15. Prevalence and Genetic Basis of Antimicrobial Resistance in Non-aureus Staphylococci Isolated from Canadian Dairy Herds

    Directory of Open Access Journals (Sweden)

    Diego B. Nobrega

    2018-02-01

    Full Text Available Emergence and spread of antimicrobial resistance is a major concern for the dairy industry worldwide. Objectives were to determine: (1 phenotypic and genotypic prevalence of drug-specific resistance for 25 species of non-aureus staphylococci, and (2 associations between presence of resistance determinants and antimicrobial resistance. Broth micro-dilution was used to determine resistance profiles for 1,702 isolates from 89 dairy herds. Additionally, 405 isolates were sequenced to screen for resistance determinants. Antimicrobial resistance was clearly species-dependent. Resistance to quinupristin/dalfopristin was common in Staphylococcus gallinarum (prevalence of 98%, whereas S. cohnii and S. arlettae were frequently resistant to erythromycin (prevalence of 63 and 100%, respectively. Prevalence of resistance was 10% against β-lactams and tetracyclines. In contrast, resistance to antimicrobials critically important for human medicine, namely vancomycin, fluoroquinolones, linezolid and daptomycin, was uncommon (< 1%. Genes encoding multidrug-resistance efflux pumps and resistance-associated residues in deducted amino acid sequences of the folP gene were the most frequent mechanisms of resistance, regardless of species. The estimated prevalence of the mecA gene was 17% for S. epidermidis. Several genes, including blaZ, mecA, fexA, erm, mphC, msrA, and tet were associated with drug-specific resistance, whereas other elements were not. There were specific residues in gyrB for all isolates of species intrinsically resistant to novobiocin. This study provided consensus protein sequences of key elements previously associated with resistance for 25 species of non-aureus staphylococci from dairy cattle. These results will be important for evaluating effects of interventions in antimicrobial use in Canadian dairy herds.

  16. Sampling, prevalence and characterization of methicillin-resistant Staphylococcus aureus on two Belgian pig farms

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    Isabelle Dewaele

    2011-02-01

    Full Text Available This study investigated the spread of MRSA (methicillin-resistant Staphylococcus aureus on two Belgian pig farms. Pigs of different ages (from farrowing to slaughter age and sows as well as the barn environment were screened extensively on two occasions three months apart. A subset of MRSA isolates was tested for antimicrobial susceptibility to 16 antibiotics and was further characterized by pulsed-field gel electrophoresis. Ninety-five percent and 77% of the tested pigs on farm A and farm B, respectively, were colonized with MRSA. MRSA positive animals were detected in all age categories sampled on each sampling day. Piglets were already colonized in the farrowing unit with the same or other MRSA strains than their mother. The prevalence of MRSA colonized pigs increased significantly after weaning and decreased during the fattening period. Pigs carried MRSA mainly in the nares, followed by the perineum and skin and to a lesser degree the rectum. A pig could be contaminated or colonized with different MRSA strains at the same time. The barn environment was also found to be contaminated with different MRSA strains, including the air inlet and outlet. All isolates tested on both farms were resistant to both tetracycline and trimethoprim, while they were susceptible to rifampicin, mupirocin and linezolid. There was a significant difference in resistance prevalence between the two farms for the antibiotics gentamicin, kanamycin, tobramycin, tylosin, lincomycin and quinupristin/dalfopristin. Furthermore, several antibiotic resistance profiles were observed within one farm. This study clearly indicates that several MRSA strains circulate on one farm, from the nursery unit to the fattening unit. This is important to consider when attempts are made to remediate these farms.

  17. 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

    Directory of Open Access Journals (Sweden)

    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.

  18. A longitudinal study on transmission of Staphylococcus aureus genotype B in Swiss communal dairy herds.

    Science.gov (United States)

    van den Borne, Bart H P; Graber, Hans U; Voelk, Verena; Sartori, Carlotta; Steiner, Adrian; Haerdi-Landerer, M Christina; Bodmer, Michèle

    2017-01-01

    Staphylococcus aureus is a common mastitis causing pathogen of dairy cattle. Several S. aureus genotypes exist, of which genotype B (GTB) is highly prevalent in Swiss dairy herds. Dairy farming in mountainous regions of Switzerland is characterised by the movement of dairy cattle to communal pasture-based operations at higher altitudes. Cows from different herds of origin share pastures and milking equipment for a period of 2 to 3 months during summer. The aim of this longitudinal observational study was to quantify transmission of S. aureus GTB in communal dairy operations. Cows (n=551) belonging to 7 communal operations were sampled at the beginning and end of the communal period. Transmission parameter β was estimated using a Susceptible-Infectious-Susceptible (SIS) model. The basic reproduction ratio R 0 was subsequently derived using previously published information about the duration of infection. Mean transmission parameter β was estimated to be 0.0232 (95% CI: 0.0197-0.0274). R 0 was 2.6 (95% CI: 2.2-3.0), indicating that S. aureus GTB is capable of causing major outbreaks in Swiss communal dairy operations. This study emphasized the contagious behaviour of S. aureus GTB. Mastitis management in communal dairy operations should be optimized to reduce S. aureus GTB transmission between cows and back to their herds of origin. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Novel patterns of ultraviolet mutagenesis and Weigle reactivation in Staphylococcus aureus and phage phi II

    International Nuclear Information System (INIS)

    Thompson, J.K.; Hart, M.G.R.

    1981-01-01

    The effects of u.v. irradiation on the survival of Staphylococcus aureus and its phage phi11 were studied. The recA and uvr mutations affected their survival like synonymous mutations in Escherichia coli. Weigle reactivation (W-reactivation) of phi11 occurred in wild-type S. aureus and in a uvr mutant. Reactivation was recA-dependent and was accompanied by u.v.-induced mutagenesis in a temperature-sensitive mutant of phi11. Bacterial mutation to streptomycin resistance was induced by u.v. and was also recA-dependent. In S. aureus, as in E. coli, u.v. was a more effective mutagen in the uvr genetic background. However, a dose-squared response for u.v.-induced mutation of wild-type and uvr strains of S. aureus to streptomycin resistance, and of a trp auxotroph to tryptophan independence, was found only with u.v. doses below 1 J m -2 . In relation to the Uvr mechanism of DNA repair, u.v. mutagenesis in S. aureus may involve both repairable and non-repairable lesions. As in E. Coli, the uvr genetic background reduced the u.v. dose required for maximal W-reactivation of u.v.-irradiated phage. However, there was no enhancement of W-reactivation by post-irradiation broth incubation of S. aureus. The results are compatible with a non-inducible mechanism for this phenomenon. (author)

  20. Predictors of Staphylococcus aureus Colonization and Results after Decolonization

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    Tennison L. Malcolm

    2016-01-01

    Full Text Available Protocols for the screening and decolonization of Staphylococcus aureus prior to total joint arthroplasty (TJA have become widely adopted. The goals of this study were to determine: (1 whether implementation of a screening protocol followed by decolonization with mupirocin/vancomycin and chlorhexidine reduces the risk of revision compared with no screening protocol (i.e., chlorhexidine alone and (2 whether clinical criteria could reliably predict colonization with MSSA and/or MRSA. Electronic medical records of primary patients undergoing TJA that were screened (n=3,927 and were not screened (n=1,751 for Staphylococcus aureus at least 4 days prior to surgery, respectively, were retrospectively reviewed. All patients received chlorhexidine body wipes preoperatively. Patients carrying MSSA and MRSA were treated preoperatively with mupirocin and vancomycin, respectively, along with the standard preoperative antibiotics and chlorhexidine body wipes. Screened patients were 50% less likely to require revision due to prosthetic joint infection compared to those not screened (p=0.04. Multivariate regression models were poorly accurate in predicting colonization with MSSA (AUC = 0.58 and MRSA (AUC = 0.62. These results support the routine screening and decolonization of S. aureus prior to TJA.

  1. A validated UPLC-MS/MS method for the analysis of linezolid and a novel oxazolidinone derivative (PH027) in plasma and its application to tissue distribution study in rabbits.

    Science.gov (United States)

    Hedaya, Mohsen A; Thomas, Vidhya; Abdel-Hamid, Mohamed E; Kehinde, Elijah O; Phillips, Oludotun A

    2017-01-01

    Linezolid is the first approved oxazolidinone antibacterial agent, whereas PH027 is a novel compound of the same class that exhibits good in vitro antibacterial activity. The objective of this study was to develop an UPLC-MS/MS assay for the analysis of linezolid and PH027 in plasma and to apply the method for comparative pharmacokinetic and tissue distribution studies of both compounds. Plasma samples and calibrators were extracted with diethyl ether after addition of the internal standard solution. After evaporation of the ether layer, the residue was reconstituted in mobile phase and injected into UPLC-MS/MS. The mobile phase consisted of 2mM ammonium acetate buffer solution and acetonitrile (70:30) at a flow rate of 0.2ml/min. Separation was achieved using UPLC BEH C 18 column, and quantitative determination of the analytes was performed using multiple-reaction monitoring (MRM) scanning mode. The method was validated by analyzing quality control tissue homogenate samples, and was applied to analyze tissue homogenate samples obtained following IV injections of linezolid and PH027 in rabbits. The developed UPLC-MS/MS method was linear in the concentration range of 50-5000ng/ml. Validation of the method proved that the method's precision, selectivity and stability were all within the acceptable limits. Linezolid and PH027 concentrations were accurately determined in the quality control tissue homogenate samples, and analysis of samples obtained following IV administration of the two compounds showed that the tissue to plasma concentration ratio of PH027 was higher than that of linezolid probably due to its higher lipophilicity. The developed UPLC-MS/MS method for the analysis of linezolid and PH027 in rabbit's plasma can accurately determine the concentrations of these compounds in different tissues. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Antimicrobial resistant coagulase positive Staphylococcus aureus ...

    African Journals Online (AJOL)

    ADEYEYE

    Staphylococcus aureus is an Important agent of food poisoning. In many countries, it ... humans and animals (Casey et al., 2007). ... of widespread use of antibiotics in animals for ... Laboratory Standards Institute methods (CLSI, 2010). Briefly ...

  3. OCCURRENCE AND ANTIBIOGRAM OF Staphylococcus aureus IN ...

    African Journals Online (AJOL)

    User

    1Federal College of Agricultural Produce Technology, Kano. 2Department of ... The presence of S.aureus and resistance to commonly used antibiotics by the isolates posses .... mastitic animals or human sources (Akram et al.,. 2013; Oliver et ...

  4. Simultaneous determination and stability studies of linezolid, meropenem and vancomycin in bacterial growth medium by high-performance liquid chromatography.

    Science.gov (United States)

    Wicha, Sebastian G; Kloft, Charlotte

    2016-08-15

    For pharmacokinetic/pharmacodynamic (PK/PD) assessment of antibiotics combinations in in vitro infection models, accurate and precise quantification of drug concentrations in bacterial growth medium is crucial for derivation of valid PK/PD relationships. We aimed to (i) develop a high-performance liquid chromatography (HPLC) assay to simultaneously quantify linezolid (LZD), vancomycin (VAN) and meropenem (MER), as typical components of broad-spectrum antibiotic combination therapy, in bacterial growth medium cation-adjusted Mueller-Hinton broth (CaMHB) and (ii) determine the stability profiles of LZD, VAN and MER under conditions in in vitro infection models. To separate sample matrix components, the final method comprised the pretreatment of 100μL sample with 400μL methanol, the evaporation of supernatant and its reconstitution in water. A low sample volume of 2μL processed sample was injected onto an Accucore C-18 column (2.6μm, 100×2.1mm) coupled to a Dionex Ultimate 3000 HPLC+ system. UV detection at 251, 240 and 302nm allowed quantification limits of 0.5, 2 and 0.5μg/mL for LZD, VAN and MER, respectively. The assay was successfully validated according to the relevant EMA guideline. The rapid method (14min) was successfully applied to quantify significant degradation of LZD, VAN and MER in in vitro infection models: LZD was stable, VAN degraded to 90.6% and MER to 62.9% within 24h compared to t=0 in CaMHB at 37°C, which should be considered when deriving PK/PD relationships in in vitro infection models. Inclusion of further antibiotics into the flexible gradient-based HPLC assay seems promising. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Alterations in the transcriptome and antibiotic susceptibility of Staphylococcus aureus grown in the presence of diclofenac

    Science.gov (United States)

    2011-01-01

    Background Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) which has been shown to increase the susceptibility of various bacteria to antimicrobials and demonstrated to have broad antimicrobial activity. This study describes transcriptome alterations in S. aureus strain COL grown with diclofenac and characterizes the effects of this NSAID on antibiotic susceptibility in laboratory, clinical and diclofenac reduced-susceptibility (DcRS) S. aureus strains. Methods Transcriptional alterations in response to growth with diclofenac were measured using S. aureus gene expression microarrays and quantitative real-time PCR. Antimicrobial susceptibility was determined by agar diffusion MICs and gradient plate analysis. Ciprofloxacin accumulation was measured by fluorescence spectrophotometry. Results Growth of S. aureus strain COL with 80 μg/ml (0.2 × MIC) of diclofenac resulted in the significant alteration by ≥2-fold of 458 genes. These represented genes encoding proteins for transport and binding, protein and DNA synthesis, and the cell envelope. Notable alterations included the strong down-regulation of antimicrobial efflux pumps including mepRAB and a putative emrAB/qacA-family pump. Diclofenac up-regulated sigB (σB), encoding an alternative sigma factor which has been shown to be important for antimicrobial resistance. Staphylococcus aureus microarray metadatabase (SAMMD) analysis further revealed that 46% of genes differentially-expressed with diclofenac are also σB-regulated. Diclofenac altered S. aureus susceptibility to multiple antibiotics in a strain-dependent manner. Susceptibility increased for ciprofloxacin, ofloxacin and norfloxacin, decreased for oxacillin and vancomycin, and did not change for tetracycline or chloramphenicol. Mutation to DcRS did not affect susceptibility to the above antibiotics. Reduced ciprofloxacin MICs with diclofenac in strain BB255, were not associated with increased drug accumulation. Conclusions The results of

  6. Contribution of hydrogen peroxide to the inhibition of Staphylococcus aureus by Lactococcus garvieae in interaction with raw milk microbial community

    OpenAIRE

    Delbes, Céline; Dorchies, Géraud; Chaabna, Zineddine; Callon, Cecile; Montel, Marie-Christine

    2010-01-01

    The response of Staphylococcus aureus growth inhibition by Lactococcus garvieae to catalase and milk lactoperoxidase, and its efficiency in raw milk cheese were evaluated. S. aureus and L. garvieae were co-cultivated in broth buffered at pH 6.8, and in raw, pasteurized and microfiltered milk, in presence and absence of catalase. Although H(2)O(2) production by L garvieae was detected only in agitated broth, the inhibition of S. aureus by L garvieae was reduced by catalase both in stati...

