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Sample records for gram-negative bloodstream infection

  1. Procalcitonin levels in gram-positive, gram-negative, and fungal bloodstream infections.

    Leli, Christian; Ferranti, Marta; Moretti, Amedeo; Al Dhahab, Zainab Salim; Cenci, Elio; Mencacci, Antonella

    2015-01-01

    Procalcitonin (PCT) can discriminate bacterial from viral systemic infections and true bacteremia from contaminated blood cultures. The aim of this study was to evaluate PCT diagnostic accuracy in discriminating Gram-positive, Gram-negative, and fungal bloodstream infections. A total of 1,949 samples from patients with suspected bloodstream infections were included in the study. Median PCT value in Gram-negative (13.8 ng/mL, interquartile range (IQR) 3.4-44.1) bacteremias was significantly higher than in Gram-positive (2.1 ng/mL, IQR 0.6-7.6) or fungal (0.5 ng/mL, IQR 0.4-1) infections (P Gram-negatives from Gram-positives at the best cut-off value of 10.8 ng/mL and an AUC of 0.944 (95% CI 0.919-0.969, P Gram-negatives from fungi at the best cut-off of 1.6 ng/mL. Additional results showed a significant difference in median PCT values between Enterobacteriaceae and nonfermentative Gram-negative bacteria (17.1 ng/mL, IQR 5.9-48.5 versus 3.5 ng/mL, IQR 0.8-21.5; P Gram-negative from Gram-positive and fungal bloodstream infections. Nevertheless, its utility to predict different microorganisms needs to be assessed in further studies.

  2. Procalcitonin Levels in Gram-Positive, Gram-Negative, and Fungal Bloodstream Infections

    Christian Leli

    2015-01-01

    Full Text Available Procalcitonin (PCT can discriminate bacterial from viral systemic infections and true bacteremia from contaminated blood cultures. The aim of this study was to evaluate PCT diagnostic accuracy in discriminating Gram-positive, Gram-negative, and fungal bloodstream infections. A total of 1,949 samples from patients with suspected bloodstream infections were included in the study. Median PCT value in Gram-negative (13.8 ng/mL, interquartile range (IQR 3.4–44.1 bacteremias was significantly higher than in Gram-positive (2.1 ng/mL, IQR 0.6–7.6 or fungal (0.5 ng/mL, IQR 0.4–1 infections (P<0.0001. Receiver operating characteristic analysis showed an area under the curve (AUC for PCT of 0.765 (95% CI 0.725–0.805, P<0.0001 in discriminating Gram-negatives from Gram-positives at the best cut-off value of 10.8 ng/mL and an AUC of 0.944 (95% CI 0.919–0.969, P<0.0001 in discriminating Gram-negatives from fungi at the best cut-off of 1.6 ng/mL. Additional results showed a significant difference in median PCT values between Enterobacteriaceae and nonfermentative Gram-negative bacteria (17.1 ng/mL, IQR 5.9–48.5 versus 3.5 ng/mL, IQR 0.8–21.5; P<0.0001. This study suggests that PCT may be of value to distinguish Gram-negative from Gram-positive and fungal bloodstream infections. Nevertheless, its utility to predict different microorganisms needs to be assessed in further studies.

  3. Optimizing empiric therapy for Gram-negative bloodstream infections in children.

    Chao, Y; Reuter, C; Kociolek, L K; Patel, R; Zheng, X; Patel, S J

    2018-06-01

    Antimicrobial stewardship can be challenging in children with bloodstream infections (BSIs) caused by Gram-negative bacilli (GNB). This retrospective cohort study explored how data elements in the electronic health record could potentially optimize empiric antibiotic therapy for BSIs caused by GNB, via the construction of customized antibiograms for categorical GNB infections and identification of opportunities to minimize organism-drug mismatch and decrease time to effective therapy. Our results suggest potential strategies that could be implemented at key decision points in prescribing at initiation, modification, and targeting of therapy. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  4. Effectiveness of oral antibiotics for definitive therapy of Gram-negative bloodstream infections.

    Kutob, Leila F; Justo, Julie Ann; Bookstaver, P Brandon; Kohn, Joseph; Albrecht, Helmut; Al-Hasan, Majdi N

    2016-11-01

    There is paucity of data evaluating intravenous-to-oral antibiotic switch options for Gram-negative bloodstream infections (BSIs). This retrospective cohort study examined the effectiveness of oral antibiotics for definitive treatment of Gram-negative BSI. Patients with Gram-negative BSI hospitalised for antibiotics were included in this study. The cohort was stratified into three groups based on bioavailability of oral antibiotics prescribed (high, ≥95%; moderate, 75-94%; and low, antibiotics were prescribed to 106, 179 and 77 patients, respectively, for definitive therapy of Gram-negative BSI. Mean patient age was 63 years, 217 (59.9%) were women and 254 (70.2%) had a urinary source of infection. Treatment failure rates were 2%, 12% and 14% in patients receiving oral antibiotics with high, moderate and low bioavailability, respectively (P = 0.02). Risk of treatment failure in the multivariate Cox model was higher in patients receiving antibiotics with moderate [adjusted hazard ratio (aHR) = 5.9, 95% CI 1.6-38.5; P = 0.005] and low bioavailability (aHR = 7.7, 95% CI 1.9-51.5; P = 0.003) compared with those receiving oral antimicrobial agents with high bioavailability. These data demonstrate the effectiveness of oral antibiotics with high bioavailability for definitive therapy of Gram-negative BSI. Risk of treatment failure increases as bioavailability of the oral regimen declines. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  5. Nosocomial bloodstream infections in a Turkish university hospital: study of Gram-negative bacilli and their sensitivity patterns.

    Köseoğlu , O; Kocagöz, S; Gür, D; Akova, M

    2001-06-01

    Treatment of nosocomial bacteraemia is usually governed by the surveillance results of the particular unit. Such results are especially important when antimicrobial resistance rates are high. Multiresistant isolates including Gram-negatives producing extended-spectrum beta-lactamases have been frequently reported in tertiary care units in Turkey. In this study, antimicrobial susceptibilities of Gram-negative blood isolates (n=348) were determined by microbroth dilution tests. The results showed carbapenems (meropenem and imipenem) to be uniformly more potent in vitro than any other drug against the Enterobacteriaceae. Quinolone antibiotics were more active in vitro than aminoglycosides against a range of bacteria. Gram-negative bloodstream isolates were highly resistant to many antimicrobial agents in the hospital. In order to prevent hospital infection and antimicrobial resistance, surveillance of aetiological agents must be performed regularly.

  6. Changing epidemiology of central venous catheter-related bloodstream infections: increasing prevalence of Gram-negative pathogens.

    Marcos, Miguel; Soriano, Alex; Iñurrieta, Amaia; Martínez, José A; Romero, Alberto; Cobos, Nazaret; Hernández, Cristina; Almela, Manel; Marco, Francesc; Mensa, Josep

    2011-09-01

    Gram-positive microorganisms have been the predominant pathogens in central venous catheter-related bloodstream infections (CRBSIs). Recent guidelines recommend empirical therapy according to this and restrict coverage for Gram-negatives to specific circumstances. This study aimed to analyse the epidemiological changes in CRBSIs over the 1991-2008 period and to analyse predictors of Gram-negative CRBSIs. A prospectively collected cohort of patients with confirmed CRBSIs was analysed. Strains isolated and antimicrobial susceptibility, as well as clinical and demographic variables were recorded. Differences observed during the study period were analysed by means of a χ² trend test and factors associated with Gram-negative CRBSIs by means of multivariable analysis. Between 1991 and 2008, 1129 episodes of monomicrobial CRBSIs were recorded. There was an increase in the incidence of CRBSIs, from 0.10 (1991-92) to 0.31 (2007-08) episodes/1000 patient-days. A significant increase in the number of Gram-negative strains among the total isolates was also found, from 3 (4.7%) in 1991-92 to 70 (40.23%) in 2007-08, with a parallel decrease in the percentage of Gram-positives. Solid organ transplantation, prior use of penicillins and hospital stay longer than 11 days were independently associated with a significantly higher risk of Gram-negative CRBSIs, while cirrhosis, diabetes and use of quinolones were associated with a higher risk of Gram-positives. Gram-negative strains are an increasing cause of CRBSIs, reaching a prevalence of 40% in the 2007-08 period in our hospital. If this trend is confirmed in other centres, a broad-spectrum empirical therapy should be considered in managing these infections.

  7. Treatment and Outcome of Carbapenem-Resistant Gram-Negative Bacilli Blood-Stream Infections in a Tertiary Care Hospital.

    Shah, Pooja G; Shah, Sweta R

    2015-07-01

    Infections caused by carbapenem-resistant bacteria constitute a major challenge for current medical practice. To describe treatment and outcome of carbapenem-resistant Gram-negative bacilli (GNB) blood-stream infection (BSI) caused by these organisms at a tertiary care hospital in Mumbai. Carbapenem-resistant isolates from blood cultures were collected from January 2013 to April 2013. Identification and antimicrobial susceptibility testing were performed using Vitek 2 analyzer (Biomerieux Ltd.). Carbapenemase production was detected by modified Hodge's test (MHT). Patient's medical history, treatment and co-morbid conditions were noted. Outcomes of BSIs were evaluated. Forty-two isolates of carbapenem-resistant GNB isolated from BSIs were Enterobacteriaceae spp. (19), Acinetobacter baumannii (15), and Pseudomonas aeruginosa (8). Colistin had maximum in vitro activity with 97% against Enterobacteriaceae, 100% against Acinetobacter, and 100% activity against Pseudomonas aeruginosa isolates. Positivity of MHT was 92.9%. Outcome of colistin mono and combination therapy was comparable with 83% and 79%, respectively. Outcome of colistin and carbapenem combination therapy was found to be 100 percent. High incidences of bacteremia by carbapenem-resistant GNB including Enterobacteriaceae is a worrisome trend. Treatment options are compromised and only available option is colistin which has its own limitation. Colistin monotherapy may be non-inferior compared to combination therapy for treating BSIs caused by isolates with minimum inhibitory concentration (MIC) for colistin as ≤0.5 mg/l. Combined use of the colistin and carbapenem may provide good therapeutic options for BSI caused by carbapenem-resistant GNB and warrants further investigations.

  8. Trends of Bloodstream Infections in a University Greek Hospital during a Three-Year Period: Incidence of Multidrug-Resistant Bacteria and Seasonality in Gram-negative Predominance.

    Kolonitsiou, Fevronia; Papadimitriou-Olivgeris, Matthaios; Spiliopoulou, Anastasia; Stamouli, Vasiliki; Papakostas, Vasileios; Apostolopoulou, Eleni; Panagiotopoulos, Christos; Marangos, Markos; Anastassiou, Evangelos D; Christofidou, Myrto; Spiliopoulou, Iris

    2017-07-06

    The aim of the study was to assess the epidemiology, the incidence of multidrug-resistant bacteria and bloodstream infections' (BSIs) seasonality in a university hospital. This retrospective study was carried out in the University General Hospital of Patras, Greece, during 2011-13 y. Blood cultures from patients with clinical presentation suggestive of bloodstream infection were performed by the BacT/ALERT System. Isolates were identified by Vitek 2 Advanced Expert System. Antibiotic susceptibility testing was performed by the disk diffusion method and E-test. Resistance genes (mecA in staphylococci; vanA/vanB/vanC in enterococci; bla KPC /bla VIM /bla NDM in Klebsiella spp.) were detected by PCR. In total, 4607 (9.7%) blood cultures were positive from 47451 sets sent to Department of Microbiology, representing 1732 BSIs. Gram-negative bacteria (52.3%) were the most commonly isolated, followed by Gram-positive (39.5%), fungi (6.6%) and anaerobes bacteria (1.8%). The highest contamination rate was observed among Gram-positive bacteria (42.3%). Among 330 CNS and 150 Staphylococcus aureus, 281 (85.2%) and 60 (40.0%) were mecA-positive, respectively. From 113 enterococci, eight were vanA, two vanB and two vanC-positives. Of the total 207 carbapenem-resistant Klebsiella pneumoniae (73.4%), 202 carried bla KPC , four bla KPC and bla VIM and one bla VIM . A significant increase in monthly BSIs' incidence was shown (R2: 0.449), which may be attributed to a rise of Gram-positive BSIs (R2: 0.337). Gram-positive BSIs were less frequent in spring (P period. The increasing incidence of BSIs can be attributed to an increase of Gram-positive BSI incidence, even though Gram-negative bacteria remained the predominant ones. Seasonality may play a role in the predominance of Gram-negative's BSI.

  9. In vitro activity of aminoglycosides against clinical isolates of Acinetobacter baumannii complex and other nonfermentative Gram-negative bacilli causing healthcare-associated bloodstream infections in Taiwan.

    Liu, Jyh-You; Wang, Fu-Der; Ho, Mao-Wang; Lee, Chen-Hsiang; Liu, Jien-Wei; Wang, Jann-Tay; Sheng, Wang-Huei; Hseuh, Po-Ren; Chang, Shan-Chwen

    2016-12-01

    Aminoglycosides possess in vitro activity against aerobic and facultative Gram-negative bacilli. However, nationwide surveillance on susceptibility data of Acinetobacter baumannii complex and Pseudomonas aeruginosa to aminoglycosides was limited, and aminoglycoside resistance has emerged in the past decade. We study the in vitro susceptibility of A. baumannii complex and other nonfermentative Gram-negative bacilli (NFGNB) to aminoglycosides. A total of 378 NFGNB blood isolates causing healthcare-associated bloodstream infections during 2008 and 2013 at four medical centers in Taiwan were tested for their susceptibilities to four aminoglycosides using the agar dilution method (gentamicin, amikacin, tobramycin, and isepamicin) and disc diffusion method (isepamicin). A. baumannii was highly resistant to all four aminoglycosides (range of susceptibility, 0-4%), whereas >80% of Acinetobacter nosocomialis and Acinetobacter pittii blood isolates were susceptible to amikacin (susceptibility: 96% and 91%, respectively), tobramycin (susceptibility: 92% and 80%, respectively), and isepamicin (susceptibility: 96% and 80%, respectively). All aminoglycosides except gentamicin possessed good in vitro activity (>94%) against P. aeruginosa. Amikacin has the best in vitro activity against P. aeruginosa (susceptibility, 98%), followed by A. nosocomialis (96%), and A. pittii (91%), whereas tobramycin and isepamicin were less potent against A. pittii (both 80%). Aminoglycoside resistances were prevalent in Stenotrophomonas maltophilia and Burkholderia cepacia complex blood isolates in Taiwan. Genospecies among the A. baumannii complex had heterogeneous susceptibility profiles to aminoglycosides. Aminoglycosides, except gentamicin, remained good in vitro antimicrobial activity against P. aeruginosa. Further in vivo clinical data and continuous resistance monitoring are warranted for clinical practice guidance. Copyright © 2015. Published by Elsevier B.V.

  10. Gram-Negative Bacterial Wound Infections

    2014-05-01

    Bovine Tuberculosis in Cattle Farms in Zaria and Kaduna and Possible Transmission Through Milk P. N. Mbianga, V. J. Umoh, A. I. 0, K. C. A; Ahmadu...Pathogenic Escherichia coli R. M. Ramirez, M-X. Haro, P. Miranda, S-H. Sanchez, L-E. Vidales; Univ. Aut6noma de Zacatecas, Zacatecas, Mexico 517...isolates. Subsequently, five representative isolates were tested in murine pulmonary and Galleria mellonella models of infection. Infections with one strain

  11. Port type is a possible risk factor for implantable venous access port-related bloodstream infections and no sign of local infection predicts the growth of gram-negative bacilli.

    Hsu, Jui-Feng; Chang, Hsu-Liang; Tsai, Ming-Ju; Tsai, Ying-Ming; Lee, Yen-Lung; Chen, Pei-Huan; Fan, Wen-Chieh; Su, Yu-Chung; Yang, Chih-Jen

    2015-09-30

    Implantable venous access port (IVAP)-related blood stream infections (BSIs) are one of the most common complications of implantable venous ports. The risk factors and pathogens for IVAP-related BSIs are still controversial. We retrospectively reviewed all patients who received IVAPs at a Hospital in Taiwan from January 1, 2011 to June 31, 2014. Two types of venous port, BardPort® 6.6 fr (Bard port) and Autosuture Chemosite® 7.5 fr (TYCO port) were used. All patients with clinically proven venous port-related BSIs were enrolled. A total of 552 patients were enrolled. There were 34 episodes of IVAP-related BSIs during the study period for a total incidence of 0.177 events/1000 catheter days. Port type (TYCO vs. Bard, HR = 7.105 (95% confidence interval (CI), 1.688-29.904), p = 0.0075), age > 65 years (HR = 2.320 (95 % CI, 1.179-4.564), p = 0.0148), and lung cancer (HR = 5.807 (95% CI, 2.946-11.447), p port infections. We also found that no local sign of infection was significantly associated with the growth of gram-negative bacilli (p = 0.031). TYCO venous ports, age > 65 years, and lung cancer were all significant risk factors for IVAP-related BSIs, and no sign of infection was significantly associated with the growth of gram-negative bacilli.

  12. Combating multidrug-resistant Gram-negative bacterial infections.

    Xu, Ze-Qi; Flavin, Michael T; Flavin, John

    2014-02-01

    Multidrug-resistant (MDR) bacterial infections, especially those caused by Gram-negative pathogens, have emerged as one of the world's greatest health threats. The development of novel antibiotics to treat MDR Gram-negative bacteria has, however, stagnated over the last half century. This review provides an overview of recent R&D activities in the search for novel antibiotics against MDR Gram-negatives. It provides emphasis in three key areas. First, the article looks at new analogs of existing antibiotic molecules such as β-lactams, tetracyclines, and aminoglycoside as well as agents against novel bacterial targets such as aminoacyl-tRNA synthetase and peptide deformylase. Second, it also examines alternative strategies to conventional approaches including cationic antimicrobial peptides, siderophores, efflux pump inhibitors, therapeutic antibodies, and renewed interest in abandoned treatments or those with limited indications. Third, the authors aim to provide an update on the current clinical development status for each drug candidate. The traditional analog approach is insufficient to meet the formidable challenge brought forth by MDR superbugs. With the disappointing results of the genomics approach for delivering novel targets and drug candidates, alternative strategies to permeate the bacterial cell membrane, enhance influx, disrupt efflux, and target specific pathogens via therapeutic antibodies are attractive and promising. Coupled with incentivized business models, governmental policies, and a clarified regulatory pathway, it is hoped that the antibiotic pipeline will be filled with an effective armamentarium to safeguard global health.

  13. Black-pigmented gram-negative anaerobes in endodontic infections.

    Haapasalo, M

    1993-03-01

    Necrotic dental root canal infections are polymicrobial infections dominated by anaerobic bacteria. The number of different species in one canal is usually low, approx. 4-7 species. The species isolated most frequently belong to the genera Prevotella, Porphyromonas, Fusobacterium, Peptostreptococcus, Eubacterium and Streptococcus. The frequency of isolation of black-pigmented Gram-negative anaerobes in endodontic infections varies from 25% to > 50%. Pr. intermedia is the most commonly found pigmented species, followed by Pr. denticola and two Porphyromonas species, P. gingivalis and P. endodontalis. Several studies have shown that P. gingivalis and P. endodontalis are closely related to the presence of acute symptoms in endodontic infections, whereas other black-pigmented Gram-negative anaerobes are not. However, several other species may also be involved in acute infections. Moreover, Porphyromonas species have occasionally been isolated from cases with no symptoms. Although Porphyromonas spp. are clearly related to symptoms at the beginning of therapy, they are not important for the prognosis of the treatment.

  14. [Diagnostic and therapeutic management of Gram-negative infections].

    Bassetti, Matteo; Repetto, Ernestina

    2008-04-01

    Among Gram negative bacteria, Pseudomonas aeruginosa, the extended spectrum beta-lactamases (ESBL)-producing strains, Acinetobacter spp, in particular the multiresistant Acinetobacter baumannii, and Stenotrophomonas maltophilia are the most implicated micrororganisms in the ever more increasing problem of bacterial resistance. Possible solutions have to be searched, on one hand, in the use of new drugs but, on the other hand, in the re-evaluation of those already available drugs, possibly considering a new role for old drugs such as colistine and fosfomycin. Concerning ESBL-producing strains, the most recent data provided by EARSS report, in Italy, an incidence rate of 10-25 percent. The insurgence of an infection sustained by an ESBL+ve strain is strictly related to some well known risk factors, like the hospital stay itself, the disease severity, the length of stay in ICU, intubation and mechanical ventilation, catheterization, urinary or artery, and the past exposure to antibiotics. The raise in ESBL producing strains is closely related to the increasing use of cephalosporins. In the setting of a Gram negative infection, the combination therapy guarantees a higher coverage by reducing insurgence of possible resistance mechanisms, possibly resulting synergistic, and allowing a de-escalation therapy, although to this latter other problems, such as tolerability, costs and compliance, can be related. Another basic aspect to take into account of, in order to achieve the maximal efficacy of the antibiotic treatment, is the right dosage. In the idea to look for the best approach for the antibiotic treatment of a severe infection in a hospital setting, when a Gram negative aetiology is implicated, it can be possibly presumed that the right way consists in avoiding inappropriate antibiotic therapies, making therapeutic choices based on guidelines resulted from local epidemiological data, initiating the therapy promptly, avoiding excessive use of antibiotics, possibly

  15. Inhaled Antibiotics for Gram-Negative Respiratory Infections

    Fraidenburg, Dustin R.; Scardina, Tonya

    2016-01-01

    SUMMARY Gram-negative organisms comprise a large portion of the pathogens responsible for lower respiratory tract infections, especially those that are nosocomially acquired, and the rate of antibiotic resistance among these organisms continues to rise. Systemically administered antibiotics used to treat these infections often have poor penetration into the lung parenchyma and narrow therapeutic windows between efficacy and toxicity. The use of inhaled antibiotics allows for maximization of target site concentrations and optimization of pharmacokinetic/pharmacodynamic indices while minimizing systemic exposure and toxicity. This review is a comprehensive discussion of formulation and drug delivery aspects, in vitro and microbiological considerations, pharmacokinetics, and clinical outcomes with inhaled antibiotics as they apply to disease states other than cystic fibrosis. In reviewing the literature surrounding the use of inhaled antibiotics, we also highlight the complexities related to this route of administration and the shortcomings in the available evidence. The lack of novel anti-Gram-negative antibiotics in the developmental pipeline will encourage the innovative use of our existing agents, and the inhaled route is one that deserves to be further studied and adopted in the clinical arena. PMID:27226088

  16. Sinus surgery postpones chronic Gram-negative lung infection

    Alanin, M C; Aanaes, K; Høiby, N

    2016-01-01

    of pulmonary samples positive for GNB. We investigated whether the effect is sustained. METHODOLOGY: We report the effect of ESS and adjuvant therapy three years postoperatively in a CF cohort participating in this prospective clinical follow-up study. The primary endpoint was the lung infection status defined......BACKGROUND: In patients with cystic fibrosis (CF) the sinuses are a bacterial reservoir for Gram-negative bacteria (GNB). From the sinuses the GNB can repeatedly migrate to the lungs. In a one-year follow-up study, endoscopic sinus surgery (ESS) with adjuvant therapy reduced the frequency....... The total cohort had decreasing lung function during follow-up; however, in 27 patients with improved lung infection status lung function was stable. Revision surgery was performed in 31 patients (28%). CONCLUSION: ESS with adjuvant therapy significantly improves the lung infection status for at least three...

  17. Sinus surgery postpones chronic gram-negative lung infection

    Alanin, M C; Aanaes, K; Høiby, N

    2016-01-01

    Background: In patients with cystic fibrosis (CF) the sinuses are a bacterial reservoir for Gram-negative bacteria (GNB). From the sinuses the GNB can repeatedly migrate to the lungs. In a one-year follow-up study, endoscopic sinus surgery (ESS) with adjuvant therapy reduced the frequency...

  18. Add-On Therapy with Ertapenem in Infections with Multidrug Resistant Gram-Negative Bacteria: Pediatric Experience

    Sevgen Tanır Basaranoglu

    2017-01-01

    Full Text Available Optimal therapy for infections with carbapenem resistant GNB is not well established due to the weakness of data. Patients presenting with bloodstream infections caused by multidrug resistant Klebsiella pneumoniae were treated with a combination treatment. Optimal therapy for infections with carbapenem resistant Gram-negative bacteria is a serious problem in pediatric patients. We presented three cases who were successfully treated with addition of ertapenem to the combination treatment for bacteremia with multidrug resistant Klebsiella pneumoniae. Dual carbapenem treatment approach is a new approach for these infections and requires more data in children.

  19. Potential strategies for the eradication of multidrug-resistant Gram-negative bacterial infections.

    Huwaitat, Rawan; McCloskey, Alice P; Gilmore, Brendan F; Laverty, Garry

    2016-07-01

    Antimicrobial resistance is one of the leading threats to society. The increasing burden of multidrug-resistant Gram-negative infection is particularly concerning as such bacteria are demonstrating resistance to nearly all currently licensed therapies. Various strategies have been hypothesized to treat multidrug-resistant Gram-negative infections including: targeting the Gram-negative outer membrane; neutralization of lipopolysaccharide; inhibition of bacterial efflux pumps and prevention of protein folding. Silver and silver nanoparticles, fusogenic liposomes and nanotubes are potential strategies for extending the activity of licensed, Gram-positive selective, antibiotics to Gram-negatives. This may serve as a strategy to fill the current void in pharmaceutical development in the short term. This review outlines the most promising strategies that could be implemented to solve the threat of multidrug-resistant Gram-negative infections.

  20. Gram negative wound infection in hospitalised adult burn patients--systematic review and metanalysis-.

    Azzopardi, Ernest A; Azzopardi, Elayne; Camilleri, Liberato; Villapalos, Jorge; Boyce, Dean E; Dziewulski, Peter; Dickson, William A; Whitaker, Iain S

    2014-01-01

    Gram negative infection is a major determinant of morbidity and survival. Traditional teaching suggests that burn wound infections in different centres are caused by differing sets of causative organisms. This study established whether Gram-negative burn wound isolates associated to clinical wound infection differ between burn centres. Studies investigating adult hospitalised patients (2000-2010) were critically appraised and qualified to a levels of evidence hierarchy. The contribution of bacterial pathogen type, and burn centre to the variance in standardised incidence of Gram-negative burn wound infection was analysed using two-way analysis of variance. Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumanni, Enterobacter spp., Proteus spp. and Escherichia coli emerged as the commonest Gram-negative burn wound pathogens. Individual pathogens' incidence did not differ significantly between burn centres (F (4, 20) = 1.1, p = 0.3797; r2 = 9.84). Gram-negative infections predominate in burn surgery. This study is the first to establish that burn wound infections do not differ significantly between burn centres. It is the first study to report the pathogens responsible for the majority of Gram-negative infections in these patients. Whilst burn wound infection is not exclusive to these bacteria, it is hoped that reporting the presence of this group of common Gram-negative "target organisms" facilitate clinical practice and target research towards a defined clinical demand.

  1. Gram negative wound infection in hospitalised adult burn patients--systematic review and metanalysis-.

    Ernest A Azzopardi

    Full Text Available BACKGROUND: Gram negative infection is a major determinant of morbidity and survival. Traditional teaching suggests that burn wound infections in different centres are caused by differing sets of causative organisms. This study established whether Gram-negative burn wound isolates associated to clinical wound infection differ between burn centres. METHODS: Studies investigating adult hospitalised patients (2000-2010 were critically appraised and qualified to a levels of evidence hierarchy. The contribution of bacterial pathogen type, and burn centre to the variance in standardised incidence of Gram-negative burn wound infection was analysed using two-way analysis of variance. PRIMARY FINDINGS: Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumanni, Enterobacter spp., Proteus spp. and Escherichia coli emerged as the commonest Gram-negative burn wound pathogens. Individual pathogens' incidence did not differ significantly between burn centres (F (4, 20 = 1.1, p = 0.3797; r2 = 9.84. INTERPRETATION: Gram-negative infections predominate in burn surgery. This study is the first to establish that burn wound infections do not differ significantly between burn centres. It is the first study to report the pathogens responsible for the majority of Gram-negative infections in these patients. Whilst burn wound infection is not exclusive to these bacteria, it is hoped that reporting the presence of this group of common Gram-negative "target organisms" facilitate clinical practice and target research towards a defined clinical demand.

  2. [Influence of serious infections due to Gram-negative bacteria on the hospital economy].

    Martínez, B; Gómez, J; Gómez Vargas, J; Guerra, B; Ruiz Gómez, J; Simarro, E; Baños, V; Canteras, M; Valdes, M

    2000-12-01

    Nosocomial infections due to Gram-negative bacteria are very important since they are associated with high morbidity and high hospital costs. A prospective study of 250 inpatients was carried out, 200 of whom had Gram-negative bacterial infections. Patients were divided into groups of 50 according to the localization of the infection (urinary, surgical wound, respiratory tract and bacteremia), with a control group of 50 patients with similar characteristics but no infection. We calculated the cost for the different groups by multiplying the average length of hospital stay in days by the daily cost of the stay. Significant differences were observed in the average length of stay per patient according to the type of infection and how it was acquired. In terms of cost, nosocomial infection due to Gram-negative bacteria was 1,049,139 pesetas more expensive than community-acquired infection. The cost of the stay for patients with postsurgical infection due to Gram-negative bacteria was 1,108, 252 pesetas more expensive than for the group of control patients. Nosocomial infection due to Gram-negative bacteria is associated with a prolongation in hospital stay of 9 to 28 days, which is the factor that most reflects the cost that can be attributed to nosocomial infection. Consensual and protocolized measures which allow for better clinical management need to be developed.

  3. Multiplex identification of sepsis-causing Gram-negative pathogens from the plasma of infected blood.

    Chung, Boram; Park, Chulmin; Cho, Sung-Yeon; Shin, Juyoun; Shin, Sun; Yim, Seon-Hee; Lee, Dong-Gun; Chung, Yeun-Jung

    2018-02-01

    Early and accurate detection of bacterial pathogens in the blood is the most crucial step for sepsis management. Gram-negative bacteria are the most common organisms causing severe sepsis and responsible for high morbidity and mortality. We aimed to develop a method for rapid multiplex identification of clinically important Gram-negative pathogens and also validated whether our system can identify Gram-negative pathogens with the cell-free plasm DNA from infected blood. We designed five MLPA probe sets targeting the genes specific to major Gram-negative pathogens (uidA and lacY for E. coli, ompA for A. baumannii, phoE for K. pneumoniae, and ecfX for P. aeruginosa) and one set targeting the CTX-M group 1 to identify the ESBL producing Gram-negative pathogens. All six target-specific peaks were clearly separated without any non-specific peaks in a multiplex reaction condition. The minimum detection limit was 100 fg of pathogen DNA. When we tested 28 Gram-negative clinical isolates, all of them were successfully identified without any non-specific peaks. To evaluate the clinical applicability, we tested seven blood samples from febrile patients. Three blood culture positive cases showed E. coli specific peaks, while no peak was detected in the other four culture negative samples. This technology can be useful for detection of major sepsis-causing, drug-resistant Gram-negative pathogens and also the major ESBL producing Gram-negatives from the blood of sepsis patients in a clinical setting. This system can help early initiation of effective antimicrobial treatment against Gram-negative pathogens for sepsis patients, which is very crucial for better treatment outcomes. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Mucositis and oral infections secondary to gram negative rods in patients with prolonged neutropenia

    Mindy M. Sampson

    2017-01-01

    Full Text Available Patients with prolonged neutropenia are at risk for a variety of complications and infections including the development of mucositis and oral ulcers. The changes in oral flora during chemotherapy and its effects on the development of infections of the oral cavity have been studied with inconsistent results. However, there is evidence that supports the colonization of gram negative rods in patients undergoing chemotherapy. In this report, we present two leukemic patients who developed oral ulcers secondary to multi-drug resistant Pseudomonas aeruginosa. It is important to suspect multi-drug resistant gram negative rods in patients with prolonged neutropenia who develop gum infections despite appropriate antibiotic coverage.