  7. Complete Genome Sequence of the Quality Control Strain Staphylococcus aureus subsp. aureus ATCC 25923.

    Science.gov (United States)

    Treangen, Todd J; Maybank, Rosslyn A; Enke, Sana; Friss, Mary Beth; Diviak, Lynn F; Karaolis, David K R; Koren, Sergey; Ondov, Brian; Phillippy, Adam M; Bergman, Nicholas H; Rosovitz, M J

    2014-11-06

    Staphylococcus aureus subsp. aureus ATCC 25923 is commonly used as a control strain for susceptibility testing to antibiotics and as a quality control strain for commercial products. We present the completed genome sequence for the strain, consisting of the chromosome and a 27.5-kb plasmid. Copyright © 2014 Treangen et al.

  8. Synthetic peptide inhibitors of DNA replication in Staphylococcus aureus

    DEFF Research Database (Denmark)

    Løbner-Olesen, Anders; Kjelstrup, Susanne

    F counterselection was developed to directly select for compounds able to disrupt selected interactions. We have subsequently constructed a cyclic peptide library for intracellular synthesis of cyclic peptides using known technology. Several cyclic peptides were able to interfere with oligomerization of Dna......N (), DnaB and DnaX (). Three peptides identified as inhibitors of DnaN have been purified. Two of these peptides inhibited growth as well as DNA replication in S. aureus. The minimal inhibitory concentration (MIC) of the peptides was approximately 50 g/ml. Overexpression of DnaN reduced the inhibitory...

  9. Impact of oral gut decontamination on Staphylococcus aureus colonisation in patients undergoing allogeneic haematopoietic stem cell transplantation.

    Science.gov (United States)

    Wilk, C Matthias; Weber, Isabel; Seidl, Kati; Rachmühl, Carole; Holzmann-Bürgel, Anne; Müller, Antonia M S; Kuster, Stefan P; Schanz, Urs; Zinkernagel, Annelies S

    2017-12-01

    Recipients of allogeneic haematopoietic stem cell transplantation (allo-HSCT) are severely immunocompromised and are at increased risk of infection. In this prospective, observational, single-centre study including 110 allo-HSCT recipients, the rate of Staphylococcus aureus colonisation was reduced from 11.8% to 0% (P <0.001) following peritransplant oral gut decontamination. No invasive S. aureus infections were observed. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  10. Effectiveness of simple control measures on methicillin-resistant Staphylococcus aureus infection status and characteristics with susceptibility patterns in a teaching hospital in Peshawar.

    Science.gov (United States)

    Rafiq, Muhammad Salman; Rafiq, Muhammad Imran; Khan, Taimur; Rafiq, Maria; Khan, Mah Muneer

    2015-09-01

    To determine the effectiveness of simple control measures on the infection status and characteristics of methicillin-resistant Staphylococcus aureus including susceptibility patterns among health professionals and patients in a teaching hospital. The cross-sectional study was conducted from September 2013 to January 2014, and comprised samples collected from healthcare personnel and patients in the various units of Khyber Teaching Hospital, Peshawar. The specimens were collected before and one month after the implementation of simple control measures for outbreak prevention of methicillin-resistant Staphylococcus aureus. These were tested for culture and antimicrobial susceptibility. Data about methicillin-sensitive and methicillin-resistant Staphylococcus aureus infection, wound characteristics and susceptibility patterns was collected and effectiveness of simple control measures was determined. SPSS 20 was used for statistical analysis. Of the total 390 isolates, 180(46.2%) were Staphylococcus aureus; 77(19.7%) from healthcare personnel and 103(26.4%) from patients. Of these, 164(42.1%) were methicillin-sensitive and 16(4.1%) were methicillin-resistant. Among the patients, 38(15.1%) methicillin-sensitive and 8(3.2%) methicillin-resistant isolates were recovered from wounds or skin and soft tissues. Pus with 33(13.1%) and 4(1.6%) cases respectively was the second most common source. Among methicillin-resistant isolates, resistance to Linezolid was 0%, all were resistant to Oxacillin, Cefoxitin, Amoxicillin, Cefotaxime and Cephradine, and resistance to both Co-Amoxiclav and Ciprofloxacin was 87.5%. After one month of implementation of simple control measures, the number of methicillin-resistant cases among healthcare professionals and patients dropped from 4(2.9%) and 7(10.8%) to 1(0.7%) and 5(2.7%), respectively. Methicillin-resistant and methicillin-sensitive Staphylococcus aureus differed in their anti-microbial susceptibility profiles. Selection of antibiotics

  11. Molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from patients with bacteremia based on MLST, SCCmec, spa, and agr locus types analysis.

    Science.gov (United States)

    Goudarzi, Mehdi; Seyedjavadi, Sima Sadat; Nasiri, Mohammad Javad; Goudarzi, Hossein; Sajadi Nia, Raheleh; Dabiri, Hossein

    2017-03-01

    The widespread emergence of methicillin resistant Staphylococcus aureus, as a common cause of nosocomial infections, is becoming a serious concern in global public health. The objective of the present study was to investigate antimicrobial susceptibility pattern, frequency of virulence genes and molecular characteristics of methicillin-resistant Staphylococcus aureus strains isolated from patients with bacteremia. A total of 128 methicillin-resistant Staphylococcus aureus isolates were collected during February 2015 to January 2016. In vitro antimicrobial susceptibility of the isolates was assessed using the disk diffusion method. Conventional PCR was performed for the detection of adhesion (can, bbp, ebp, fnbB, fnbA, clfB, clfA) and toxin (etb, eta, pvl, tst) encoding genes, determining the agr type, SCCmec, MLST and spa typing of the isolates. All the methicillin-resistant Staphylococcus aureus isolates were found to be sensitive to linezolid, teicoplanin, and vancomycin. Resistance to the tested antibiotics varied from 97.7% for penicillin to 24.2% for mupirocin. The rate of multi drug resistance (MDR) in the present study was 97.7%. The most commonly detected toxin and adhesion genes were tst (58.6%), and clfB (100%), respectively. The majority of SCCmec III isolates were found in agr group I while SCCmec IV and II isolates were distributed among agr group III. Multilocus Sequence Typing (MLST) of the MRSA isolates showed five different sequence types: ST239 (43%), ST22 (39.8%), ST585 (10.9%), ST45 (3.9%) and ST240 (2.3%). All of the pvl positive strains belonged to ST22-SCCmec IV/t790 clone and were MDR. Among different 7 spa types, the most common were t790 (27.3%), t037 (21.9%), and t030 (14.1%). spa types t016, t924 and spa type t383 were reported for the first time from Asia and Iran, respectively. It was shown that spa types circulating in the studied hospitals varied which support the need to perform future surveillance studies in order to understand

  12. Single- and Multiple-Dose Study To Determine the Safety, Tolerability, Pharmacokinetics, and Food Effect of Oral MRX-I versus Linezolid in Healthy Adult Subjects.

    Science.gov (United States)

    Eckburg, Paul B; Ge, Yigong; Hafkin, Barry

    2017-04-01

    A multipart phase 1 study was conducted to determine the safety, tolerability, pharmacokinetics, and food effect of the novel oral oxazolidinone, MRX-I, in healthy adults, as well as the tolerability of longer-term exposure of both oral MRX-I and linezolid. Thirty subjects in part 1 received single ascending doses of MRX-I or placebo under fasting or fed condition in a double-blind crossover design. Twelve subjects in part 2 received MRX-I at 800 mg every 12 h (q12h) for 14 days in a double-blind, placebo-controlled design. In part 3, 24 subjects were randomized to receive 28 days of MRX-I at 800 mg q12h or oral linezolid at 600 mg q12h for 28 days in a double-blind, double-dummy design. Oral MRX-I was associated with a greater bioavailability and exposure when administered with food, and minimal accumulation of MRX-I occurred after multiple-dose administration. Oral MRX-I was well tolerated at single doses of up to 1,200 and 800 mg q12h for up to 28 days; all adverse events were mild to moderate in severity, and there was no drug discontinuation due to adverse events. These data support further clinical development of oral MRX-I in the treatment of resistant Gram-positive bacterial infections. Copyright © 2017 American Society for Microbiology.

  13. Radiocharacterization of the 99mTc-rufloxacin complex and biological evaluation in Staphylococcus aureus infected rat model

    International Nuclear Information System (INIS)

    Syed Qaiser Shah; Muhammad Rafiullah Khan

    2011-01-01

    99m Tc-rufloxacin ( 99m Tc-RUN) complex was prepared by reaction of different amounts of reduced sodium pertechnetate with different amount of Rufloxacin (RUN) antibiotic for the in vivo scintigraphic localization of the Staphylococcus aureus (S. aureus) infectious foci in Male Wister Rats (MWR) model. The 99m Tc-RUN complex was radiochemically and biologically characterized in terms of radiochemical stability in saline, serum, in vitro binding with S. aureus and biodistribution in artificially infected with S. aureus MWR. The 99m Tc-RUN complex showed stability more than 90% up to 240 min in normal saline with a maximum stability value of 98.10 ± 0.18% at 30 min after reconstitution. At 37 deg C the complex showed in vitro permanence in serum up to 16 h with 13.90% side products during incubation. The 99m Tc-RUN complex showed saturated in vitro binding with S. aureus at different intervals with a maximum uptake value of 71.50%. Infected to normal muscle, infected to inflamed and inflamed to normal muscles ratios were approximately 6.04, 4.31 and 1.40. Based on the stability of the complex in saline, serum, in vitro binding with S. aureus and biodistribution results, the 99m Tc-RUN complex is recommended for in vivo scintigraphic localization of the S. aureus in vivo infectious foci in human. (author)

  14. Tumor Necrosis Factor-α Is Required for Mast Cell-Mediated Host Immunity Against Cutaneous Staphylococcus aureus Infection.

    Science.gov (United States)

    Liu, Chao; Ouyang, Wei; Xia, Jingyan; Sun, Xiaoru; Zhao, Liying; Xu, Feng

    2018-05-08

    Mast cells (MCs) play a key role in immune process response to invading pathogens. This study assessed the involvement of MCs in controlling Staphylococcus aureus infection in a cutaneous infection model of MC-deficient (KitW-sh/W-sh) mice. KitW-sh/W-sh mice developed significantly larger skin lesions after the cutaneous S. aureus challenge, when compared to wild-type (WT) mice, while MC dysfunction reduced the inflammation response to S. aureus. The levels of tumor necrosis factor (TNF)-α in skin tissues were significantly decreased in KitW-sh/W-sh mice upon infection. Moreover, the exogenous administration of MCs or recombinant TNF-α effectively restored the immune response against S. aureus in KitW-sh/W-sh mice via the recruitment of neutrophils to the infected site. These results indicate that the effects of MC deficiency are largely attributed to the decrease in production of TNF-α in cutaneous S. aureus infection. In addition, S. aureus-induced MC activation was dependent on the c-kit receptor-activated phosphoinositide 3-kinase (PI3K)/AKT/P65-nuclear factor (NF-κB) pathway, which was confirmed by treatment with Masitinib (a c-kit receptor inhibitor), Wortmannin (a PI3K inhibitor), and pyrrolidine dithiocarbamate (a NF-κB inhibitor), respectively. The present study identifies the critical role of MCs in the host defense against S. aureus infection.

  15. The potential of the endolysin Lysdb from Lactobacillus delbrueckii phage for combating Staphylococcus aureus during cheese manufacture from raw milk.

    Science.gov (United States)

    Guo, Tingting; Xin, YongPing; Zhang, Chenchen; Ouyang, Xudong; Kong, Jian

    2016-04-01

    Phage endolysins have received increased attention in recent times as potential antibacterial agents and the biopreservatives in food production processes. Staphylococcus aureus is one of the most common pathogens in bacterial food poisoning outbreaks. In this study, the endolysin Lysdb, one of the two-component cell lysis cassette of Lactobacillus delbrueckii phage phiLdb, was shown to possess a muramidase domain and catalytic sites with homology to Chalaropsis-type lysozymes. Peptidoglycan hydrolytic bond specificity determination revealed that Lysdb was able to cleave the 6-O-acetylated peptidoglycans present in the cell walls of S. aureus. Turbidity reduction assays demonstrated that Lysdb could effectively lyse the S. aureus live cells under acidic and mesothermal conditions. To further evaluate the ability of Lysdb as a potential antibacterial agent against S. aureus in cheese manufacture, Lactobacillus casei BL23 was engineered to constitutively deliver active Lysdb to challenge S. aureus in lab-scale cheese making from raw milk. Compared with the raw milk, the viable counts of S. aureus were reduced by 10(5)-fold in the cheese inoculated with the engineered L. casei strain during the fermentation process, and the pathogenic bacterial numbers remained at a low level (10(4) CFU/g) after 6 weeks of ripening at 10 °C. Taken together, all results indicated that the Lysdb has the function as an effective tool for combating S. aureus during cheese manufacture from raw milk.

  16. Infertility as a consequence of spermagglutinating Staphylococcus aureus colonization in genital tract of female mice.

    Directory of Open Access Journals (Sweden)

    Siftjit Kaur

    Full Text Available Various studies have shown Staphylococcus aureus to be one of the most prevalent organism in male and female genital tract but most practitioners dismiss it as mere contamination which is assumed to be of no significance. However, it is now suggested that the presence of this organism should not be ignored, as incubation of spermatozoa with S. aureus results in reduced sperm motility. Although S. aureus has been reported to cause immobilization of spermatozoa, however, its role in infertility has yet to be elucidated. The present study was designed to establish a spermagglutinating strain of S. aureus isolated from the cervix of a woman with unexplained infertility, in mouse and evaluate its effect on fertility outcome. Female Balb/c mice were inoculated intravaginally with different doses of S. aureus (10(4, 10(6 or 10(8cfu/20 µl for 10 consecutive days. Microbial colonization monitored every 3(rd day by vaginal cultures, revealed that strain could efficiently colonize mouse vagina. Mating on day 12, with proven breeder males led to 100% decrease in fertility as compared to control. Even a single dose of 10(6 or 10(8cfu could lead to vaginal colonization which persisted for 10 days followed by gradual clearing till 21 days, vaginal cultures were negative thereafter. Female mice mated on day 7 (culture positive, were rendered infertile, however, the mice mated on day 22 (culture negative, retained fertility and delivered pups indicating its role in provoking infertility. Further, except infertility, no other clinical manifestation could be seen apparently or histologically. However, when a non-spermagglutinating/immobilizing standard strain of S. aureus MTCC6625 was inoculated intravaginally at 10(8cfu for 10 days followed by mating on day 12, fertility was observed in all the female mice. This supports the hypothesis that infertility observed in the former groups was as a result of colonization with spermagglutinating strain of S. aureus.

  17. A 12-year review of Staphylococcus aureus bloodstream infections in haemodialysis patients: more work to be done.

    LENUS (Irish Health Repository)

    Fitzgerald, S F

    2012-02-01

    Staphylococcus aureus bloodstream infections (BSI) are a significant cause of morbidity and mortality in haemodialysis patients. This study describes a 12-year retrospective review of S. aureus BSI in a large haemodialysis centre in a tertiary referral hospital. The overall rate of S. aureus BSI was 17.9 per 100 patient-years (range 9.7-36.8). The rate of meticillin-resistant S. aureus (MRSA) BSI was 5.6 per 100 patient-years (range 0.9-13.8). Infective complications occurred in 11% of episodes, the most common being infective endocarditis (7.6%). Ten percent of patients died within 30 days of S. aureus being isolated from blood. Most cases of S. aureus BSI (83%) were related to vascular catheters. The provision of lower-risk vascular access, such as arteriovenous fistulae, and reduced use of intravascular catheters should be priorities in all haemodialysis units. Where alternative vascular access cannot be established, interventions to reduce the risk of catheter-related infections should be implemented to reduce morbidity and mortality in this vulnerable patient group.

  18. Kaempferol Inhibits the Primary Attachment Phase of Biofilm Formation in Staphylococcus aureus.

    Science.gov (United States)

    Ming, Di; Wang, Dacheng; Cao, Fengjiao; Xiang, Hua; Mu, Dan; Cao, Junjie; Li, Bangbang; Zhong, Ling; Dong, Xiaoyun; Zhong, Xiaobo; Wang, Lin; Wang, Tiedong

    2017-01-01

    The ability to form biofilms on surfaces makes Staphylococcus aureus the main pathogenic factor in implanted medical device infections. The aim of this study was to discover a biofilm inhibitor distinct from the antibiotics used to prevent infections resulting from S. aureus biofilms. Here, we describe kaempferol, a small molecule with anti-biofilm activity that specifically inhibited the formation of S. aureus biofilms. Crystal violet (CV) staining and fluorescence microscopy clearly showed that 64 μg/ml kaempferol inhibited biofilm formation by 80%. Meanwhile, the minimum inhibitory concentration (MIC) and growth curve results indicated that kaempferol had no antibacterial activity against the tested bacterial strain. Kaempferol inhibited the primary attachment phase of biofilm formation, as determined by a fibrinogen-binding assay. Moreover, a fluorescence resonance energy transfer (FRET) assay and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analyses revealed that kaempferol reduced the activity of S. aureus sortaseA (SrtA) and the expression of adhesion-related genes. Based on these results, kaempferol provides a starting point for the development of novel anti-biofilm drugs, which may decrease the risk of bacterial drug resistance, to prevent S. aureus biofilm-related infections.

  19. Staphylococcus aureus keratinocyte invasion is mediated by integrin-linked kinase and Rac1.

    Science.gov (United States)

    Sayedyahossein, Samar; Xu, Stacey X; Rudkouskaya, Alena; McGavin, Martin J; McCormick, John K; Dagnino, Lina

    2015-02-01

    Staphylococcus aureus is a major component of the skin microbiota and causes a large number of serious infections. S. aureus first interacts with epidermal keratinocytes to breach the epidermal barrier through mechanisms not fully understood. By use of primary keratinocytes from mice with epidermis-restricted Ilk gene inactivation and control integrin-linked kinase (ILK)-expressing littermates, we investigated the role of ILK in epidermal S. aureus invasion. Heat-killed, but not live, bacteria were internalized to Rab5- and Rab7-positive phagosomes, and incubation with keratinocyte growth factor increased their uptake 2.5-fold. ILK-deficient mouse keratinocytes internalized bacteria 2- to 4-fold less efficiently than normal cells. The reduced invasion by live S. aureus of ILK-deficient cells was restored in the presence of exogenous, constitutively active Rac1. Thus, Rac1 functions downstream from ILK during invasion. Further, invasion by S. aureus of Rac1-deficient cells was 2.5-fold lower than in normal cells. Paradoxically, staphylococcal cutaneous penetration of mouse skin explants with ILK-deficient epidermis was 35-fold higher than that of normal skin, indicating defects in epidermal barrier function in the absence of ILK. Thus, we identified an ILK-Rac1 pathway essential for bacterial invasion of keratinocytes, and established ILK as a key contributor to prevent invasive staphylococcal cutaneous infection. © FASEB.

  20. Portación y caracterización de Staphylococcus aureus en manipuladores de alimentos Carriage and characterization of Staphylococcus aureus in food handlers

    Directory of Open Access Journals (Sweden)

    Graciela B Jordá

    2012-06-01

    Full Text Available Staphylococcus aureus es una causa de intoxicaciones alimentarias por su capacidad de producir enterotoxinas. Los manipuladores de alimentos que portan S. aureus productores de enterotoxinas pueden provocar intoxicaciones alimentarias. Se estudiaron muestras tomadas de fosas nasales de 88 manipuladores de alimentos en la provincia de Misiones. El 37,5 % de los individuos analizados eran portadores de S. aureus. Mediante técnicas de amplificación (PCR, se detectaron genes que codifican la producción de enterotoxinas en 13 de los 33 aislamientos obtenidos (39,4 % y en el 14,7 % de los manipuladores. De estos aislamientos, 10 portaban el gen sea y 3 el gen sec. El estudio de sensibilidad a los antibióticos mostró un 100 % de sensibilidad a teicoplanina, gentamiclna y rifampicina; 2 aislamientos fueron resistentes a clindamicina y a eritromicina y 4 resultaron resistentes a la meticilina. Estos resultados son un alerta e indicarían la necesidad de desarrollar medidas racionales para reducir el riesgo potencial de intoxicaciones alimentarias.Staphylococcus aureus causes food poisoning due to its ability to produce enterotoxins. Food handlers carrying enterotoxin-producing S. aureus can contaminate food, thus leading to food poisoning. Samples were obtained from 88 food handlers in the Province of Misiones, Argentina. S. aureus was isolated from nasal swaps and PCR amplification was performed for genes encoding staphylococcal enterotoxins. A total of 37.5 % food handlers were positive for S. aureus. Expression of enterotoxin genes was found in 13 of the 33 (39.4 % S. aureus isolates studied, accounting for 14.7 % of food handlers. Gene sea was detected in 10 isolates followed by gene sec in 3 isolates. All isolates were susceptible to teicoplanin, gentamicin and rifampicin. Four isolates were resistant to methicillin whereas 2 isolates were resistant to clindamycin and erythromycin. These results constitute a critical alert and indicate the need

  1. Applicability of a Single Time Point Strategy for the Prediction of Area Under the Concentration Curve of Linezolid in Patients: Superiority of Ctrough- over Cmax-Derived Linear Regression Models.

    Science.gov (United States)

    Srinivas, Nuggehally R; Syed, Muzeeb

    2016-03-01

    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. 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 values rendered fold difference calculation. The mean absolute error (MAE), root mean square error (RMSE), correlation coefficient (r), and the goodness of the AUC fold prediction were used to evaluate the two models. The Cmax versus AUC and trough plasma concentration (Ctrough) versus AUC models displayed excellent correlation, with r values of >0.9760. However, linezolid AUC values were predicted to be within the narrower boundary of 0.76 to 1.5-fold by a higher percentage by the Ctrough (78.3%) versus Cmax model (48.2%). The Ctrough model showed superior correlation of predicted versus observed values and RMSE (r = 0.9031; 28.54%, respectively) compared with the Cmax model (r = 0.5824; 61.34%, respectively). A single time point strategy of using Ctrough level is possible as a prospective tool to measure the AUC of linezolid in the patient population.

  2. Mode of action of Buddleja cordata verbascoside against Staphylococcus aureus.

    Science.gov (United States)

    Avila, J G; de Liverant, J G; Martínez, A; Martínez, G; Muñoz, J L; Arciniegas, A; Romo de Vivar, A

    1999-07-01

    We evaluate the mode of action of verbascoside obtained from Buddleja cordata against Staphylococcus aureus by killing kinetics and incorporation of precursors methods. Verbascoside induced lethal effect on S. aureus, by affecting protein synthesis and inhibiting leucine incorporation.

  3. Antibiotic resistance of Staphylococcus aureus isolated from fresh ...

    African Journals Online (AJOL)

    Antibiotic resistance of Staphylococcus aureus isolated from fresh cow milk in settled ... produced alpha haemolysin, 45.5% (n=25) produced beta haemolysin and ... resistant strains of S. aureus of animal and human biotypes and can serve as ...

  4. Combinations of maggot excretions/secretions and antibiotics are effective against Staphylococcus aureus biofilms and the bacteria derived therefrom

    DEFF Research Database (Denmark)

    van der Plas, Mariena J A; Dambrot, Cheryl; Dogterom-Ballering, Heleen C M

    2010-01-01

    OBJECTIVES: Maggots of the blowfly Lucilia sericata are used for the treatment of chronic wounds. Previously we reported that maggot excretions/secretions (ES) break down Staphylococcus aureus biofilms but do not kill the bacteria. As many antibiotics are not effective against biofilms we assessed...... the effect of combinations of ES and antibiotics on S. aureus biofilms and on the survival of the bacteria released from the biofilms. METHODS: Effects of ES, antibiotics (vancomycin, daptomycin or clindamycin) and combinations thereof on S. aureus ATCC 29 213 biofilms and bacterial viability were determined...... using microtitre plates and in vitro killing assays. RESULTS: Vancomycin and daptomycin dose-dependently enhanced biofilm formation, whereas clindamycin reduced S. aureus biofilm size. Adding ES to antibiotic incubations caused a complete biofilm breakdown. After a lag time the bacteria derived from...

  5. Staphylococcus aureus spa type t437

    DEFF Research Database (Denmark)

    Glasner, C; Pluister, G; Westh, H

    2015-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) belonging to the multilocus sequence type clonal complex 59 (MLST CC59) is the predominant community-associated MRSA clone in Asia. This clone, which is primarily linked with the spa type t437, has so far only been reported in low numbers among...... included. Most isolates were shown to be monophyletic with 98% of the isolates belonging to the single MLVA complex 621, to which nearly all included isolates from China also belonged. More importantly, all MLST-typed isolates belonged to CC59. Our study implies that the European S. aureus t437 population...