  5. Retrospective Analysis of Blood Stream Infections and Antibiotic Susceptibility Pattern of Gram Negative Bacteria in a Tertiary Care Cancer Hospital

    Radha Rani D

    2017-12-01

    Full Text Available Background: Bacterial bloodstream infections are important causes of morbidity and mortality globally. The aim of the present study was to determine the bacterial profile of bloodstream infections and their antibiotic susceptibility pattern among the clinically diagnosed cases of sepsis in cancer patients. Methods: In the present study, etiological and antimicrobial susceptibility profile of blood cultures over a period of 1 year at a tertiary cancer care hospital was done. Blood culture positive isolates were identified using standard microbiological methods and by Fully automated BD Phoenix 100. The antibiotic susceptibility pattern of the organisms was performed by Kirby-Bauer disc diffusion method and MIC (Minimum inhibitory concentration was done by Fully automated BD Phoenix 100. Results: There were 1178 blood culture samples, of which 327 (27.7% were identified to be culture positive. Out of 327 positive cultures, 299 (91.4% showed bacterial growth, Gram negative were 161 (53.8% and Gram positive were 138 (46.1%. Candida species were isolated from 13 (3.97% of positive samples and 15 samples showed contamination. The most common Gram-negative isolate was. Escherichia coli (37.80% and Gram-positive isolate was coagulasenegative staphylococci (52.80%. Escherichia coli showed highest sensitivity to amikacin (83.60% and sensitivity to piperacillin+ tazobactum and cefaperazone+sulbactam was 54.09% and 52.45% respectively. High degree of resistance was found to cephalosporins and levofloxacin. Conclusion: The results indicate high level of antimicrobial resistance among Gram negative bacilli in septicemic patients. The results warrant continuous monitoring of antimicrobial pattern so as to build geographical epidemiological data.

  6. STUDY ON SURGICAL SITE INFECTIONS CAUSED BY ESBL PRODUCING GRAM NEGATIVE BACTERIA

    Rambabu

    2015-09-01

    Full Text Available Surgical site infections have been a major problem, because of the emergence of drug resistant bacteria, in particular B - lactamase producing bacteria. Extended spectrum beta lactamase producing gram negative organisms pose a great challenge in treatment o f SSI present study is aimed at determining multiple drug resistance in gram negative bacteria & to find out ESBL producers, in correlation with treatment outcome. A total of 120 wound infected cases were studied. Staphylococcus aureus was predominant bact erium - 20.Among gram negative bacteria, Pseudomonas species is predominant (14 followed by Escherichia coli (13 , Klebsiella species (12 , Proteus (9 Citrobacter (4 Providencia (2 & Acinetobacter species (2 . Out of 56 gramnegative bacteria isolated, 20 were i dentified as ESBL producers, which was statistically significant. Delay in wound healing correlated with infection by ESBL producers, which alarms the need of abstinence from antibiotic abuse

  7. Risk factors for multidrug-resistant Gram-negative infection in burn patients.

    Vickers, Mark L; Dulhunty, Joel M; Ballard, Emma; Chapman, Paul; Muller, Michael; Roberts, Jason A; Cotta, Menino O

    2018-05-01

    Infection with multidrug-resistant (MDR) Gram-negative organisms leads to poorer outcomes in the critically ill burn patient. The aim of this study was to identify the risk factors for MDR Gram-negative pathogen infection in critically ill burn patients admitted to a major tertiary referral intensive care unit (ICU) in Australia. A retrospective case-control study of all adult burn patients admitted over a 7-year period was conducted. Twenty-one cases that cultured an MDR Gram-negative organism were matched with 21 controls of similar age, gender, burn size and ICU stay. Multivariable conditional logistic regression was used to individually assess risk factors after adjusting for Acute Burn Severity Index. Adjusted odds ratios (ORs) were reported. P-values negative infection included superficial partial thickness burn size (OR: 1.08; 95% confidence interval (CI): 1.01-1.16; P-value: 0.034), prior meropenem exposure (OR: 10.39; 95% CI: 0.96-112.00; P-value: 0.054), Gram-negative colonization on admission (OR: 9.23; 95% CI: 0.65-130.15; P-value: 0.10) and escharotomy (OR: 2.66; 95% CI: 0.52-13.65; P-value: 0.24). For cases, mean age was 41 (SD: 13) years, mean total body surface area burned was 47% (SD: 18) and mean days in ICU until MDR specimen collection was 17 (SD: 10) days. Prior meropenem exposure, Gram-negative colonization on admission, escharotomy and superficial partial thickness burn size may be potentially important factors for increasing the risk of MDR Gram-negative infection in the critically ill burn patient. © 2017 Royal Australasian College of Surgeons.

  8. Gram-Negative Infections in Adult Intensive Care Units of Latin America and the Caribbean

    Carlos M. Luna

    2014-01-01

    Full Text Available This review summarizes recent epidemiology of Gram-negative infections in selected countries from Latin American and Caribbean adult intensive care units (ICUs. A systematic search of the biomedical literature (PubMed was performed to identify articles published over the last decade. Where appropriate, data also were collected from the reference list of published articles, health departments of specific countries, and registries. Independent cohort data from all countries (Argentina, Brazil, Chile, Colombia, Cuba, Mexico, Trinidad and Tobago, and Venezuela signified a high rate of ICU infections (prevalence: Argentina, 24%; Brazil, 57%. Gram-negative pathogens, predominantly Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli, accounted for >50% of ICU infections, which were often complicated by the presence of multidrug-resistant strains and clonal outbreaks. Empirical use of antimicrobial agents was identified as a strong risk factor for resistance development and excessive mortality. Infection control strategies utilizing hygiene measures and antimicrobial stewardship programs reduced the rate of device-associated infections. To mitigate the poor health outcomes associated with infections by multidrug-resistant Gram-negative bacteria, urgent focus must be placed on infection control strategies and local surveillance programs.

  9. Dual beta-lactam therapy for serious Gram-negative infections: is it time to revisit?

    Rahme, Christine; Butterfield, Jill M; Nicasio, Anthony M; Lodise, Thomas P

    2014-12-01

    We are rapidly approaching a crisis in antibiotic resistance, particularly among Gram-negative pathogens. This, coupled with the slow development of novel antimicrobial agents, underscores the exigency of redeploying existing antimicrobial agents in innovative ways. One therapeutic approach that was heavily studied in the 1980s but abandoned over time is dual beta-lactam therapy. This article reviews the evidence for combination beta-lactam therapy. Overall, in vitro, animal and clinical data are positive and suggest that beta-lactam combinations produce a synergistic effect against Gram-negative pathogens that rivals that of beta-lactam-aminoglycoside or beta-lactam-fluoroquinolone combination therapy. Although the precise mechanism of improved activity is not completely understood, it is likely attributable to an enhanced affinity to the diverse penicillin-binding proteins found among Gram negatives. The collective data indicate that dual beta-lactam therapy should be revisited for serious Gram-negative infections, especially in light of the near availability of potent beta-lactamase inhibitors, which neutralize the effect of problematic beta-lactamases. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. The Growing Threat of Multidrug-Resistant Gram-Negative Infections in Patients with Hematologic Malignancies

    Baker, Thomas M.; Satlin, Michael J.

    2016-01-01

    Prolonged neutropenia and chemotherapy-induced mucositis render patients with hematologic malignancies highly vulnerable to Gram-negative bacteremia. Unfortunately, multidrug-resistant (MDR) Gram-negative bacteria are increasingly encountered globally, and current guidelines for empirical antibiotic coverage in these patients may not adequately treat these bacteria. This expansion of resistance, coupled with traditional culturing techniques requiring 2-4 days for bacterial identification and antimicrobial susceptibility results, have grave implications for these immunocompromised hosts. This review characterizes the epidemiology, risk factors, resistance mechanisms, recommended treatments, and outcomes of the MDR Gram-negative bacteria that commonly cause infections in patients with hematologic malignancies. We also examine infection prevention strategies in hematology patients, such as infection control practices, antimicrobial stewardship, and targeted decolonization. Finally, we assess strategies to improve outcomes of infected patients, including gastrointestinal screening to guide empirical antibiotic therapy, new rapid diagnostic tools for expeditious identification of MDR pathogens, and use of two new antimicrobial agents, ceftolozane/tazobactam and ceftazidime/avibactam. PMID:27339405

  11. Synergistic antibacterial effect of silver and ebselen against multidrug-resistant Gram-negative bacterial infections.

    Zou, Lili; Lu, Jun; Wang, Jun; Ren, Xiaoyuan; Zhang, Lanlan; Gao, Yu; Rottenberg, Martin E; Holmgren, Arne

    2017-08-01

    Multidrug-resistant (MDR) Gram-negative bacteria account for a majority of fatal infections, and development of new antibiotic principles and drugs is therefore of outstanding importance. Here, we report that five most clinically difficult-to-treat MDR Gram-negative bacteria are highly sensitive to a synergistic combination of silver and ebselen. In contrast, silver has no synergistic toxicity with ebselen on mammalian cells. The silver and ebselen combination causes a rapid depletion of glutathione and inhibition of the thioredoxin system in bacteria. Silver ions were identified as strong inhibitors of Escherichia coli thioredoxin and thioredoxin reductase, which are required for ribonucleotide reductase and DNA synthesis and defense against oxidative stress. The bactericidal efficacy of silver and ebselen was further verified in the treatment of mild and acute MDR E. coli peritonitis in mice. These results demonstrate that thiol-dependent redox systems in bacteria can be targeted in the design of new antibacterial drugs. The silver and ebselen combination offers a proof of concept in targeting essential bacterial systems and might be developed for novel efficient treatments against MDR Gram-negative bacterial infections. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

  12. Exploring the hidden potential of fosfomycin for the fight against severe Gram-negative infections

    P V Saiprasad

    2016-01-01

    Full Text Available Gram-negative resistance is a serious global crisis putting the world on the cusp of 'pre-antibiotic era'. This serious crisis has been catalysed by the rapid increase in carbapenem-resistant Enterobacteriaceae (CRE. Spurge in colistin usage to combat CRE infections leads to the reports of (colistin and carbapenem resistant enterobacteriaceae CCRE (resistance to colistin in isolates of CRE infections further jeopardising our last defence. The antibacterial apocalypse imposed by global resistance crisis requires urgent alternative therapeutic options. Interest in the use of fosfomycin renewed recently for serious systemic infections caused by multidrug-resistant Enterobacteriaceae. This review aimed at analysing the recent evidence on intravenous fosfomycin to explore its hidden potential, especially when fosfomycin disodium is going to be available in India. Although a number of promising evidence are coming up for fosfomycin, there are still areas where more work is required to establish intravenous fosfomycin as the last resort antibacterial for severe Gram-negative infections.

  13. DMPD: Lipopolysaccharide sensing an important factor in the innate immune response toGram-negative bacterial infections: benefits and hazards of LPShypersensitivity. [Dynamic Macrophage Pathway CSML Database

    Full Text Available se toGram-negative bacterial infections: benefits and hazards of LPShypersensitivity. Freudenberg MA, Tchapt...portant factor in the innate immune response toGram-negative bacterial infections: benefits and hazards of L...une response toGram-negative bacterial infections: benefits and hazards of LPShyp

  14. Antiseptic and antibiotic resistance in Gram-negative bacteria causing urinary tract infection.

    Stickler, D J; Thomas, B

    1980-01-01

    A collection of 802 isolates of Gram-negative bacteria causing urinary tract infections was made from general practice, antenatal clinics, and local hospitals. The organisms were tested for their sensitivity to chlorhexidine, cetrimide, glutaraldehyde, phenyl mercuric nitrate, a phenolic formulation, and a proprietary antiseptic containing a mixture of picloxydine, octyl phenoxy polyethoxyethanol, and benzalkonium chloride. Escherichia coli, the major species isolated, proved to be uniformly sensitive to these agents. Approximately 10% of the total number of isolates, however, exhibited a degree of resistance to the cationic agents. These resistant organisms were members of the genera Proteus, Providencia, and Pseudomonas; they were also generally resistant to five, six, or seven antibiotics. It is proposed therefore that an antiseptic policy which involves the intensive use of cationic antiseptics might lead to the selection of a flora of notoriously drug-resistant species. PMID:6769972

  15. [Uncommon non-fermenting Gram-negative rods as pathogens of lower respiratory tract infection].

    Juhász, Emese; Iván, Miklós; Pongrácz, Júlia; Kristóf, Katalin

    2018-01-01

    Glucose non-fermenting Gram-negative bacteria are ubiquitous environmental organisms. Most of them are identified as opportunistic, nosocomial pathogens in patients. Uncommon species are identified accurately, mainly due to the introduction of matrix-assisted laser desorption-ionization time of flight mass spectrometry (MALDI-TOF MS) in clinical microbiology practice. Most of these uncommon non-fermenting rods are isolated from lower respiratory tract samples. Their significance in lower respiratory tract infections, such as rules of their testing are not clarified yet. The aim of this study was to review the clinical microbiological features of these bacteria, especially their roles in lower respiratory tract infections and antibiotic treatment options. Lower respiratory tract samples of 3589 patients collected in a four-year period (2013-2016) were analyzed retrospectively at Semmelweis University (Budapest, Hungary). Identification of bacteria was performed by MALDI-TOF MS, the antibiotic susceptibility was tested by disk diffusion method. Stenotrophomonas maltophilia was revealed to be the second, whereas Acinetobacter baumannii the third most common non-fermenting rod in lower respiratory tract samples, behind the most common Pseudomonas aeruginosa. The total number of uncommon non-fermenting Gram-negative isolates was 742. Twenty-three percent of isolates were Achromobacter xylosoxidans. Beside Chryseobacterium, Rhizobium, Delftia, Elizabethkingia, Ralstonia and Ochrobactrum species, and few other uncommon species were identified among our isolates. The accurate identification of this species is obligatory, while most of them show intrinsic resistance to aminoglycosides. Resistance to ceftazidime, cefepime, piperacillin-tazobactam and carbapenems was frequently observed also. Ciprofloxacin, levofloxacin and trimethoprim-sulfamethoxazole were found to be the most effective antibiotic agents. Orv Hetil. 2018; 159(1): 23-30.

  16. Investigational drugs for the treatment of infections caused by multidrug-resistant Gram-negative bacteria.

    Avery, Lindsay M; Nicolau, David P

    2018-04-01

    Infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) are associated with significant mortality and costs. New drugs in development to combat these difficult-to-treat infections primarily target carbapenem-resistant Enterobacteriaceae, MDR Pseudomonas aeruginosa, and MDR Acinetobacter baumannii. Areas covered: The authors summarize in vitro and in vivo efficacy studies, as well as available clinical trial findings, for new agents in development for treatment of infection caused by MDR-GNB. Information regarding dosage regimens utilized in clinical trials and key pharmacokinetic and pharmacodynamic considerations are provided if available. A summary of recently approved agents, delafloxacin and meropenem/vaborbactam, is also included. Expert opinion: The development of multiple novel agents to fight MDR-GNB is promising to help save the lives of patients who acquire infection, and judicious use of these agents is imperative once they come to market to prevent the development of resistance. The other component paramount to this field of research is implementation of effective infection control policies and carbapenem-resistant Enterobacteriaceae (CRE) carrier screening protocols to mitigate the worldwide spread of MDR-GNB. Further investigation of anti-infective synergistic combinations will also be important, as well as support for economic research to reveal the true cost-benefit of utilization of the new agents discussed herein.

  17. Relative uptake of technetium 99m stannous colloid by neutrophils and monocytes is altered by gram-negative infection

    Ramsay, Stuart C.; Maggs, Jacqueline A.; Ketheesan, Natkunam; Norton, Robert; LaBrooy, Justin

    2005-01-01

    Gram-negative infection alters phagocytic cell function; hence, it could affect phagocytic uptake of inorganic colloids by these cells. Neutrophil and monocyte uptake of technetium 99m stannous colloid ( 99m Tc SnC) in whole blood was measured in 10 patients with gram-negative infection (Burkholderia pseudomallei) and 7 controls. Mean uptake per individual neutrophil was reduced in infection. Uptake per monocyte was not significantly different. Blood from six normal individuals was incubated with lysed B. pseudomallei and colloid, which showed reduced neutrophil uptake, but increased monocyte uptake. These results indicate that uptake of 99m Tc SnC stannous colloid can be used to measure alteration in phagocytic cell function. They suggest that infection with B. pseudomallei is associated with reduced phagocytosis by individual neutrophils, possibly through toxic effects of bacterial products. This could have immunopathogenic consequences for this gram-negative infection and may explain why it responds to granulocyte colony-stimulating factor

  18. Curative Treatment of Severe Gram-Negative Bacterial Infections by a New Class of Antibiotics Targeting LpxC

    Nadine Lemaître

    2017-07-01

    Full Text Available The infectious diseases caused by multidrug-resistant bacteria pose serious threats to humankind. It has been suggested that an antibiotic targeting LpxC of the lipid A biosynthetic pathway in Gram-negative bacteria is a promising strategy for curing Gram-negative bacterial infections. However, experimental proof of this concept is lacking. Here, we describe our discovery and characterization of a biphenylacetylene-based inhibitor of LpxC, an essential enzyme in the biosynthesis of the lipid A component of the outer membrane of Gram-negative bacteria. The compound LPC-069 has no known adverse effects in mice and is effective in vitro against a broad panel of Gram-negative clinical isolates, including several multiresistant and extremely drug-resistant strains involved in nosocomial infections. Furthermore, LPC-069 is curative in a murine model of one of the most severe human diseases, bubonic plague, which is caused by the Gram-negative bacterium Yersinia pestis. Our results demonstrate the safety and efficacy of LpxC inhibitors as a new class of antibiotic against fatal infections caused by extremely virulent pathogens. The present findings also highlight the potential of LpxC inhibitors for clinical development as therapeutics for infections caused by multidrug-resistant bacteria.

  19. Curative Treatment of Severe Gram-Negative Bacterial Infections by a New Class of Antibiotics Targeting LpxC.

    Lemaître, Nadine; Liang, Xiaofei; Najeeb, Javaria; Lee, Chul-Jin; Titecat, Marie; Leteurtre, Emmanuelle; Simonet, Michel; Toone, Eric J; Zhou, Pei; Sebbane, Florent

    2017-07-25

    The infectious diseases caused by multidrug-resistant bacteria pose serious threats to humankind. It has been suggested that an antibiotic targeting LpxC of the lipid A biosynthetic pathway in Gram-negative bacteria is a promising strategy for curing Gram-negative bacterial infections. However, experimental proof of this concept is lacking. Here, we describe our discovery and characterization of a biphenylacetylene-based inhibitor of LpxC, an essential enzyme in the biosynthesis of the lipid A component of the outer membrane of Gram-negative bacteria. The compound LPC-069 has no known adverse effects in mice and is effective in vitro against a broad panel of Gram-negative clinical isolates, including several multiresistant and extremely drug-resistant strains involved in nosocomial infections. Furthermore, LPC-069 is curative in a murine model of one of the most severe human diseases, bubonic plague, which is caused by the Gram-negative bacterium Yersinia pestis Our results demonstrate the safety and efficacy of LpxC inhibitors as a new class of antibiotic against fatal infections caused by extremely virulent pathogens. The present findings also highlight the potential of LpxC inhibitors for clinical development as therapeutics for infections caused by multidrug-resistant bacteria. IMPORTANCE The rapid spread of antimicrobial resistance among Gram-negative bacilli highlights the urgent need for new antibiotics. Here, we describe a new class of antibiotics lacking cross-resistance with conventional antibiotics. The compounds inhibit LpxC, a key enzyme in the lipid A biosynthetic pathway in Gram-negative bacteria, and are active in vitro against a broad panel of clinical isolates of Gram-negative bacilli involved in nosocomial and community infections. The present study also constitutes the first demonstration of the curative treatment of bubonic plague by a novel, broad-spectrum antibiotic targeting LpxC. Hence, the data highlight the therapeutic potential of Lpx

  20. Curative Treatment of Severe Gram-Negative Bacterial Infections by a New Class of Antibiotics Targeting LpxC

    Lemaître, Nadine; Liang, Xiaofei; Najeeb, Javaria; Lee, Chul-Jin; Titecat, Marie; Leteurtre, Emmanuelle; Simonet, Michel; Toone, Eric J.; Zhou, Pei; Sebbane, Florent; Nacy, Carol A.

    2017-07-25

    ABSTRACT

    The infectious diseases caused by multidrug-resistant bacteria pose serious threats to humankind. It has been suggested that an antibiotic targeting LpxC of the lipid A biosynthetic pathway in Gram-negative bacteria is a promising strategy for curing Gram-negative bacterial infections. However, experimental proof of this concept is lacking. Here, we describe our discovery and characterization of a biphenylacetylene-based inhibitor of LpxC, an essential enzyme in the biosynthesis of the lipid A component of the outer membrane of Gram-negative bacteria. The compound LPC-069 has no known adverse effects in mice and is effectivein vitroagainst a broad panel of Gram-negative clinical isolates, including several multiresistant and extremely drug-resistant strains involved in nosocomial infections. Furthermore, LPC-069 is curative in a murine model of one of the most severe human diseases, bubonic plague, which is caused by the Gram-negative bacteriumYersinia pestis. Our results demonstrate the safety and efficacy of LpxC inhibitors as a new class of antibiotic against fatal infections caused by extremely virulent pathogens. The present findings also highlight the potential of LpxC inhibitors for clinical development as therapeutics for infections caused by multidrug-resistant bacteria.

    IMPORTANCEThe rapid spread of antimicrobial resistance among Gram-negative bacilli highlights the urgent need for new antibiotics. Here, we describe a new class of antibiotics lacking cross-resistance with conventional antibiotics. The compounds inhibit LpxC, a key enzyme in the lipid A biosynthetic pathway in Gram-negative bacteria, and are activein vitroagainst a broad panel of clinical isolates of Gram-negative bacilli involved in nosocomial and community infections. The present study also constitutes the first demonstration of the curative treatment of bubonic plague by a novel, broad

  1. Complicated urinary tract infections: practical solutions for the treatment of multiresistant Gram-negative bacteria.

    Pallett, Ann; Hand, Kieran

    2010-11-01

    Resistance in Gram-negative bacteria has been increasing, particularly over the last 6 years. This is mainly due to the spread of strains producing extended-spectrum β-lactamases (ESBLs) such as CTX-M enzymes or AmpC β-lactamases. Many of the isolates producing these enzymes are also resistant to trimethoprim, quinolones and aminoglycosides, often due to plasmid co-expression of other resistance mechanisms. CTX-M-producing Escherichia coli often occurs in the community and as E. coli is one of the commonest organisms causing urinary tract infections (UTIs) the choice of agents to treat these infections is diminishing. Novel combinations of antibiotics are being used in the community and broad-spectrum agents such as carbapenems are being used increasingly as empirical treatment for severe infections. Of particular concern therefore are reports in the UK of organisms that produce carbapenemases. As resistance is becoming more widespread, prudent use of antimicrobials is imperative and, as asymptomatic bacteriuria is typically benign in the elderly, antibiotics should not be prescribed without clinical signs of UTI. The use of antibiotics as suppressive therapy or long-term prophylaxis may no longer be defensible.

  2. Controlling the spread of carbapenemase-producing Gram-negatives: therapeutic approach and infection control.

    Carmeli, Y; Akova, M; Cornaglia, G; Daikos, G L; Garau, J; Harbarth, S; Rossolini, G M; Souli, M; Giamarellou, H

    2010-02-01

    Although the rapid spread of carbapenemase-producing Gram-negatives (CPGNs) is providing the scientific community with a great deal of information about the molecular epidemiology of these enzymes and their genetic background, data on how to treat multidrug-resistant or extended drug-resistant carbapenemase-producing Enterobacteriaceae and how to contain their spread are still surprisingly limited, in spite of the rapidly increasing prevalence of these organisms and of their isolation from patients suffering from life-threatening infections. Limited clinical experience and several in vitro synergy studies seem to support the view that antibiotic combinations should be preferred to monotherapies. But, in light of the data available to date, it is currently impossible to quantify the real advantage of drug combinations in the treatment of these infections. Comprehensive clinical studies of the main therapeutic options, broken down by pathogen, enzyme and clinical syndrome, are definitely lacking and, as carbapenemases keep spreading, are urgently needed. This spread is unveiling the substantial unpreparedness of European public health structures to face this worrisome emergency, although experiences from different countries-chiefly Greece and Israel-have shown that CPGN transmission and cross-infection can cause a substantial threat to the healthcare system. This unpreparedness also affects the treatment of individual patients and infection control policies, with dramatic scarcities of both therapeutic options and infection control measures. Although correct implementation of such measures is presumably cumbersome and expensive, the huge clinical and public health problems related to CPGN transmission, alongside the current scarcity of therapeutic options, seem to fully justify this choice.

  3. [Antimicrobial therapy in severe infections with multidrug-resistant Gram-negative bacterias].

    Duszyńska, Wiesława

    2010-01-01

    Multidrug-resistant Gram-negative bacteria pose a serious and rapidly emerging threat to patients in healthcare settings, and are especially prevalent and problematic in intensive therapy units. Recently, the emergence of pandrug-resistance in Gram-negative bacteria poses additional concerns. This review examines the clinical impact and epidemiology of multidrug-resistant Gram-negative bacteria as a cause of increased morbidity and mortality among ITU patients. Beta-lactamases, cephalosporinases and carbapenemases play the most important role in resistance to antibiotics. Despite the tendency to increased resistance, carbapenems administered by continuous infusion remain the most effective drugs in severe sepsis. Drug concentration monitoring, albeit rarely used in practice, is necessary to ensure an effective therapeutic effect.

  4. Epidemiology of infections caused by multiresistant gram-negatives: ESBLs, MBLs, panresistant strains.

    Rossolini, Gian Maria; Mantengoli, Elisabetta; Docquier, Jean-Denis; Musmanno, Rosa Anna; Coratza, Grazietta

    2007-07-01

    Microbial drug resistance is a growing problem of global magnitude. In gram-negative pathogens, the most important resistance problems are encountered in Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter, with increasing trends observed for all major anti-gram-negative agents (beta-lactams, fluoroquinolones and aminoglycosides). A matter of major concern is the emergence of new beta-lactamases capable of degrading the expanded-spectrum cephalosporins and/or carbapenems, such as the extended-spectrum beta-lactamases (ESBLs) and the carbapenemases. These beta-lactamase genes are often associated with resistance determinants to non-beta-lactam agents (e.g. aminoglycosides and fluoroquinolones), and strains producing ESBLs or carbapenemases often exhibit complex multidrug resistant phenotypes and sometimes are panresistant. The problem is worsened by the dearth of new agents active on multidrug-resistant Gram-negatives in the pipeline. The importance to develop better strategies to control resistance is underscored.

  5. Intravenous Colistin Use for Multidrug-Resistant Gram-Negative Infections in Pediatric Patients.

    Karaaslan, Ayşe; Çağan, Eren; Kadayifci, Eda Kepenekli; Atıcı, Serkan; Akkoç, Gülşen; Yakut, Nurhayat; Demir, Sevliya Öcal; Soysal, Ahmet; Bakır, Mustafa

    2016-11-01

    The emergence of infections due to multidrug-resistant Gram-negative bacilli (MDR-GNB) has led to the resurrection of colistin use. The data on colistin use and drug-related adverse effects in children are scarce. In this study, we aimed to evaluate the clinical efficacy and safety of colistin use in critically ill pediatric patients. This study has a retrospective study design. Sixty-one critically ill children were identified through the department's patient files archive during the period from January 2011 to November 2014. Twenty-nine females and thirty-two males with a mean±standard deviation (SD) age of 61±9 months (range 0-216, median 12 months) received IV colistin due to MDR-GNB infections. Bacteremia (n=23, 37.7%) was the leading diagnosis, followed by pneumonia (n=19, 31%), clinical sepsis (n=7, 11.4%), wound infection (n=6, 9.8%), urinary tract infection (n=5, 8.1%) and meningitis (n=1, 1.6%). All of the isolates were resistant to carbapenems; however, all were susceptible to colistin. The isolated microorganisms in decreasing order of frequency were: Acinetobacter baumanni (n=27, 44.2%), Pseudomonas aeruginosa (n=17, 27.8%), Klebsiella pneumoniae (n=6, 9.8%), K. pneumoniae and Stenotrophomonas maltophilia (n=1, 1.6%), K. pneumoniae and A. baumanni (n=1, 1.6%), K. oxytoca (n=1, 1.6%) and Enterobacter cloacae (n=1, 1.6%). In seven patients, no microorganisms were detected; however, five of these patients were colonized by carbapenem-resistant K. pneumoniae. The mean duration of colistin therapy was 12 days (range 3-45). Colistin was administered concomitantly with one of the following antibiotics: carbapenem (n=50, %82), ampicillin-sulbactam (n=5, 8%), quinolones (n=5, 8%), rifampicin (n=1, 1.6%). Carbapenem was the most frequently used antibiotic. Nephrotoxicity was observed in only 1 patient, and we did not observe neurotoxicity in this study. All the patients received intravenous colistin (colisthimethate) at a dosage of 5 mg/kg daily by dividing it

  6. Intravenous Colistin Use for Multidrug-Resistant Gram-Negative Infections in Pediatric Patients

    Ayşe Karaaslan

    2016-12-01

    Full Text Available Background: The emergence of infections due to multidrug-resistant Gram-negative bacilli (MDR-GNB has led to the resurrection of colistin use. The data on colistin use and drug-related adverse effects in children are scarce. Aims: In this study, we aimed to evaluate the clinical efficacy and safety of colistin use in critically ill pediatric patients. Study Design: This study has a retrospective study design. Methods: Sixty-one critically ill children were identified through the department’s patient files archive during the period from January 2011 to November 2014. Results: Twenty-nine females and thirty-two males with a mean±standard deviation (SD age of 61±9 months (range 0-216, median 12 months received IV colistin due to MDR-GNB infections. Bacteremia (n=23, 37.7% was the leading diagnosis, followed by pneumonia (n=19, 31%, clinical sepsis (n=7, 11.4%, wound infection (n=6, 9.8%, urinary tract infection (n=5, 8.1% and meningitis (n=1, 1.6%. All of the isolates were resistant to carbapenems; however, all were susceptible to colistin. The isolated microorganisms in decreasing order of frequency were: Acinetobacter baumanni (n=27, 44.2%, Pseudomonas aeruginosa (n=17, 27.8%, Klebsiella pneumoniae (n=6, 9.8%, K. pneumoniae and Stenotrophomonas maltophilia (n=1, 1.6%, K. pneumoniae and A. baumanni (n=1, 1.6%, K. oxytoca (n=1, 1.6% and Enterobacter cloacae (n=1, 1.6%. In seven patients, no microorganisms were detected; however, five of these patients were colonized by carbapenem-resistant K. pneumoniae. The mean duration of colistin therapy was 12 days (range 3-45. Colistin was administered concomitantly with one of the following antibiotics: carbapenem (n=50, %82, ampicillin-sulbactam (n=5, 8%, quinolones (n=5, 8%, rifampicin (n=1, 1.6%. Carbapenem was the most frequently used antibiotic. Nephrotoxicity was observed in only 1 patient, and we did not observe neurotoxicity in this study. All the patients received intravenous colistin

  7. Association between preterm labor and genitourinary tract infections caused by Trichomonas vaginalis, Mycoplasma hominis, Gram-negative bacilli, and coryneforms

    Alaa El-Dien M.S. Hosny

    2017-09-01

    Conclusion: Our study demonstrated that the main risk factors for PTL were vaginal infection with T. vaginalis, M. hominis, coryneforms, and Gram-negative bacilli, and their determinants (vaginal pH>5, positive whiff test, heavy vaginal bleeding. Both young age (< 20 years and poor obstetric history were also the risk factors. Therefore, screening for genitourinary tract infections is strongly recommended to be included in prenatal care.