  6. A sensitive assay for Staphylococcus aureus nucleases

    Energy Technology Data Exchange (ETDEWEB)

    Kohli, J K; Vakil, B V; Patil, M S; Pandey, V N; Pradhan, D S [Bhabha Atomic Reserach Centre, Bombay (India). Biochemistry Div.

    1989-10-01

    A sensitive assay for staphylococcal nuclease involving incubation of the enzyme sample with heat-denatured ({sup 3}H) thymidine labelled DNA from E.coli, precipitation with trichloroacetic acid and measurement of the radioactivity of acid-soluble nucleotides released has been developed. The assay is sensitive enough to be used for comparing the levels of nucleases elaborated by different strains of S. aureus as well as for determining the extent of contamination of S. aureus in food and water samples even at levels at which the conventional spectrophotometric and toluidine blue-DNA methods are totally inadequate. (author). 26 refs., 3 figs ., 3 tabs.

  7. Evolution of methicillin-resistant Staphylococcus aureus towards increasing resistance

    DEFF Research Database (Denmark)

    Strommenger, Birgit; Bartels, Mette Damkjær; Kurt, Kevin

    2014-01-01

    To elucidate the evolutionary history of Staphylococcus aureus clonal complex (CC) 8, which encompasses several globally distributed epidemic lineages, including hospital-associated methicillin-resistant S. aureus (MRSA) and the highly prevalent community-associated MRSA clone USA300.......To elucidate the evolutionary history of Staphylococcus aureus clonal complex (CC) 8, which encompasses several globally distributed epidemic lineages, including hospital-associated methicillin-resistant S. aureus (MRSA) and the highly prevalent community-associated MRSA clone USA300....

  8. Effect of lactation therapy on Staphylococcus aureus transmission dynamics in two commercial dairy herds.

    Science.gov (United States)

    Barlow, John W; Zadoks, Ruth N; Schukken, Ynte H

    2013-02-11

    Treatment of subclinical mastitis during lactation can have both direct (individual animal level) and indirect (population level) effects. With a few exceptions, prior research has focused on evaluating the direct effects of mastitis treatment, and to date no controlled field trials have been conducted to test whether beneficial indirect effects of lactation treatment strategies targeting subclinical mastitis can be demonstrated on commercial dairy farms. Furthermore, there is limited knowledge on the impact of such interventions on the population dynamics of specific bacterial strains. The purpose of this study was to test the hypothesis that lactation therapy targeting S. aureus subclinical intramammary infection reduces transmission of S. aureus strains within dairy herds. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) were used to determine strain specific infection dynamics in treated and control groups in a split herd trial conducted on 2 commercial dairy farms. The direct effect of 8 days intramammary lactation therapy with pirlimycin hydrochloride was demonstrated by an increased proportion of cure and a reduction in duration of infection in quarters receiving treatment compared to untreated controls. The indirect effect of lactation therapy was demonstrated by reduction of new S. aureus intramammary infections (IMI) caused by the dominant strain type in both herds. Strain typing of representative isolates taken over the duration of all IMI, including pre- and post-treatment isolates, provided more precise estimates of new infection, cure, and re-infection rates. New S. aureus infections in recovered susceptible quarters and the emergence of a new strain type in one herd influenced incidence measures. In addition to demonstrating positive direct effects of lactation therapy, this study provides evidence that treatment of subclinical S. aureus mastitis during lactation can have indirect effects including preventing new IMI and

  9. Effect of lactation therapy on Staphylococcus aureus transmission dynamics in two commercial dairy herds

    Directory of Open Access Journals (Sweden)

    Barlow John W

    2013-02-01

    Full Text Available Abstract Background Treatment of subclinical mastitis during lactation can have both direct (individual animal level and indirect (population level effects. With a few exceptions, prior research has focused on evaluating the direct effects of mastitis treatment, and to date no controlled field trials have been conducted to test whether beneficial indirect effects of lactation treatment strategies targeting subclinical mastitis can be demonstrated on commercial dairy farms. Furthermore, there is limited knowledge on the impact of such interventions on the population dynamics of specific bacterial strains. The purpose of this study was to test the hypothesis that lactation therapy targeting S. aureus subclinical intramammary infection reduces transmission of S. aureus strains within dairy herds. Pulsed-field gel electrophoresis (PFGE and multilocus sequence typing (MLST were used to determine strain specific infection dynamics in treated and control groups in a split herd trial conducted on 2 commercial dairy farms. Results The direct effect of 8 days intramammary lactation therapy with pirlimycin hydrochloride was demonstrated by an increased proportion of cure and a reduction in duration of infection in quarters receiving treatment compared to untreated controls. The indirect effect of lactation therapy was demonstrated by reduction of new S. aureus intramammary infections (IMI caused by the dominant strain type in both herds. Strain typing of representative isolates taken over the duration of all IMI, including pre- and post-treatment isolates, provided more precise estimates of new infection, cure, and re-infection rates. New S. aureus infections in recovered susceptible quarters and the emergence of a new strain type in one herd influenced incidence measures. Conclusion In addition to demonstrating positive direct effects of lactation therapy, this study provides evidence that treatment of subclinical S. aureus mastitis during lactation can

  10. Genotyping of Staphylococcus aureus in bovine mastitis and correlation to phenotypic characteristics.

    Science.gov (United States)

    Artursson, Karin; Söderlund, Robert; Liu, Lihong; Monecke, Stefan; Schelin, Jenny

    2016-09-25

    Reducing the prevalence of mastitis caused by Staphylococcus aureus (S. aureus) is essential to improve animal health and reduce economic losses for farmers. The clinical outcome of acute mastitis and risk of progression to persistent mastitis can, at least to some extent, be related to genetic variants of the strain causing the infection. In the present study we have used microarrays to investigate the presence of virulence genes in S. aureus isolates from dairy cows with acute clinical mastitis (n=70) and correlated the findings to other genotypic and phenotypic characteristics. Among the most commonly found virulence factors were genes encoding several hemolysin types, leukocidins D and lukM/lukF-P83, clumping factors A and B, fibrinogen binding protein and fibronectin-binding protein A. Some virulence factors e.g. fibronectin-binding protein B and Staphylococcus aureus surface protein G were less common. Genes coding for several staphylococcal enterotoxins and toxic shock syndrome toxin-1 (TSST-1) were commonly found, especially in one major pulsotype. No beta-lactamase genes were found in any common pulsotype, while present in some rare pulsotypes, indicated to be of human origin. Production of TSST-1, enterotoxins, hemolysins and beta-lactamase could all be positively correlated to presence of the corresponding genes. This study reveals a number of genotypic differences and similarities among common and rare pulsotypes of S. aureus from cases of mastitis in Sweden. The results could help the design of diagnostic tools to guide on-farm interventions according to the expected impact on udder health from a specific S. aureus genotype. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Determinants of carriage of resistant Staphylococcus aureus among S. aureus carriers in the Indonesian population inside and outside hospitals

    NARCIS (Netherlands)

    E.S. Lestari (Endang Sri); D.O. Duerink (Offra); U. Hadi (Usman); J.A. Severin (Juliëtte); N.J.D. Nagelkerke (Nico); K. Kuntaman (Kuntaman); H. Wahjono (Hendro); W. Gardjito (Widjoseno); A. Soejoenoes (Ariawan); P. van den Broek (Peterhans); M. Keuter (Monique); I.C. Gyssens (Inge); H.A. Verbrugh (Henri)

    2010-01-01

    textabstractOBJECTIVES: To identify determinants of carriage of resistant Staphylococcus aureus in both hospitalized patients and individuals from the community in two urban centres in Indonesia. METHODS: Staphylococcus aureus cultures and data on recent antibiotic use, demographic, socioeconomic,

  12. A pig model of acute Staphylococcus aureus induced pyemia

    DEFF Research Database (Denmark)

    Nielsen, O. L.; Iburg, T.; Aalbæk, B.

    2009-01-01

    Background: Sepsis caused by Staphylococcus aureus constitutes an important cause of morbidity and mortality in humans, and the incidence of this disease-entity is increasing. In this paper we describe the initial microbial dynamics and lesions in pigs experimentally infected with S. aureus....... aureus isolated from man and an extension of the timeframe aiming at inducing sepsis, severe sepsis and septic shock....

  13. The sensitivity status of community-acquired Staphylococcus aureus ...

    African Journals Online (AJOL)

    Community acquired Staphylococcus aureus was isolated from various infectious sites in two private laboratories in Kano-city, Nigeria. A total of 247 (11%) Staphylococcu aureus isolates were recovered from all infectious sites except cerebro-spinal fluid. The least Staphylococcus aureus isolates were found in urine ...

  14. Methicillin-Susceptible, Vancomycin-Resistant Staphylococcus aureus, Brazil

    OpenAIRE

    Panesso , Diana; Planet , Paul J.; Diaz , Lorena; Hugonnet , Jean-Emannuel; Tran , Truc T.; Narechania , Apurva; Munita , José M.; Rincon , Sandra; Carvajal , Lina P.; Reyes , Jinnethe; Londono , Alejandra; Smith , Hannah; Sebra , Robert; Deikus , Gintaras; Weinstock , George M

    2015-01-01

    International audience; We report characterization of a methicillin-susceptible, vancomycin-resistant bloodstream isolate of Staphylococcus aureus recovered from a patient in Brazil. Emergence of vancomycin resistance in methicillin-susceptible S. aureus would indicate that this resistance trait might be poised to disseminate more rapidly among S. aureus and represents a major public health threat.

  15. Impact of Early Valve Surgery on Outcome of Staphylococcus aureus Prosthetic Valve Infective Endocarditis: Analysis in the International Collaboration of Endocarditis–Prospective Cohort Study

    OpenAIRE

    Chirouze, Catherine; Alla, François; Fowler, Vance G.; Sexton, Daniel J.; Corey, G. Ralph; Chu, Vivian H.; Wang, Andrew; Erpelding, Marie-Line; Durante-Mangoni, Emanuele; Fernández-Hidalgo, Nuria; Giannitsioti, Efthymia; Hannan, Margaret M.; Lejko-Zupanc, Tatjana; Miró, José M.; Muñoz, Patricia

    2014-01-01

    Using appropriate analytical methods to examine data from the International Collaboration on Endocarditis–Prospective Cohort Study, we found that early valve surgery was not associated with reduced 1-year mortality in Staphylococcus aureus prosthetic valve infective endocarditis.

  16. Staphylococcus aureus entrance into the dairy chain: Tracking S. aureus from dairy cow to cheese

    Directory of Open Access Journals (Sweden)

    Judith Kümmel

    2016-10-01

    Full Text Available Staphylococcus aureus is one of the most important contagious mastitis pathogens in dairy cattle. Due to its zoonotic potential, control of S. aureus is not only of great economic importance in the dairy industry but also a significant public health concern. The aim of this study was to decipher the potential of bovine udder associated S. aureus as reservoir for S. aureus contamination in dairy production and processing. From 18 farms, delivering their milk to an alpine dairy plant for the production of smeared semi-hard and hard cheese. 1176 quarter milk (QM samples of all cows in lactation (n = 294 and representative samples form bulk tank milk (BTM of all farms were surveyed for coagulase positive (CPS and coagulase negative Staphylococci (CNS. Furthermore, samples from different steps of the cheese manufacturing process were tested for CPS and CNS. As revealed by chemometric-assisted FTIR spectroscopy and molecular subtyping (spa typing and multi locus sequence typing, dairy cattle represent indeed an important, yet underreported, entrance point of S. aureus into the dairy chain. Our data clearly show that certain S. aureus subtypes are present in primary production as well as in the cheese processing at the dairy plant. However, although a considerable diversity of S. aureus subtypes was observed in QM and BTM at the farms, only certain S. aureus subtypes were able to enter and persist in the cheese manufacturing at the dairy plant and could be isolated from cheese until day fourteen of ripening. Farm strains belonging to the FTIR cluster B1 and B3, which show genetic characteristics (t2953, ST8, enterotoxin profile: sea/sed/sej of the recently described S. aureus genotype B, most successfully contaminated the cheese production at the dairy plant. Thus our study fosters the hypothesis that genotype B S. aureus represent a specific challenge in control of S. aureus in the dairy chain that requires effective clearance strategies and hygienic

  17. Evaluation of the synergistic potential of vancomycin combined with other antimicrobial agents against methicillin-resistant Staphylococcus aureus and coagulase-negative Staphylococcus spp strains

    Directory of Open Access Journals (Sweden)

    Lívia Viganor da Silva

    2011-02-01

    Full Text Available Methicillin-resistant Staphylococcus aureus (MRSA and coagulase-negative Staphylococcus spp (CNS are the most common pathogens that cause serious long term infections in patients. Despite the existence of new antimicrobial agents, such as linezolid, vancomycin (VAN remains the standard therapy for the treatment of infections caused by these multidrug-resistant strains. However, the use of VAN has been associated with a high frequency of therapeutic failures in some clinical scenarios, mainly with decreasing concentration of VAN. This work aims to evaluate the synergic potential of VAN plus sulfamethoxazole/trimethoprim (SXT, VAN plus rifampin (RIF and VAN plus imipenem (IPM in sub-minimum inhibitory concentrations against 22 clinical strains of MRSA and CNS. The checkerboard method showed synergism of VAN/RIF and VAN/SXT against two and three of the 22 strains, respectively. The combination of VAN with IPM showed synergistic effects against 21 out of 22 strains by the E-test method. Four strains were analyzed by the time-kill curve method and synergistic activity was observed with VAN/SXT, VAN/RIF and especially VAN/IPM in sub-inhibitory concentrations. It would be interesting to determine if synergy occurs in vivo. Evidence of in vivo synergy could lead to a reduction of the standard VAN dosage or treatment time.

  18. Meticillineresistente Staphylococcus aureus (MRSA) in de gemeenschap

    NARCIS (Netherlands)

    Vonk, A. G.; Vandenbroucke-Grauls, C. M. J. E.

    2007-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) infections have been confined to healthcare centres for decades. However, MRSA infections are increasingly seen in young healthy individuals with no exposure to healthcare centres. These community-acquired MRSA (CA-MRSA) strains differ from

  19. Staphylococcus aureus resistente a la meticilina (SARM)

    Centers for Disease Control (CDC) Podcasts

    2007-10-22

    Datos importantes sobre las infecciones por SARM en Estados Unidos, en las escuelas y los entornos médicos. (Title: Methicillin-resistant Staphylococcus aureus (MRSA)Created: 10/2007).  Created: 10/22/2007 by National Center for Preparedness, Detection, and Control of Infectious Diseases.   Date Released: 11/9/2007.

  20. Resistance patterns of Staphylococcus aureus and Pseudomonas ...

    African Journals Online (AJOL)

    Two hundred (200) strains of S. aureus and P. aeruginosa were isolated from clinical samples collected from patients in Murtala Muhammad Specialist Hospital and Infectious Diseases Hospital, Kano. The confirmed isolates were tested for resistance to quinolones by the agar disk diffusion susceptibility test and the agar ...

  1. Misidentification of methicillinresistant Staphylococcus aureus (MRSA)

    African Journals Online (AJOL)

    Conclusions: Misidentification of nosocomial S. aureus as MRSA is a serious problem in Libyan hospitals. There is an urgent need for the proper training of microbiology laboratory technicians in standard antimicrobial susceptibility procedures and the implementation of quality control programs in microbiology laboratories ...

  2. Staphylococcus aureus enterotoxins A- and B

    DEFF Research Database (Denmark)

    Danielsen, E Michael; Hansen, Gert H; Karlsdóttir, Edda

    2013-01-01

    Enterotoxins of Staphylococcus aureus are among the most common causes of food poisoning. Acting as superantigens they intoxicate the organism by causing a massive uncontrolled T cell activation that ultimately may lead to toxic shock and death. In contrast to our detailed knowledge regarding...

  3. Deposition and transport of linezolid mediated by a synthetic surfactant Synsurf® within a pressurized metered dose inhaler: a Calu-3 model

    Science.gov (United States)

    van Rensburg, Lyné; van Zyl, Johann M; Smith, Johan

    2018-01-01

    Background Previous studies in our laboratory demonstrated that a synthetic peptide containing lung surfactant enhances the permeability of chemical compounds through bronchial epithelium. The purpose of this study was to test two formulations of Synsurf® combined with linezolid as respirable compounds using a pressurized metered dose inhaler (pMDI). Methods Aerosolization efficiency of the surfactant-drug microparticles onto Calu-3 monolayers as an air interface culture was analyzed using a Next Generation Impactor™. Results The delivered particles and drug dose showed a high dependency from the preparation that was aerosolized. Scanning electron microscopy imaging allowed for visualization of the deposited particles, establishing them as liposomal-type structures (diameter 500 nm to 2 μm) with filamentous features. Conclusion The different surfactant drug combinations allow for an evaluation of the significance of the experimental model system, as well as assessment of the formulations providing a possible noninvasive, site-specific, delivery model via pMDI.

  4. Síndrome serotoninérgico en anciano con falla renal crónica tratada con linezolid: reporte de caso

    Directory of Open Access Journals (Sweden)

    Mauricio Montoya Cañón

    2016-04-01

    Entre los factores de riesgo para desarrollo de síndrome serotoninérgico se encuentra el uso de linezolid, que en combinación de otros medicamentos con acción serotoninérgica —como los inhibidores selectivos de recaptación de serotonina, el litio, la trazodona, entre otros— se asocia con la presentación de este cuadro. El síndrome serotoninérgico puede ser evitado con una buena educación al personal médico y la modificación de las conductas de prescripción de medicamentos; el pilar del tratamiento se basa en la suspensión de los fármacos que están causando el cuadro y el planteamiento de medidas de soporte.

  5. [Carriage of Staphylococcus aureus among food service workers].

    Science.gov (United States)

    Alarcón-Lavín, María Paula; Oyarzo, Carolina; Escudero, Carlos; Cerda-Leal, Fabiola; Valenzuela, Francisco J

    2017-12-01

    Background Staphylococcus aureus produces 11 serotypes of endotoxins that may cause food poisoning. Aim To determine the prevalence of type A enterotoxigenic Staphylococcus aureus carriage among food service workers in Chillan, Chile. Material and Methods Pharyngeal swabs were obtained from 100 food service workers and were cultured in Agar plates. After identifying the presence of Staphylococcus aureus, DNA was extracted to identify type A toxin by conventional PCR. Results Thirty eight percent of samples were colonized with Staphylococcus aureus. Among these, 26% were toxin A producers. Conclusions Half of the sampled workers carried Staphylococcus aureus and a quarter of these produced type A enterotoxin.

  6. Reversal of methicillin resistance in Staphylococcus aureus by thioridazine

    DEFF Research Database (Denmark)

    Klitgaard, Janne K; Skov, Marianne N; Kallipolitis, Birgitte H

    2008-01-01

    of thioridazine in the presence of a fixed amount of oxacillin. Furthermore, the protein level of PBP2a was reduced when bacteria were treated with the combination of oxacillin and thioridazine. The two drugs also affected the mRNA level of the beta-lactamase gene, blaZ. Conclusions The present study indicates......Objectives Thioridazine has been shown to reverse oxacillin resistance in methicillin-resistant Staphylococcus aureus (MRSA) in vitro. The aim of this study was to investigate whether thioridazine alone or in combination with oxacillin affects the transcription of the methicillin resistance gene...... blotting in the presence of thioridazine and oxacillin. Results We observed an increased susceptibility of MRSA towards oxacillin in the presence of thioridazine compared with bacteria grown with oxacillin or thioridazine alone. Transcription of mecA was reduced with increasing concentrations...

  7. Study of Prevalence and Characteristics of Staphylococcus aureus and CA-MRSA Nasal Colonization in 2-5 Years Old Children in Isfahan

    Directory of Open Access Journals (Sweden)

    Ramin Dibaj

    2014-10-01

    Full Text Available Background and Aim: We carried out a descriptive study to determine the extent of nasal colonization and characteristics of Staphylococcus aureus and CA-MRSA isolates in 2-5 year old children of day care centers in Isfahan. Materials and Methods: The characteristics of isolates were determined using standard phenotypic profiles including colony morphology, Gram staining, catalase, hyaluronidase, coagulase and Dnase tests as well as mannitol fermentation. The MRSA detection was carried out according to CLSI guidelines with oxacillin agar screen test. Methicillin resistance was further confirmed by detection of a 310 bp fragment of mecA gene of MRSA by PCR. Drug susceptibility testing to antibiotics other than methicillin was conducted by disk diffusion. The Beta-lactamase production and inducible clindamycin resistance were also determined by performing the double-disc diffusion(D-test. Results: Out of 323 children, 115 (35.6% carried S. aureus and 11 (9.5% carried MRSA. All MRSA strains were found to contain mecA gene. The susceptibility of strains to vancomycin, rifampicin and Linezolid were 100%. The susceptibility of strains to gentamicin, clindamycin, erythromycin, co-trimoxazole, amoxiclav, ciprofloxacin, tetracycline and penicillin were 99%, 97%, 94%, 94%, 93%, 88%, 44.4% and 1.8% respectively. Beta-lactamase production was seen in 19 (16.5% of staphylococcal strains. Inducible clindamycin resistance was seen in 4 (3.5% of the isolates. Conclusions: Our data indicates that the spread of CA-MRSA within Iranian population is worthy of consideration and merits further molecular investigation to determine the source and mode of transmission.

  8. State-wide surveillance of antibiotic resistance patterns and spa types of methicillin-resistant Staphylococcus aureus from blood cultures in North Rhine-Westphalia, 2011-2013.

    Science.gov (United States)

    Cuny, C; Layer, F; Werner, G; Harmsen, D; Daniels-Haardt, I; Jurke, A; Mellmann, A; Witte, W; Köck, R

    2015-08-01

    Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of bacteraemia. We aimed to obtain a complete picture of severe MRSA infections by characterizing all MRSA isolates from bloodstream infections in the largest German federal state (North Rhine-Westphalia, 18 million inhabitants) using S. aureus protein A (spa) sequence-typing and antimicrobial susceptibility testing. MRSA isolates (n = 1952) were collected prospectively (2011-2013) and spa-typed. Among 181 different spa types, t003 (n = 746 isolates; 38.2%) and t032 (n = 594; 30.4%) were predominant. Analysis of the geographical occurrence of spa clonal complexes (spa-CCs) and spa types revealed divergent distribution between federal state districts for spa-CCs 003 (p resistant to fluoroquinolones, 78% to erythromycin, 70% to clindamycin, 4% to gentamicin, 2% to rifampicin, 0.4% to daptomycin, 0.1% to linezolid and 0% to vancomycin, respectively. Vancomycin MICs of 2 mg/L involved 0.5% of the isolates. In conclusion, the detection of regional molecular clusters added valuable information for epidemiological case tracing and allowed conclusions to be reached on the importance of newly emerging MRSA reservoirs, such as livestock (spa-CC011), for MRSA bacteraemia in some parts of the federal state. Susceptibility testing revealed broad resistance to substances used for oral treatment, but demonstrated that those antibiotics that are mostly applied for treatment of MRSA bacteraemia and important combination partners were highly susceptible. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  9. In Vitro Evaluation of Linezolid and Meropenem Against Clinical Isolates of Multi Drug Resistant Tuberculosis By Mycobacterial Growth Indicator Tube (MGIT) 960

    International Nuclear Information System (INIS)

    Mirza, I. A.; Satti, L.; Khan, F. A.; Khan, K. A.

    2015-01-01

    Objective: To evaluate the in vitro effectiveness of multiple breakpoint concentrations of newer antituberculosis agents (Linezolid and Meropenem) against Multi Drug-Resistant Tuberculosis (MDR-TB) isolates. Study Design: Adescriptive cross-sectional study. Place and Duration of Study: Microbiology Department, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from September 2011 to August 2013. Methodology: Atotal of 100 MDR-TB isolates recovered during the study period were subjected to susceptibility testing against multiple breakpoint concentrations of Linezolid (LZD) and Meropenem (MER). The breakpoint concentration used for LZD were 0.5, 1.0 and 2.0 micro g/ml, while for MER were 4.0, 8.0 and 16 micro g/ml. Mycobacterial Growth Indicator Tube (MGIT) 960 system was used to carry out drug susceptibility testing as per recommended protocol. Results: At break point concentration of 0.5 micro g/ml, 80 out of 100 (80%) MDR-TB isolates were susceptible to LZD while at breakpoint concentration of 1.0 micro g/ml and 2.0 micro g/ml, 96/100, (96%) of MDR-TB isolates were susceptible. For MER, at breakpoint concentrations of 4.0 micro g/ml no MDR-TB isolate was susceptible, while at 8.0 micro g/ml 3/100, (3%) and at 16.0 micro g/ml 11/100, (11%) of MDR-TB isolates were susceptible. Conclusion: LZD was found to have excellent in vitroefficacy as 96% of MDR-TB isolates were susceptible at breakpoint concentration of 1.0 micro g/ml or more. In case of MER it was found that in vitrosusceptibility improved as the break point concentrations were increased. (author)

  10. Influence of growth media on the sensitivity of Staphylococcus aureus and Pseudomonas aeruginosa to cationic biocides.

    Science.gov (United States)

    Brill, Florian; Goroncy-Bermes, Peter; Sand, Wolfgang

    2006-01-01

    In this study, the influence of culturing Staphylococcus aureus and Pseudomonas aeruginosa under different growth conditions on their inactivation by the cationic active compounds benzalkonium chloride, chlorhexidine digluconate and octenidine dihydrochloride was investigated. Cells were grown in non-agitated tryptone soya broth as well as on tryptone soya agar according to national and international standards for evaluating chemical disinfectants. In quantitative suspension tests, cells of both test organisms grown on agar were significantly more sensitive to all three biocides than cells grown in broth. The differences in antimicrobial activity were greater in the case of S. aureus than in the case of P. aeruginosa. With S. aureus cultures, differences in the reduction factor of up to 5 log steps were found, with P. aeruginosa up to 2.5 log steps. The results of our uptake tests performed with S. aureus and octenidine dihydrochloride indicated that the growth conditions and the associated different stress factors either had an influence on the composition of the cell surface of this test organism or induced the formation of an efflux system. Cells of S. aureus cultured in broth took up only one-fifth of the amount of biocide molecules compared to cells from agar cultures. These data correlated with the results of the suspension tests. A low uptake of biocides apparently led to a reduced killing rate. In contrast to S. aureus, no significant differences in the uptake of octenidine dihydrochloride by cells of P. aeruginosa could be observed. These cells took up the same amount of the antimicrobial substance, whether on agar or in broth. In view of these results, possible consequences should be considered prior to changing test regulations.