  8. Community-acquired multidrug-resistant Gram-negative bacterial infective endocarditis.

    Naha, Sowjanya; Naha, Kushal; Acharya, Vasudev; Hande, H Manjunath; Vivek, G

    2014-08-05

    We describe two cases of bacterial endocarditis secondary to multidrug-resistant Gram-negative organisms. In both cases, the diagnosis was made in accordance with the modified Duke's criteria and confirmed by histopathological analysis. Furthermore, in both instances there were no identifiable sources of bacteraemia and no history of contact with hospital or other medical services prior to the onset of symptoms. The patients were managed in similar fashion with prolonged broad-spectrum antibiotic therapy and surgical intervention and made complete recoveries. These cases highlight Gram-negative organisms as potential agents for endocarditis, as well as expose the dissemination of such multidrug-resistant bacteria into the community. The application of an integrated medical and surgical approach and therapeutic dilemmas encountered in managing these cases are described. 2014 BMJ Publishing Group Ltd.

  9. Long-term outcome of acute prosthetic joint infections due to gram-negative bacilli treated with retention of prosthesis.

    Jaén, N; Martínez-Pastor, J C; Muñoz-Mahamud, E; García-Ramiro, S; Bosch, J; Mensa, J; Soriano, A

    2012-09-01

    To update the clinical information of the 47 patients with a prosthetic joint infection due to Gram-negative bacilli included in a previous study and to reassess the predictors of failure after a longer follow-up. Using the electronic files of our hospital, all the information regarding readmissions to the hospital, new surgical procedures and the reason for the new surgery (infection, aseptic loosening), and the last visit in the hospital were registered. The medical chart of the 35 patients that were considered in remission in the previous publication was reviewed. In 30 patients no clinical evidence of failure was detected and no additional surgery on the previously infected prosthesis was necessary and they were considered in long-term remission. In 5 cases a late complication was identified. One case had a reinfection due to coagulase-negative staphylococci after 22 months from the open debridement and required a 2-stage revision surgery. The other 4 cases developed an aseptic loosening and it was necessary to perform a 1-stage exchange. Receiving a fluoroquinolone when all the Gram-negatives involved in the infection were susceptible to fluoroquinolones was the only factor associated with remission in the univariate analysis (p=0.002). After a long-term follow-up, our results support the importance of using fluoroquinolones in acute PJI due to Gram-negative bacilli.

  10. Associations Between Enteral Colonization With Gram-Negative Bacteria and Intensive Care Unit-Acquired Infections and Colonization of the Respiratory Tract.

    Frencken, Jos F; Wittekamp, Bastiaan H J; Plantinga, Nienke L; Spitoni, Cristian; van de Groep, Kirsten; Cremer, Olaf L; Bonten, Marc J M

    2018-02-01

    Enteral and respiratory tract colonization with gram-negative bacteria may lead to subsequent infections in critically ill patients. We aimed to clarify the interdependence between gut and respiratory tract colonization and their associations with intensive care unit (ICU)-acquired infections in patients receiving selective digestive tract decontamination (SDD). Colonization status of the rectum and respiratory tract was determined using twice-weekly microbiological surveillance in mechanically ventilated subjects receiving SDD between May 2011 and June 2015 in a tertiary medical-surgical ICU in the Netherlands. Acquisition of infections was monitored daily by dedicated observers. Marginal structural models were used to determine the associations between gram-negative rectal colonization and respiratory tract colonization, ICU-acquired gram-negative infection, and ICU-acquired gram-negative bacteremia. Among 2066 ICU admissions, 1157 (56.0%) ever had documented gram-negative carriage in the rectum during ICU stay. Cumulative incidences of ICU-acquired gram-negative infection and bacteremia were 6.0% (n = 124) and 2.1% (n = 44), respectively. Rectal colonization was an independent risk factor for both respiratory tract colonization (cause-specific hazard ratio [CSHR], 2.93 [95% confidence interval {CI}, 2.02-4.23]) and new gram-negative infection in the ICU (CSHR, 3.04 [95% CI, 1.99-4.65]). Both rectal and respiratory tract colonization were associated with bacteremia (CSHR, 7.37 [95% CI, 3.25-16.68] and 2.56 [95% CI, 1.09-6.03], respectively). Similar associations were observed when Enterobacteriaceae and glucose nonfermenting gram-negative bacteria were analyzed separately. Gram-negative rectal colonization tends to be stronger associated with subsequent ICU-acquired gram-negative infections than gram-negative respiratory tract colonization. Gram-negative rectal colonization seems hardly associated with subsequent ICU-acquired gram-negative respiratory tract

  11. Altered glucose kinetics in diabetic rats during Gram-negative infection

    Lang, C.H.; Dobrescu, C.; Bagby, G.J.; Spitzer, J.J.

    1987-01-01

    The present study examined the purported exacerbating effect of sepsis on glucose metabolism in diabetes. Diabetes was induced in rats by an intravenous injection of 70 or 45 mg/kg streptozotocin. The higher dose produced severe diabetes, whereas the lower dose of streptozotocin produced a miler, latent diabetes. After a chronic diabetic state had developed for 4 wk, rats had catheters implanted and sepsis induced by intraperitoneal injections of live Escherichia coli. After 24 h of sepsis the blood glucose concentration was unchanged in nondiabetics and latent diabetics, but glucose decreased from 15 to 8 mM in the septic severe diabetic group. This decrease in blood glucose was not accompanied by alterations in the plasma insulin concentration. Glucose turnover, assessed by the constant intravenous infusion of [6- 3 H]- and [U- 14 C]glucose, was elevated in the severe diabetic group, compared with either latent diabetics or nondiabetics. Sepsis increased the rate of glucose disappearance in nondiabetic rats but had no effect in either group of diabetic animals. Sepsis also failed to alter the insulinogenic index, used to estimate the insulin secretory capacity, in diabetic rats. Thus the present study suggests that the imposition of nonlethal Gram-negative sepsis on severe diabetic animals does not further impair glucose homeostasis and that the milder latent diabetes was not converted to a more severe diabetic state by the septic challenge

  12. Incidence of carbapenem resistant nonfermenting gram negative bacilli from patients with respiratory infections in the intensive care units

    Gladstone P

    2005-01-01

    Full Text Available Resistance to carbapenems is commonly seen in nonfermenting gram negative bacilli (NFGNB. We document herein the prevalence of carbapenem resistance in NFGNB isolated from patients with respiratory tract infections in the intensive care units (ICUs. A total of 460 NFGNB were isolated from 606 endotracheal aspirate specimens during January through December 2003, of which 56 (12.2% were found to be resistant to imipenem and meropenem. Of these, 24 (42.8% were Pseudomonas aeruginosa , 8 (14.2% were Acinetobacter spp. and 24 (42.8% were other NFGNB. Stringent protocols such as antibiotic policies and resistance surveillance programs are mandatory to curb these bacteria in ICU settings.

  13. Gram-negative prosthetic joint infection: outcome of a debridement, antibiotics and implant retention approach. A large multicentre study.

    Rodríguez-Pardo, D; Pigrau, C; Lora-Tamayo, J; Soriano, A; del Toro, M D; Cobo, J; Palomino, J; Euba, G; Riera, M; Sánchez-Somolinos, M; Benito, N; Fernández-Sampedro, M; Sorli, L; Guio, L; Iribarren, J A; Baraia-Etxaburu, J M; Ramos, A; Bahamonde, A; Flores-Sánchez, X; Corona, P S; Ariza, J

    2014-11-01

    We aim to evaluate the epidemiology and outcome of gram-negative prosthetic joint infection (GN-PJI) treated with debridement, antibiotics and implant retention (DAIR), identify factors predictive of failure, and determine the impact of ciprofloxacin use on prognosis. We performed a retrospective, multicentre, observational study of GN-PJI diagnosed from 2003 through to 2010 in 16 Spanish hospitals. We define failure as persistence or reappearance of the inflammatory joint signs during follow-up, leading to unplanned surgery or repeat debridement>30 days from the index surgery related death, or suppressive antimicrobial therapy. Parameters predicting failure were analysed with a Cox regression model. A total of 242 patients (33% men; median age 76 years, interquartile range (IQR) 68-81) with 242 episodes of GN-PJI were studied. The implants included 150 (62%) hip, 85 (35%) knee, five (2%) shoulder and two (1%) elbow prostheses. There were 189 (78%) acute infections. Causative microorganisms were Enterobacteriaceae in 78%, Pseudomonas spp. in 20%, and other gram-negative bacilli in 2%. Overall, 19% of isolates were ciprofloxacin resistant. DAIR was used in 174 (72%) cases, with an overall success rate of 68%, which increased to 79% after a median of 25 months' follow-up in ciprofloxacin-susceptible GN-PJIs treated with ciprofloxacin. Ciprofloxacin treatment exhibited an independent protective effect (adjusted hazard ratio (aHR) 0.23; 95% CI, 0.13-0.40; pInfection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

  14. Nonfermenting gram-negative bacilli infections in a tertiary care hospital in Kolar, Karnataka

    A Malini

    2009-01-01

    Conclusion : P. aeruginosa and A. baumannii were the common NFGNB isolated in our study from patients of, urinary tract infection, bacteremia, surgical site infections, and ventilator associated pneumonia. P. aeruginosa showed good sensitivity to imipenem, amikacin, and cefoperazone while A. baumannii showed good sensitivity to imipenem and piperacillin.

  15. Outcome of Transplantation Using Organs From Donors Infected or Colonized With Carbapenem-Resistant Gram-Negative Bacteria.

    Mularoni, A; Bertani, A; Vizzini, G; Gona, F; Campanella, M; Spada, M; Gruttadauria, S; Vitulo, P; Conaldi, P; Luca, A; Gridelli, B; Grossi, P

    2015-10-01

    Donor-derived infections due to multidrug-resistant bacteria are a growing problem in solid organ transplantation, and optimal management options are not clear. In a 2-year period, 30/214 (14%) recipients received an organ from 18/170 (10.5%) deceased donors with infection or colonization caused by a carbapenem-resistant gram-negative bacteria that was unknown at the time of transplantation. Among them, 14/30 recipients (47%) received a transplant from a donor with bacteremia or with infection/colonization of the transplanted organ and were considered at high risk of donor-derived infection transmission. The remaining 16/30 (53%) recipients received an organ from a nonbacteremic donor with colonization of a nontransplanted organ and were considered at low risk of infection transmission. Proven transmission occurred in 4 of the 14 high-risk recipients because donor infection was either not recognized, underestimated, or not communicated. These recipients received late, short or inappropriate posttransplant antibiotic therapy. Transmission did not occur in high-risk recipients who received appropriate and prompt antibiotic therapy for at least 7 days. The safe use of organs from donors with multidrug-resistant bacteria requires intra- and inter-institutional communication to allow appropriate management and prompt treatment of recipients in order to avoid transmission of infection. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  16. Orthopedic infections caused by obligatory anaerobic Gram-negative rods: report of two cases.

    Kierzkowska, Marta; Pedzisz, Piotr; Babiak, Ireneusz; Janowicz, Jakub; Kulig, Mateusz; Majewska, Anna; Sawicka-Grzelak, Anna; Mlynarczyk, Grazyna

    2017-10-01

    Anaerobic bone and joint infections are uncommon, although the number of anaerobic infections is presumably underestimated because of difficulties with isolation and identification of obligate anaerobes. This study describes two cases of complicated Bacteroides fragilis peri-implant infection of the lumbar spine, infection of the hip and osteomyelitis. Bacteria were identified with the use of a mass spectrometer, VITEK MS system. Drug susceptibility was performed with the use of E-test. The EUCAST breakpoints were used for interpretation with B. fragilis ATCC 25285 as a control. In the two described cases clinical samples were collected for microbiological examination intraoperatively and simultaneously empirical treatment was applied. B. fragilis was isolated in monoculture or in a combination with other bacteria. The treatment was continued according to the susceptibility tests. In a case one clindamycin failure was observed and clindamycin resistance of the isolate was likely due to inadequate time of therapy. Difficulties in collecting an adequate samples and culturing anaerobic bacteria cause that not all infections are properly recognized. In a successful therapy, identification and determination of the susceptibility of the pathogen are essential as well as an appropriate surgical debridement.

  17. Central venous catheter-related bloodstream infections in cancer patients

    Butt, T.; Afzal, R.K.; Ahmad, R.N.; Hussain, I.; Anwar, M.

    2004-01-01

    Objective: To determine the frequency of central venous catheter-related bloodstream infections (CR-BSI) in cancer patients and the antimicrobial susceptibility pattern of the isolates. Subjects and Methods: Cancer patients requiring short or long-term central venous catheterization at the time of admission or thereafter were included. Catheter tips on removal were cultured quantitatively; specimens of blood and pus were cultured qualitatively. Isolates were identified and antimicrobial susceptibility testing was performed by standard techniques. Results: Eighty-nine patients were included in the study. The frequency of CR-BSI was 17%. Out of the 19 organisms isolated, 10 (53%) were Gram-positive cocci, 8 (42%) were Gram-negative rods and 1 (5%) was a fungus. Coagulase negative staphylococci (27%) were the predominant pathogens. Among the staphylococci, 46% of the isolates were methicillin-resistant. All Gram-positive isolates were susceptive to glycopeptides. Gram-negative rods were resistant to most of the commonly used antimicrobial groups. Conclusion: Central venous catheter is an important source of bloodstream infections in cancer patients. Most of the infections are caused by Gram-positive cocci. Rigorous infection control measures and continuous surveillance is required to curb the frequency of these infections. (author)

  18. Antimicrobial susceptibility of Gram-negative bacteria causing intra-abdominal infections in China: SMART China 2011.

    Zhang, Hui; Yang, Qiwen; Xiao, Meng; Chen, Minjun; Badal, Robert E; Xu, Yingchun

    2014-01-01

    The Study for Monitoring Antimicrobial Resistance Trends program monitors the activity of antibiotics against aerobic and facultative Gram-negative bacilli (GNBs) from intra-abdominal infections (IAIs) in patients worldwide. In 2011, 1 929 aerobic and facultative GNBs from 21 hospitals in 16 cities in China were collected. All isolates were tested using a panel of 12 antimicrobial agents, and susceptibility was determined following the Clinical Laboratory Standards Institute guidelines. Among the Gram-negative pathogens causing IAIs, Escherichia coli (47.3%) was the most commonly isolated, followed by Klebsiella pneumoniae (17.2%), Pseudomonas aeruginosa (10.1%), and Acinetobacter baumannii (8.3%). Enterobacteriaceae comprised 78.8% (1521/1929) of the total isolates. Among the antimicrobial agents tested, ertapenem and imipenem were the most active agents against Enterobacteriaceae, with susceptibility rates of 95.1% and 94.4%, followed by amikacin (93.9%) and piperacillin/tazobactam (87.7%). Susceptibility rates of ceftriaxone, cefotaxime, ceftazidime, and cefepime against Enterobacteriaceae were 38.3%, 38.3%, 61.1%, and 50.8%, respectively. The leastactive agent against Enterobacteriaceae was ampicillin/sulbactam (25.9%). The extended-spectrum β-lactamase (ESBL) rates among E. coli, K. pneumoniae, Klebsiella oxytoca, and Proteus mirabilis were 68.8%, 38.1%, 41.2%, and 57.7%, respectively. Enterobacteriaceae were the major pathogens causing IAIs, and the most active agents against the study isolates (including those producing ESBLs) were ertapenem, imipenem, and amikacin. Including the carbapenems, most agents exhibited reduced susceptibility against ESBL-positive and multidrug-resistant isolates.

  19. Antimicrobial resistance predicts death in Tanzanian children with bloodstream infections: a prospective cohort study

    Msangi Viola

    2007-05-01

    Full Text Available Abstract Background Bloodstream infection is a common cause of hospitalization, morbidity and death in children. The impact of antimicrobial resistance and HIV infection on outcome is not firmly established. Methods We assessed the incidence of bloodstream infection and risk factors for fatal outcome in a prospective cohort study of 1828 consecutive admissions of children aged zero to seven years with signs of systemic infection. Blood was obtained for culture, malaria microscopy, HIV antibody test and, when necessary, HIV PCR. We recorded data on clinical features, underlying diseases, antimicrobial drug use and patients' outcome. Results The incidence of laboratory-confirmed bloodstream infection was 13.9% (255/1828 of admissions, despite two thirds of the study population having received antimicrobial therapy prior to blood culture. The most frequent isolates were klebsiella, salmonellae, Escherichia coli, enterococci and Staphylococcus aureus. Furthermore, 21.6% had malaria and 16.8% HIV infection. One third (34.9% of the children with laboratory-confirmed bloodstream infection died. The mortality rate from Gram-negative bloodstream infection (43.5% was more than double that of malaria (20.2% and Gram-positive bloodstream infection (16.7%. Significant risk factors for death by logistic regression modeling were inappropriate treatment due to antimicrobial resistance, HIV infection, other underlying infectious diseases, malnutrition and bloodstream infection caused by Enterobacteriaceae, other Gram-negatives and candida. Conclusion Bloodstream infection was less common than malaria, but caused more deaths. The frequent use of antimicrobials prior to blood culture may have hampered the detection of organisms susceptible to commonly used antimicrobials, including pneumococci, and thus the study probably underestimates the incidence of bloodstream infection. The finding that antimicrobial resistance, HIV-infection and malnutrition predict fatal

  20. The Role of Adjunctive Therapies in Septic Shock by Gram Negative MDR/XDR Infections.

    Busani, Stefano; Roat, Erika; Serafini, Giulia; Mantovani, Elena; Biagioni, Emanuela; Girardis, Massimo

    2017-01-01

    Patients with septic shock by multidrug resistant microorganisms (MDR) are a specific sepsis population with a high mortality risk. The exposure to an initial inappropriate empiric antibiotic therapy has been considered responsible for the increased mortality, although other factors such as immune-paralysis seem to play a pivotal role. Therefore, beyond conventional early antibiotic therapy and fluid resuscitation, this population may benefit from the use of alternative strategies aimed at supporting the immune system. In this review we present an overview of the relationship between MDR infections and immune response and focus on the rationale and the clinical data available on the possible adjunctive immunotherapies, including blood purification techniques and different pharmacological approaches.

  1. The Role of Adjunctive Therapies in Septic Shock by Gram Negative MDR/XDR Infections

    Stefano Busani

    2017-01-01

    Full Text Available Patients with septic shock by multidrug resistant microorganisms (MDR are a specific sepsis population with a high mortality risk. The exposure to an initial inappropriate empiric antibiotic therapy has been considered responsible for the increased mortality, although other factors such as immune-paralysis seem to play a pivotal role. Therefore, beyond conventional early antibiotic therapy and fluid resuscitation, this population may benefit from the use of alternative strategies aimed at supporting the immune system. In this review we present an overview of the relationship between MDR infections and immune response and focus on the rationale and the clinical data available on the possible adjunctive immunotherapies, including blood purification techniques and different pharmacological approaches.

  2. Infection with multidrug-resistant gram-negative bacteria in a pediatric oncology intensive care unit: risk factors and outcomes.

    Costa, Patrícia de Oliveira; Atta, Elias Hallack; Silva, André Ricardo Araújo da

    2015-01-01

    This study aimed at evaluating the predictors and outcomes associated with multidrug-resistant gram-negative bacterial (MDR-GNB) infections in an oncology pediatric intensive care unit (PICU). Data were collected relating to all episodes of GNB infection that occurred in a PICU between January of 2009 and December of 2012. GNB infections were divided into two groups for comparison: (1) infections attributed to MDR-GNB and (2) infections attributed to non-MDR-GNB. Variables of interest included age, gender, presence of solid tumor or hematologic disease, cancer status, central venous catheter use, previous Pseudomonas aeruginosa infection, healthcare-associated infection, neutropenia in the preceding 7 days, duration of neutropenia, length of hospital stay before ICU admission, length of ICU stay, and the use of any of the following in the previous 30 days: antimicrobial agents, corticosteroids, chemotherapy, or radiation therapy. Other variables included initial appropriate antimicrobial treatment, definitive inadequate antimicrobial treatment, duration of appropriate antibiotic use, time to initiate adequate antibiotic therapy, and the 7- and 30-day mortality. Multivariate logistic regression analyses showed significant relationships between MDR-GNB and hematologic diseases (odds ratio [OR] 5.262; 95% confidence interval [95% CI] 1.282-21.594; p=0.021) and healthcare-associated infection (OR 18.360; 95% CI 1.778-189.560; p=0.015). There were significant differences between MDR-GNB and non-MDR-GNB patients for the following variables: inadequate initial empirical antibiotic therapy, time to initiate adequate antibiotic treatment, and inappropriate antibiotic therapy. Hematologic malignancy and healthcare-associated infection were significantly associated with MDR-GNB infection in this sample of pediatric oncology patients. Copyright © 2015 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  3. Resistance to oral antibiotics in 4569 Gram-negative rods isolated from urinary tract infection in children.

    Calzi, Anna; Grignolo, Sara; Caviglia, Ilaria; Calevo, Maria Grazia; Losurdo, Giuseppe; Piaggio, Giorgio; Bandettini, Roberto; Castagnola, Elio

    2016-09-01

    To investigate antibiotic resistance among pathogens isolated from urines in a tertiary care children's hospital in Italy. Retrospective analysis of prospectively collected data on antibiotic susceptibility of Gram-negatives isolated from urines at the Istituto Giannina Gaslini, Genoa - Italy from 2007 to 2014. Antibiotic susceptibility was evaluated. By means of CLSI criteria from 2007 to 2010, while from 2011 EUCAST criteria were adopted. Data on susceptibility to amoxicillin-clavulanate, co-trimoxazole, cefuroxime, nitrofurantoin, fosfomycin and ciprofloxacin were evaluated for Escherichia coli, while for other Enterobacteriaceae data were collected for amoxicillin-clavulanate, co-trimoxazole and ciprofloxacin and for ciprofloxacin against Pseudomonas aeruginosa. Univariate and multivariable analyses were performed for risk factors associated with resistance. A total of 4596 Gram-negative strains were observed in 3364 patients. A significant increase in the proportion of resistant strains was observed for E.coli against amoxicillin-clavulanate, cefuroxime and ciprofloxacin and for others Enterobacteriaceae against co-trimoxazole and ciprofloxacin. Resistance to nitrofurantoin and fosfomycin was very infrequent in E.coli. Logistic regression analysis showed that repeated episode of urinary tract infections was a risk factor for E.coli resistance to amoxicillin-clavulanate, co-trimoxazole and cefuroxime, while admission in one of the Units usually managing children with urinary tract malformations was significantly associated to resistance to amoxicillin-clavulanate and cefuroxime. In conclusion the present study shows an increase in antibiotic resistance in pediatric bacteria isolated from urines in children, especially in presence of repeated episodes and/or urinary tract malformations. This resistance is worrisome for beta-lactams and cotrimoxazole, and start to increase also for fluoroquinolones while nitrofurantoin and fosfomycin still could represent useful

  4. Catheter-related bloodstream infection.

    Goede, Matthew R; Coopersmith, Craig M

    2009-04-01

    Catheter-related bloodstream infections (CR-BSIs) are a common, frequently preventable complication of central venous catheterization. CR-BSIs can be prevented by strict attention to insertion and maintenance of central venous catheters and removing unneeded catheters as soon as possible. Antiseptic- or antibiotic-impregnated catheters are also an effective tool to prevent infections. The diagnosis of CR-BSI is made largely based on culture results. CR-BSIs should always be treated with antibiotics, and except in rare circumstances the infected catheter needs to be removed.

  5. Pink-pigmented non-fermentative gram-negative rods associated with human infections: a clinical and diagnostic challenge.

    Hogue, R; Graves, M; Moler, S; Janda, J M

    2007-06-01

    Over the past several decades, the appearance of pink-pigmented bacteria in clinical specimens has gone from being a microbiologic curiosity in the clinical laboratory to the recognition of these aerobic microorganisms as etiologic agents of human disease, most notably bloodstream infections. Advances in the fields of molecular taxonomy and phylogenetics indicate that at least four distinct genera and eight different species are associated with clinical infections in susceptible patient populations. However, these bacteria are slow growing and present multiple diagnostic challenges to the microbiology laboratory including culture, isolation, and identification to species rank. This article provides a current review of these unusual non-fermentative chromogenic bacteria including their disease spectrum, taxonomy, and laboratory identification. The review also highlights the pitfalls or shortcomings we currently have in our knowledge of these microbes and their disease-producing capabilities.

  6. Resistance among Gram-negative ESKAPE pathogens isolated from hospitalized patients with intra-abdominal and urinary tract infections in Latin American countries: SMART 2013–2015

    James A. Karlowsky

    2017-05-01

    Full Text Available Gram-negative ESKAPE pathogens (Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species are important etiologic agents of nosocomial infection that are frequently resistant to broad-spectrum antimicrobial agents. Gram-negative ESKAPE pathogens were collected from hospitalized patients in 11 Latin American countries from 2013 to 2015 as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART global surveillance program. In total, 2113 isolates from intra-abdominal infections (IAI and 970 isolates from urinary tract infections (UTI were tested against antimicrobial agents using standardized CLSI broth microdilution methodology. Of the agents tested, amikacin demonstrated the highest rates of susceptibility (% for K. pneumoniae (92.2, 92.3, Enterobacter spp. (97.5, 92.1, and P. aeruginosa (85.3, 75.2 isolates from both IAI and UTI, respectively. Ertapenem (68.5, 62.6 and imipenem (79.2, 75.9 showed substantially higher rates of susceptibility (% than other β-lactams, including piperacillin-tazobactam (35.9, 37.4 against ESBL-positive isolates of K. pneumoniae from IAI and UTI, respectively. Rates of susceptibility to all agents tested against A. baumannii were ≤30.9%. Gram-negative ESKAPE pathogens isolated from Latin America demonstrated compromised in vitro susceptibility to commonly prescribed broad-spectrum, parenteral antimicrobial agents. Continued surveillance is warranted. New antimicrobial agents with potent activity against Gram-negative ESKAPE pathogens are urgently needed.

  7. Doripenem: an expected arrival in the treatment of infections caused by multidrug-resistant Gram-negative pathogens.

    Poulakou, Garyphallia; Giamarellou, Helen

    2008-05-01

    Potent new drugs against multidrug-resistant Gram-negative bacteria, namely Pseudomonas aeruginosa and Acinetobacter spp. and pan-drug-resistant Klebsiella pneumoniae, which constitute an increasing medical threat, are almost absent from the future pharmaceutical pipeline. This drug evaluation focuses on the position of doripenem, a novel forthcoming carbapenem. Mechanisms of resistance and new drugs with anti-Gram-negative activity are also briefly reviewed. Literature search was performed for new carbapenems, new antibiotics, doripenem, metallo-beta-lactamase inhibitors, multidrug-resistant pathogens, antipseudomonal antibiotics and multidrug-resistant epidemiology. Doripenem possesses a broad spectrum of activity against Gram-negative bacteria, similar to that of meropenem, while retaining the spectrum of imipenem against Gram-positive pathogens. Against P. aeruginosa, doripenem exhibits rapid bactericidal activity with 2 - 4-fold lower MIC values, compared to meropenem. Exploitation of pharmacokinetic/pharmacodynamic applications could offer a treatment opportunity against strains exhibiting borderline resistance to doripenem. Stability against numerous beta-lactamases, low adverse event potential and more potent in vitro antibacterial activity against P. aeruginosa and A. baumanni compared to the existing carbapenems, are its principal features.

  8. Novel insights in preventing Gram-negative bacterial infection in cirrhotic patients: review on the effects of GM-CSF in maintaining homeostasis of the immune system.

    Xu, Dong; Zhao, Manzhi; Song, Yuhu; Song, Jianxin; Huang, Yuancheng; Wang, Junshuai

    2015-01-01

    Cirrhotic patients with dysfunctional and/or low numbers of leukocytes are often infected with bacteria, especially Gram-negative bacteria, which is characterized by producing lipopolysaccharide (LPS). Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine that influences the production, maturation, function, and survival of various immune cells. In this paper, we reviewed not only Toll-like receptors 4 (TLR4) signaling pathway and its immunological effect, but also the specific stimulating function and autocrine performance of GM-CSF on hematopoietic cells, as well as the recent discovery of innate response activator-B cells in protection against microbial sepsis and the direct LPS-TLR4 signaling on hematopoiesis. Thus we concluded that GM-CSF might play important roles in preventing Gram-negative bacterial infections in cirrhotic patients through maintaining immune system functions and homeostasis.

  9. Candida Infection of the Bloodstream - Candidemia

    Candida Infection of the Bloodstream– Candidemia Fungal Disease Series #4 Candida is the single most important cause of fungal infections worldwide. In the U.S., Candida is the 4th most common cause of bloodstream ...

  10. Resistance among Gram-negative ESKAPE pathogens isolated from hospitalized patients with intra-abdominal and urinary tract infections in Latin American countries: SMART 2013-2015.

    Karlowsky, James A; Hoban, Daryl J; Hackel, Meredith A; Lob, Sibylle H; Sahm, Daniel F

    Gram-negative ESKAPE pathogens (Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are important etiologic agents of nosocomial infection that are frequently resistant to broad-spectrum antimicrobial agents. Gram-negative ESKAPE pathogens were collected from hospitalized patients in 11 Latin American countries from 2013 to 2015 as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART) global surveillance program. In total, 2113 isolates from intra-abdominal infections (IAI) and 970 isolates from urinary tract infections (UTI) were tested against antimicrobial agents using standardized CLSI broth microdilution methodology. Of the agents tested, amikacin demonstrated the highest rates of susceptibility (%) for K. pneumoniae (92.2, 92.3), Enterobacter spp. (97.5, 92.1), and P. aeruginosa (85.3, 75.2) isolates from both IAI and UTI, respectively. Ertapenem (68.5, 62.6) and imipenem (79.2, 75.9) showed substantially higher rates of susceptibility (%) than other β-lactams, including piperacillin-tazobactam (35.9, 37.4) against ESBL-positive isolates of K. pneumoniae from IAI and UTI, respectively. Rates of susceptibility to all agents tested against A. baumannii were ≤30.9%. Gram-negative ESKAPE pathogens isolated from Latin America demonstrated compromised in vitro susceptibility to commonly prescribed broad-spectrum, parenteral antimicrobial agents. Continued surveillance is warranted. New antimicrobial agents with potent activity against Gram-negative ESKAPE pathogens are urgently needed. Copyright © 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

  11. A fresh look at polymicrobial bloodstream infection in cancer patients.

    Cristina Royo-Cebrecos

    Full Text Available To assess the current incidence, clinical features, risk factors, aetiology, antimicrobial resistance and outcomes of polymicrobial bloodstream infection (PBSI in patients with cancer.All prospectively collected episodes of PBSI in hospitalised patients were compared with episodes of monomicrobial bloodstream infection (MBSI between 2006 and 2015.We identified 194 (10.2% episodes of PBSI and 1702 MBSI (89.8%. The presence of cholangitis, biliary stenting, neutropenia, corticosteroids, neutropenic enterocolitis and other abdominal infections were identified as risk factors for PBSI. Overall, Gram-negative organisms were the most frequent aetiology, but Enterococcus spp. were especially frequent causes of Gram-positive PBSI (30.8%. Multidrug-resistant (MDR organisms were more commonly found in PBSI than in MBSI (20.6% vs 12.9%; p = 0.003. Compared to patients with MBSI, those with PBSI presented with higher early (15% vs 1.4%; p = 0.04 and overall (32% vs 20.9%; p<0.001 case-fatality rates. Risk factors for overall case-fatality were a high-risk MASCC (Multinational Association of Supportive Care in Cancer index score, corticosteroid use, persistent bacteraemia and septic shock.PBSI is a frequent complication in patients with cancer and is responsible for high mortality rates. Physicians should identify patients at risk for PBSI and provide empiric antibiotic therapy that covers the most frequent pathogens involved in these infections, including MDR strains.

  12. Oral Gram-negative anaerobic bacilli as a reservoir of β-lactam resistance genes facilitating infections with multiresistant bacteria.

    Dupin, Clarisse; Tamanai-Shacoori, Zohreh; Ehrmann, Elodie; Dupont, Anais; Barloy-Hubler, Frédérique; Bousarghin, Latifa; Bonnaure-Mallet, Martine; Jolivet-Gougeon, Anne

    2015-02-01

    Many β-lactamases have been described in various Gram-negative bacilli (Capnocytophaga, Prevotella, Fusobacterium, etc.) of the oral cavity, belonging to class A of the Ambler classification (CepA, CblA, CfxA, CSP-1 and TEM), class B (CfiA) or class D in Fusobacterium nucleatum (FUS-1). The minimum inhibitory concentrations of β-lactams are variable and this variation is often related to the presence of plasmids or other mobile genetic elements (MGEs) that modulate the expression of resistance genes. DNA persistence and bacterial promiscuity in oral biofilms also contribute to genetic transformation and conjugation in this particular microcosm. Overexpression of efflux pumps is facilitated because the encoding genes are located on MGEs, in some multidrug-resistant clinical isolates, similar to conjugative transposons harbouring genes encoding β-lactamases. All these facts lead us to consider the oral cavity as an important reservoir of β-lactam resistance genes and a privileged place for genetic exchange, especially in commensal strictly anaerobic Gram-negative bacilli. Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  13. Specific Clinical Profile and Risk Factors for Mortality in General Surgery Patients with Infections by Multi-Drug-Resistant Gram-Negative Bacteria.

    Rubio-Perez, Ines; Martin-Perez, Elena; Domingo-García, Diego; Garcia-Olmo, Damian

    2017-07-01

    The incidence of gram-negative multi-drug-resistant (MDR) infections is increasing worldwide. This study sought to determine the incidence, clinical profiles, risk factors, and mortality of these infections in general surgery patients. All general surgery patients with a clinical infection by gram-negative MDR bacteria were studied prospectively for a period of five years (2007-2011). Clinical, surgical, and microbiologic parameters were recorded, with a focus on the identification of risk factors for MDR infection and mortality. Incidence of MDR infections increased (5.6% to 15.2%) during the study period; 106 patients were included, 69.8% presented nosocomial infections. Mean age was 65 ± 15 years, 61% male. Extended-spectrum β-lactamases (ESBL) Escherichia coli was the most frequent MDR bacteria. Surgical site infections and abscesses were the most common culture locations. The patients presented multiple pre-admission risk factors and invasive measures during hospitalization. Mortality was 15%, and related to older age (odds ratio [OR] 1.07), malnutrition (OR 13.5), chronic digestive conditions (OR 4.7), chronic obstructive pulmonary disease (OR 3.9), and surgical re-intervention (OR 9.2). Multi-drug resistant infections in the surgical population are increasing. The most common clinical profile is a 65-year-old male, with previous comorbidities, who has undergone a surgical intervention, intensive care unit (ICU) admission, and invasive procedures and who has acquired the MDR infection in the nosocomial setting.

  14. Antimicrobial Activity of Ephedra pachyclada Methanol Extract on Some Enteric Gram Negative Bacteria Which Causes Nosocomial Infections by Agar Dilution Method

    Amin Sadeghi Dosari

    2016-10-01

    Full Text Available Background Past history indicates that plants were served as an important source of medicine. Otherwise, in developing countries people use medicinal plants against infectious disease because they cannot afford expensive drugs. Due to increasing rate of drug-resistant diseases, there is an urgent need to detect novel antimicrobial compounds from medicinal plants. Objectives The aim of the present study was to determine Antimicrobial activity of Ephedra pachyclada methanol extract on some enteric Gram-negative bacteria which causes nosocomial infections by agar dilution method. Methods In this cross-sectional study, in order to examine the antimicrobial effects of Ephedra pachyclada extract on intestinal Gram-negative bacteria, we exposed them to 0/128, 0/25, 0/5, 1, 2, 4 and 8 mg/mL of the extract. Ephedra pachyclada was collected from Jiroft Heights and methanolic extract was prepared with maceration method, during which, 50 gr powder of Ephedra pachyclada was dissolved in 300 mL of 80% methanol. Results In this study, the antibacterial effects of Ephedra pachyclada extract on Gram-negative bacteria such as Pseudomonas aeruginosa, Escherichia coli (PTCC-O157, Escherichia coli (ATCC-25922, Klebsiella pnemoniae, Serratia marcescens was investigated, defining the minimum inhibitory concentration (MIC by agar dilution method. It has been demonstrated that methanolic extract of Ephedra pachyclada affect intestinal Gram-negative bacteria. Conclusions The result showed that, Ephedra pachyclada extract has effective antimicrobial ingredients which are cheap and readily available. It can be used for medicinal purposes in the production of antimicrobial drug.

  15. Comparison of beta-lactam regimens for the treatment of gram-negative pulmonary infections in the intensive care unit based on pharmacokinetics/pharmacodynamics.

    Burgess, David S; Frei, Christopher R

    2005-11-01

    This study utilized pharmacokinetics/pharmacodynamics to compare beta-lactam regimens for the empirical and definitive treatment of gram-negative pulmonary infections in the ICU. Susceptibility data were extracted from the 2002 Intensive Care Unit Surveillance System (ISS) and pharmacokinetic parameters were obtained from published human studies. Monte Carlo simulation was used to model the free percent time above the MIC (free %T > MIC) for 18 beta-lactam regimens against all gram-negative isolates, Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii. The cumulative fraction of response (CFR) was determined for bacteriostatic and bactericidal targets (free %T > MIC): penicillins (> or = 30/50%), cephalosporins/monobactams (> or = 40/70%) and carbapenems (> or = 20/40%). The 2002 ISS database contained MICs for 2408 gram-negative isolates including 1430 Enterobacteriaceae, 799 P. aeruginosa, and 179 A. baumannii. Imipenem had the highest percentage susceptible for all gram-negatives, Enterobacteriaceae and A. baumannii, while piperacillin/tazobactam had the highest percentage susceptible for P. aeruginosa. For empirical therapy, imipenem 0.5 g every 6 h, cefepime 2 g every 8 h and ceftazidime 2 g every 8 h demonstrated the highest CFR. For definitive therapy, imipenem 0.5 g every 6 h, ertapenem 1 g daily and cefepime 2 g every 8 h, cefepime 1 g every 8 h and cefepime 1 g every 12 h had the highest bactericidal CFR against Enterobacteriaceae; ceftazidime 2 g every 8 h, cefepime 2 g every 8 h, piperacillin/tazobactam 3.375 g every 4 h, ceftazidime 1 g every 8 h and aztreonam 1 g every 8 h against P. aeruginosa; and imipenem 0.5 g every 6 h, ticarcillin/clavulanate 3.1 g every 4 h, ceftazidime 2 g every 8 h, cefepime 2 g every 8 h and ticarcillin/clavulanate 3.1 g every 6 h against A. baumannii. Based on pharmacokinetics/pharmacodynamics, imipenem 0.5 g every 6 h, cefepime 2 g every 8 h and ceftazidime 2 g every 8 h should be the preferred beta

  16. Molecular epidemiology of carbapenem resistant gram-negative bacilli from infected pediatric population in tertiary - care hospitals in Medellín, Colombia: an increasing problem.

    Vanegas, Johanna M; Parra, O Lorena; Jiménez, J Natalia

    2016-09-01

    Gram-negative bacilli are a cause of serious infections in the pediatric population. Carbapenem are the treatment of choice for infections caused by multidrug-resistant Gram-negative bacilli, but the emergence of carbapenem resistance has substantially reduced access to effective antimicrobial regimens. Children are a population vulnerable to bacterial infections and the emergence of resistance can worsen prognosis. The aim of this study is to describe the clinical and molecular characteristics of infections caused by carbapenem-resistant Gram-negative bacilli in pediatric patients from five tertiary-care hospitals in Medellín, Colombia. A cross-sectional study was conducted in five tertiary-care hospitals from June 2012 to June 2014. All pediatric patients infected by carbapenem-resistant Gram-negative bacilli were included. Clinical information for each patient was obtained from medical records. Molecular analyses included PCR for detection of bla VIM, bla IMP bla NDM, bla OXA-48 and bla KPC genes and PFGE and MLST for molecular typing. A total of 59 patients were enrolled, most of them less than 1 year old (40.7 % n = 24), with a previous history of antibiotic use (94.9 %; n = 56) and healthcare-associated infections - predominately urinary tract infections (31.0 %; n = 18). Klebsiella pneumoniae was the most frequent bacteria (47.4 %), followed by Enterobacter cloacae (40.7 %) and Pseudomonas aeruginosa (11.9 %). For K. pneumoniae, KPC was the predominant resistance mechanism (85.7 %; n = 24) and ST14 was the most common clone (39.3 % n = 11), which included strains closely related by PFGE. In contrast, E. cloacae and P. aeruginosa were prevailing non-carbapenemase-producing isolates (only KPC and VIM were detected in 1 and 3 isolates, respectively) and high genetic diversity according to PFGE and MLST was found in the majority of the cases. In recent years, increasing carbapenem-resistant bacilli in children has become in a matter

  17. Pleural effusion adenosine deaminase: a candidate biomarker to discriminate between Gram-negative and Gram-positive bacterial infections of the pleural space

    Ruolin Li

    2016-05-01

    Full Text Available OBJECTIVES: Delay in the treatment of pleural infection may contribute to its high mortality. In this retrospective study, we aimed to evaluate the diagnostic accuracy of pleural adenosine deaminase in discrimination between Gram-negative and Gram-positive bacterial infections of the pleural space prior to selecting antibiotics. METHODS: A total of 76 patients were enrolled and grouped into subgroups according to Gram staining: 1 patients with Gram-negative bacterial infections, aged 53.2±18.6 years old, of whom 44.7% had empyemas and 2 patients with Gram-positive bacterial infections, aged 53.5±21.5 years old, of whom 63.1% had empyemas. The pleural effusion was sampled by thoracocentesis and then sent for adenosine deaminase testing, biochemical testing and microbiological culture. The Mann-Whitney U test was used to examine the differences in adenosine deaminase levels between the groups. Correlations between adenosine deaminase and specified variables were also quantified using Spearman’s correlation coefficient. Moreover, receiver operator characteristic analysis was performed to evaluate the diagnostic accuracy of pleural effusion adenosine deaminase. RESULTS: Mean pleural adenosine deaminase levels differed significantly between Gram-negative and Gram-positive bacterial infections of the pleural space (191.8±32.1 U/L vs 81.0±16.9 U/L, p<0.01. The area under the receiver operator characteristic curve was 0.689 (95% confidence interval: 0.570, 0.792, p<0.01 at the cutoff value of 86 U/L. Additionally, pleural adenosine deaminase had a sensitivity of 63.2% (46.0-78.2%; a specificity of 73.7% (56.9-86.6%; positive and negative likelihood ratios of 2.18 and 0.50, respectively; and positive and negative predictive values of 70.6% and 66.7%, respectively. CONCLUSIONS: Pleural effusion adenosine deaminase is a helpful alternative biomarker for early and quick discrimination of Gram-negative from Gram-positive bacterial infections of the

  18. Bloodstream Infections with Mycobacterium tuberculosis among HIV patients

    This podcast looks at bloodstream infections with Mycobacterium tuberculosis and other pathogens among outpatients infected with HIV in Southeast Asia. CDC health scientist Kimberly McCarthy discusses the study and why bloodstream infections occur in HIV-infected populations.

  19. Nosocomial bloodstream infection in a neonatal intensive care unit of a medical center: a three-year review.

    Tseng, Ya-Chun; Chiu, Yu-Chiao; Wang, Jen-Hsien; Lin, Hsiao-Chuan; Lin, Hung-Chih; Su, Bai-Horng; Chiu, Hsiu-Hui

    2002-09-01

    Bloodstream infections are the most frequent nosocomial infections in neonatal intensive care units. This retrospective study surveyed the epidemiologic characteristics of nosocomial bloodstream infections which occurred in the neonatal intensive care unit from January 1, 1997 to December 31, 1999. The overall infection patient rate was 5.5% in the 3-year period, and the overall infection patient-day rate was 4.4 per 1000 patient-days. Low birth weight was a risk factor for bloodstream infections. The rate of infection for neonates with birth weight below 1000 g ranged from 36.6% to 45.8% (1997: 36.6%; 1998: 45.8% and 1999: 38.9%). The most common pathogens causing nosocomial bloodstream infection were: Staphylococcus aureus (18.5%) (with 92% oxacillin-resistant), Acinectobacter baumannii (16.3%), Klebsiella pneumoniae (11.9%), Escherichia coli (9.6%), and Pseudomonas aeruginosa (8.1%). The mortality due to nosocomial bloodstream infection was highest among gram-negative bacteria, especially with P. aeruginosa (45.5%). Therefore, surveillance of nosocomial bloodstream infection and successful strategies to decrease nosocomial bloodstream infection, such as infection control and optimal antibiotic use, are warranted.

  20. [Antimicrobial susceptibility patterns of Gram-negative bacteria isolated in urinary tract infections in Venezuela: Results of the SMART study 2009-2012].

    Guevara, Napoleón; Guzmán, Manuel; Merentes, Altagracia; Rizzi, Adele; Papaptzikos, Juana; Rivero, Narlesky; Oranges, Carmela; Vlllarroel, Héctor; Limas, Yoxsivell

    2015-12-01

    Antimicrobial resistance of pathogens causing urinary tract infection (UTI) is a growing problem, which complicates their effective treatment. Surveillance is needed to guide appropriate empiric therapy. to describe the susceptibility patterns of Gram-negative bacteria isolated of patients with UTI to twelve antibiotics as part of the Study for Monitoring Antimicrobial Resistance Trends in Venezuela. Between 2009-2012 a total of 472 Gram-negative bacteria were isolated from hospitalized patients with UTI. The isolates were sent to Central Laboratory (Central Laboratory of International Health Management Associates) to confirm their identification, and to make susceptibility testing as recommended by the Clinical and Laboratory Standards Institute. Enterobacteriacea comprised 96.6% of the total, where Escherichia coli (76.9%) and Klebsiella pneumoniae (10.6%) were the most frequent. Extended-spectrum β-lactamases (ESBL) was detected in 21.6% of isolates. Top antimicrobial activity were ertapenem, imipenem, and amikacin (> 90.0%), slightly lower for amikacin (85.1%) in ESBL-producing strains. Resistance rates to fluoroquinolones and ampicillin/sulbactam were high (40 y 64%, respectively). These data suggest a necessary revision of the therapeutic regimens for the empirical treatment of UTI in Venezuela.

  1. Antimicrobial-resistant Gram-negative bacteria in febrile neutropenic patients with cancer: current epidemiology and clinical impact.

    Trecarichi, Enrico M; Tumbarello, Mario

    2014-04-01

    In the recent years, several studies involving cancer patients have demonstrated a clear trend in the epidemiology of bacterial infections showing a shift in the prevalence from Gram-positive to Gram-negative bacteria and the extensive emergence of antimicrobial-resistant strains among Gram-negatives isolated from the blood. The aim of this systematic review was to examine the recent trends in epidemiology and antimicrobial resistance in Gram-negatives recovered from neutropenic cancer patients, with particular emphasis on the impact of antimicrobial resistance on the clinical outcome of severe infections caused by such microorganisms. Overall, from 2007 to date, the rate of Gram-negative bacteria recovery ranged from 24.7 to 75.8% (mean 51.3%) in cancer patient cohorts. Escherichia coli represented the most common species (mean frequency of isolation 32.1%) among the Gram-negatives, followed by Pseudomonas aeruginosa (mean frequency of isolation 20.1%). An increasing frequency of Acinetobacter spp. and Stenotrophomonas maltophilia was also reported. Increased rates of multidrug-resistant Gram-negative strains have been highlighted among Enterobacteriaceae and nonfermenting Gram-negative rods, despite discontinuation of fluoroquinolone-based antibacterial prophylaxis for neutropenic patients. In addition, antimicrobial resistance and/or the inadequacy of empirical antibiotic treatment have been frequently linked to a worse outcome in cancer patients with bloodstream infections caused by Gram-negative isolates. Sound knowledge of the local distribution of pathogens and their susceptibility patterns and prompt initiation of effective antimicrobial treatment for severe infections caused by Gram-negative bacteria are essential in cancer patients.

  2. Antimicrobial susceptibility profiles of gram-negative bacteria causing infections collected across India during 2014–2016: Study for monitoring antimicrobial resistance trend report

    Balaji Veeraraghavan

    2018-01-01

    Full Text Available Background: The emergence of antibiotic resistance among bacterial pathogens in the hospital and community has increased the concern to the health-care providers due to the limited treatment options. Surveillance of antimicrobial resistance (AMR in frequently isolated bacterial pathogens causing severe infections is of great importance. The data generated will be useful for the clinicians to decide empiric therapy on the local epidemiological resistance profile of the antimicrobial agents. This study aims to monitor the distribution of bacterial pathogen and their susceptibility pattern to the commonly used antimicrobial agents. Materials and Methods: This study includes Gram-negative bacilli collected from intra-abdominal, urinary tract and respiratory tract infections during 2014–2016. Isolates were collected from seven hospitals across India. All the study isolates were characterised up to species level, and minimum inhibitory concentration was determined for a wide range of antimicrobials included in the study panel. The test results were interpreted as per standard Clinical Laboratory Standards Institute guidelines. Results: A total of 2731 isolates of gram-negative bacteria were tested during study period. The most frequently isolated pathogens were 44% of Escherichia coli (n = 1205 followed by 25% of Klebsiella pneumoniae (n = 676 and 11% of Pseudomonas aeruginosa (n = 308. Among the antimicrobials tested, carbapenems were the most active, followed by amikacin and piperacillin/tazobactam. The rate of extended-spectrum beta-lactamase (ESBL-positive isolates were ranged from 66%–77% in E. coli to 61%–72% in K. pneumoniae, respectively. Overall, colistin retains its activity in > 90% of the isolates tested and appear promising. Conclusion: Increasing rates of ESBL producers have been noted, which is alarming. Further, carbapenem resistance was also gradually increasing, which needs much attention. Overall, this study data show that

  3. Bloodstream Infections in a Neonatal Intensive Care Unit

    Mehmet Sah Ižpek

    2016-09-01

    Full Text Available Aim: To determine the pattern of bloodstream infections (BSIs and antimicrobial susceptibility of pathogens in a neonatal intensive care unit (NICU.Material and Method: Positive hemoculture of neonates diagnosed with nosocomial sepsis from March 2011 to March 2014 in the NICU of Diyarbakir Maternity and Children%u2019s Hospital, in the southeastern region of Anatolia, Turkey, were retrospectively reviewed. Results: A total of 148 pathogens were isolated in 142 neonates. The most common microorganisms isolated were Klebsiella pneumoniae (40.5% and Acinetobacter baumannii (29.7% which was a result of a hospital outbreak. Multi-drug resistant (MDR strains accounted for 20.0% of K. pneumoniae isolates and 93.2% of A. baumannii isolates. The sepsis-attributable mortality rate was higher in cases infected with MDR strains than in cases infected without MDR strains or Candida spp (24% vs. 9.7%, p=0.032. Discussion: In our unit, BSIs were more often caused by Gram negative bacteria. BSIs caused by MDR strains were associated with a higher rate of sepsis-attributable mortality.

  4. Soluble granzymes are released during human endotoxemia and in patients with severe infection due to gram-negative bacteria

    Lauw, F. N.; Simpson, A. J.; Hack, C. E.; Prins, J. M.; Wolbink, A. M.; van Deventer, S. J.; Chaowagul, W.; White, N. J.; van der Poll, T.

    2000-01-01

    Extracellular release of granzymes is considered to reflect the involvement of cytotoxic T lymphocytes and NK cells in various disease states. To obtain insight into granzyme release during bacterial infection, granzyme levels were measured during experimental human endotoxemia and in patients with

  5. TmCactin plays an important role in Gram-negative and -positive bacterial infection by regulating expression of 7 AMP genes in Tenebrio molitor

    Jo, Yong Hun; Jung Kim, Yu; Beom Park, Ki; Hwan Seong, Jeong; Gon Kim, Soo; Park, Soyi; Young Noh, Mi; Seok Lee, Yong; Soo Han, Yeon

    2017-01-01

    Cactin was originally identified as an interactor of the Drosophila IκB factor Cactus and shown to play a role in controlling embryonic polarity and regulating the NF-κB signaling pathway. While subsequent studies have identified the roles for Cactin in the mammalian immune response, the immune function of Cactin in insects has not been described yet. Here, we identified a Cactin gene from the mealworm beetle, Tenebrio molitor (TmCactin) and characterized its functional role in innate immunity. TmCactin was highly expressed in prepupa to last instar stages, and its expression was high in the integument and Malpighian tubules of last instar larvae and adults. TmCactin was induced in larvae after infection with different pathogens and detectable within 3 hours of infection. The highest levels of TmCactin expression were detected at 9 hours post infection. TmCactin RNAi significantly decreased the survival rates of larvae after challenge with Escherichia coli and Staphylococcus aureus, but had no significant effect after challenge with Candida albicans. Furthermore, TmCactin RNAi significantly reduced the expression of seven antimicrobial peptide genes (AMPs) after bacterial challenge. Our results suggest that TmCactin may serve as an important regulator of innate immunity, mediating AMP responses against both Gram-positive and Gram-negative bacteria in T. molitor. PMID:28418029

  6. Prevalence of Device-associated Nosocomial Infections Caused By Gram-negative Bacteria in a Trauma Intensive Care Unit in Libya

    Abdulaziz Zorgani

    2015-07-01

    Full Text Available Objectives: Device-associated nosocomial infections (DANIs have a major impact on patient morbidity and mortality. Our study aimed to determine the distribution rate of DANIs and causative agents and patterns of antibiotic resistance in the trauma-surgical intensive care unit (ICU. Methods: Our study was conducted at Abusalim Trauma Hospital in Tripoli, Libya. All devices associated with nosocomial infections, including central venous catheters (CVC, endotracheal tubes (ETT, Foley’s urinary catheters, chest tubes, nasogastric tubes (NGT, and tracheostomy tubes, were removed aseptically and examined for Gram-negative bacteria (GNB. Results: During a one-year study period, 363 patients were hospitalized; the overall mortality rate was 29%. A total of 79 DANIs were identified, the most common site of infection was ETT (39.2%, followed by urinary catheters (19%, NGTs (18%, tracheostomy tubes (11%, CVCs (10%, and chest tubes (3%. The most frequently isolated organisms were Klebsiella pneumonia, Acinetobacter baumannii, and Pseudomonas aeruginosa (30%, 20%, and 14%, respectively. Extremely high resistance rates were observed among GNB to ampicillin (99%, cefuroxime (95%, amoxicillin-clavulante (92%, and nitrofurantoin (91%. Lower levels of resistance were exhibited to amikacin (38%, imipenem (38%, and colistin (29%. About 39% of the isolates were defined as multi-drug resistant (MDR. Overall, extended spectrum β-lactmase producers were expressed in 39% of isolates mainly among K. pneumonia (88%. A. baumannii isolates exhibited extremely high levels of resistance to all antibiotics except colistin (100% sensitive. In addition, 56.3% of A. baumannii isolates were found to be MDR. P. aeruginosa isolates showed 46%–55% effectiveness to anti-pseudomonas antibiotics. Conclusion: High rates of DANI’s and the emergence of MDR organisms poses a serious threat to patients. There is a need to strengthen infection control within the ICU environment

  7. Procalcitonin levels in bloodstream infections caused by different sources and species of bacteria.

    Yan, Sheng Tao; Sun, Li Chao; Jia, Hong Bing; Gao, Wen; Yang, Jian Ping; Zhang, Guo Qiang

    2017-04-01

    The aim of this study was to evaluate procalcitonin (PCT) diagnostic accuracy in discriminating gram-negative (GN) from gram-positive (GP) bloodstream infections and determining the relationship between PCT levels, infection sites, and pathogen types. Clinical and laboratory data were collected from patients with blood culture (BC)-positive sepsis between January 2014 and December 2015. PCT levels at different infection sites were compared, as was the presence of GN and GP bloodstream infection. A receiver operating characteristic (ROC) curve was generated to assess diagnostic accuracy. Of the 486 monomicrobial BCs, 254 (52.26%) were positive for GN bacteria (GNB), and 202 (42.18%) for GP bacteria (GPB). Median PCT levels were higher in BCs positive for GN (2.42ng/ml, IQR: 0.38-15.52) than in those positive for GPB (0.49ng/ml, IQR: 0.13-5.89) (PAcinetobacter baumanni/Burkholderia cepacia, Klebsiella pneumonia and Acinetobacter baumanni. PCT levels caused by GPB differed between Staphylococcus epidermidis/Staphylococcus aureus and Staphylococcus hominis/Staphylococcus haemolyticus, Enterococcus faecium and Enterococcus faecalis/S.hominis/S. haemolyticus. Among patients with known infection sites, there were statistical differences in PCT levels between abdominal infection and pneumonia/infective endocarditis, urinary tract infection and pneumonia/catheter-related infection/infective endocarditis. PCT can distinguish between GNB and GPB infection, as well as between different bacterial species and infection sites. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Integrating rapid diagnostics and antimicrobial stewardship improves outcomes in patients with antibiotic-resistant Gram-negative bacteremia.

    Perez, Katherine K; Olsen, Randall J; Musick, William L; Cernoch, Patricia L; Davis, James R; Peterson, Leif E; Musser, James M

    2014-09-01

    An intervention for Gram-negative bloodstream infections that integrated mass spectrometry technology for rapid diagnosis with antimicrobial stewardship oversight significantly improved patient outcomes and reduced hospital costs. As antibiotic resistance rates continue to grow at an alarming speed, the current study was undertaken to assess the impact of this intervention in a challenging patient population with bloodstream infections caused by antibiotic-resistant Gram-negative bacteria. A total of 153 patients with antibiotic-resistant Gram-negative bacteremia hospitalized prior to the study intervention were compared to 112 patients treated post-implementation. Outcomes assessed included time to optimal antibiotic therapy, time to active treatment when inactive, hospital and intensive care unit length of stay, all-cause 30-day mortality, and total hospital expenditures. Integrating rapid diagnostics with antimicrobial stewardship improved time to optimal antibiotic therapy (80.9 h in the pre-intervention period versus 23.2 h in the intervention period, P Gram-negatives. The intervention decreased hospital and intensive care unit length of stay, total hospital costs, and reduced all-cause 30-day mortality. Copyright © 2014. Published by Elsevier Ltd.

  9. Long-term adherence to a 5 day antibiotic course guideline for treatment of intensive care unit (ICU)-associated Gram-negative infections.

    Edgeworth, Jonathan D; Chis Ster, Irina; Wyncoll, Duncan; Shankar-Hari, Manu; McKenzie, Catherine A

    2014-06-01

    To determine long-term adherence to a 5 day antibiotic course guideline for treating intensive care unit (ICU)-acquired Gram-negative bacteria (GNB) infections. Descriptive analysis of patient-level data on all GNB-active antibiotics prescribed from day 3 and all GNB identified in clinical samples in 5350 patients admitted to a 30 bed general ICU between 2002 and 2009. Four thousand five hundred and eleven of 5350 (84%) patients were treated with one or more antibiotics active against GNB commenced from day 3. Gentamicin was the most frequently prescribed antibiotic (92.2 days of therapy/1000 patient-days). Only 6% of courses spanned >6 days of therapy and 89% of antibiotic therapy days were with a single antibiotic active against GNB. There was no significant difference between gentamicin and meropenem in the number of first courses in which a resistant GNB was identified in blood cultures [11/1177 (0.9%) versus 5/351 (1.4%); P = 0.43] or respiratory tract specimens [59/951 (6.2%) versus 17/246 (6.9%); P = 0.68] at the time of starting therapy. This study demonstrates long-term adherence to a 5 day course antibiotic guideline for treatment of ICU-associated GNB infections. This guideline is a potential antibiotic-sparing alternative to currently recommended dual empirical courses extending to ≥7 days. © The Author 2014. 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.

  10. Pediatric bloodstream infections in Cambodia, 2007 to 2011.

    Stoesser, Nicole; Moore, Catrin E; Pocock, Joanna M; An, Khun Peng; Emary, Kate; Carter, Michael; Sona, Soeng; Poda, Sar; Day, Nicholas; Kumar, Varun; Parry, Christopher M

    2013-07-01

    Pediatric bacterial bloodstream infections (BSIs) are a major cause of morbidity and mortality worldwide. Epidemiological data from resource-limited settings in southeast Asia, such as Cambodia, are sparse but have important implications for treatment and public health strategies. We retrospectively investigated BSI in children at a pediatric hospital and its satellite clinic in Siem Reap, Cambodia, from January 1, 2007, to July 31, 2011. The range of bacterial pathogens and their antimicrobial susceptibility patterns were analyzed in conjunction with demographic, clinical and outcome data. Of 7682 blood cultures with results (99.9% of cultures taken), 606 (7.9%) episodes of BSI were identified in 588 children. The incidence of BSI increased from 14 to 50/1000 admissions (P < 0.001); this was associated with an increased sampling rate. Most BSI were community acquired (89.1%). Common pathogens included Salmonella Typhi (22.8% of all isolates), Staphylococcus aureus (12.2%), Streptococcus pneumoniae (10.0%), Klebsiella pneumoniae (6.4%) and Escherichia coli (6.3%). 21.5% of BSI were caused by a diverse group of uncommon organisms, the majority of which were environmental Gram-negative species. No Listeria monocytogenes or Group B streptococcal BSI were identified. Antimicrobial resistance, particularly among the Enterobacteriaceae, was common. Overall mortality was substantial (19.0%), higher in neonates (36.9%) and independently associated with meningitis/meningoencephalitis and K. pneumoniae infection. BSI is a common problem in Cambodian children attending hospital and associated with significant mortality. Further studies are needed to clarify the epidemiology of neonatal sepsis, the contribution of atypical organisms and the epidemiology of pneumococcal disease before the introduction of vaccine.