  11. Preconditioning with Lipopolysaccharide or Lipoteichoic Acid Protects against Staphylococcus aureus Mammary Infection in Mice

    Directory of Open Access Journals (Sweden)

    Koen Breyne

    2017-07-01

    Full Text Available Staphylococcus aureus is one of the most causative agents of mastitis and is associated with chronic udder infections. The persistency of the pathogen is believed to be the result of an insufficient triggering of local inflammatory signaling. In this study, the preclinical mastitis model was used, aiming to evaluate if lipopolysaccharide (LPS or lipoteichoic acid (LTA preconditioning could aid the host in more effectively clearing or at least limiting a subsequent S. aureus infection. A prototypic Gram-negative virulence factor, i.e., LPS and Gram-positive virulence factor, i.e., LTA were screened whether they were able to boost the local immune compartment. Compared to S. aureus-induced inflammation, both toxins had a remarkable high potency to efficiently induce two novel selected innate immunity biomarkers i.e., lipocalin 2 (LCN2 and chitinase 3-like 1 (CHI3L1. When combining mammary inoculation of LPS or LTA prior to a local S. aureus infection, we were able to modulate the innate immune response, reduce local bacterial loads, and induce either LCN2 or CHI3L1 at 24 h post-infection. Clodronate depletion of mammary macrophages also identified that macrophages contribute only to a limited extend to the LPS/LTA-induced immunomodulation upon S. aureus infection. Based on histological neutrophil influx evaluation, concomitant local cytokine profiles and LCN2/CHI3L1 patterns, the macrophage-independent signaling plays a major role in the LPS- or LTA-pretreated S. aureus-infected mouse mammary gland. Our results highlight the importance of a vigilant microenvironment during the innate immune response of the mammary gland and offer novel insights for new approaches concerning effective immunomodulation against a local bacterial infection.

  12. Preclinical Efficacy of Clumping Factor A in Prevention of Staphylococcus aureus Infection

    Directory of Open Access Journals (Sweden)

    Xue Li

    2016-02-01

    Full Text Available Treatment of Staphylococcus aureus infections has become increasingly difficult because of the emergence of multidrug-resistant isolates. Development of a vaccine to prevent staphylococcal infections remains a priority. To determine whether clumping factor A (ClfA is a good target protein for inclusion in a multivalent vaccine, we evaluated its efficacy in a variety of relevant staphylococcal infection models, challenging with different S. aureus strains. ClfA adsorbed to Alhydrogel and mixed with Sigma Adjuvant System was more immunogenic and stimulated a more robust Th17 response than ClfA administered with alum alone. ClfA immunization induced the production of functional antibodies in rabbits and mice that blocked S. aureus binding to fibrinogen and were opsonic for S. aureus strains that produced little or no capsular polysaccharide. Mice immunized with ClfA showed a modest reduction in the bacterial burden recovered from subcutaneous abscesses provoked by S. aureus USA300 strain LAC. In addition, the ClfA vaccine reduced lethality in a sepsis model following challenge with strain Newman, but not ST80. Vaccination with ClfA did not protect against surgical wound infection, renal abscess formation, or bacteremia. Passive immunization with antibodies to ClfA did not protect against staphylococcal bacteremia in mice or catheter-induced endocarditis in rats. Some enhancement of bacteremia was observed by ClfA immunization or passive administration of ClfA antibodies when mice were challenged by the intraperitoneal route. Although rodent models of staphylococcal infection have their limitations, our data do not support the inclusion of ClfA in an S. aureus multivalent vaccine.

  13. Preclinical Efficacy of Clumping Factor A in Prevention of Staphylococcus aureus Infection

    Science.gov (United States)

    Li, Xue; Wang, Xiaogang; Thompson, Christopher D.; Park, Saeyoung; Park, Wan Beom

    2016-01-01

    ABSTRACT Treatment of Staphylococcus aureus infections has become increasingly difficult because of the emergence of multidrug-resistant isolates. Development of a vaccine to prevent staphylococcal infections remains a priority. To determine whether clumping factor A (ClfA) is a good target protein for inclusion in a multivalent vaccine, we evaluated its efficacy in a variety of relevant staphylococcal infection models, challenging with different S. aureus strains. ClfA adsorbed to Alhydrogel and mixed with Sigma Adjuvant System was more immunogenic and stimulated a more robust Th17 response than ClfA administered with alum alone. ClfA immunization induced the production of functional antibodies in rabbits and mice that blocked S. aureus binding to fibrinogen and were opsonic for S. aureus strains that produced little or no capsular polysaccharide. Mice immunized with ClfA showed a modest reduction in the bacterial burden recovered from subcutaneous abscesses provoked by S. aureus USA300 strain LAC. In addition, the ClfA vaccine reduced lethality in a sepsis model following challenge with strain Newman, but not ST80. Vaccination with ClfA did not protect against surgical wound infection, renal abscess formation, or bacteremia. Passive immunization with antibodies to ClfA did not protect against staphylococcal bacteremia in mice or catheter-induced endocarditis in rats. Some enhancement of bacteremia was observed by ClfA immunization or passive administration of ClfA antibodies when mice were challenged by the intraperitoneal route. Although rodent models of staphylococcal infection have their limitations, our data do not support the inclusion of ClfA in an S. aureus multivalent vaccine. PMID:26838725

  14. COMPARISON OF METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS IN HEALTHY COMMUNITY HOSPITAL VISITORS[CA-MRSA] AND HOSPITAL STAFF [HA-MRSA

    Directory of Open Access Journals (Sweden)

    Nirmal A Pathare

    2015-10-01

    Full Text Available Background: The prevalence of community associated methicillin resistant Staphylococcus aureus [CA-MRSA] in unknown in Oman. Methods: Nasal and cell phones swabs were collected from hospital visitors and health-care workers on sterile polyester swabs and directly inoculated onto a mannitol salt agar containing oxacillin, allowing growth of methicillin-resistant microorganisms. Antibiotic susceptibility tests were performed using Kirby Bauer’s disc diffusion method on the isolates. A brief survey questionnaire was requested be filled to ascertain the exposure to known risk factors for CA-MRSA carriage. Results: Overall, nasal colonization with CA-MRSA was seen in 34 individuals (18%, 95% confidence interval [CI] =12.5%-23.5%, whereas, CA-MRSA was additionally isolated from the cell phone surface in 12 participants (6.3%, 95% CI =5.6%-6.98%. Nasal colonization prevalence with HA-MRSA was seen in 16 individuals (13.8%, 95% confidence interval [CI] =7.5%-20.06%, whereas, HA-MRSA was additionally isolated from the cell phone surface in 3 participants (2.6%, 95% CI =1.7-4.54.  Antibiotic sensitivity was 100% to linezolid and rifampicin in the CA-MRSA isolates. Antibiotic resistance to vancomycin and clindamycin varied between 9-11 % in the CA-MRSA isolates.  There was no statistically significant correlation between CA-MRSA nasal carriage and the risk factors (P>0.05, Chi-square test. Conclusions: The prevalence of CA-MRSA in the healthy community hospital visitors was 18 % (95% CI, 12.5% to 23.5% as compared to 13.8% [HA-MRSA] in the hospital health-care staff. In spite of a significant prevalence of CA-MRSA, these strains were mostly sensitive. Recommendation the universal techniques of hand washing, personal hygiene and sanitation are thus warranted.

  15. Enzymatic properties of Staphylococcus aureus adenosine synthase (AdsA)

    Science.gov (United States)

    2011-01-01

    Background Staphylococcus aureus is a human pathogen that produces extracellular adenosine to evade clearance by the host immune system, an activity attributed to the 5'-nucleotidase activity of adenosine synthase (AdsA). In mammals, conversion of adenosine triphosphate to adenosine is catalyzed in a two-step process: ecto-nucleoside triphosphate diphosphohydrolases (ecto-NTDPases) hydrolyze ATP and ADP to AMP, whereas 5'-nucleotidases hydrolyze AMP to adenosine. NTPDases harbor apyrase conserved regions (ACRs) that are critical for activity. Results NTPDase ACR motifs are absent in AdsA, yet we report here that recombinant AdsA hydrolyzes ADP and ATP in addition to AMP. Competition assays suggest that hydrolysis occurs following binding of all three substrates at a unique site. Alanine substitution of two amino acids, aspartic acid 127 and histidine 196 within the 5'-nucleotidase signature sequence, leads to reduced AMP or ADP hydrolysis but does not affect the binding of these substrates. Conclusion Collectively, these results provide insight into the unique ability of AdsA to produce adenosine through the consecutive hydrolysis of ATP, ADP and AMP, thereby endowing S. aureus with the ability to modulate host immune responses. PMID:22035583

  16. Antimicrobial activity of essential oils against Staphylococcus aureus biofilms.

    Science.gov (United States)

    Vázquez-Sánchez, Daniel; Cabo, Marta L; Rodríguez-Herrera, Juan J

    2015-12-01

    The present study was aimed to evaluate the potential of essential oils to remove the foodborne pathogen Staphylococcus aureus from food-processing facilities. The effectiveness of 19 essential oils against planktonic cells of S. aureus was firstly assessed by minimal inhibitory concentration. Planktonic cells showed a wide variability in resistance to essential oils, with thyme oil as the most effective, followed by lemongrass oil and then vetiver oil. The eight essential oils most effective against planktonic cells were subsequently tested against 48-h-old biofilms formed on stainless steel. All essential oils reduced significantly (p oils were the most effective, but high concentrations were needed to achieve logarithmic reductions over 4 log CFU/cm(2) after 30 min exposure. Alternatively, the use of sub-lethal doses of thyme oil allowed to slow down biofilm formation and to enhance the efficiency of thyme oil and benzalkonium chloride against biofilms. However, some cellular adaptation to thyme oil was detected. Therefore, essential oil-based treatments should be based on the rotation and combination of different essential oils or with other biocides to prevent the emergence of antimicrobial-resistant strains. © The Author(s) 2014.

  17. Relationship between Vancomycin-Resistant Staphylococcus aureus, Vancomycin-Intermediate S. aureus, High Vancomycin MIC, and Outcome in Serious S. aureus Infections

    OpenAIRE

    Holmes, Natasha E.; Johnson, Paul D. R.; Howden, Benjamin P.

    2012-01-01

    Vancomycin has been used successfully for over 50 years for the treatment of Staphylococcus aureus infections, particularly those involving methicillin-resistant S. aureus. It has proven remarkably reliable, but its efficacy is now being questioned with the emergence of strains of S. aureus that display heteroresistance, intermediate resistance, and, occasionally, complete vancomycin resistance. More recently, an association has been established between poor outcome and infections with strain...

  18. The SaeR/S gene regulatory system induces a pro-inflammatory cytokine response during Staphylococcus aureus infection.

    Directory of Open Access Journals (Sweden)

    Robert L Watkins

    Full Text Available Community-associated methicillin-resistant Staphylococcus aureus accounts for a large portion of the increased staphylococcal disease incidence and can cause illness ranging from mild skin infections to rapidly fatal sepsis syndromes. Currently, we have limited understanding of S. aureus-derived mechanisms contributing to bacterial pathogenesis and host inflammation during staphylococcal disease. Herein, we characterize an influential role for the saeR/S two-component gene regulatory system in mediating cytokine induction using mouse models of S. aureus pathogenesis. Invasive S. aureus infection induced the production of localized and systemic pro-inflammatory cytokines, including tumor necrosis factor alpha (TNF-α, interferon gamma (IFN-γ, interleukin (IL-6 and IL-2. In contrast, mice infected with an isogenic saeR/S deletion mutant demonstrated significantly reduced pro-inflammatory cytokine levels. Additionally, secreted factors influenced by saeR/S elicited pro-inflammatory cytokines in human blood ex vivo. Our study further demonstrated robust saeR/S-mediated IFN-γ production during both invasive and subcutaneous skin infections. Results also indicated a critical role for saeR/S in promoting bacterial survival and enhancing host mortality during S. aureus peritonitis. Taken together, this study provides insight into specific mechanisms used by S. aureus during staphylococcal disease and characterizes a relationship between a bacterial global regulator of virulence and the production of pro-inflammatory mediators.

  19. Characterization of a Staphylococcus aureus surface virulence factor that promotes resistance to oxidative killing and infectious endocarditis.