  11. Evaluating the Trends of Bloodstream Infections among Pediatric and Adult Patients at a Teaching Hospital of Kathmandu, Nepal: Role of Drug Resistant Pathogens

    Narayan Prasad Parajuli

    2017-01-01

    Full Text Available Bloodstream infections (BSIs are among the significant causes of morbidity and mortality for patients of all age groups. However, very little is known about the trends of bacterial bloodstream infections and antimicrobial susceptibilities among pediatric and adult population from Nepal. In this study, we have investigated the different etiological agents responsible for bloodstream infections among pediatric and adult patients and the role of drug resistant organisms in these infections at a tertiary care teaching hospital of Kathmandu, Nepal. A total of 3,088 blood culture specimens obtained from pediatric and adult patients suspected to have bloodstream infections were processed by standard microbiological methods. Significant bacterial pathogens were identified by morphological, biochemical, and serological methods as suggested by American Society for Microbiology. In vitro antimicrobial susceptibility testing was performed by Kirby-Bauer disk diffusion method and interpreted according to the guidelines of Clinical and Laboratory Standards Institute. Overall, incidence of bloodstream infections among the suspected patients was 7.48%. Pediatric patients (n=90, 9.37% were the significant subgroup of patients affected with bloodstream infections compared to adults (p<0.05, CI-95%. Gram positive (n=49, 54.4% bacteria in pediatric and gram negative bacteria (n=141, 78.7% in adult patients were the most common isolates for BSI. Staphylococcus aureus (n=41, 45.6% in pediatric patients and Salmonella enterica (n=40, 28.3% in adult patients were the leading pathogens. Trends of antimicrobial resistance among isolated bacterial strains were significantly high in adults compared to pediatric patients. Methicillin resistant Staphylococcus aureus (MRSA (31.4%, extended spectrum beta-lactamase (ESBL (12.5%, and metallo-beta-lactamase (MBL (3.9% producing gram negatives were major resistant strains. Our study shows higher rates of bloodstream infections in

  12. Outcome of Acute Prosthetic Joint Infections Due to Gram-Negative Bacilli Treated with Open Debridement and Retention of the Prosthesis▿

    Martínez-Pastor, Juan C.; Muñoz-Mahamud, Ernesto; Vilchez, Félix; García-Ramiro, Sebastián; Bori, Guillem; Sierra, Josep; Martínez, José A.; Font, Lluis; Mensa, Josep; Soriano, Alex

    2009-01-01

    The aim of our study was to evaluate the outcome of acute prosthetic joint infections (PJIs) due to gram-negative bacilli (GNB) treated without implant removal. Patients with an acute PJI due to GNB diagnosed from 2000 to 2007 were prospectively registered. Demographics, comorbidity, type of implant, microbiology data, surgical treatment, antimicrobial therapy, and outcome were recorded. Classification and regression tree analysis, the Kaplan-Meier survival method, and the Cox regression model were applied. Forty-seven patients were included. The mean age was 70.7 years, and there were 15 hip prostheses and 32 knee prostheses. The median number of days from the time of arthroplasty was 20. The most frequent pathogens were members of the Enterobacteriaceae family in 41 cases and Pseudomonas spp. in 20 cases. Among the Enterobacteriaceae, 14 were resistant to ciprofloxacin, while all Pseudomonas aeruginosa isolates were susceptible to ciprofloxacin. The median durations of intravenous and oral antibiotic treatment were 14 and 64 days, respectively. A total of 35 (74.5%) patients were in remission after a median follow-up of 463 days (interquartile range, 344 to 704) days. By use of the Kaplan-Meier survival curve, a C-reactive protein (CRP) concentration of ≤15 mg/dl (P = 0.03) and receipt of a fluoroquinolone, when all GNB isolated were susceptible (P = 0.0009), were associated with a better outcome. By use of a Cox regression model, a CRP concentration of ≤15 mg/dl (odds ratio [OR], 3.57; 95% confidence interval [CI], 1.05 to 12.5; P = 0.043) and receipt of a fluoroquinolone (OR, 9.09; 95% CI, 1.96 to 50; P = 0.005) were independently associated with better outcomes. Open debridement without removal of the implant had a success rate of 74.5%, and the factors associated with good prognosis were a CRP concentration at the time of diagnosis ≤15 mg/dl and treatment with a fluoroquinolone. PMID:19687237

  13. Bloodstream Infections with Mycobacterium tuberculosis among HIV patients

    2010-09-23

    This podcast looks at bloodstream infections with Mycobacterium tuberculosis and other pathogens among outpatients infected with HIV in Southeast Asia. CDC health scientist Kimberly McCarthy discusses the study and why bloodstream infections occur in HIV-infected populations.  Created: 9/23/2010 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 9/23/2010.

  14. Nosocomial Bloodstream Infections in Brazilian Pediatric Patients: Microbiology, Epidemiology, and Clinical Features

    Pereira, Carlos Alberto Pires; Marra, Alexandre R.; Camargo, Luis Fernando Aranha; Pignatari, Antônio Carlos Campos; Sukiennik, Teresa; Behar, Paulo Renato Petersen; Medeiros, Eduardo Alexandrino Servolo; Ribeiro, Julival; Girão, Evelyne; Correa, Luci; Guerra, Carla; Carneiro, Irna; Brites, Carlos; Reis, Marise; de Souza, Marta Antunes; Tranchesi, Regina; Barata, Cristina U.; Edmond, Michael B.

    2013-01-01

    Background Nosocomial bloodstream infections (nBSIs) are an important cause of morbidity and mortality and are the most frequent type of nosocomial infection in pediatric patients. Methods We identified the predominant pathogens and antimicrobial susceptibilities of nosocomial bloodstream isolates in pediatric patients (≤16 years of age) in the Brazilian Prospective Surveillance for nBSIs at 16 hospitals from 12 June 2007 to 31 March 2010 (Br SCOPE project). Results In our study a total of 2,563 cases of nBSI were reported by hospitals participating in the Br SCOPE project. Among these, 342 clinically significant episodes of BSI were identified in pediatric patients (≤16 years of age). Ninety-six percent of BSIs were monomicrobial. Gram-negative organisms caused 49.0% of these BSIs, Gram-positive organisms caused 42.6%, and fungi caused 8.4%. The most common pathogens were Coagulase-negative staphylococci (CoNS) (21.3%), Klebsiella spp. (15.7%), Staphylococcus aureus (10.6%), and Acinetobacter spp. (9.2%). The crude mortality was 21.6% (74 of 342). Forty-five percent of nBSIs occurred in a pediatric or neonatal intensive-care unit (ICU). The most frequent underlying conditions were malignancy, in 95 patients (27.8%). Among the potential factors predisposing patients to BSI, central venous catheters were the most frequent (66.4%). Methicillin resistance was detected in 37 S. aureus isolates (27.1%). Of the Klebsiella spp. isolates, 43.2% were resistant to ceftriaxone. Of the Acinetobacter spp. and Pseudomonas aeruginosa isolates, 42.9% and 21.4%, respectively, were resistant to imipenem. Conclusions In our multicenter study, we found a high mortality and a large proportion of gram-negative bacilli with elevated levels of resistance in pediatric patients. PMID:23861860

  15. Nosocomial bloodstream infection in a tertiary care paediatric intensive care unit

    Hamid, M.H.; Maqbool, S.

    2007-01-01

    To determine the frequency, causative organisms and susceptibility pattern of nosocomial bloodstream infections in children. All children admitted to the unit during the study period were daily evaluated for features suggestive of nosocomial infection. In addition to other investigations, blood cultures were done in all suspected cases for the confirmation of nosocomial bloodstream infection (BSI). Nosocomial infection was defined according to the criteria set by Centre for Disease Control and Prevention. Demographic, microbiological and other variables were carefully studied to analyze frequency, incidence rate, spectrum of isolates and susceptibility pattern. Children with and without nosocomial BSI were compared with regard to age, duration of stay in hospital, need and duration of ventilation and the outcome. Of the total 406 admissions, 134 children were suspected to have nosocomial infection on at least 214 occasions (episodes). Blood cultures yielded growth of pathological organisms in 62 of these episodes, giving the frequency of nosocomial BSI as 15.2 per 100 admissions (62/406 episodes). Children with nosocomial bloodstream infection were found to have younger mean age (2.1 vs. 4.1 years), longer average duration of stay (13.1 vs. 6.6 days), more frequent need for ventilation (64% vs. 34%) and longer duration of ventilation (9.7 vs. 4.8 days). Majority of isolates (77%) were gram-negative bacteria; Klebsiella being the most common isolate (n= 23). Aztreonam, Ceftiazidime, Ceforuxime and Ciprofloxacin showed high resistance pattern (33-50%). Isolates showed good sensitivity to Vancomycin (100%), Imipenem (80%), Meropenem (100%) and Co-amoxiclav (88%). The frequency of nosocomial BSI in the observed setting was quite high, having marked impact on the duration of stay and outcome. Emergence of resistant pathogens is alarming. (author)

  16. ESRD QIP - NHSN Bloodstream Infection - Payment Year 2018

    U.S. Department of Health & Human Services — This dataset includes facility details, performance ratio, measure score, and the state and national average measure scores for the NHSN bloodstream infection...

  17. Silver enhances antibiotic activity against gram-negative bacteria.

    Morones-Ramirez, J Ruben; Winkler, Jonathan A; Spina, Catherine S; Collins, James J

    2013-06-19

    A declining pipeline of clinically useful antibiotics has made it imperative to develop more effective antimicrobial therapies, particularly against difficult-to-treat Gram-negative pathogens. Silver has been used as an antimicrobial since antiquity, yet its mechanism of action remains unclear. We show that silver disrupts multiple bacterial cellular processes, including disulfide bond formation, metabolism, and iron homeostasis. These changes lead to increased production of reactive oxygen species and increased membrane permeability of Gram-negative bacteria that can potentiate the activity of a broad range of antibiotics against Gram-negative bacteria in different metabolic states, as well as restore antibiotic susceptibility to a resistant bacterial strain. We show both in vitro and in a mouse model of urinary tract infection that the ability of silver to induce oxidative stress can be harnessed to potentiate antibiotic activity. Additionally, we demonstrate in vitro and in two different mouse models of peritonitis that silver sensitizes Gram-negative bacteria to the Gram-positive-specific antibiotic vancomycin, thereby expanding the antibacterial spectrum of this drug. Finally, we used silver and antibiotic combinations in vitro to eradicate bacterial persister cells, and show both in vitro and in a mouse biofilm infection model that silver can enhance antibacterial action against bacteria that produce biofilms. This work shows that silver can be used to enhance the action of existing antibiotics against Gram-negative bacteria, thus strengthening the antibiotic arsenal for fighting bacterial infections.

  18. Clinical pulmonary infection score and a spot serum procalcitonin level to guide discontinuation of antibiotics in ventilator-associated pneumonia: a study in a single institution with high prevalence of nonfermentative gram-negative bacilli infection.

    Wongsurakiat, Phunsup; Tulatamakit, Sirapat

    2018-01-01

    Background We wanted to determine the impact of combined Clinical Pulmonary Infection Score (CPIS) and a spot serum procalcitonin (PCT)-guided protocol to shorten the duration of antibiotic treatment in patients with ventilator-associated pneumonia (VAP), mainly caused by nonfermentative gram-negative bacilli (NF-GNB). Methods Patients with VAP who received appropriate antibiotics for 7 days, temperature ⩽ 37.8°C, without shock, and CPIS ⩽ 6 were allocated to the PCT group or conventional group according to the treating physicians' decisions. In the PCT group, antibiotics were stopped if the PCT level on day 8 level appeared effective and safe to guide discontinuation of antibiotic treatment in patients with VAP caused by NF-GNB. TCTR20160726002.

  19. Drug-resistant gram-negative uropathogens: A review.

    Khoshnood, Saeed; Heidary, Mohsen; Mirnejad, Reza; Bahramian, Aghil; Sedighi, Mansour; Mirzaei, Habibollah

    2017-10-01

    Urinary tract infection(UTI) caused by Gram-negative bacteria is the second most common infectious presentation in community medical practice. Approximately 150 million people are diagnosed with UTI each year worldwide. Drug resistance in Gram-negative uropathogens is a major global concern which can lead to poor clinical outcomes including treatment failure, development of bacteremia, requirement for intravenous therapy, hospitalization, and extended length of hospital stay. The mechanisms of drug resistance in these bacteria are important due to they are often not identified by routine susceptibility tests and have an exceptional potential for outbreaks. Treatment of UTIs depends on the access to effective drugs, which is now threatened by antibiotic resistant Gram-negative uropathogens. Although several effective antibiotics with activity against highly resistant Gram-negatives are available, there is not a unique antibiotic with activity against the high variety of resistance. Therefore, antimicrobial susceptibility tests, correlation between clinicians and laboratories, development of more rapid diagnostic methods, and continuous monitoring of drug resistance are urgent priorities. In this review, we will discuss about the current global status of drug-resistant Gram-negative uropathogens and their mechanisms of drug resistance to provide new insights into their treatment options. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  20. The changing epidemiology of Staphylococcus aureus bloodstream infection

    Laupland, K.B.; Lyytikäinen, O.; Søgaard, Mette

    2013-01-01

    Clin Microbiol Infect ABSTRACT: Although the epidemiology of Staphylococcus aureus bloodstream infection (BSI) has been changing, international comparisons are lacking. We sought to determine the incidence of S. aureus BSI and assess trends over time and by region. Population-based surveillance w...

  1. Temporal Trends in Enterobacter Species Bloodstream Infection: A Population-Based Study, 1998-2007

    Al-Hasan, Majdi N.; Lahr, Brian D.; Eckel-Passow, Jeanette E.; Baddour, Larry M.

    2010-01-01

    Enterobacter species are the fourth most common cause of gram-negative bloodstream infection (BSI). We examined temporal changes and seasonal variation in the incidence rate of Enterobacter spp. BSI, estimated 28-day and 1-year mortality, and determined in vitro antimicrobial resistance rates of Enterobacter spp. bloodstream isolates in Olmsted County, Minnesota, from 1/1/1998 to 12/31/2007. Multivariable Poisson regression was used to examine temporal changes and seasonal variation in incidence rate and Kaplan-Meier method to estimate 28-day and 1-year mortality. The median age of patients with Enterobacter spp. BSI was 58 years and 53% were female. The overall age- and gender-adjusted incidence rate of Enterobacter spp. BSI was 3.3/100,000 person-years (95% confidence interval [CI]: 2.3-4.4). There was a linear trend of increasing incidence rate from 0.8 (95% CI: 0-1.9) to 6.2 (95% CI: 3.0-9.3) per 100,000 person-years between 1998 and 2007 (p=0.002). There was no significant difference in the incidence rate of Enterobacter spp. BSI during the warmest four months compared to the remainder of the year (incidence rate ratio 1.06 [95% CI: 0.47-2.01]). The overall 28-day and 1-year mortality rates of Enterobacter spp. BSI were 21% (95% CI: 8-34%) and 38% (95% CI: 22-53%), respectively. Up to 13% of Enterobacter spp. bloodstream isolates were resistant to third-generation cephalosporins. To our knowledge, this is the first population-based study to describe the epidemiology and outcome of Enterobacter spp. BSI. The increase in incidence rate of Enterobacter spp. BSI over the past decade, coupled with its associated antimicrobial resistance, dictate more investigation of this syndrome. PMID:20518795

  2. Veillonella, Firmicutes: Microbes disguised as Gram negatives

    Vesth, Tammi Camilla; Ozen, Asli; Andersen, Sandra Christine

    2013-01-01

    Negativicutes, including the genus Veillonella, stain Gram negative. Veillonella are among the most abundant organisms of the oral and intestinal microflora of animals and humans, in spite of being strict anaerobes. In this work, the genomes of 24 Negativicutes, including eight Veillonella spp., are compared......, with the exception of a shared LPS biosynthesis pathway. The clade within the class Negativicutes to which the genus Veillonella belongs exhibits unique properties, most of which are in common with Gram-positives and some with Gram negatives. They are only distantly related to Clostridia, but are even less closely...... related to Gram-negative species. Though the Negativicutes stain Gram-negative and possess two membranes, the genome and proteome analysis presented here confirm their place within the (mainly) Gram positive phylum of the Firmicutes. Further studies are required to unveil the evolutionary history...

  3. Gram-negative diabetic foot osteomyelitis: risk factors and clinical presentation.

    Aragón-Sánchez, Javier; Lipsky, Benjamin A; Lázaro-Martínez, Jose L

    2013-03-01

    Osteomyelitis frequently complicates infections in the feet of patients with diabetes. Gram-positive cocci, especially Staphylococcus aureus, are the most commonly isolated pathogens, but gram-negative bacteria also cause some cases of diabetic foot osteomyelitis (DFO). These gram-negatives require different antibiotic regimens than those commonly directed at gram-positives. There are, however, few data on factors related to their presence and how they influence the clinical picture. We conducted a retrospective study to determine the variables associated with the isolation of gram-negative bacteria from bone samples in cases of DFO and the clinical presentation of these infections. Among 341 cases of DFO, 150 had a gram-negative isolate (alone or combined with a gram-positive isolate) comprising 44.0% of all patients and 50.8% of those with a positive bone culture. Compared with gram-positive infections, wounds with gram-negative organisms more often had a fetid odor, necrotic tissue, signs of soft tissue infection accompanying osteomyelitis, and clinically severe infection. By multivariate analysis, the predictive variables related to an increased likelihood of isolating gram-negatives from bone samples were glycated hemoglobin gram-negatives had a statistically significantly higher prevalence of leukocytosis and higher white blood cell counts than those without gram-negatives. In conclusion, gram-negative organisms were isolated in nearly half of our cases of DFO and were associated with more severe infections, higher white blood cell counts, lower glycated hemoglobin levels, and wounds of traumatic etiology.

  4. The Antibiotic Resistance Profiles of Bacterial Strains Isolated from Patients with Hospital-Acquired Bloodstream and Urinary Tract Infections

    Hamed Ghadiri

    2012-01-01

    Full Text Available Treatment of nosocomial infections is becoming difficult due to the increasing trend of antibiotics resistance. Current knowledge on antibiotic resistance pattern is essential for appropriate therapy. We aimed to evaluate antibiotic resistance profiles in nosocomial bloodstream and urinary tract pathogens. A total of 129 blood stream and 300 urinary tract positive samples were obtained from patients referring to Besat hospital over a two-year period (2009 and 2010. Antibiotic sensitivity was ascertained using the Kirby-Bauer disk diffusion technique according to CLSI guidelines. Patient's data such as gender and age were recorded. The ratio of gram-negative to gram-positive bacteria in BSIs was 1.6 : 1. The most prevalent BSI pathogen was Coagulase-Negative Staphylococci (CoNS. The highest resistance rate of CoNS was against penicillin (91.1% followed by ampicillin (75.6%, and the lowest rate was against vancomycin (4.4%. Escherichia coli was the most prevalent pathogen isolated from urinary tract infections (UTIs. Ratio of gram-negative to gram-positive bacteria was 3.2 : 1. The highest resistance rate of E. coli isolates was against nalidixic acid (57.7%. The present study showed that CoNS and E. coli are the most common causative agents of nosocomial BSIs and UTIs, and control of infection needs to be addressed in both antibiotic prescription and general hygiene.

  5. 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

    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

  6. Results of the national surveillance of antimicrobial resistance of Enterobacteriaceae and Gram negative bacilli in health care-associated infections in Colombia, 2012-2014

    María Victoria Ovalle

    2017-12-01

    Conclusion: The data from the surveillance of healthcare-associated infections revealed significant carbapenem resistance profiles and antimicrobial resistance mechanisms circulating in Colombian healthcare institutions.

  7. Distribution and Antimicrobial Susceptibility Pattern of Gram Negative Bacteria Causing Urinary Tract Infection (UTI and Detection New Delhi Metallo-beta-lactamase-1 (NDM-1 Producing Isolates in Ahwaz

    Parviz Afrugh

    2016-04-01

    Full Text Available Background: Urinary tract infection (UTI is the commonest bacterial infectious disease in worldwide (especially in developing countries with a high rate of morbidity and financial cost. The management of UTI infections has been jeopardized by increase in immergence of antimicrobial drug resistance. Knowledge of the local bacterial etiology and susceptibility patterns is required to trace any change that might have occurred in time so that updated recommendation for optimal empirical therapy of UTI can be made. The aim of this investigation was distribution and antimicrobial susceptibility pattern of gram negative bacteria causing urinary tract infection (UTI and detection NDM-1 (new-delhi-metallo-beta-lactamase-1 producing isolates in Ahwaz. Materials and Methods: This cross-sectional study was done during a period of one year from April 2013 to March 2014. Clean catch midstream urine samples were collected from suspected patients to UTI. The isolates were identified based on morphological and biochemical testes. Culture was performed on routine microbiological media. Susceptibility testing was performed according CLSI (2013 guidelines. Detection of carbapenemase producing isolates was performed by modified hodge test (MHT. Metallo-beta-lactamase isolates were detected by imipenem-EDTA combined disc test (CDT. Results: In this study 708 gram negative organisms were isolated from urine samples. E.coli was the most common isolated bacteria (67% followed by Klebsiella spp. (26.5% and Enterobacter spp. (2.5%. In antibiotic susceptibility testing more than 90% of isolates were sensitive to tetracycline, ceftazidime, meropenem, amikacin, cefotaxime, imipenem, and cefepime. Isolates were more resistant to cephalothin (32%, co-trimoxazol (30.5%, and nalidixic acid (25%. Conclusion: In our results isolated organisms from outpatients showed very high sensitivity to common antibiotics. Continuous and regular monitoring of susceptibility pattern of

  8. Neonatal bloodstream infections in a pediatric hospital in Vietnam

    Kruse, Alexandra Yasmin; Thieu Chuong, Do Huu; Phuong, Cam Ngoc

    2013-01-01

    Septicemia and bloodstream infections (BSIs) are major causes of neonatal morbidity and mortality in developing countries. We prospectively recorded all positive blood cultures (BSI) among neonates admitted consecutively to a tertiary pediatric hospital in Vietnam during a 12-month period. Among...

  9. A multidisciplinary intervention to reduce infections of ESBL- and AmpC-producing, gram-negative bacteria at a University Hospital.

    Jenny Dahl Knudsen

    Full Text Available In response to a considerable increase in the infections caused by ESBL/AmpC-producing Klebsiella pneumonia in 2008, a multidisciplinary intervention, with a main focus on antimicrobial stewardship, was carried out at one university hospital. Four other hospitals were used as controls. Stringent guidelines for antimicrobial treatment and prophylaxis were disseminated throughout the intervention hospital; cephalosporins were restricted for prophylaxis use only, fluoroquinolones for empiric use in septic shock only, and carbapenems were selected for penicillin-allergic patients, infections due to ESBL/AmpC-producing and other resistant bacteria, in addition to their use in severe sepsis/septic shock. Piperacillin-tazobactam ± gentamicin was recommended for empiric treatments of most febrile conditions. The intervention also included education and guidance on infection control, as well as various other surveillances. Two year follow-up data on the incidence rates of patients with selected bacterial infections, outcomes, and antibiotic consumption were assessed, employing before-and-after analysis and segmented regression analysis of interrupted time series, using the other hospitals as controls. The intervention led to a sustained change in antimicrobial consumption, and the incidence of patients infected with ESBL-producing K. pneumoniae decreased significantly (p<0.001. The incidences of other hospital-associated infections also declined (p's<0.02, but piperacillin-tazobactam-resistant Pseudomonas aeruginosa and Enterococcus faecium infections increased (p's<0.033. In wards with high antimicrobial consumption, the patient gut carrier rate of ESBL-producing bacteria significantly decreased (p = 0.023. The unadjusted, all-cause 30-day mortality rates of K. pneumoniae and E. coli were unchanged over the four-year period, with similar results in all five hospitals. Although not statistically significant, the 30-day mortality rate of patients

  10. A multidisciplinary intervention to reduce infections of ESBL- and AmpC-producing, gram-negative bacteria at a University Hospital

    Knudsen, Inge Jenny Dahl; Andersen, Stig Ejdrup

    2014-01-01

    aeruginosa and Enterococcus faecium infections increased (p'sproducing bacteria significantly decreased (p = 0.023). The unadjusted, all-cause 30-day mortality rates of K. pneumoniae and E. coli were unchanged over......In response to a considerable increase in the infections caused by ESBL/AmpC-producing Klebsiella pneumonia in 2008, a multidisciplinary intervention, with a main focus on antimicrobial stewardship, was carried out at one university hospital. Four other hospitals were used as controls. Stringent...... guidelines for antimicrobial treatment and prophylaxis were disseminated throughout the intervention hospital; cephalosporins were restricted for prophylaxis use only, fluoroquinolones for empiric use in septic shock only, and carbapenems were selected for penicillin-allergic patients, infections due to ESBL/AmpC-producing...

  11. High prevalence of hospital-acquired infections caused by gram-negative carbapenem resistant strains in Vietnamese pediatric ICUs: A multi-centre point prevalence survey

    Le, N.K.; Wertheim, H.F.L.; Vu, P.D.; Khu, D.T.; Le, H.T.; Hoang, B.T.; Vo, V.T.; Lam, Y.M.; Vu, D.T.; Nguyen, Thanh Son; Thai, T.Q.; Nilsson, L.E.; Rydell, U.; Nguyen, K.V.; Nadjm, B.; Clarkson, L.; Hanberger, H.; Larsson, M.

    2016-01-01

    There is scarce information regarding hospital-acquired infections (HAIs) among children in resource-constrained settings. This study aims to measure prevalence of HAIs in Vietnamese pediatric hospitals.Monthly point prevalence surveys (PPSs) in 6 pediatric intensive care units (ICUs) in 3 referral

  12. Neither Single nor a Combination of Routine Laboratory Parameters can Discriminate between Gram-positive and Gram-negative Bacteremia

    Ratzinger, Franz; Dedeyan, Michel; Rammerstorfer, Matthias; Perkmann, Thomas; Burgmann, Heinz; Makristathis, Athanasios; Dorffner, Georg; Loetsch, Felix; Blacky, Alexander; Ramharter, Michael

    2015-01-01

    Adequate early empiric antibiotic therapy is pivotal for the outcome of patients with bloodstream infections. In clinical practice the use of surrogate laboratory parameters is frequently proposed to predict underlying bacterial pathogens; however there is no clear evidence for this assumption. In this study, we investigated the discriminatory capacity of predictive models consisting of routinely available laboratory parameters to predict the presence of Gram-positive or Gram-negative bacteremia. Major machine learning algorithms were screened for their capacity to maximize the area under the receiver operating characteristic curve (ROC-AUC) for discriminating between Gram-positive and Gram-negative cases. Data from 23,765 patients with clinically suspected bacteremia were screened and 1,180 bacteremic patients were included in the study. A relative predominance of Gram-negative bacteremia (54.0%), which was more pronounced in females (59.1%), was observed. The final model achieved 0.675 ROC-AUC resulting in 44.57% sensitivity and 79.75% specificity. Various parameters presented a significant difference between both genders. In gender-specific models, the discriminatory potency was slightly improved. The results of this study do not support the use of surrogate laboratory parameters for predicting classes of causative pathogens. In this patient cohort, gender-specific differences in various laboratory parameters were observed, indicating differences in the host response between genders. PMID:26522966

  13. Multidrug-Resistant Gram-Negative Bacterial and Carbapenem-Resistant Enterobacteriaceae Infections in the Department of the Navy: Annual Report 2013

    2015-03-19

    Department per patient per admission. Device- and procedure-associated metrics (CLABSI, VAP , SSI) require the use of International Classification of...Overall Prevalence 0.28 HO Bacteremia 0.002 HO UTI 0.008 CLABSI -- VAP -- SSI 0.01 Per 100 Procedures per 1,000 Patient -Days...policy or position of the Department of the Navy, Department of Defense, nor the U.S. Government. i MDRGNB/CRE Infections in the DON: Annual

  14. Bloodstream infection following 217 consecutive systemic-enteric drained pancreas transplants

    Mark Walter

    2006-08-01

    Full Text Available Abstract Background Combined kidney pancreas transplantation (PTx evolved as excellent treatment for diabetic nephropathy. Infections remain common and serious complications. Methods 217 consecutive enteric drained PTxs performed from 1997 to 2004 were retrospectively analyzed with regard to bloodstream infection. Immunosuppression consisted of antithymocyteglobuline induction, tacrolimus, mycophenolic acid and steroids for the majority of cases. Standard perioperative antimicrobial prophylaxis consisted of pipercillin/tazobactam in combination with ciprofloxacin and fluconazole. Results One year patient, pancreas and kidney graft survival were 96.4%, 88.5% and 94.8%, surgical complication rate was 35%, rejection rate 30% and rate of infection 59%. In total 46 sepsis episodes were diagnosed in 35 patients (16% with a median onset on day 12 (range 1–45 post transplant. Sepsis source was intraabdominal infection (IAI (n = 21, a contaminated central venous line (n = 10, wound infection (n = 5, urinary tract infection (n = 2 and graft transmitted (n = 2. Nine patients (4% experienced multiple episodes of sepsis. Overall 65 pathogens (IAI sepsis 39, line sepsis 15, others 11 were isolated from blood. Gram positive cocci accounted for 50 isolates (77%: Coagulase negative staphylococci (n = 28, i.e. 43% (nine multi-resistant, Staphylococcus aureus (n = 11, i.e. 17% (four multi-resistant, enterococci (n = 9, i.e. 14% (one E. faecium. Gram negative rods were cultured in twelve cases (18%. Patients with blood borne infection had a two year pancreas graft survival of 76.5% versus 89.4% for those without sepsis (p = 0.036, patient survival was not affected. Conclusion Sepsis remains a serious complication after PTx with significantly reduced pancreas graft, but not patient survival. The most common source is IAI.

  15. Revisiting the gram-negative lipoprotein paradigm

    The processing of lipoproteins (lpps) in Gram-negative bacteria is generally considered to be an essential pathway. Mature lipoproteins in these bacteria are triacylated, with the final fatty acid addition performed by Lnt, an apolipoprotein n-acyltransferase. The mature lipoproteins are then sorted...

  16. Characteristics of gram-negative urinary tract infections caused by extended spectrum beta lactamases: pivmecillinam as a treatment option within South Dublin, Ireland

    Fardod O’Kelly

    2016-11-01

    Full Text Available Abstract Background The prevalence of urinary tract infections (UTIs caused by extended-spectrum β-lactamase (ESBL-producing Enterobacteriaceae is increasing and the therapeutic options are limited, especially in primary care. Recent indications have suggested pivmecillinam to be a suitable option. This pilot study aimed to assess the viability of pivmecillinam as a therapeutic option in a Dublin cohort of mixed community and healthcare origin. Methods A prospective measurement of mean and fractional inhibitory concentrations of antibiotic use in 95 patients diagnosed with UTI caused by ESBL-producing Enterobacteriaceae was carried out. 36 % patients were from general practice, 40 % were admitted to hospital within south Dublin, and 25 % samples arose from nursing homes. EUCAST breakpoints were used to determine if an isolate was sensitive or resistant to antibiotic agents. Results Sixty-nine percent of patients (N = 66 with urinary ESBL isolates were female. The mean age of females was 66 years compared with a mean age of 74 years for males. Thirty-six percent of isolates originated from primary care, hospital inpatients (26 %, and nursing homes (24 %. The vast majority of ESBL isolates were E. coli (80 %. The E tests for mecillinam and co-amoxiclav had concentration ranges from 0.16 mg/L up to 256 mg/L. The mean inhibitory concentration (MIC of mecillinam ranged from 0.25 to 256 mg/L, while co-amoxiclav MICs ranged from 6 to 256 mg/L. The percentage of isolates resistant to mecillinam and co-amoxiclav was found to be 5.26 and 94.74 % respectively. Conclusions This is the first study exploring the use of pivmecillinam in an Irish cohort and has demonstrated that its use in conjunction with or without co-amoxiclav is an appropriate and useful treatment for urinary tract infections caused by ESBL-producing organisms.