    Science.gov (United States)

    Malachowa, Natalia; Kohler, Petra L; Schlievert, Patrick M; Chuang, Olivia N; Dunny, Gary M; Kobayashi, Scott D; Miedzobrodzki, Jacek; Bohach, Gregory A; Seo, Keun Seok

    2011-01-01

    Staphylococcus aureus is a prominent human pathogen and a leading cause of community- and hospital-acquired bacterial infections worldwide. Herein, we describe the identification and characterization of the S. aureus 67.6-kDa hypothetical protein, named for the surface factor promoting resistance to oxidative killing (SOK) in this study. Sequence analysis showed that the SOK gene is conserved in all sequenced S. aureus strains and homologous to the myosin cross-reactive antigen of Streptococcus pyogenes. Immunoblotting and immunofluorescence analysis showed that SOK was copurified with membrane fractions and was exposed on the surface of S. aureus Newman and RN4220. Comparative analysis of wild-type S. aureus and an isogenic deletion strain indicated that SOK contributes to both resistance to killing by human neutrophils and to oxidative stress. In addition, the S. aureus sok deletion strain showed dramatically reduced aortic valve vegetation and bacterial cell number in a rabbit endocarditis model. These results, plus the suspected role of the streptococcal homologue in certain diseases such as acute rheumatic fever, suggest that SOK plays an important role in cardiovascular and other staphylococcal infections.

  20. Balance between beneficial microflora and Staphylococcus aureus colonisation: in vivo evaluation in patients with atopic dermatitis during hydrotherapy.

    Science.gov (United States)

    Bourrain, Muriel; Ribet, Virginie; Calvez, Audrey; Lebaron, Philippe; Schmitt, Anne-Marie

    2013-01-01

    The role of the balance between Staphylococcus aureus and commensal flora in the severity of atopic dermatitis (AD) lesions is not well understood. To determine the structure of skin microbiome in patients with AD and its changes during an 18-day course of hydrotherapy and to assess the association between S. aureus and micro-organism colonisation, local skin condition and AD severity. Three skin areas (xerotic, inflammatory and healthy) were identified in 25 moderate to severe AD patients for sampling before treatment, just after (day 1), and at day 10 and day 18. The structure of the bacterial community in the samples was assessed using a molecular biology approach based on 16S rRNA gene profiling. At each visit, AD severity was measured globally by the SCORAD index and at the lesional and healthy sampling sites. Clustering analysis of 296 samples showed two different bacterial community profiles: one with 2 peaks corresponding to S. aureus, the other displayed multiple peaks, identified as diversified microflora. At baseline, xerotic areas seemed to be less colonised by S. aureus than inflammatory areas. After 18 days of hydrotherapy, the number of lesional sites colonised by S. aureus (p<0.05) and the SCORAD index (p<0.00001) were significantly reduced, mainly in inflammatory and moist areas, promoting the emergence of a diversified microflora. We identified two bacterial community profiles corresponding to S. aureus and diversified microflora. The competitive balance between both profiles appears to be a key element associated with the severity of AD lesions.

  1. Comparative effectiveness of linezolid versus vancomycin as definitive antibiotic therapy for heterogeneously resistant vancomycin-intermediate coagulase-negative staphylococcal central-line-associated bloodstream infections in a neonatal intensive care unit.

    Science.gov (United States)

    Blanchard, A C; Fortin, E; Laferrière, C; Goyer, I; Moussa, A; Autmizguine, J; Quach, C

    2017-06-01

    Heterogeneously resistant vancomycin-intermediate coagulase-negative staphylococci (hVICoNS) are emerging pathogens causing central-line-associated bloodstream infections (CLABSIs) in neonatal intensive care unit (NICU) patients. Given the burden of disease associated with CLABSI and the current lack of therapeutic guidelines, we aimed to compare the effectiveness of linezolid versus vancomycin used as the definitive antibiotic therapy for hVICoNS CLABSI. We performed a retrospective cohort study of infants with hVICoNS CLABSI from a single NICU between 2009 and 2014, treated with either linezolid or vancomycin as definitive antibiotic therapy. CLABSI duration, early and late recurrence and in-hospital mortality were compared using propensity score-adjusted proportional hazards and logistic regression models. Of 89 infants with hVICoNS CLABSI, 33 (37.1%) treated with linezolid were compared with 56 (62.9%) treated with vancomycin. The median duration of CLABSI was 5 (range 1-12) versus 4 days (range 0-14) ( P  =   0.11), early recurrences were 3.0% versus 7.1% ( P  =   0.42), late recurrences 0% versus 14.3% ( P  =   0.02) and mortality 27.3% versus 28.6% ( P  =   0.90), when treated with linezolid versus vancomycin, respectively. When adjusting using a continuous propensity score, linezolid had an HR of 0.78 (95% CI 0.48-1.27) for CLABSI duration, an OR of 0.23 (95% CI 0.02-2.56) for early recurrence and an OR of 0.9 (95% CI 0.3-2.67) for mortality, relative to vancomycin. There was no statistically significant difference between linezolid and vancomycin when used as definitive treatment for hVICoNS CLABSI in NICU patients, in terms of CLABSI duration, recurrence or all-cause mortality. © 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.

  2. Impact of currently marketed tampons and menstrual cups on Staphylococcus aureus growth and TSST-1 production in vitro.

    Science.gov (United States)

    Nonfoux, Louis; Chiaruzzi, Myriam; Badiou, Cédric; Baude, Jessica; Tristan, Anne; Thioulouse, Jean; Muller, Daniel; Prigent Combaret, Claire; Lina, Gérard

    2018-04-20

    Fifteen currently marketed intravaginal protection products (11 types of tampon and four menstrual cups) were tested by the modified tampon sac method to determine their effect on Staphylococcus aureus growth and toxic shock toxin 1 (TSST-1) production. Most tampons reduced S. aureus growth and TSST-1 production, with differences based on brand and composition, and S. aureus growth was higher in de-structured than in unaltered tampons. We observed higher S. aureus growth and toxin production in menstrual cups than in tampons, potentially due to the additional air introduced to the bag by cups, with differences based on cup composition and size. Importance Menstrual toxic shock syndrome is a rare but severe disease. It occurs in healthy women vaginally colonized by Staphylococcus aureus producing toxic shock syndrome toxin 1 using intravaginal protection such as tampons or menstrual cups. Intravaginal protection induces TSS production by collecting catamenial products which act as a growth medium for S. aureus Previous studies have evaluated the impact of tampon composition on S. aureus producing toxic shock syndrome toxin 1, but they are not recent and did not include menstrual cups. This study demonstrates that highly reproducible results for S. aureus growth and TSST-1 production can be obtained using a simple protocol that reproduces the physiological conditions of tampon and cup usage as closely as possible, providing recommendations for tampon or cup use to both manufacturers and consumers. Notably, our results do not show that menstrual cups are safer than tampons and suggest that they require similar precautions. Copyright © 2018 American Society for Microbiology.

  3. Elucidating the crucial role of poly N-acetylglucosamine from Staphylococcus aureus in cellular adhesion and pathogenesis.

    Directory of Open Access Journals (Sweden)

    Mei Hui Lin

    Full Text Available Staphylococcus aureus is an important pathogen that forms biofilms on the surfaces of medical implants. Biofilm formation by S. aureus is associated with the production of poly N-acetylglucosamine (PNAG, also referred to as polysaccharide intercellular adhesin (PIA, which mediates bacterial adhesion, leading to the accumulation of bacteria on solid surfaces. This study shows that the ability of S. aureus SA113 to adhere to nasal epithelial cells is reduced after the deletion of the ica operon, which contains genes encoding PIA/PNAG synthesis. However, this ability is restored after a plasmid carrying the entire ica operon is transformed into the mutant strain, S. aureus SA113Δica, showing that the synthesis of PIA/PNAG is important for adhesion to epithelial cells. Additionally, S. carnosus TM300, which does not produce PIA/PNAG, forms a biofilm and adheres to epithelial cells after the bacteria are transformed with a PIA/PNAG-expressing plasmid, pTXicaADBC. The adhesion of S. carnosus TM300 to epithelial cells is also demonstrated by adding purified exopolysaccharide (EPS, which contains PIA/PNAG, to the bacteria. In addition, using a mouse model, we find that the abscess lesions and bacterial burden in lung tissues is higher in mice infected with S. aureus SA113 than in those infected with the mutant strain, S. aureus SA113Δica. The results indicate that PIA/PNAG promotes the adhesion of S. aureus to human nasal epithelial cells and lung infections in a mouse model. This study elucidates a mechanism that is important to the pathogenesis of S. aureus infections.

  4. Elucidating the crucial role of poly N-acetylglucosamine from Staphylococcus aureus in cellular adhesion and pathogenesis.

    Science.gov (United States)

    Lin, Mei Hui; Shu, Jwu Ching; Lin, Li Ping; Chong, Kowit Yu; Cheng, Ya Wen; Du, Jia Fu; Liu, Shih-Tung

    2015-01-01

    Staphylococcus aureus is an important pathogen that forms biofilms on the surfaces of medical implants. Biofilm formation by S. aureus is associated with the production of poly N-acetylglucosamine (PNAG), also referred to as polysaccharide intercellular adhesin (PIA), which mediates bacterial adhesion, leading to the accumulation of bacteria on solid surfaces. This study shows that the ability of S. aureus SA113 to adhere to nasal epithelial cells is reduced after the deletion of the ica operon, which contains genes encoding PIA/PNAG synthesis. However, this ability is restored after a plasmid carrying the entire ica operon is transformed into the mutant strain, S. aureus SA113Δica, showing that the synthesis of PIA/PNAG is important for adhesion to epithelial cells. Additionally, S. carnosus TM300, which does not produce PIA/PNAG, forms a biofilm and adheres to epithelial cells after the bacteria are transformed with a PIA/PNAG-expressing plasmid, pTXicaADBC. The adhesion of S. carnosus TM300 to epithelial cells is also demonstrated by adding purified exopolysaccharide (EPS), which contains PIA/PNAG, to the bacteria. In addition, using a mouse model, we find that the abscess lesions and bacterial burden in lung tissues is higher in mice infected with S. aureus SA113 than in those infected with the mutant strain, S. aureus SA113Δica. The results indicate that PIA/PNAG promotes the adhesion of S. aureus to human nasal epithelial cells and lung infections in a mouse model. This study elucidates a mechanism that is important to the pathogenesis of S. aureus infections.

  5. Detection of Staphylococcus aureus by functional gold nanoparticle-based affinity surface-assisted laser desorption/ionization mass spectrometry.

    Science.gov (United States)

    Lai, Hong-Zheng; Wang, Sin-Ge; Wu, Ching-Yi; Chen, Yu-Chie

    2015-02-17

    Staphylococcus aureus is one of the common pathogenic bacteria responsible for bacterial infectious diseases and food poisoning. This study presents an analytical method based on the affinity nanoprobe-based mass spectrometry that enables detection of S. aureus in aqueous samples. A peptide aptamer DVFLGDVFLGDEC (DD) that can recognize S. aureus and methicillin-resistant S. aureus (MRSA) was used as the reducing agent and protective group to generate DD-immobilized gold nanoparticles (AuNPs@DD) from one-pot reactions. The thiol group from cysteine in the peptide aptamer, i.e., DD, can interact with gold ions to generate DD-immobilized AuNPs in an alkaline solution. The generated AuNPs@DD has an absorption maximum at ∼518 nm. The average particle size is 7.6 ± 1.2 nm. Furthermore, the generated AuNPs@DD can selectively bind with S. aureus and MRSA. The conjugates of the target bacteria with AuNPs were directly analyzed by surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS). The gold ions generated from the AuNPs@DD anchored on the target bacteria were monitored. Gold ions (m/z 197 and 394) were only generated from the conjugates of the target bacterium-AuNP@DD in the SALDI process. Thus, the gold ions could be used as the indicators for the presence of the target bacteria. The detection limit of S. aureus using this method is in the order of a few tens of cells. The low detection limit is due to the ease of generation of gold cluster ion derived from AuNPs under irradiation with a 355 nm laser beam. Apple juice mixed with S. aureus was used as the sample to demonstrate the suitability of the method for real-world application. Because of its low detection limit, this approach can potentially be used to screen the presence of S. aureus in complex samples.

  6. Genetic diversity of Staphylococcus aureus in Buruli ulcer.

    Directory of Open Access Journals (Sweden)

    Nana Ama Amissah

    2015-02-01

    Full Text Available Buruli ulcer (BU is a necrotizing skin disease caused by Mycobacterium ulcerans. Previous studies have shown that wounds of BU patients are colonized with M. ulcerans and several other microorganisms, including Staphylococcus aureus, which may interfere with wound healing. The present study was therefore aimed at investigating the diversity and topography of S. aureus colonizing BU patients during treatment.We investigated the presence, diversity, and spatio-temporal distribution of S. aureus in 30 confirmed BU patients from Ghana during treatment. S. aureus was isolated from nose and wound swabs, and by replica plating of wound dressings collected bi-weekly from patients. S. aureus isolates were characterized by multiple-locus variable number tandem repeat fingerprinting (MLVF and spa-typing, and antibiotic susceptibility was tested.Nineteen (63% of the 30 BU patients tested positive for S. aureus at least once during the sampling period, yielding 407 S. aureus isolates. Detailed analysis of 91 isolates grouped these isolates into 13 MLVF clusters and 13 spa-types. Five (26% S. aureus-positive BU patients carried the same S. aureus genotype in their anterior nares and wounds. S. aureus isolates from the wounds of seven (37% patients were distributed over two different MLVF clusters. Wounds of three (16% patients were colonized with isolates belonging to two different genotypes at the same time, and five (26% patients were colonized with different S. aureus types over time. Five (17% of the 30 included BU patients tested positive for methicillin-resistant S. aureus (MRSA.The present study showed that the wounds of many BU patients were contaminated with S. aureus, and that many BU patients from the different communities carried the same S. aureus genotype during treatment. This calls for improved wound care and hygiene.