  17. Revisiting the Gram-negative lipoprotein paradigm.

    LoVullo, Eric D; Wright, Lori F; Isabella, Vincent; Huntley, Jason F; Pavelka, Martin S

    2015-05-01

    The processing of lipoproteins (Lpps) in Gram-negative bacteria is generally considered an essential pathway. Mature lipoproteins in these bacteria are triacylated, with the final fatty acid addition performed by Lnt, an apolipoprotein N-acyltransferase. The mature lipoproteins are then sorted by the Lol system, with most Lpps inserted into the outer membrane (OM). We demonstrate here that the lnt gene is not essential to the Gram-negative pathogen Francisella tularensis subsp. tularensis strain Schu or to the live vaccine strain LVS. An LVS Δlnt mutant has a small-colony phenotype on sucrose medium and increased susceptibility to globomycin and rifampin. We provide data indicating that the OM lipoprotein Tul4A (LpnA) is diacylated but that it, and its paralog Tul4B (LpnB), still sort to the OM in the Δlnt mutant. We present a model in which the Lol sorting pathway of Francisella has a modified ABC transporter system that is capable of recognizing and sorting both triacylated and diacylated lipoproteins, and we show that this modified system is present in many other Gram-negative bacteria. We examined this model using Neisseria gonorrhoeae, which has the same Lol architecture as that of Francisella, and found that the lnt gene is not essential in this organism. This work suggests that Gram-negative bacteria fall into two groups, one in which full lipoprotein processing is essential and one in which the final acylation step is not essential, potentially due to the ability of the Lol sorting pathway in these bacteria to sort immature apolipoproteins to the OM. This paper describes the novel finding that the final stage in lipoprotein processing (normally considered an essential process) is not required by Francisella tularensis or Neisseria gonorrhoeae. The paper provides a potential reason for this and shows that it may be widespread in other Gram-negative bacteria. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  18. Bloodstream Infections in a Neonatal Intensive Care Unit

    Mehmet Sah Ipek

    2016-01-01

    Aim: To determine the pattern of bloodstream infections (BSIs) and antimicrobial susceptibility of pathogens in a neonatal intensive care unit (NICU).Material and Method: Positive hemoculture of neonates diagnosed with nosocomial sepsis from March 2011 to March 2014 in the NICU of Diyarbakir Maternity and Children%u2019s Hospital, in the southeastern region of Anatolia, Turkey, were retrospectively reviewed. Results: A total of 148 pathogens were isolated in 142 neonates. The most common micr...

  19. Gram-Negative Bacterial Wound Infections

    2016-07-01

    A155, one of the first CC109 isolates from Argentina that includes a AbaR-type island inserted within comM, and the aac(6′)-Ib gene, which confers...extremely drug-resistant (XDR) or totally drug-resistant (TDR) strains, an outcome that has recreated the preantibiotic era (3, 4). This crisis has...Rossolini GM, Arena F, Pecile P, Pollini S. 2014. Update on the antibi- otic resistance crisis . Curr Opin Pharmacol 18:56 – 60. http://dx.doi.org

  20. Veillonella, Firmicutes: Microbes disguised as Gram negatives.

    Vesth, Tammi; Ozen, Aslı; Andersen, Sandra C; Kaas, Rolf Sommer; Lukjancenko, Oksana; Bohlin, Jon; Nookaew, Intawat; Wassenaar, Trudy M; Ussery, David W

    2013-12-20

    The Firmicutes represent a major component of the intestinal microflora. The intestinal Firmicutes are a large, diverse group of organisms, many of which are poorly characterized due to their anaerobic growth requirements. Although most Firmicutes are Gram positive, members of the class Negativicutes, including the genus Veillonella, stain Gram negative. Veillonella are among the most abundant organisms of the oral and intestinal microflora of animals and humans, in spite of being strict anaerobes. In this work, the genomes of 24 Negativicutes, including eight Veillonella spp., are compared to 20 other Firmicutes genomes; a further 101 prokaryotic genomes were included, covering 26 phyla. Thus a total of 145 prokaryotic genomes were analyzed by various methods to investigate the apparent conflict of the Veillonella Gram stain and their taxonomic position within the Firmicutes. Comparison of the genome sequences confirms that the Negativicutes are distantly related to Clostridium spp., based on 16S rRNA, complete genomic DNA sequences, and a consensus tree based on conserved proteins. The genus Veillonella is relatively homogeneous: inter-genus pair-wise comparison identifies at least 1,350 shared proteins, although less than half of these are found in any given Clostridium genome. Only 27 proteins are found conserved in all analyzed prokaryote genomes. Veillonella has distinct metabolic properties, and significant similarities to genomes of Proteobacteria are not detected, with the exception of a shared LPS biosynthesis pathway. The clade within the class Negativicutes to which the genus Veillonella belongs exhibits unique properties, most of which are in common with Gram-positives and some with Gram negatives. They are only distantly related to Clostridia, but are even less closely related to Gram-negative species. Though the Negativicutes stain Gram-negative and possess two membranes, the genome and proteome analysis presented here confirm their place within the

  1. Support for higher ciprofloxacin AUC 24/MIC targets in treating Enterobacteriaceae bloodstream infection.

    Zelenitsky, Sheryl A; Ariano, Robert E

    2010-08-01

    Given concerns regarding optimal therapy for serious Gram-negative infections, the goal was to characterize the pharmacodynamics of ciprofloxacin in the context of treating bloodstream infection. Data were collected from the medical records of 178 clinical cases. Blood isolates were retrieved and ciprofloxacin MICs were measured. Forty-two cases in which ciprofloxacin was initiated within 24 h of the positive blood culture were used in the pharmacodynamic analysis. Significant factors with regard to treatment failure were low ciprofloxacin AUC(24)/MIC (P AUC(24) (P = 0.01). AUC(24)/MIC (P = 0.012) and MIC (P = 0.019) were significant variables in multivariate analyses; however, only the former remained significant (P = 0.038) after excluding two cases with ciprofloxacin-resistant isolates. An AUC(24)/MIC breakpoint of 250 was most significant, with cure rates of 91.4% (32/35) and 28.6% (2/7) in patients with values above and below this threshold, respectively (P = 0.001). The risk of ciprofloxacin treatment failure was 27.8 times (95% confidence interval, 2.1-333) greater in those not achieving an AUC(24)/MIC >or=250 (P = 0.011). Monte Carlo simulation of 5000 study subjects predicted that 0.88 of the population would achieve an AUC(24)/MIC >or=250 with standard-dose ciprofloxacin (400 mg intravenously every 12 h). This study confirms the pharmacodynamic parameters of ciprofloxacin that are important for optimizing the treatment of serious infections, particularly the benefits of achieving an AUC(24)/MIC >or=250, rather than the conventional target of >or=125. It also shows the relevance of dose selection in optimizing target attainment, with important differences among pathogens, even those with MICs within the susceptible range.

  2. Will new antimicrobials overcome resistance among Gram-negatives?

    Bassetti, Matteo; Ginocchio, Francesca; Mikulska, Małgorzata; Taramasso, Lucia; Giacobbe, Daniele Roberto

    2011-10-01

    The spread of resistance among Gram-positive and Gram-negative bacteria represents a growing challenge for the development of new antimicrobials. The pace of antibiotic drug development has slowed during the last decade and, especially for Gram-negatives, clinicians are facing a dramatic shortage in the availability of therapeutic options to face the emergency of the resistance problem throughout the world. In this alarming scenario, although there is a shortage of compounds reaching the market in the near future, antibiotic discovery remains one of the keys to successfully stem and maybe overcome the tide of resistance. Analogs of already known compounds and new agents belonging to completely new classes of antimicrobials are in early stages of development. Novel and promising anti-Gram-negative antimicrobials belong both to old (cephalosporins, carbapenems, β-lactamase inhibitors, monobactams, aminoglycosides, polymyxin analogues and tetracycline) and completely new antibacterial classes (boron-containing antibacterial protein synthesis inhibitors, bis-indoles, outer membrane synthesis inhibitors, antibiotics targeting novel sites of the 50S ribosomal subunit and antimicrobial peptides). However, all of these compounds are still far from being introduced into clinical practice. Therefore, infection control policies and optimization in the use of already existing molecules are still the most effective approaches to reduce the spread of resistance and preserve the activity of antimicrobials.

  3. Antimicrobial Photodynamic Therapy to Kill Gram-negative Bacteria

    Sperandio, Felipe F; Huang, Ying-Ying; Hamblin, Michael R

    2013-01-01

    Antimicrobial photodynamic therapy (PDT) or photodynamic inactivation (PDI) is a new promising strategy to eradicate pathogenic microorganisms such as Gram-positive and Gram-negative bacteria, yeasts and fungi. The search for new approaches that can kill bacteria but do not induce the appearance of undesired drug-resistant strains suggests that PDT may have advantages over traditional antibiotic therapy. PDT is a non-thermal photochemical reaction that involves the simultaneous presence of visible light, oxygen and a dye or photosensitizer (PS). Several PS have been studied for their ability to bind to bacteria and efficiently generate reactive oxygen species (ROS) upon photostimulation. ROS are formed through type I or II mechanisms and may inactivate several classes of microbial cells including Gram-negative bacteria such as Pseudomonas aeruginosa, which are typically characterized by an impermeable outer cell membrane that contains endotoxins and blocks antibiotics, dyes, and detergents, protecting the sensitive inner membrane and cell wall. This review covers significant peer-reviewed articles together with US and World patents that were filed within the past few years and that relate to the eradication of Gram-negative bacteria via PDI or PDT. It is organized mainly according to the nature of the PS involved and includes natural or synthetic food dyes; cationic dyes such as methylene blue and toluidine blue; tetrapyrrole derivatives such as phthalocyanines, chlorins, porphyrins, chlorophyll and bacteriochlorophyll derivatives; functionalized fullerenes; nanoparticles combined with different PS; other formulations designed to target PS to bacteria; photoactive materials and surfaces; conjugates between PS and polycationic polymers or antibodies; and permeabilizing agents such as EDTA, PMNP and CaCl2. The present review also covers the different laboratory animal models normally used to treat Gram-negative bacterial infections with antimicrobial PDT. PMID

  4. Outcomes of critically ill intensive care unit patients treated with fosfomycin for infections due to pandrug-resistant and extensively drug-resistant carbapenemase-producing Gram-negative bacteria.

    Pontikis, Konstantinos; Karaiskos, Ilias; Bastani, Styliani; Dimopoulos, George; Kalogirou, Michalis; Katsiari, Maria; Oikonomou, Angelos; Poulakou, Garyphallia; Roilides, Emmanuel; Giamarellou, Helen

    2014-01-01

    Fosfomycin is active in vitro against extensively drug-resistant (XDR) and pandrug-resistant (PDR) Pseudomonas aeruginosa and Klebsiella pneumoniae carbapenemase-producing strains; however, the in vivo effectiveness against such pathogens is almost unknown. A multicentre, observational, prospective case-series study was performed in 11 ICUs. All consecutive fosfomycin-treated patients suffering from XDR or PDR fosfomycin-susceptible, microbiologically documented infections were recorded. Clinical and microbiological outcomes were assessed. A safety analysis was performed. In total, 68 patients received fosfomycin during the study period, 48 of whom were considered suitable for effectiveness analysis based on predefined criteria. Bacteraemia and ventilator-associated pneumonia were the main infections. Carbapenemase-producing K. pneumoniae and P. aeruginosa were isolated in 41 and 17 cases, respectively. All isolates exhibited an XDR or PDR profile, being fosfomycin-susceptible by definition. Fosfomycin was administered intravenously at a median dose of 24g/day for a median of 14 days, mainly in combination with colistin or tigecycline. Clinical outcome at Day 14 was successful in 54.2% of patients, whilst failure, indeterminate outcome and superinfection were documented in 33.3%, 6.3% and 6.3%, respectively. All-cause mortality at Day 28 was 37.5%. Bacterial eradication was observed in 56.3% of cases. Fosfomycin resistance developed in three cases. The main adverse event was reversible hypokalaemia. In conclusion, fosfomycin could have a place in the armamentarium against XDR and PDR Gram-negative infections in the critically ill. Resistance development during therapy, which has been a matter of concern in previous studies, did not occur frequently. The necessity of combination with other antibiotics requires further investigation. Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  5. Resistance trends in gram-negative bacteria: surveillance results from two Mexican hospitals, 2005–2010

    Morfin-Otero Rayo

    2012-06-01

    Full Text Available Abstract Background Hospital-acquired infections caused by multiresistant gram-negative bacteria are difficult to treat and cause high rates of morbidity and mortality. The analysis of antimicrobial resistance trends of gram-negative pathogens isolated from hospital-acquired infections is important for the development of antimicrobial stewardship programs. The information obtained from antimicrobial resistant programs from two hospitals from Mexico will be helpful in the selection of empiric therapy for hospital-acquired gram-negative infections. Findings Two thousand one hundred thirty two gram-negative bacteria collected between January 2005 and December 2010 from hospital-acquired infections occurring in two teaching hospitals in Mexico were evaluated. Escherichia coli was the most frequently isolated gram-negative bacteria, with >50% of strains resistant to ciprofloxacin and levofloxacin. Klebsiella spp. showed resistance rates similar to Escherichia coli for ceftazidime (33.1% vs 33.2%, but exhibited lower rates for levofloxacin (18.2% vs 56%. Of the samples collected for the third most common gram-negative bacteria, Pseudomonas aeruginosa, >12.8% were resistant to the carbapenems, imipenem and meropenem. The highest overall resistance was found in Acinetobacter spp. Enterobacter spp. showed high susceptibility to carbapenems. Conclusions E. coli was the most common nosocomial gram-negative bacilli isolated in this study and was found to have the second-highest resistance to fluoroquinolones (>57.9%, after Acinetobacter spp. 81.2%. This finding represents a disturbing development in a common nosocomial and community pathogen.

  6. Quorum sensing in gram-negative bacteria

    Wu, H.; Song, Z.J.; Høiby, N.

    2004-01-01

    Bacteria can communicate with each other by means of signal molecules to coordinate the behavior of the entire community, and the mechanism is referred to as quorum sensing (QS). Signal systems enable bacteria to sense the size of their densities by monitoring the concentration of the signal...... molecules. Among Gram-negative bacteria N-acyl-L-homoserine lactone (acyl-HSL)-dependent quorum sensing systems are particularly widespread. These systems are used to coordinate expression of phenotypes that are fundamental to the interaction of bacteria with each other and with their environment...

  7. Bloodstream infection in patients with end-stage renal disease in a teaching hospital in central-western Brazil

    Tamara Trelha Gauna

    2013-08-01

    Full Text Available Introduction Vascular access in patients undergoing hemodialysis is considered a critical determinant of bloodstream infection (BSI and is associated with high morbidity and mortality. The purpose of this study was to investigate the occurrence of BSI in patients with end-stage renal disease using central venous catheters for hemodialysis. Methods A cohort study was conducted in a public teaching hospital in central-western Brazil from April 2010 to December 2011. For every patient, we noted the presence of hyperemia/exudation upon catheter insertion, as well as fever, shivering, and chills during hemodialysis. Results Fifty-nine patients were evaluated. Thirty-five (59.3% patients started dialysis due to urgency, 37 (62.7% had BSI, and 12 (20% died. Hyperemia at the catheter insertion site (64.9% was a significant clinical manifestation in patients with BSI. Statistical analysis revealed 1.7 times more cases of BSI in patients with hypoalbuminemia compared with patients with normal albumin levels. The principal infective agents identified in blood cultures and catheter-tip cultures were Staphylococcus species (24 cases, non-fermentative Gram-negative bacilli (7 cases of Stenotrophomonas maltophilia and 5 cases of Chryseobacterium indologenes, and Candida species (6. Among the Staphylococci identified, 77.7% were methicillin-resistant, coagulase-negative Staphylococci. Of the bacteria isolated, the most resistant were Chryseobacterium indologenes and Acinetobacter baumannii. Conclusions Blood culture was demonstrated to be an important diagnostic test and identified over 50% of positive BSI cases. The high frequency of BSI and the isolation of multiresistant bacteria were disturbing findings. Staphylococcus aureus was the most frequently isolated microorganism, although Gram-negative bacteria predominated overall. These results highlight the importance of infection prevention and control measures in dialysis units.

  8. The Changing Epidemiology of Bloodstream Infections and Resistance in Hematopoietic Stem Cell Transplantation Recipients

    Mücahit Yemişen

    2016-08-01

    Full Text Available Objective: Patients receiving hematopoietic stem cell transplantation (HSCT are exposed to highly immunosuppressive conditions and bloodstream infections (BSIs are one of the most common major complications within this period. Our aim, in this study, was to evaluate the epidemiology of BSIs in these patients retrospectively. Materials and Methods: The epidemiological properties of 312 patients with HSCT were retrospectively evaluated. Results: A total of 312 patients, followed between 2000 and 2011, who underwent autologous (62% and allogeneic (38% HSCT were included in the study. The most common underlying malignancies were multiple myeloma (28% and Hodgkin lymphoma (21.5%. A total of 142 (45% patients developed at least 1 episode of BSI and 193 separate pathogens were isolated from the blood cultures. There was a trend of increase in the numbers of BSIs in 2005-2008 and a relative increase in the proportion of gram-positive infections in recent years (2009-2011, and central venous catheter-related BSI was found to be most common source. Coagulase-negative staphylococci (49.2% and Acinetobacter baumannii (8.8% were the most common pathogens. Extended-spectrum beta-lactamase-producing strains were 23% and 22% among Escherichia coli and Klebsiella spp. isolates, respectively. Quinolone resistance was detected in 10% of Enterobacteriaceae. Resistance to carbapenems was not detected in Enterobacteriaceae, while it was seen at 11.1% and 23.5% in Pseudomonas and Acinetobacter strains, respectively. Conclusion: A shift was detected from gram-negative bacteria to gram-positive in the etiology over the years and central lines were the most common sources of BSIs.

  9. Tenebrio molitor Gram-negative-binding protein 3 (TmGNBP3) is essential for inducing downstream antifungal Tenecin 1 gene expression against infection with Beauveria bassiana JEF-007.

    Yang, Yi-Ting; Lee, Mi Rong; Lee, Se Jin; Kim, Sihyeon; Nai, Yu-Shin; Kim, Jae Su

    2017-05-23

    The Toll signaling pathway is responsible for defense against both Gram-positive bacteria and fungi. Gram-negative binding protein 3 (GNBP3) has a strong affinity for the fungal cell wall component, β-1,3-glucan, which can activate the prophenoloxidase (proPO) cascade and induce the Toll signaling pathway. Myeloid differentiation factor 88 (MyD88) is an intracellular adaptor protein involved in the Toll signaling pathway. In this study, we monitored the response of 5 key genes (TmGNBP3, TmMyD88, and Tenecin 1, 2, and 3) in the Toll pathway of the mealworm Tenebrio molitor immune system against the fungus Beauveria bassiana JEF-007 using RT-PCR. TmGNBP3, Tenecin 1, and Tenecin 2 were significantly upregulated after fungal infection. To better understand the roles of the Toll signaling pathway in the mealworm immune system, TmGNBP3 and TmMyD88 were knocked down by RNAi silencing. Target gene expression levels decreased at 2 d postknockdown and were dramatically reduced at 6 d post-dsRNA injection. Therefore, mealworms were compromised by B. bassiana JEF-007 at 6 d post-dsRNA injection. Silencing of TmMyD88 and TmGNBP3 resulted in reduced resistance of the host to fungal infection. Particularly, reducing TmGNBP3 levels obviously downregulated Tenecin 1 and Tenecin 2 expression levels, whereas silencing TmMyD88 expression resulted in decreased Tenecin 2 expression. These results indicate that TmGNBP3 is essential to induce downstream antifungal peptide Tenecin 1 expression against B. bassiana JEF-007. © 2017 Institute of Zoology, Chinese Academy of Sciences.

  10. Surveillance of antimicrobial susceptibility of aerobic and facultative Gram-negative bacilli isolated from patients with intra-abdominal infections in China: the 2002-2009 Study for Monitoring Antimicrobial Resistance Trends (SMART).

    Yang, Qiwen; Wang, Hui; Chen, Minjun; Ni, Yuxing; Yu, Yunsong; Hu, Bijie; Sun, Ziyong; Huang, Wenxiang; Hu, Yunjian; Ye, Huifen; Badal, Robert E; Xu, Yingchun

    2010-12-01

    The objective of this study was to investigate the distribution and susceptibility of aerobic and facultative Gram-negative bacilli (GNB) isolated from patients with intra-abdominal infections (IAIs) in China. From 2002 to 2009, minimum inhibitory concentrations of 14 antibiotics for 3420 aerobic and facultative GNB from up to eight hospitals in six cities were determined by the broth microdilution method. Enterobacteriaceae comprised 82.9% (2834/3420) of the total isolates, with Escherichia coli (49.2%) being the most commonly isolated species followed by Klebsiella pneumoniae (17.0%), Enterobacter cloacae (5.8%) and Citrobacter freundii (2.3%). Amongst the antimicrobial agents tested, the three carbapenems (ertapenem, imipenem and meropenem) were the most active agents against Enterobacteriaceae, with susceptibility rates of 96.1-99.6% (2002-2009), 98.2-100% (2002-2009) and 99.6-100% (2002-2004), respectively, followed by amikacin (86.8-95.1%) and piperacillin/tazobactam (84.5-94.3%). Susceptibility rates of all tested third- and fourth-generation cephalosporins against Enterobacteriaceae declined by nearly 30%, with susceptibility rates of 40.2%, 39.1%, 56.3% and 51.8% in 2009 for ceftriaxone, cefotaxime, ceftazidime and cefepime, respectively. The occurrence of extended-spectrum β-lactamases increased rapidly, especially for E. coli (from 20.8% in 2002 to 64.9% in 2009). Susceptibility of E. coli to ciprofloxacin decreased from 57.6% in 2002 to 24.2% in 2009. The least active agent against Enterobacteriaceae was ampicillin/sulbactam (SAM) (25.3-44.3%). In conclusion, Enterobacteriaceae were the major pathogens causing IAIs, and carbapenems retained the highest susceptibility rates over the 8-year study period. Third- and fourth-generation cephalosporins, fluoroquinolones and SAM may not be ideal choices for empirical therapy of IAIs in China. Copyright © 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  11. Effects of Methicillin-Resistant Staphylococcus aureus/Multiresistant Gram-Negative Bacteria Colonization or Infection and Isolation Measures in End of Life on Family Caregivers: Results of a Qualitative Study.

    Heckel, Maria; Sturm, Alexander; Herbst, Franziska A; Ostgathe, Christoph; Stiel, Stephanie

    2017-03-01

    Little is known about the experiences of family caregivers of hospitalized patients with confirmed methicillin-resistant Staphylococcus aureus/multiresistant gram-negative bacteria (MRSA/MRGN) diagnosis at the end of life. The study at hand is a subproject of an interdisciplinary cooperation project that aims at developing a patient-, family-, and team-centered approach in dealing with MRSA/MRGN-positive hospitalized patients in palliative and geriatric care. The present study aimed to assess the individual effects of the patient's MRSA/MRGN colonization or infection and isolation measures on family caregivers. Between April 2014 and September 2015, all known family caregivers associated with an MRSA/MRGN-positive patient from a palliative care unit, a hospital palliative care support team, and a geriatric ward were considered for study participation. A qualitative interview study with family caregivers and an additional focus group was conducted. Data were analyzed using the principles of Grounded Theory. Family caregivers (N = 62) raised suggestions regarding the provision of information and communication on the MRSA/MRGN diagnosis and hygiene measures from staff members and the consistency of hygiene procedures. Family caregivers requested not to be stigmatized or being disadvantaged due to the MRSA/MRGN diagnosis of the patient, and they wished to receive psychosocial and emotional support. Staff members and institutional stakeholders should be aware that family caregivers might be burdened and upset by positive MRSA/MRGN diagnosis and the required hygiene measures. The need for detailed and understandable information on MRSA/MRGN, adequate communication between staff members and family caregivers, and support for family caregivers should be of special attention in particular in end-of-life care.

  12. Costs and length of stay associated with antimicrobial resistance in acute kidney injury patients with bloodstream infection.

    Vandijck, D M; Blot, S I; Decruyenaere, J M; Vanholder, R C; De Waele, J J; Lameire, N H; Claus, S; De Schuijmer, J; Dhondt, A W; Verschraegen, G; Hoste, E A

    2008-01-01

    Antimicrobial resistance negatively impacts on prognosis. Intensive care unit (ICU) patients, and particularly those with acute kidney injury (AKI), are at high risk for developing nosocomial bloodstream infections (BSI) due to multi-drug-resistant strains. Economic implications in terms of costs and length of stay (LOS) attributable to antimicrobial resistance are underevaluated. This study aimed to assess whether microbial susceptibility patterns affect costs and LOS in a well-defined cohort of ICU patients with AKI undergoing renal replacement therapy (RRT) who developed nosocomial BSI. Historical study (1995-2004) enrolling all adult RRT-dependent ICU patients with AKI and nosocomial BSI. Costs were considered as invoiced in the Belgian reimbursement system, and LOS was used as a surrogate marker for hospital resource allocation. Of the 1330 patients with AKI undergoing RRT, 92 had microbiologic evidence of nosocomial BSI (57/92, 62% due to a multi-drug-resistant microorganism). Main patient characteristics were equal in both groups. As compared to patients with antimicro-4 bial-susceptible BSI, patients with antimicrobial-resistant BSI were more likely to acquire Gram-positive infection (72.6% vs 25.5%, P0.05) or hospital costs (all P>0.05) when comparing patients with antimicrobial-resistant vs antimicrobial-susceptible BSI. However, although not statistically significant, patients with BSI caused by resistant Gram-negative-, Candida-, or anaerobic bacteria incurred substantial higher costs than those without. In a cohort of ICU patients with AKI and nosocomial BSI undergoing RRT, patients with antimicrobial-resistant vs antimicrobial-susceptible Gram-positive BSI did not have longer hospital stays, or higher hospital costs. Patients with resistant "other" (i.e. Gram-negative, Candida, or anaerobic) BSI were found to have a distinct trend towards increased resources use as compared to patients with susceptible "other" BSI, respectively.

  13. Risk of vancomycin-resistant enterococci bloodstream infection among patients colonized with vancomycin-resistant enterococci

    Ahu Kara

    2015-01-01

    Conclusion: In conclusion, our study found that 1.55% of vancomycin-resistant enterococci-colonized children had developed vancomycin-resistant enterococci bloodstream infection among the pediatric intensive care unit and hematology/oncology patients; according to our findings, we suggest that immunosupression is the key point for developing vancomycin-resistant enterococci bloodstream infections.

  14. Candida bloodstream infection: a clinical microbiology laboratory perspective.

    Pongrácz, Júlia; Kristóf, Katalin

    2014-09-01

    The incidence of Candida bloodstream infection (BSI) has been on the rise in several countries worldwide. Species distribution is changing; an increase in the percentage of non-albicans species, mainly fluconazole non-susceptible C. glabrata was reported. Existing microbiology diagnostic methods lack sensitivity, and new methods need to be developed or further evaluation for routine application is necessary. Although reliable, standardized methods for antifungal susceptibility testing are available, the determination of clinical breakpoints remains challenging. Correct species identification is important and provides information on the intrinsic susceptibility profile of the isolate. Currently, acquired resistance in clinical Candida isolates is rare, but reports indicate that it could be an issue in the future. The role of the clinical microbiology laboratory is to isolate and correctly identify the infective agent and provide relevant and reliable susceptibility data as soon as possible to guide antifungal therapy.

  15. Antimicrobial susceptibility of gram-negative pathogens isolated from patients with complicated intra-abdominal infections in South African hospitals (SMART Study 2004-2009): impact of the new carbapenem breakpoints.

    Brink, Adrian J; Botha, Roelof F; Poswa, Xoliswa; Senekal, Marthinus; Badal, Robert E; Grolman, David C; Richards, Guy A; Feldman, Charles; Boffard, Kenneth D; Veller, Martin; Joubert, Ivan; Pretorius, Jan

    2012-02-01

    The Study for Monitoring Antimicrobial Resistance Trends (SMART) follows trends in resistance among aerobic and facultative anaerobic gram-negative bacilli (GNB) isolated from complicated intra-abdominal infections (cIAIs) in patients around the world. During 2004-2009, three centralized clinical microbiology laboratories serving 59 private hospitals in three large South African cities collected 1,218 GNB from complicated intra-abdominal infections (cIAIs) and tested them for susceptibility to 12 antibiotics according to the 2011 Clinical Laboratory Standards Institute (CLSI) guidelines. Enterobacteriaceae comprised 83.7% of the isolates. Escherichia coli was the species isolated most commonly (46.4%), and 7.6% of these were extended-spectrum β-lactamase (ESBL)-positive. The highest ESBL rate was documented for Klebsiella pneumoniae (41.2%). Overall, ertapenem was the antibiotic most active against susceptible species for which it has breakpoints (94.6%) followed by amikacin (91.9%), piperacillin-tazobactam (89.3%), and imipenem-cilastatin (87.1%), whereas rates of resistance to ceftriaxone, cefotaxime, ciprofloxacin, and levofloxacin were documented to be 29.7%, 28.7%, 22.5%, and 21.1%, respectively. Multi-drug resistance (MDR), defined as resistance to three or more antibiotic classes, was significantly more common in K. pneumoniae (27.9%) than in E. coli (4.9%; p<0.0001) or Proteus mirabilis (4.1%; p<0.05). Applying the new CLSI breakpoints for carbapenems, susceptibility to ertapenem was reduced significantly in ESBL-positive E. coli compared with ESBL-negative isolates (91% vs. 98%; p<0.05), but this did not apply to imipenem-cilastatin (95% vs. 99%; p=0.0928). A large disparity between imipenem-cilastatin and ertapenem susceptibility in P. mirabilis and Morganella morganii was documented (24% vs. 96% and 15% vs. 92%, respectively), as most isolates of these two species had imipenem-cilastatin minimum inhibitory concentrations in the 2-4 mcg/mL range, which

  16. Epidemiology, surveillance, and prevention of bloodstream infections in hemodialysis patients.

    Patel, Priti R; Kallen, Alexander J; Arduino, Matthew J

    2010-09-01

    Infections cause significant morbidity and mortality in patients undergoing hemodialysis. Bloodstream infections (BSIs) are particularly problematic, accounting for a substantial number of hospitalizations in these patients. Hospitalizations for BSI and other vascular access infections appear to have increased dramatically in hemodialysis patients since 1993. These infections frequently are related to central venous catheter (CVC) use for dialysis access. Regional initiatives that have shown successful decreases in catheter-related BSIs in hospitalized patients have generated interest in replicating this success in outpatient hemodialysis populations. Several interventions have been effective in preventing BSIs in the hemodialysis setting. Avoiding the use of CVCs in favor of access types with lower associated BSI risk is among the most important. When CVCs are used, adherence to evidence-based catheter insertion and maintenance practices can positively influence BSI rates. In addition, facility-level surveillance to detect BSIs and stimulate examination of vascular access use and care practices is essential to a comprehensive approach to prevention. This article describes the current epidemiology of BSIs in hemodialysis patients and effective prevention strategies to decrease the incidence of these devastating infections.

  17. Patients with Central Lines - What You Need to Know to Avoid a Bloodstream Infection PSA (:60)

    This 60 second PSA is based on the March, 2011 CDC Vital Signs report which indicates bloodstream infections in patients with central lines are largely preventable when healthcare providers use CDC-recommended infection control steps.

  18. Cytokine responses to Staphylococcus aureus bloodstream infection differ between patient cohorts that have different clinical courses of infection.