  7. Genetic diversity of Staphylococcus aureus in Buruli ulcer.

    Science.gov (United States)

    Amissah, Nana Ama; Glasner, Corinna; Ablordey, Anthony; Tetteh, Caitlin S; Kotey, Nana Konama; Prah, Isaac; van der Werf, Tjip S; Rossen, John W; van Dijl, Jan Maarten; Stienstra, Ymkje

    2015-02-01

    Buruli ulcer (BU) is a necrotizing skin disease caused by Mycobacterium ulcerans. Previous studies have shown that wounds of BU patients are colonized with M. ulcerans and several other microorganisms, including Staphylococcus aureus, which may interfere with wound healing. The present study was therefore aimed at investigating the diversity and topography of S. aureus colonizing BU patients during treatment. We investigated the presence, diversity, and spatio-temporal distribution of S. aureus in 30 confirmed BU patients from Ghana during treatment. S. aureus was isolated from nose and wound swabs, and by replica plating of wound dressings collected bi-weekly from patients. S. aureus isolates were characterized by multiple-locus variable number tandem repeat fingerprinting (MLVF) and spa-typing, and antibiotic susceptibility was tested. Nineteen (63%) of the 30 BU patients tested positive for S. aureus at least once during the sampling period, yielding 407 S. aureus isolates. Detailed analysis of 91 isolates grouped these isolates into 13 MLVF clusters and 13 spa-types. Five (26%) S. aureus-positive BU patients carried the same S. aureus genotype in their anterior nares and wounds. S. aureus isolates from the wounds of seven (37%) patients were distributed over two different MLVF clusters. Wounds of three (16%) patients were colonized with isolates belonging to two different genotypes at the same time, and five (26%) patients were colonized with different S. aureus types over time. Five (17%) of the 30 included BU patients tested positive for methicillin-resistant S. aureus (MRSA). The present study showed that the wounds of many BU patients were contaminated with S. aureus, and that many BU patients from the different communities carried the same S. aureus genotype during treatment. This calls for improved wound care and hygiene.

  8. Staphylococcus aureus adherence to Candida albicans hyphae is mediated by the hyphal adhesin Als3p.

    Science.gov (United States)

    Peters, Brian M; Ovchinnikova, Ekaterina S; Krom, Bastiaan P; Schlecht, Lisa Marie; Zhou, Han; Hoyer, Lois L; Busscher, Henk J; van der Mei, Henny C; Jabra-Rizk, Mary Ann; Shirtliff, Mark E

    2012-12-01

    The bacterium Staphylococcus (St.) aureus and the opportunistic fungus Candida albicans are currently among the leading nosocomial pathogens, often co-infecting critically ill patients, with high morbidity and mortality. Previous investigations have demonstrated preferential adherence of St. aureus to C. albicans hyphae during mixed biofilm growth. In this study, we aimed to characterize the mechanism behind this observed interaction. C. albicans adhesin-deficient mutant strains were screened by microscopy to identify the specific receptor on C. albicans hyphae recognized by St. aureus. Furthermore, an immunoassay was developed to validate and quantify staphylococcal binding to fungal biofilms. The findings from these experiments implicated the C. albicans adhesin agglutinin-like sequence 3 (Als3p) in playing a major role in the adherence process. This association was quantitatively established using atomic force microscopy, in which the adhesion force between single cells of the two species was significantly reduced for a C. albicans mutant strain lacking als3. Confocal microscopy further confirmed these observations, as St. aureus overlaid with a purified recombinant Als3 N-terminal domain fragment (rAls3p) exhibited robust binding. Importantly, a strain of Saccharomyces cerevisiae heterologously expressing Als3p was utilized to further confirm this adhesin as a receptor for St. aureus. Although the parental strain does not bind bacteria, expression of Als3p on the cell surface conferred upon the yeast the ability to strongly bind St. aureus. To elucidate the implications of these in vitro findings in a clinically relevant setting, an ex vivo murine model of co-infection was designed using murine tongue explants. Fluorescent microscopic images revealed extensive hyphal penetration of the epithelium typical of C. albicans mucosal infection. Interestingly, St. aureus bacterial cells were only seen within the epithelial tissue when associated with the invasive

  9. Mechanism of antagonistic effects of Andrographis paniculata methanolic extract against Staphylococcus aureus.

    Science.gov (United States)

    Hussain, Roslinah Mohamad; Razak, Zayan Nabilah Rasyidah Abd; Saad, Wan Mazlina Md; Mustakim, Maimunah

    2017-07-01

    To investigate the effects of Andrographis paniculata (Burm.f.) Wall. Ex Nees (A. paniculata) on expressions and activities of catalase, superoxide dismutase and alkylhydroperoxide reductase C in Staphylococcus aureus (S. aureus) with respect to its survival in vitro. Antioxidative property of methanolic leaves extract of A. paniculata (0.06 mg/mL). Minimum inhibitory concentration (MIC) was determined by its ability to reduce hydrogen peroxide (H 2 O 2 ) toxicity against S. aureus ATCC 25923 [(3.8 × 10 8 ) cfu/mL]. Effects of the extract on expressions of katA (encoding catalase), sodA and sodM [encoding superoxide dismutases (SODs)], and ahpC [encoding alkylhydroperoxide reductase C (AhpC)] in S. aureus were determined by RT-qPCR and corresponding enzyme activity assays were performed. Nitroblue tetrazolium reduction (NBT) assay was performed to determine effects of the extract on intracellular and extracellular levels of O 2- in S. aureus. Cells challenged with 7.5 mmol/L H 2 O 2 showed 0% survival in 30 min whereas 25% survived after treatment with the extract and H 2 O 2 . Cells that were treated with the extract alone had 43% survival in the same exposure period. Expressions of sodA and sodM genes in extract-treated cells were lowered 0.8-fold and 0.7-fold, respectively with decrease in total SOD activity of 26.8 U compared to untreated cells, 32.4 U (P paniculata methanolic leaves extract (0.06 mg/mL) reduce H 2 O 2 toxicity and more importantly, was in itself effectively inhibitory against S. aureus. Further, our observations suggest that a probable mode of its inhibitory mechanism against S. aureus is by reducing total SOD activity through downregulation of sodA and sodM expressions. Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.

  10. CCR-2 neutralization augments murine fresh BMC activation by Staphylococcus aureus via two distinct mechanisms: at the level of ROS production and cytokine response.

    Science.gov (United States)

    Nandi, Ajeya; Bishayi, Biswadev

    2017-05-01

    CCR-2 signaling regulates recruitment of monocytes from the bone marrow into the bloodstream and then to sites of infection. We sought to determine whether CCL-2/CCR-2 signaling is involved in the killing of Staphylococcus aureus by murine bone marrow cells (BMCs). The intermittent link of reactive oxygen species (ROS)-NF-κB/p38-MAPK-mediated CCL-2 production in CCR-2 signaling prompted us to determine whether neutralization of CCR-2 augments the response of murine fresh BMCs (FBMCs) after S. aureus infection. It was observed that anti-CCR-2 Ab-treated FBMCs released fewer ROS on encountering S. aureus infection than CCR-2 non-neutralized FBMCs, also correlating with reduced killing of S. aureus in CCR-2 neutralized FBMCs. Staphylococcal catalase and SOD were also found to play a role in protecting S. aureus from the ROS-mediated killing of FBMC. S. aureus infection of CCR-2 intact FBMCs pre-treated with either NF-κB or p-38-MAPK blocker induced less CCL-2, suggesting that NF-κB or p-38-MAPK is required for CCL-2 production by FBMCs. Moreover, blocking of CCR-2 along with NF-κB or p-38-MAPK resulted in elevated CCL-2 production and reduced CCR-2 expression. Inhibition of CCR-2 impairs the response of murine BMCs to S. aureus infection by attenuation ROS production and modulating the cytokine response.

  11. Bacteriophage ΦSA012 Has a Broad Host Range against Staphylococcus aureus and Effective Lytic Capacity in a Mouse Mastitis Model

    Directory of Open Access Journals (Sweden)

    Hidetomo Iwano

    2018-01-01

    Full Text Available Bovine mastitis is an inflammation of the mammary gland caused by bacterial infection in dairy cattle. It is the most costly disease in the dairy industry because of the high use of antibiotics. Staphylococcus aureus is one of the major causative agents of bovine mastitis and antimicrobial resistance. Therefore, new strategies to control bacterial infection are required in the dairy industry. One potential strategy is bacteriophage (phage therapy. In the present study, we examined the host range of previously isolated S. aureus phages ΦSA012 and ΦSA039 against S. aureus strains isolated from mastitic cows. These phages could kill all S. aureus (93 strains from 40 genotypes and methicillin-resistant S. aureus (six strains from six genotypes strains tested. Using a mouse mastitis model, we demonstrated that ΦSA012 reduced proliferation of S. aureus and inflammation in the mammary gland. Furthermore, intravenous or intraperitoneal phage administration reduced proliferation of S. aureus in the mammary glands. These results suggest that broad host range phages ΦSA012 is potential antibacterial agents for dairy production medicine.

  12. Transcriptomic and metabolic responses of Staphylococcus aureus in mixed culture with Lactobacillus plantarum, Streptococcus thermophilus and Enterococcus durans in milk.

    Science.gov (United States)

    Zdenkova, Kamila; Alibayov, Babek; Karamonova, Ludmila; Purkrtova, Sabina; Karpiskova, Renata; Demnerova, Katerina

    2016-09-01

    Staphylococcus aureus is a major food-borne pathogen due to the production of enterotoxin and is particularly prevalent in contaminated milk and dairy products. The lactic acid bacteria (LAB) are widely used as biocontrol agents in fermented foods which can inhibit pathogenic flora. In our work, we investigated the influence of three strains of LAB (Lactobacillus plantarum, Streptococcus thermophilus and Enterococcus durans) on the relative expression of three enterotoxin genes (sea, sec, sell) and eight virulence and/or regulatory genes (sarA, saeS, codY, srrA, rot, hld/RNAIII, agrA/RNAII, sigB) in two S. aureus strains (MW2 and Sa1612) in TSB and reduced-fat milk (1.5 %) at 30 °C over a 24-h period. The tested LAB and S. aureus strains proved to be mutually non-competitive or only slightly competitive during co-cultivation. In addition, under the above-mentioned conditions, differential gene expression between the S. aureus MW2 and Sa1612 strains was well documented. S. aureus growth was changed in mixed culture with LAB; however, its effect on the repression of sea and sec expression correlated with production of these virulence factors. In comparison, the presence of LAB strains generally inhibited the expression of sec, sell, sarA, seaS, agrA/RNAII and hld/RNAIII genes. The effect of LAB strains presence on the expression of sea, codY, srrA, rot and sigB genes was medium, time, LAB and S. aureus strain specific. SEA and SEC production was significantly reduced in milk compared to TSB in pure culture. After the 24-h cultivation, S. aureus MW2 and Sa1612 SEC production was 187 and 331 times lower in milk compared to TSB, respectively (0.07 and 0.39 ng/mL in milk, versus 13.1 and 129.2 ng/mL in TSB, respectively). At the same time S. aureus MW2 and Sa1612 SEA production was 77 and 68 times lower in milk compared to TSB, respectively (0.99 and 0.17 ng/mL in milk, versus 76.4 and 11.5 ng/mL in TSB, respectively). This study has revealed new insights into the

  13. Staphylococcus aureus shifts towards commensalism in response to Corynebacterium species

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    Matthew M Ramsey

    2016-08-01

    Full Text Available Staphylococcus aureus–human interactions result in a continuum of outcomes from commensalism to pathogenesis. S. aureus is a clinically important pathogen that asymptomatically colonizes ~25% of humans as a member of the nostril and skin microbiota, where it resides with other bacteria including commensal Corynebacterium species. Commensal Corynebacterium spp. are also positively correlated with S. aureus in chronic polymicrobial diabetic foot infections, distinct from acute monomicrobial S. aureus infections. Recent work by our lab and others indicates that microbe-microbe interactions between S. aureus and human skin/nasal commensals, including Corynebacterium species, affect S. aureus behavior and fitness. Thus, we hypothesized that S. aureus interactions with Corynebacterium spp. diminish S. aureus virulence. We tested this by assaying for changes in S. aureus gene expression during in vitro mono- versus coculture with Corynebacterium striatum, a common skin and nasal commensal. We observed a broad shift in S. aureus gene transcription during in vitro growth with C. striatum, including increased transcription of genes known to exhibit increased expression during human nasal colonization and decreased transcription of virulence genes. S. aureus uses several regulatory pathways to transition between commensal and pathogenic states. One of these, the quorum signal accessory gene regulator (agr system, was strongly inhibited in response to Corynebacterium spp. Phenotypically, S. aureus exposed to C. striatum exhibited increased adhesion to epithe