    McNicholas, Sinead; Talento, Alida Fe; O'Gorman, Joanne; Hannan, Margaret M; Lynch, Maureen; Greene, Catherine M; Humphreys, Hilary; Fitzgerald-Hughes, Deirdre

    2014-11-15

    The clinical course of Staphylococcus aureus bloodstream infection is unpredictable and bacterial virulence, host immune response and patient characteristics are among the factors that contribute to the clinical course of infection. To investigate the relationship between cytokine response and clinical outcome, circulating cytokine levels were investigated in response to S. aureus bloodstream infection in patients with different clinical courses of infection. A prospective study was carried out in 61 patients with S. aureus bloodstream infection and circulating levels of IL-6, GRO-γ, RANTES and leptin were assessed over the course of the infection. Levels were compared in patients with complicated courses of infection (e.g. infective endocarditis) versus uncomplicated courses of S. aureus bloodstream infection and methicillin-resistant S. aureus Vs methicillin-susceptible S. aureus infection. Significantly lower leptin levels (p < 0.05) and significantly higher IL-6 levels (p < 0.05) were detected at laboratory diagnosis in patients with complicated compared to uncomplicated S. aureus bloodstream infection. Significantly higher levels of GRO-γ were associated with MRSA infection compared to MSSA infection. IL-6 may be an early inflammatory marker of complicated S. aureus bloodstream infection. Leptin may be protective against the development of a complicated S. aureus bloodstream infection.

  19. Incidence of carbapenem-resistant gram negatives in Italian transplant recipients: a nationwide surveillance study.

    Lanini, Simone; Costa, Alessandro Nanni; Puro, Vincenzo; Procaccio, Francesco; Grossi, Paolo Antonio; Vespasiano, Francesca; Ricci, Andrea; Vesconi, Sergio; Ison, Michael G; Carmeli, Yehuda; Ippolito, Giuseppe

    2015-01-01

    Bacterial infections remain a challenge to solid organ transplantation. Due to the alarming spread of carbapenem-resistant gram negative bacteria, these organisms have been frequently recognized as cause of severe infections in solid organ transplant recipients. Between 15 May and 30 September 2012 we enrolled 887 solid organ transplant recipients in Italy with the aim to describe the epidemiology of gram negative bacteria spreading, to explore potential risk factors and to assess the effect of early isolation of gram negative bacteria on recipients' mortality during the first 90 days after transplantation. During the study period 185 clinical isolates of gram negative bacteria were reported, for an incidence of 2.39 per 1000 recipient-days. Positive cultures for gram negative bacteria occurred early after transplantation (median time 26 days; incidence rate 4.33, 1.67 and 1.14 per 1,000 recipient-days in the first, second and third month after SOT, respectively). Forty-nine of these clinical isolates were due to carbapenem-resistant gram negative bacteria (26.5%; incidence 0.63 per 1000 recipient-days). Carbapenems resistance was particularly frequent among Klebsiella spp. isolates (49.1%). Recipients with longer hospital stay and those who received either heart or lung graft were at the highest risk of testing positive for any gram negative bacteria. Moreover recipients with longer hospital stay, lung recipients and those admitted to hospital for more than 48h before transplantation had the highest probability to have culture(s) positive for carbapenem-resistant gram negative bacteria. Forty-four organ recipients died (0.57 per 1000 recipient-days) during the study period. Recipients with at least one positive culture for carbapenem-resistant gram negative bacteria had a 10.23-fold higher mortality rate than those who did not. The isolation of gram-negative bacteria is most frequent among recipient with hospital stays >48 hours prior to transplant and in those

  20. Incidence of carbapenem-resistant gram negatives in Italian transplant recipients: a nationwide surveillance study.

    Simone Lanini

    Full Text Available Bacterial infections remain a challenge to solid organ transplantation. Due to the alarming spread of carbapenem-resistant gram negative bacteria, these organisms have been frequently recognized as cause of severe infections in solid organ transplant recipients.Between 15 May and 30 September 2012 we enrolled 887 solid organ transplant recipients in Italy with the aim to describe the epidemiology of gram negative bacteria spreading, to explore potential risk factors and to assess the effect of early isolation of gram negative bacteria on recipients' mortality during the first 90 days after transplantation. During the study period 185 clinical isolates of gram negative bacteria were reported, for an incidence of 2.39 per 1000 recipient-days. Positive cultures for gram negative bacteria occurred early after transplantation (median time 26 days; incidence rate 4.33, 1.67 and 1.14 per 1,000 recipient-days in the first, second and third month after SOT, respectively. Forty-nine of these clinical isolates were due to carbapenem-resistant gram negative bacteria (26.5%; incidence 0.63 per 1000 recipient-days. Carbapenems resistance was particularly frequent among Klebsiella spp. isolates (49.1%. Recipients with longer hospital stay and those who received either heart or lung graft were at the highest risk of testing positive for any gram negative bacteria. Moreover recipients with longer hospital stay, lung recipients and those admitted to hospital for more than 48h before transplantation had the highest probability to have culture(s positive for carbapenem-resistant gram negative bacteria. Forty-four organ recipients died (0.57 per 1000 recipient-days during the study period. Recipients with at least one positive culture for carbapenem-resistant gram negative bacteria had a 10.23-fold higher mortality rate than those who did not.The isolation of gram-negative bacteria is most frequent among recipient with hospital stays >48 hours prior to transplant

  1. Relationship between neighborhood poverty rate and bloodstream infections in the critically ill.

    Mendu, Mallika L; Zager, Sam; Gibbons, Fiona K; Christopher, Kenneth B

    2012-05-01

    Poverty is associated with increased risk of chronic illness, but its contribution to bloodstream infections is not well-defined. We performed a multicenter observational study of 14,657 patients, aged 18 yrs or older, who received critical care and had blood cultures drawn between 1997 and 2007 in two hospitals in Boston, Massachusetts. Data sources included 1990 U.S. Census and hospital administrative data. Census tracts were used as the geographic units of analysis. The exposure of interest was neighborhood poverty rate categorized as 40%. Neighborhood poverty rate is the percentage of residents with income below the federal poverty line. The primary end point was bloodstream infection occurring 48 hrs before critical care initiation to 48 hrs after. Associations between neighborhood poverty rate and bloodstream infection were estimated by logistic regression models. Adjusted odds ratios were estimated by multivariable logistic regression models. Two thousand four-hundred thirty-five patients had bloodstream infections. Neighborhood poverty rate was a strong predictor of risk of bloodstream infection, with a significant risk gradient across neighborhood poverty rate quintiles. After multivariable analysis, neighborhood poverty rate in the highest quintiles (20%-40% and >40%) were associated with a 26% and 49% increase in bloodstream infection risk, respectively, relative to patients with neighborhood poverty rate of poverty rate, a proxy for decreased socioeconomic status, appears to be associated with risk of bloodstream infection among patients who receive critical care.

  2. Marine Compounds with Therapeutic Potential in Gram-Negative Sepsis

    Irina Yermak

    2013-06-01

    Full Text Available This paper concerns the potential use of compounds, including lipid A, chitosan, and carrageenan, from marine sources as agents for treating endotoxemic complications from Gram-negative infections, such as sepsis and endotoxic shock. Lipid A, which can be isolated from various species of marine bacteria, is a potential antagonist of bacterial endotoxins (lipopolysaccharide (LPSs. Chitosan is a widespread marine polysaccharide that is derived from chitin, the major component of crustacean shells. The potential of chitosan as an LPS-binding and endotoxin-neutralizing agent is also examined in this paper, including a discussion on the generation of hydrophobic chitosan derivatives to increase the binding affinity of chitosan to LPS. In addition, the ability of carrageenan, which is the polysaccharide of red alga, to decrease the toxicity of LPS is discussed. We also review data obtained using animal models that demonstrate the potency of carrageenan and chitosan as antiendotoxin agents.

  3. Efficacy of an infection control programme in reducing nosocomial bloodstream infections in a Senegalese neonatal unit.

    Landre-Peigne, C; Ka, A S; Peigne, V; Bougere, J; Seye, M N; Imbert, P

    2011-10-01

    Neonatal nosocomial infections are public health threats in the developing world, and successful interventions are rarely reported. A before-and-after study was conducted in the neonatal unit of the Hôpital Principal de Dakar, Senegal to assess the efficacy of a multi-faceted hospital infection control programme implemented from March to May 2005. The interventions included clustering of nursing care, a simple algorithm for empirical therapy of suspected early-onset sepsis, minimal invasive care and promotion of early discharge of neonates. Data on nosocomial bloodstream infections, mortality, bacterial resistance and antibiotic use were collected before and after implementation of the infection control programme. One hundred and twenty-five infants were admitted immediately before the programme (Period 1, January-February 2005) and 148 infants were admitted immediately after the programme (Period 2, June-July 2005). The two groups of infants were comparable in terms of reason for admission and birth weight. After implementation of the infection control programme, the overall rate of nosocomial bloodstream infections decreased from 8.8% to 2.0% (P=0.01), and the rate of nosocomial bloodstream infections/patient-day decreased from 10.9 to 2.9/1000 patient-days (P=0.03). Overall mortality rates did not differ significantly. The proportion of neonates who received antimicrobial therapy for suspected early-onset sepsis decreased significantly from 100% to 51% of at-risk infants (Punit, simple, low-cost and sustainable interventions led to the control of a high incidence of bacterial nosocomial bloodstream infections, and the efficacy of these interventions was long-lasting. Such interventions could be extended to other low-income countries. Copyright © 2011 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  4. Catheter Removal versus Retention in the Management of Catheter-Associated Enterococcal Bloodstream Infections

    Jonas Marschall

    2013-01-01

    Full Text Available BACKGROUND: Enterococci are an important cause of central venous catheter (CVC-associated bloodstream infections (CA-BSI. It is unclear whether CVC removal is necessary to successfully manage enterococcal CA-BSI.

  5. Impact of removing mucosal barrier injury laboratory-confirmed bloodstream infections from central line-associated bloodstream infection rates in the National Healthcare Safety Network, 2014.

    See, Isaac; Soe, Minn M; Epstein, Lauren; Edwards, Jonathan R; Magill, Shelley S; Thompson, Nicola D

    2017-03-01

    Central line-associated bloodstream infection (CLABSI) event data reported to the National Healthcare Safety Network from 2014, the first year of required use of the mucosal barrier injury laboratory-confirmed bloodstream infection (MBI-LCBI) definition, were analyzed to assess the impact of removing MBI-LCBI events from CLABSI rates. CLABSI rates decreased significantly in some location types after removing MBI-LCBI events, and MBI-LCBI events will be removed from publicly reported CLABSI rates. Published by Elsevier Inc.

  6. Recent advances in the microbiological diagnosis of bloodstream infections.

    Florio, Walter; Morici, Paola; Ghelardi, Emilia; Barnini, Simona; Lupetti, Antonella

    2018-05-01

    Rapid identification (ID) and antimicrobial susceptibility testing (AST) of the causative agent(s) of bloodstream infections (BSIs) are essential for the prompt administration of an effective antimicrobial therapy, which can result in clinical and financial benefits. Immediately after blood sampling, empirical antimicrobial therapy, chosen on clinical and epidemiological data, is administered. When ID and AST results are available, the clinician decides whether to continue or streamline the antimicrobial therapy, based on the results of the in vitro antimicrobial susceptibility profile of the pathogen. The aim of the present study is to review and discuss the experimental data, advantages, and drawbacks of recently developed technological advances of culture-based and molecular methods for the diagnosis of BSI (including mass spectrometry, magnetic resonance, PCR-based methods, direct inoculation methods, and peptide nucleic acid fluorescence in situ hybridization), the understanding of which could provide new perspectives to improve and fasten the diagnosis and treatment of septic patients. Although blood culture remains the gold standard to diagnose BSIs, newly developed methods can significantly shorten the turnaround time of reliable microbial ID and AST, thus substantially improving the diagnostic yield.

  7. Rhodotorula mucilaginosa Bloodstream Infection in a Case of Duodenal Perforation

    Rajmane

    2016-08-01

    Full Text Available Introduction Rhodotorula species are widespread in nature and can be isolated from a variety of sources, including air, soil, seawater, plants, and the household environment. They are also widely distributed in hospitals, and their presence could be considered a risk factor for hospitalized patients. These commensal yeasts have emerged as a cause of life-threatening fungemia in patients with depressed immune systems. Case Presentation We report a case of duodenal perforation with peritonitis in a 36-year-old female who was scheduled immediately for exploratory laparotomy followed by closure of perforation and omentopexy. The peritoneal fluid was sent to the microbiology laboratory for routine investigations. On the 4th postoperative day, the patient had a fever that did not subside with antipyretics; hence, blood cultures were sent the next day. The peritoneal fluid and blood culture reports both yielded Rhodotorula mucilaginosa after 3 days of incubation. The patient was started on IV amphotericin B therapy, which resulted in a favorable outcome. Conclusions In humans, Rhodotorula species have been recovered as commensal organisms from the nails, the skin, and the respiratory, gastrointestinal (GI, and urinary tracts. Due to their presence in the GI flora, broad-spectrum antibiotics could contribute to their overgrowth in the GI tract. Localized infections, such as peritonitis, due to Rhodotorula species following infected peritoneal dialysis catheters have been reported in the literature. However, in our case, it seems possible that the fungus might have entered the bloodstream through disruption of the GI mucosa, and to prove this, further study is mandatory. It should also be noted that both amphotericin B and flucytosine have good activity against Rhodotorula in vitro, whereas fluconazole is inactive.

  8. Extended spectrum beta-lactamases in urinary gram-negative bacilli and their susceptibility pattern

    Mumtaz, S.

    2008-01-01

    Beta-lactamases of gram-negative bacteria are the most important mechanism of resistance against beta lactams. Two types of beta-lactamases can confer resistance against third generation cephalosporins inducible Chromosomal beta -lactamases and extended-spectrum beta-lactamases. The extended-spectrum beta lactamases producing Strains of Enterobacteriaceae have emerged as a major problem in hospitalized as well as community based infections resulting in range of infections from uncomplicated urinary tract infection to life threatening sepsis. The study was conducted at the Microbiology Department of Fauji Foundation Hospital, Rawalpindi over a period of two years (April 2004-March 2006). Multidrug resistance and extended spectrum beta-lactamases production was studied in 111 enteric Gram-negative bacilli isolated from urine of symptomatic patients (1- 70 years) including males and females from indoor and outdoor patients by using double disc diffusion technique. Prevalence of extended-spectrum beta-lactamases production was seen in 71 (61.2%) enteric gram-negative organisms, the most prevalent gram-negative organism was Klebsiella pneumoniae 40 (71.4%) followed by Escherichia coli 27 (62.8%) and Pseudomonas aeruginosa 3 (25%). The extended-spectrum beta-lactamases producers were more prevalent in indoor patients 63 (88.7%) compared to outdoor patients 8 (11.3%), more in females 43 (60.6%) than males, 28 (39.4%). The extended-spectrum beta-lactamases producing gram-negative rods had more antibiotic-resistant profile than non-producers. All enteric gram negative rods should be tested for the production of extended-spectrum beta-lactamases in routine microbiology laboratory. (author)

  9. Antibiotic susceptibility of Gram-negatives isolated from bacteremia in children with cancer. Implications for empirical therapy of febrile neutropenia.

    Castagnola, Elio; Caviglia, Ilaria; Pescetto, Luisa; Bagnasco, Francesca; Haupt, Riccardo; Bandettini, Roberto

    2015-01-01

    Monotherapy is recommended as the first choice for initial empirical therapy of febrile neutropenia, but local epidemiological and antibiotic susceptibility data are now considered pivotal to design a correct management strategy. To evaluate the proportion of Gram-negative rods isolated in bloodstream infections in children with cancer resistant to antibiotics recommended for this indication. The in vitro susceptibility to ceftazidime, piperacillin-tazobactam, meropenem and amikacin of Gram-negatives isolated in bacteremic episodes in children with cancer followed at the Istituto "Giannina Gaslini", Genoa, Italy in the period of 2001-2013 was retrospectively analyzed using the definitions recommended by EUCAST in 2014. Data were analyzed for any single drug and to the combination of amikacin with each β-lactam. The combination was considered effective in absence of concomitant resistance to both drugs, and not evaluated by means of in vitro analysis of antibiotic combinations (e.g., checkerboard). A total of 263 strains were evaluated: 27% were resistant to piperacillin-tazobactam, 23% to ceftazidime, 12% to meropenem and 13% to amikacin. Concomitant resistance to β-lactam and amikacin was detected in 6% of strains for piperacillin-tazobactam, 5% for ceftazidime and 5% for meropenem. During the study period there was a nonsignificant increase in the proportions of strains resistant to β-lactams indicated for monotherapy, and also increase in the resistance to combined therapies. in an era of increasing resistance to antibiotics guideline-recommended monotherapy could be not appropriate for initial empirical therapy of febrile neutropenia. Strict local survey on etiology and antibiotic susceptibility is mandatory for a correct management of this complication in cancer patients.

  10. Volatile metabolites from some gram-negative bacteria

    Schöller, Charlotte; Molin, Søren; Wilkins, Ken

    1997-01-01

    A survey of volatile organic compounds (VOCs) excreted from various Gram-negative bacteria (Pseudomonas spp., Serratia spp. and Enterobacter spp.) was carried out. Compounds were identified by gas chromatography-mass spectrometry. VOCs identified included dimethyl disulphide, dimethyl trisulphide...

  11. Pulmonary infiltrates during community acquired Gram-negative bacteremia

    Fjeldsøe-Nielsen, Hans; Gjeraa, Kirsten; Berthelsen, Birgitte G

    2013-01-01

    The primary aim of this study was to describe the frequency of pulmonary infiltrates on chest X-ray (CXR) during community acquired Gram-negative bacteremia at a single centre in Denmark.......The primary aim of this study was to describe the frequency of pulmonary infiltrates on chest X-ray (CXR) during community acquired Gram-negative bacteremia at a single centre in Denmark....

  12. Prevalence of AmpC β-lactamase among Gram-negative bacteria ...

    Purpose: Infections caused by AmpC-positive bacteria results in high patient morbidity and mortality making their detection clinically important as they cannot be detected in routine susceptibility testing. This study aim to determine the prevalence of AmpC β-lactamase among Gram negative bacteria recovered from clinical ...

  13. Extended-spectrum ß-lactamases in gram negative bacteria

    Deepti Rawat

    2010-01-01

    Full Text Available Extended-spectrum ß-lactamases (ESBLs are a group of plasmid-mediated, diverse, complex and rapidly evolving enzymes that are posing a major therapeutic challenge today in the treatment of hospitalized and community-based patients. Infections due to ESBL producers range from uncomplicated urinary tract infections to life-threatening sepsis. Derived from the older TEM is derived from Temoniera, a patient from whom the strain was first isolated in Greece. ß-lactamases, these enzymes share the ability to hydrolyze third-generation cephalosporins and aztreonam and yet are inhibited by clavulanic acid. In addition, ESBL-producing organisms exhibit co-resistance to many other classes of antibiotics, resulting in limitation of therapeutic option. Because of inoculum effect and substrate specificity, their detection is also a major challenge. At present, however, organizations such as the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards provide guidelines for the detection of ESBLs in Klebsiella pneumoniae, K. oxytoca, Escherichia coli and Proteus mirabilis. In common to all ESBL-detection methods is the general principle that the activity of extended-spectrum cephalosporins against ESBL-producing organisms will be enhanced by the presence of clavulanic acid. Carbapenems are the treatment of choice for serious infections due to ESBL-producing organisms, yet carbapenem-resistant isolates have recently been reported. ESBLs represent an impressive example of the ability of gram-negative bacteria to develop new antibiotic-resistance mechanisms in the face of the introduction of new antimicrobial agents. Thus there is need for efficient infection-control practices for containment of outbreaks; and intervention strategies, e.g., antibiotic rotation to reduce further selection and spread of these increasingly resistant pathogens.

  14. Patients with Central Lines - What You Need to Know to Avoid a Bloodstream Infection PSA (:60)

    2011-03-01

    This 60 second PSA is based on the March, 2011 CDC Vital Signs report which indicates bloodstream infections in patients with central lines are largely preventable when healthcare providers use CDC-recommended infection control steps.  Created: 3/1/2011 by Centers for Disease Control and Prevention (CDC).   Date Released: 3/1/2011.

  15. Risk factors for laboratory-confirmed bloodstream infection in neonates undergoing surgical procedures

    Roberta Maia de Castro Romanelli

    2014-07-01

    Conclusions: Shortening time on parenteral nutrition whenever possible and preference for non-invasive ventilation in neonates undergoing surgery should be considered in the assistance of these patients, with the goal of reducing Healthcare Associated Infections, especially laboratory-confirmed bloodstream infection.

  16. Emerging trends of bloodstream infection: A six-year study at a paediatric tertiary care hospital in kabul

    Tariq, T.M.; Rasool, E.

    2016-01-01

    To determine the frequency of pathogens causing bloodstream infections and evaluate their trends and antibiogram patterns among in-patients in a paediatric tertiary care centre. Study Design: Descriptive study. Place and Duration of Study: French Medical Institute for Mothers and Children (FMIC), Kabul, Afghanistan in two phases, from January 2010 to December 2015. Methodology: Results of blood cultures from suspected cases of sepsis admitted in the FMIC, from January 2010 to December 2012 (Period-1), and from January 2013 to December 2015 (Period-2) were completed. Standard microbiological methods were followed for blood culture and antibiotic sensitivity testing. Results: Out of total 1,040 cases of culture proven sepsis, 528 (50.77%) Gram-negative bacilli (GNB), 474 (45.58%) Gram-positive cocci (GPC), and 38 (3.65%) Candida species were isolated during the entire study period. Out of 528 GNB isolates, 373 (70.64%) belonged to the Enterobacteriaceae and 155 (29.36%) were non-fermenters. Among Enterobacteriaceae, 168 (31.82%) were Klebsiella species (K. pneumoniae=124, K. oxytoca=44), 70 (13.26%) were Enterobacter species (E. cloacae=52, E. aerogenes=18), 65 (12.31%) were E. coli, 37 (7.01%) were Serratia marcescens and 31 (5.87%) were others. Out of 155 non-fermenters, 88 (16.67%) were Pseudomonas aeruginosa, 39 (7.39%) were Burkholderia cepacia and 18 (3.41%) were Stenotrophomonas maltophilia. There was a drop in the frequency of Enterobacteriaceae from 85% in Period-1 to 58.68% in Period-2. There was an increase in the frequency of nonuniformities from 15% to 41.32%, particularly 18 new cases of sepsis caused by Stenotrophomonas maltophilia during Period-2. Among GPC, there was an overall rise of 16.14% in the prevalence of Staphylococcus epidermidis during Period-2 and a drop of 9.64% in the frequency of Staphylococcus aureus during Period-2. The majority of Gram-negative isolates were multidrug-resistant to commonly used antibiotics. However, most of the

  17. Distribution of multi-resistant Gram-negative versus Gram-positive bacteria in the hospital inanimate environment.

    Lemmen, S W; Häfner, H; Zolldann, D; Stanzel, S; Lütticken, R

    2004-03-01

    We prospectively studied the difference in detection rates of multi-resistant Gram-positive and multi-resistant Gram-negative bacteria in the inanimate environment of patients harbouring these organisms. Up to 20 different locations around 190 patients were surveyed. Fifty-four patients were infected or colonized with methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE) and 136 with multi-resistant Gram-negative bacteria. The environmental detection rate for MRSA or VRE was 24.7% (174/705 samples) compared with 4.9% (89/1827 samples) for multi-resistant Gram-negative bacteria (PGram-positive bacteria were isolated more frequently than Gram-negatives from the hands of patients (PGram-positive and Gram-negative isolates. Our results suggest that the inanimate environment serves as a secondary source for MRSA and VRE, but less so for Gram-negative bacteria. Thus, strict contact isolation in a single room with complete barrier precautions is recommended for MRSA or VRE; however, for multi-resistant Gram-negative bacteria, contact isolation with barrier precautions for close contact but without a single room seems sufficient. This benefits not only the patients, but also the hospital by removing some of the strain placed on already over-stretched resources.

  18. Rapid and cost-effective identification and antimicrobial susceptibility testing in patients with Gram-negative bacteremia directly from blood-culture fluid.

    Sakarikou, Christina; Altieri, Anna; Bossa, Maria Cristina; Minelli, Silvia; Dolfa, Camilla; Piperno, Micol; Favalli, Cartesio

    2018-03-01

    Rapid pathogen identification (ID) and antimicrobial susceptibility testing (AST) in bacteremia cases or sepsis could improve patient prognosis. Thus, it is important to provide timely reports, which make it possible for clinicians to set up appropriate antibiotic therapy during the early stages of bloodstream infection (BSI). This study evaluates an in-house microbiological protocol for early ID as well as AST on Gram negative bacteria directly from positive monomicrobial and polymicrobial blood cultures (BCs). A total of 102 non-duplicated positive BCs from patients with Gram-negative bacteremia were tested. Both IDs and ASTs were performed from bacterial pellets extracted directly from BCs using our protocol, which was applied through the combined use of a MALDI-TOF MS and Vitek2 automated system. The results of our study showed a 100% agreement in bacterial ID and 98.25% categorical agreement in AST when compared to those obtained by routine conventional methods. We recorded only a 0.76% minor error (mE), 0.76% major error (ME) and a 0.20% very major error (VME). Moreover, the turnaround time (TAT) regarding the final AST report was significantly shortened (ΔTAT = 8-20 h, p patient management, by early and appropriate antimicrobial treatment and could potentially optimize antimicrobial stewardship programs. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Rapid and reliable identification of Gram-negative bacteria and Gram-positive cocci by deposition of bacteria harvested from blood cultures onto the MALDI-TOF plate.

    Barnini, Simona; Ghelardi, Emilia; Brucculeri, Veronica; Morici, Paola; Lupetti, Antonella

    2015-06-18

    Rapid identification of the causative agent(s) of bloodstream infections using the matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) methodology can lead to increased empirical antimicrobial therapy appropriateness. Herein, we aimed at establishing an easier and simpler method, further referred to as the direct method, using bacteria harvested by serum separator tubes from positive blood cultures and placed onto the polished steel target plate for rapid identification by MALDI-TOF. The results by the direct method were compared with those obtained by MALDI-TOF on bacteria isolated on solid media. Identification of Gram-negative bacilli was 100 % concordant using the direct method or MALDI-TOF on isolated bacteria (96 % with score > 2.0). These two methods were 90 % concordant on Gram-positive cocci (32 % with score > 2.0). Identification by the SepsiTyper method of Gram-positive cocci gave concordant results with MALDI-TOF on isolated bacteria in 87 % of cases (37 % with score > 2.0). The direct method herein developed allows rapid identification (within 30 min) of Gram-negative bacteria and Gram-positive cocci from positive blood cultures and can be used to rapidly report reliable and accurate results, without requiring skilled personnel or the use of expensive kits.

  20. The epidemiology, antibiograms and predictors of mortality among critically-ill patients with central line-associated bloodstream infections

    Shin-Huei Kuo

    2018-06-01

    Conclusion: We identified Gram-negative bacteria as leading pathogens of CLABSIs in a Taiwan medical center, and good compliance to care bundle is associated with reduced CLABSI incidence rate. Malignancy, infection by MDROs or fungi, inadequate empirical or definite antimicrobial therapy are significant factors for 14-day mortality.

  1. Breaking barriers: expansion of the use of endolysins as novel antibacterials against Gram-negative bacteria.

    Briers, Yves; Lavigne, Rob

    2015-01-01

    The emergence and spread of antibiotic-resistant bacteria drives the search for novel classes of antibiotics to replenish our armamentarium against bacterial infections. This is particularly critical for Gram-negative pathogens, which are intrinsically resistant to many existing classes of antibiotics due to the presence of a protective outer membrane. In addition, the antibiotics development pipeline is mainly oriented to Gram-positive pathogens such as methicillin-resistant Staphylococcus aureus. A promising novel class of antibacterials is endolysins. These enzymes encoded by bacterial viruses hydrolyze the peptidoglycan layer with high efficiency, resulting in abrupt osmotic lysis and cell death. Their potential as novel antibacterials to treat Gram-positive bacteria has been extensively demonstrated; however, the Gram-negative outer membrane has presented a formidable barrier for the use of endolysins against Gram-negatives until recently. This review reports on the most recent advances in the development of endolysins to kill Gram-negative species with a special focus on endolysin-engineered Artilysins(®).

  2. [Clinical features of invasive candidiasis and risk factors for Candida bloodstream infection in children: a multicenter study in Urumqi, China].

    Ai Er Ken, Ai Bi Bai; Ma, Zhi-Hua; Xiong, Dai-Qin; Xu, Pei-Ru

    2017-04-01

    To investigate the clinical features of invasive candidiasis in children and the risk factors for Candida bloodstream infection. A retrospective study was performed on 134 children with invasive candidiasis and hospitalized in 5 tertiary hospitals in Urumqi, China, between January 2010 and December 2015. The Candida species distribution was investigated. The clinical data were compared between the patients with and without Candida bloodstream infection. The risk factors for Candida bloodstream infection were investigated using multivariate logistic regression analysis. A total of 134 Candida strains were isolated from 134 children with invasive candidiasis, and non-albicans Candida (NAC) accounted for 53.0%. The incidence of invasive candidiasis in the PICU and other pediatric wards were 41.8% and 48.5% respectively. Sixty-eight patients (50.7%) had Candida bloodstream infection, and 45 patients (33.6%) had Candida urinary tract infection. There were significant differences in age, rate of use of broad-spectrum antibiotics, and incidence rates of chronic renal insufficiency, heart failure, urinary catheterization, and NAC infection between the patients with and without Candida bloodstream infection (Pcandidiasis is similar between the PICU and other pediatric wards. NAC is the most common species of invasive candidiasis. Candida bloodstream infection is the most common invasive infection. Younger age (1-24 months) and NAC infection are the risk factors for Candida bloodstream infection.

  3. Prevention of bloodstream infections by photodynamic inactivation of multiresistant Pseudomonas aeruginosa in burn wounds

    Hashimoto, M. C. E.; Prates, R. A.; Toffoli, D. J.; Courrol, L. C.; Ribeiro, M. S.

    2010-02-01

    Bloodstream infections are potentially life-threatening diseases. They can cause serious secondary infections, and may result in endocarditis, severe sepsis or toxic-shock syndrome. Pseudomonas aeruginosa is an opportunistic pathogen and one of the most important etiological factors responsible for nosocomial infections, mainly in immuno-compromissed hosts, characteristic of patients with severe burns. Its multiresistance to antibiotics produces many therapeutic problems, and for this reason, the development of an alternative method to antibiotic therapy is needed. Photodynamic inactivation (PDI) may be an effective and alternative therapeutic option to prevent bloodstream infections in patients with severe burns. In this study we report the use of PDI to prevent bloodstream infections in mice with third-degree burns. Burns were produced on the back of the animals and they were infected with 109 cfu/mL of multi-resistant (MR) P. aeruginosa. Fifteen animals were divided into 3 groups: control, PDT blue and PDT red. PDT was performed thirty minutes after bacterial inoculation using 10μM HB:La+3 and a light-emitting diode (LED) emitting at λ=460nm+/-20nm and a LED emitting at λ=645 nm+/-10nm for 120s. Blood of mice were colected at 7h, 10h, 15h, 18h and 22h pos-infection (p.i.) for bacterial counting. Control group presented 1×104 cfu/mL in bloodstream at 7h p.i. increasing to 1×106 at 22h, while mice PDT-treated did not present any bacteria at 7h; only at 22h p.i. they presented 1×104cfu/mL. These results suggest that HB:La+3 associated to blue LED or red LED is effective to delay and diminish MR P.aeruginosa bloodstream invasion in third-degree-burned mice.

  4. Distribution of Gram Negative Bacteria and Evaluation of Resistance Profiles

    Serap Pamukcuoglu

    2014-03-01

    Full Text Available Aim: In this study, we aimed to examine the distributon of Gram negative bacteria isolated from urine cultures of out-patients in Afyonkarahisar State Hospital and evaluate the antimicrobial resistance rates of these pathogens. Material and Method: Urine samples of out-patients which were sent to microbiology laboratory between 2012-2013 were retrospectively evaluated. The isolates were identified using conventional methods and/or automated Vitec 2.0 system. Antibiogram sensitivities were determined by Kirby-Bauer disc diffusion method or automated system and interpreted on the basis of Clinical and Laboratory Standards Institute (CSI criteria. Double disc sinergy test (DDST or Vitec 2.0 system was used to detect extended spectrum beta-lactamase (ESBL.When conventional methods could%u2019t be clarified according to their colony morphologies, gram staining patterns, biochemical test; automated system has been used. Results: A total of 671 isolates acquired from urine samples were studied. 427 Escherichia coli (63.6 %, 165 Klebsiella spp. (24.6 %, 22 Pseudomonas spp. (3.3 %, nine Acinetobacter spp. (1.3 %, 41 Proteus spp. (6.1 % and seven Serratia (1.0 % strains were identified among isolates. 97 E.coli (22.8 % and 41 Klebsiella (24.8 % isolates were ESBL positive. Most common bacteria were E.coli, 31.1 % of which were resistant to trimethoprim-sulfamethoxazole, 16 % to ciprofloxacin and 3.6 % to nitrofurantoin. Among Enterobacteriaceae, no resistance aganist carbapenems were detected. Moreover, aminoglicoside sensitivity rate was significantly high in this group. Discussion: Microorganisms that have progressively increasing antimicrobial resistance should be considered in the treatment of urinary tract infections. It is also important to use the most appropriate antibiotics to avoid unnecessary usage of these drugs in order to decrease drug resistance rates and ESBL production which may effect the success of the treatment.

  5. Routine Surveillance for Bloodstream Infections in a Pediatric Hematopoietic Stem Cell Transplant Cohort: Do Patients Benefit?

    Heather Rigby

    2007-01-01

    Full Text Available BACKGROUND: Hematopoietic stem cell transplant (HSCT recipients are at a high risk for late bloodstream infection (BSI. Controversy exists regarding the benefit of surveillance blood cultures in this immunosuppressed population. Despite the common use of this practice, the practical value is not well established in non-neutropenic children following HSCT.

  6. Emergence of Livestock-Associated Methicillin-Resistant Staphylococcus aureus Bloodstream Infections in Denmark

    Larsen, Jesper; Petersen, Andreas; Larsen, Anders R.

    2017-01-01

    Background: Livestock-associated methicillin-resistant Staphylococcus aureus clonal complex 398 (LA-MRSA CC398) is causing an increasing number of skin and soft tissue infections (SSTIs) in Denmark and other European countries with industrial pig production. Yet, its impact on MRSA bloodstream...

  7. Blood culture procedures and diagnosis of Malassezia furfur bloodstream infections : Strength and weakness

    Iatta, Roberta; Battista, Michela; Miragliotta, Giuseppe; Boekhout, Teun; Otranto, Domenico; Cafarchia, Claudia

    2017-01-01

    The occurrence of Malassezia spp. bloodstream infections (BSIs) in neonatal intensive care unit was evaluated by using pediatric Isolator, BacT/Alert systems and central venous catheter (CVC) culture. The efficacy of BacT/Alert system in detecting Malassezia was assessed by conventional procedures,

  8. Occurrence of yeast bloodstream infections between 1987 and 1995 in five Dutch university hospitals

    A. Voss (Andreas); J.A.J.W. Kluytmans (Jan); J.G. Koeleman; L. Spanjaard (Lodewijk); C.M.J.E. Vandenbroucke-Grauls (Christina); H.A. Verbrugh (Henri); M.C. Vos (Margreet); A.Y.L. Weersink (A. Y L); J.A.A. Hoogkamp-Korstanje (J. A A); J.F. Meis

    1996-01-01

    textabstractThe aim of this study was to identify retrospectively trends in fungal bloodstream infections in The Netherlands in the period from 1987 to 1995. Results of over 395,000 blood cultures from five Dutch university hospitals were evaluated. Overall, there were more than 12 million patient

  9. Epidemiological investigation of Candida species causing bloodstream infection in paediatric small bowel transplant recipients.

    Suhr, Mallory J; Gomes-Neto, João Carlos; Banjara, Nabaraj; Florescu, Diana F; Mercer, David F; Iwen, Peter C; Hallen-Adams, Heather E

    2017-06-01

    Small bowel transplantation (SBT) can be a life-saving medical procedure. However, these recipients experience high risk of bloodstream infections caused by Candida. This research aims to characterise the SBT recipient gut microbiota over time following transplantation and investigate the epidemiology of candidaemia in seven paediatric patients. Candida species from the recipients' ileum and bloodstream were identified by internal transcribed spacer sequence and distinguished to strain by multilocus sequence typing and randomly amplified polymorphic DNA. Antifungal susceptibility of bloodstream isolates was determined against nine antifungals. Twenty-two ileostomy samples harboured at least one Candida species. Fungaemia were caused by Candida parapsilosis, Candida albicans, Candida glabrata, Candida orthopsilosis and Candida pelliculosa. All but three bloodstream isolates showed susceptibility to all the antifungals tested. One C. glabrata isolate showed multidrug resistance to itraconazole, amphotericin B and posaconazole and intermediate resistance to caspofungin. Results are congruent with both endogenous (C. albicans, C. glabrata) and exogenous (C. parapsilosis) infections; results also suggest two patients were infected by the same strain of C. parapsilosis. Continuing to work towards a better understanding of sources of infection-particularly the exogenous sources-would lead to targeted prevention strategies. © 2017 Blackwell Verlag GmbH.

  10. Prevalence of Gram-negative Pathogens and their antimicrobial ...

    The present study was conducted to find out the prevalence and spectrum of Gram negative pathogens causing bacterial meningitis and their antimicrobial susceptibility pattern in a tertiary care hospital. The cerebrospinal fluid (CSF) (3-5 ml) was collected from 638 admitted children clinically suspected of septic meningitis.

  11. NDM 1 Gene Carrying Gram negative Bacteria Isolated from Rats ...

    In this study, we screened 56 Gram negative bacteria comprising: 3 isolates of Enterobacter ludwigii, 30 Pseudomonas aeruginosa, 22 Proteus mirabilis, and 1 Aeromonas caviae isolated from oral cavity and rectum of rats captured from commercial poultry houses in Ibadan, Oyo State, Nigeria that were resistant to at least ...

  12. Prediction of lipoprotein signal peptides in Gram-negative bacteria

    Juncker, Agnieszka; Willenbrock, Hanni; Von Heijne, G.

    2003-01-01

    A method to predict lipoprotein signal peptides in Gram-negative Eubacteria, LipoP, has been developed. The hidden Markov model (HMM) was able to distinguish between lipoproteins (SPaseII-cleaved proteins), SPaseI-cleaved proteins, cytoplasmic proteins, and transmembrane proteins. This predictor ...

  13. Patients with Central Lines — What You Need to Know to Avoid a Bloodstream Infection

    This podcast is based on the March, 2011 CDC Vital Signs report which indicates bloodstream infections in patients with central lines are largely preventable when healthcare providers use CDC-recommended infection control steps.

  14. Ten-year surveillance of nosocomial bloodstream infections: trends of aetiology and antimicrobial resistance in a comprehensive cancer centre.

    Passerini, R; Ghezzi, Tl; Sandri, Mt; Radice, D; Biffi, R

    2011-01-01

    , passing from 33.9% to 67.4% (p = 0.01) and from 5.6% to 25.7% (p = 0.01), respectively. Gram-positives are the main pathogens of BSIs; there is no difference in aetiology of CRBSIs between surgical and oncological patients. The lower incidence of gram-positive non-CRBSIs in surgical patients was probably due to gram-negative infections secondary to surgical complications.

  15. Risk factors for central line-associated bloodstream infection in pediatric oncology patients with a totally implantable venous access port: A cohort study.

    Viana Taveira, Michelle Ribeiro; Lima, Luciana Santana; de Araújo, Cláudia Corrêa; de Mello, Maria Júlia Gonçalves

    2017-02-01

    Totally implantable venous access ports (TIVAPs) are used for prolonged central venous access, allowing the infusion of chemotherapy and other fluids and improving the quality of life of children with cancer. TIVAPs were developed to reduce the infection rates associated with central venous catheters; however, infectious events remain common and have not been fully investigated in pediatric oncology patients. A retrospective cohort was formed to investigate risk factors for central line-associated bloodstream infection (CLABSI) in pediatric cancer patients. Sociodemographic, clinical, and TIVAP insertion-related variables were evaluated, with the endpoint being the first CLABSI. A Kaplan-Meier analysis was performed to determine CLABSI-free catheter survival. Overall, 188 children were evaluated over 77,541 catheter days, with 94 being diagnosed with CLABSI (50%). Although coagulase-negative staphylococci were the pathogens most commonly isolated, Gram-negative microorganisms (46.8%) were also prevalent. In the multivariate analysis, factors that increased the risk for CLABSI were TIVAP insertion prior to chemotherapy (risk ratio [RR] = 1.56; P Risk factors for CLABSI in pediatric cancer patients with a TIVAP may be related to the severity of the child's condition at catheter insertion. Insertion of the catheter before chemotherapy and unfavorable conditions such as malnutrition and bone marrow aplasia can increase the risk of CLABSI. Protocols must be revised and surveillance increased over the first 10 weeks of treatment. © 2016 Wiley Periodicals, Inc.

  16. Development and transmission of antimicrobial resistance among Gram-negative bacteria in animals and their public health impact.

    Mukerji, Shewli; O'Dea, Mark; Barton, Mary; Kirkwood, Roy; Lee, Terence; Abraham, Sam

    2017-02-28

    Gram-negative bacteria are known to cause severe infections in both humans and animals. Antimicrobial resistance (AMR) in Gram-negative bacteria is a major challenge in the treatment of clinical infections globally due to the propensity of these organisms to rapidly develop resistance against antimicrobials in use. In addition, Gram-negative bacteria possess highly efficient mechanisms through which the AMR can be disseminated between pathogenic and commensal bacteria of the same or different species. These unique traits of Gram-negative bacteria have resulted in evolution of Gram-negative bacterial strains demonstrating resistance to multiple classes of antimicrobials. The evergrowing resistance issue has not only resulted in limitation of treatment options but also led to increased treatment costs and mortality rates in humans and animals. With few or no new antimicrobials in production to combat severe life-threatening infections, AMR has been described as the one of the most severe, long-term threats to human health. Aside from overuse and misuse of antimicrobials in humans, another factor that has exacerbated the emergence of AMR in Gram-negative bacteria is the veterinary use of antimicrobials that belong to the same classes considered to be critically important for treating serious life-threatening infections in humans. Despite the fact that development of AMR dates back to before the introduction of antimicrobials, the recent surge in the resistance towards all available critically important antimicrobials has emerged as a major public health issue. This review thus focuses on discussing the development, transmission and public health impact of AMR in Gram-negative bacteria in animals. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  17. Blood culture contamination with Enterococci and skin organisms: implications for surveillance definitions of primary bloodstream infections.

    Freeman, Joshua T; Chen, Luke Francis; Sexton, Daniel J; Anderson, Deverick J

    2011-06-01

    Enterococci are a common cause of bacteremia but are also common contaminants. In our institution, approximately 17% of positive blood cultures with enterococci are mixed with skin organisms. Such isolates are probable contaminants. The specificity of the current definition of primary bloodstream infection could be increased by excluding enterococci mixed with skin organisms. Copyright © 2011 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

  18. Tsukamurella catheter-related bloodstream infection in a pediatric patient with pulmonary hypertension

    Kristen A. Wendorf

    2010-03-01

    Full Text Available Catheter-related bloodstream infections (CR-BSI are important complications in patients with long-term indwelling central venous catheters. In this report, we present the case of a 14-year-old male with pulmonary hypertension treated with continuous treprostinil infusion, who presented with a CR-BSI caused by a Tsukamurella species. This case highlights the potential for this unusual organism to cause infection in immunocompetent patients.

  19. Bacteremias in liver transplant recipients: shift toward gram-negative bacteria as predominant pathogens.

    Singh, Nina; Wagener, Marilyn M; Obman, Asia; Cacciarelli, Thomas V; de Vera, Michael E; Gayowski, Timothy

    2004-07-01

    During the 1990s, gram-positive bacteria emerged as major pathogens after liver transplantation. We sought to determine whether the pathogens associated with bacteremias in liver transplant recipients have changed. Patients included 233 liver transplant recipients transplanted between 1989 and 2003. The proportion of all infections due to bacteremias increased significantly over time (P gram-negatives increased from 25% in the period of 1989-1993 to 51.8% in 1998-03, that of gram-positive bacteria decreased from 75% in the period of 1989-93 to 48.2% in the period of 1998-2003. Methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae, and Pseudomonas aeruginosa were the most frequent pathogens in bacteremic patients. The incidence of bacteremias due to MRSA and Pseudomonas aeruginosa has remained unchanged (P gram-negative bacteria, particularly Klebsiella pneumoniae has increased (P =.02). Klebsiella pneumoniae isolates in the current quartile were not clonally related. In conclusion, bacteremias as a proportion of all infections in liver transplant recipients have increased significantly over time, due in part to a decline in infections due to other major pathogens, e.g., fungi, primarily Candida species, and CMV. Gram-negative bacteria have emerged as predominant pathogens in bacteremic liver transplant recipients.

  20. Protein A Suppresses Immune Responses during Staphylococcus aureus Bloodstream Infection in Guinea Pigs

    Kim, Hwan Keun; Falugi, Fabiana; Thomer, Lena; Missiakas, Dominique M.

    2015-01-01

    ABSTRACT   Staphylococcus aureus infection is not associated with the development of protective immunity, and disease relapses occur frequently. We hypothesize that protein A, a factor that binds immunoglobulin Fcγ and cross-links VH3 clan B cell receptors (IgM), is the staphylococcal determinant for host immune suppression. To test this, vertebrate IgM was examined for protein A cross-linking. High VH3 binding activity occurred with human and guinea immunoglobulin, whereas mouse and rabbit immunoglobulins displayed little and no binding, respectively. Establishing a guinea pig model of S. aureus bloodstream infection, we show that protein A functions as a virulence determinant and suppresses host B cell responses. Immunization with SpAKKAA, which cannot bind immunoglobulin, elicits neutralizing antibodies that enable guinea pigs to develop protective immunity. Importance  Staphylococcus aureus is the leading cause of soft tissue and bloodstream infections; however, a vaccine with clinical efficacy is not available. Using mice to model staphylococcal infection, earlier work identified protective antigens; however, corresponding human clinical trials did not reach their endpoints. We show that B cell receptor (IgM) cross-linking by protein A is an important immune evasion strategy of S. aureus that can be monitored in a guinea pig model of bloodstream infection. Further, immunization with nontoxigenic protein A enables infected guinea pigs to elicit antibody responses that are protective against S. aureus. Thus, the guinea pig model may support preclinical development of staphylococcal vaccines. PMID:25564466

  1. Bovine mastitis caused by gram negative bacteria in Mosul

    S. Y. A. Al-Dabbagh

    2012-01-01

    Full Text Available A total of 90 milk samples were collected from cows with clinical and subclinical mastitis from different areas in Mosul city, in a period from October 2009 to June 2010, for the detection of gram negative bacteriological causative agents. The bacteria were identified using morphological, cultural and biochemical characteristics. thirty tow (35.3% gram negative bacterial isolates were obtained from the total count which included 14 isolates (15.5% for Escherichia coli, 7 isolates (7.7% for Klebsiella spp, 4 isolates (4.4% for Pseudomonas aeruginosa, 3 isolates (3.3% for Enterobacter aerogenes ,2 isolates for Serratia marcescens and one isolates (1.1% for each of Aeromonas hydrophila and Pasteurella multocida. Results of antibiotic sensitivity test indicated that most of these isolates were sensitive to Ciprofloxacin following by Gentamycin and Cotrimoxazole, while most of these organisms were resistant to Ampicillin, the isolates showed different percentages of sensitivity to Doxycycline, Tetracycline, Neomycin and Chloramphenicol.

  2. Multidrug resistance in enteric and other gram-negative bacteria.

    George, A M

    1996-05-15

    In Gram-negative bacteria, multidrug resistance is a term that is used to describe mechanisms of resistance by chromosomal genes that are activated by induction or mutation caused by the stress of exposure to antibiotics in natural and clinical environments. Unlike plasmid-borne resistance genes, there is no alteration or degradation of drugs or need for genetic transfer. Exposure to a single drug leads to cross-resistance to many other structurally and functionally unrelated drugs. The only mechanism identified for multidrug resistance in bacteria is drug efflux by membrane transporters, even though many of these transporters remain to be identified. The enteric bacteria exhibit mostly complex multidrug resistance systems which are often regulated by operons or regulons. The purpose of this review is to survey molecular mechanisms of multidrug resistance in enteric and other Gram-negative bacteria, and to speculate on the origins and natural physiological functions of the genes involved.

  3. Value of Public Health Funding in Preventing Hospital Bloodstream Infections in the United States.

    Whittington, Melanie D; Bradley, Cathy J; Atherly, Adam J; Campbell, Jonathan D; Lindrooth, Richard C

    2017-11-01

    To estimate the association of 1 activity of the Prevention and Public Health Fund with hospital bloodstream infections and calculate the return on investment (ROI). The activity was funded for 1 year (2013). A difference-in-differences specification evaluated hospital standardized infection ratios (SIRs) before funding allocation (years 2011 and 2012) and after funding allocation (years 2013 and 2014) in the 15 US states that received the funding compared with hospital SIRs in states that did not receive the funding. We estimated the association of the funded public health activity with SIRs for bloodstream infections. We calculated the ROI by dividing cost offsets from infections averted by the amount invested. The funding was associated with a 33% (P < .05) reduction in SIRs and an ROI of $1.10 to $11.20 per $1 invested in the year of funding allocation (2013). In 2014, after the funding stopped, significant reductions were no longer evident. This activity was associated with a reduction in bloodstream infections large enough to recoup the investment. Public health funding of carefully targeted areas may improve health and reduce health care costs.

  4. The changing epidemiology of group B streptococcus bloodstream infection

    Ballard, Mark S; Schønheyder, Henrik C; Knudsen, Jenny Dahl

    2016-01-01

    Background Population-based studies conducted in single regions or countries have identified significant changes in the epidemiology of invasive group B streptococcus (GBS) infection. However, no studies have concurrently compared the epidemiology of GBS infections among multiple different region...

  5. Restriction of cephalosporins and control of extended spectrum beta-lactamase producing gram negative bacteria in a neonatal intensive care unit.

    Murki, Srinivas; Jonnala, Sravanthi; Mohammed, Faheemuddin; Reddy, Anupama

    2010-09-01

    This interventional study with historical controls was conducted to study the effect of cephalosporin restriction on the incidence of extended spectrum beta-lactamase (ESBL) gram negative infections in neonates admitted to intensive care unit. All gram negative isolates from the blood were evaluated for beta lactamase production. The incidence of ESBL production was compared before (year 2007) and after cephalosporin restriction (year 2008). Thirty two neonates (3% of NICU admissions) in the year 2007 and fifty six (5.2%) in the year 2008, had gram negative septicemia. The incidence of ESBL gram negatives decreased by 22% (47% to 25%, P=0.03). Restriction of all class of cephalosporins significantly decreased the incidence of ESBL gram negative infections.

  6. Intrinsic, adaptive and acquired antimicrobial resistance in Gram-negative bacteria.

    Arzanlou, Mohsen; Chai, Wern Chern; Venter, Henrietta

    2017-02-28

    Gram-negative bacteria are responsible for a large proportion of antimicrobial-resistant infections in humans and animals. Among this class of bacteria are also some of the most successful environmental organisms. Part of this success is their adaptability to a variety of different niches, their intrinsic resistance to antimicrobial drugs and their ability to rapidly acquire resistance mechanisms. These mechanisms of resistance are not exclusive and the interplay of several mechanisms causes high levels of resistance. In this review, we explore the molecular mechanisms underlying resistance in Gram-negative organisms and how these different mechanisms enable them to survive many different stress conditions. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  7. Prediction of lipoprotein signal peptides in Gram-negative bacteria.

    Juncker, Agnieszka S; Willenbrock, Hanni; Von Heijne, Gunnar; Brunak, Søren; Nielsen, Henrik; Krogh, Anders

    2003-08-01

    A method to predict lipoprotein signal peptides in Gram-negative Eubacteria, LipoP, has been developed. The hidden Markov model (HMM) was able to distinguish between lipoproteins (SPaseII-cleaved proteins), SPaseI-cleaved proteins, cytoplasmic proteins, and transmembrane proteins. This predictor was able to predict 96.8% of the lipoproteins correctly with only 0.3% false positives in a set of SPaseI-cleaved, cytoplasmic, and transmembrane proteins. The results obtained were significantly better than those of previously developed methods. Even though Gram-positive lipoprotein signal peptides differ from Gram-negatives, the HMM was able to identify 92.9% of the lipoproteins included in a Gram-positive test set. A genome search was carried out for 12 Gram-negative genomes and one Gram-positive genome. The results for Escherichia coli K12 were compared with new experimental data, and the predictions by the HMM agree well with the experimentally verified lipoproteins. A neural network-based predictor was developed for comparison, and it gave very similar results. LipoP is available as a Web server at www.cbs.dtu.dk/services/LipoP/.

  8. Invitro activity of imipenem-relebactam against gram-negative bacilli isolated from patients with lower respiratory tract infections in the United States in 2015 - Results from the SMART global surveillance program.

    Lob, Sibylle H; Hackel, Meredith A; Kazmierczak, Krystyna M; Hoban, Daryl J; Young, Katherine; Motyl, Mary R; Karlowsky, James A; Sahm, Daniel F

    2017-06-01

    The β-lactamase inhibitor relebactam inactivates class A β-lactamases, including KPC-type carbapenemases, and class C β-lactamases. Relebactam combined with imipenem is in clinical development for several indications, including hospital-acquired and ventilator-associated pneumonia. Employing CLSI-defined broth microdilution methodology, we evaluated the activities of imipenem-relebactam (using imipenem MIC breakpoints) and comparators against non-Proteeae Enterobacteriaceae (n=853) and Pseudomonas aeruginosa (n=598) isolated from lower respiratory tract infection samples in 20 hospital laboratories in the United States participating in the 2015 SMART (Study for Monitoring Antimicrobial Resistance Trends) global surveillance program. Imipenem-relebactam and imipenem susceptibilities were 97.2% and 91.6% for non-Proteeae Enterobacteriaceae and 93.1% and 68.1% for P. aeruginosa. Relebactam restored imipenem susceptibility to 66.7% and 78.5% of imipenem-non-susceptible non-Proteeae Enterobacteriaceae isolates (n=72) and P. aeruginosa (n=191), respectively. Further development of imipenem-relebactam as therapy for lower respiratory tract infections is warranted given relebactam's ability to restore activity to imipenem against non-susceptible non-Proteeae Enterobacteriaceae and P. aeruginosa. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Prognostic factors and monomicrobial necrotizing fasciitis: gram-positive versus gram-negative pathogens

    Hsu Wei-Hsiu

    2011-01-01

    Full Text Available Abstract Background Monomicrobial necrotizing fasciitis is rapidly progressive and life-threatening. This study was undertaken to ascertain whether the clinical presentation and outcome for patients with this disease differ for those infected with a gram-positive as compared to gram-negative pathogen. Methods Forty-six patients with monomicrobial necrotizing fasciitis were examined retrospectively from November 2002 to January 2008. All patients received adequate broad-spectrum antibiotic therapy, aggressive resuscitation, prompt radical debridement and adjuvant hyperbaric oxygen therapy. Eleven patients were infected with a gram-positive pathogen (Group 1 and 35 patients with a gram-negative pathogen (Group 2. Results Group 2 was characterized by a higher incidence of hemorrhagic bullae and septic shock, higher APACHE II scores at 24 h post-admission, a higher rate of thrombocytopenia, and a higher prevalence of chronic liver dysfunction. Gouty arthritis was more prevalent in Group 1. For non-survivors, the incidences of chronic liver dysfunction, chronic renal failure and thrombocytopenia were higher in comparison with those for survivors. Lower level of serum albumin was also demonstrated in the non-survivors as compared to those in survivors. Conclusions Pre-existing chronic liver dysfunction, chronic renal failure, thrombocytopenia and hypoalbuminemia, and post-operative dependence on mechanical ventilation represent poor prognostic factors in monomicrobial necrotizing fasciitis. Patients with gram-negative monobacterial necrotizing fasciitis present with more fulminant sepsis.

  10. Comparing the harmful effects of nontuberculous mycobacteria and Gram negative bacteria on lung function in patients with cystic fibrosis

    Qvist, Tavs; Taylor-Robinson, David; Waldmann, Elisabeth

    2015-01-01

    BACKGROUND: To better understand the relative effects of infection with nontuberculous mycobacteria and Gram negative bacteria on lung function decline in cystic fibrosis, we assessed the impact of each infection in a Danish setting. METHODS: Longitudinal registry study of 432 patients with cystic...

  11. Antiseptic barrier cap effective in reducing central line-associated bloodstream infections : A systematic review and meta-analysis

    Voor In 't Holt, Anne F; Helder, Onno K; Vos, Margreet C; Schafthuizen, Laura; Sülz, Sandra; van den Hoogen, Agnes; Ista, Erwin

    2017-01-01

    BACKGROUND: Microorganisms can intraluminally access a central venous catheter via the catheter hub. The catheter hub should be appropriately disinfected to prevent central line-associated bloodstream infections (CLABSIs). However, compliance with the time-consuming manual disinfection process is

  12. Carbapenem-Resistant Non-Glucose-Fermenting Gram-Negative Bacilli: the Missing Piece to the Puzzle

    Gniadek, Thomas J.; Carroll, Karen C.

    2016-01-01

    The non-glucose-fermenting Gram-negative bacilli Pseudomonas aeruginosa and Acinetobacter baumannii are increasingly acquiring carbapenem resistance. Given their intrinsic antibiotic resistance, this can cause extremely difficult-to-treat infections. Additionally, resistance gene transfer can occur between Gram-negative species, regardless of their ability to ferment glucose. Thus, the acquisition of carbapenemase genes by these organisms increases the risk of carbapenemase spread in general. Ultimately, infection control practitioners and clinical microbiologists need to work together to determine the risk carried by carbapenem-resistant non-glucose-fermenting Gram-negative bacilli (CR-NF) in their institution and what methods should be considered for surveillance and detection of CR-NF. PMID:26912753

  13. [Characteristic of clinical strains of gram-negative obligate anaerobes].

    Kadzielska, Joanna; Kierzkowska, Marta; Sawicka-Grzelak, Anna; Rokosz, Alicja; Łuczak, Mirosław

    2007-01-01

    The aim of the study was to assess prevalence and antibiotic susceptibility profiles ofGram-negative strictly anaerobic bacteria isolated from clinical specimens taken from hospitalized patients in 2005-2006. Biochemical identification and antibiotic susceptibility were done in an automated system ATB Expression (bioMerieux sa). From 12262 specimens examined 867 strains of obligate anaerobes were isolated. Gram-negative strictly anaerobic bacteria were cultured in number of 138 strains (15,9%). All cultures were performed on Columbia agar and Schaedler agar media (bioMerieux sa) supplemented with 5% sheep blood and incubated at 37 degrees C for 48-120 h in 85% N2, 10% H2, 5% CO2. Most frequently isolated was Bacteroides spp. (41,3%). For this group beta-lactamase activity was evaluated by using nitrocefin disc test (Cefinase BBL, Becton Dickinson and Co., Cockeysville, MD, USA). Production of ESBLs was detected with the use of two disc diffusion methods: the double-disc synergy test (DDST) according to Jarlier et al. and the diagnostic disc (DD) test according to Appleton. ESBLs were produced by 5,3% strains of Bacteroides spp. For all Bacteroides spp. strains MIC values were determined by gradient diffusion method Etest (AB BIODISK, Sweden). ESBLs and MIC were performed on Wilkins-Chalgren solid medium supplemented with 5% sheep blood (Difco Lab., USA) and all plates were incubated at 35 degrees C for 48 hours in 85% N2, 10% H2, 5% CO2. Most Gram-negative obligate anaerobes isolated from clinical specimens are still susceptible to imipenem (100%), metronidazole (99,3%) and beta-lactam antibiotics with beta-lactamase inhibitors: piperacillin/tazobactam (99,3%), ticarcillin/clavulanate (99.3%), amoxicillin/clavulanate (97.8%).

  14. Extended spectrum β-lactamases, carbapenemases and mobile genetic elements responsible for antibiotics resistance in Gram-negative bacteria.

    El Salabi, Allaaeddin; Walsh, Timothey R; Chouchani, Chedly

    2013-05-01

    Infectious diseases due to Gram-negative bacteria are a leading cause of morbidity and mortality worldwide. Antimicrobial agents represent one major therapeutic tools implicated to treat these infections. The misuse of antimicrobial agents has resulted in the emergence of resistant strains of Gram-negatives in particular Enterobacteriaceae and non-fermenters; they have an effect not only on a human but on the public health when bacteria use the resistance mechanisms to spread in the hospital environment and to the community outside the hospitals by means of mobile genetic elements. Gram-negative bacteria have become increasingly resistant to antimicrobial agents. They have developed several mechanisms by which they can withstand to antimicrobials, these mechanisms include the production of Extended-spectrum β-lactamases (ESBLs) and carbapenemases, furthermore, Gram-negative bacteria are now capable of spreading such resistance between members of the family Enterobacteriaceae and non-fermenters using mobile genetic elements as vehicles for such resistance mechanisms rendering antibiotics useless. Therefore, addressing the issue of mechanisms of antimicrobial resistance is considered one of most urgent priorities. This review will help to illustrate different resistance mechanisms; ESBLs, carbapenemases encoded by genes carried by mobile genetic elements, which are used by Gram-negative bacteria to escape antimicrobial effect.

  15. Cluster of Candida parapsilosis primary bloodstream infection in a neonatal intensive care unit

    Carmem Lúcia P. da Silva

    Full Text Available Candida parapsilosis is an increasingly important bloodstream pathogen in neonatal intensive care units (NICU. We investigated a cluster of bloodstream infections in a NICU to determine whether nosocomial transmission occurred. During a 3-day period, 3 premature infants hospitalized in the same unit presented with sepsis caused by C. parapsilosis. Electrophoretic karyotype of the organisms was performed by using pulsed field gel electrophoresis in a countour-clamped homogeneous electric field system. The isolate from 1 newborn could not be typed, and the isolates from the remaining 2 infants had identical patterns. All 3 cases are described. We conclude that nosocomial transmission of C. parapsilosis occurred and that neonates under intensive care may represent a risk group for this pathogen.

  16. Cluster of Candida parapsilosis primary bloodstream infection in a neonatal intensive care unit

    Silva Carmem Lúcia P. da

    2001-01-01

    Full Text Available Candida parapsilosis is an increasingly important bloodstream pathogen in neonatal intensive care units (NICU. We investigated a cluster of bloodstream infections in a NICU to determine whether nosocomial transmission occurred. During a 3-day period, 3 premature infants hospitalized in the same unit presented with sepsis caused by C. parapsilosis. Electrophoretic karyotype of the organisms was performed by using pulsed field gel electrophoresis in a countour-clamped homogeneous electric field system. The isolate from 1 newborn could not be typed, and the isolates from the remaining 2 infants had identical patterns. All 3 cases are described. We conclude that nosocomial transmission of C. parapsilosis occurred and that neonates under intensive care may represent a risk group for this pathogen.

  17. VIP as a potential therapeutic agent in gram negative sepsis.

    Ibrahim, Hiba; Barrow, Paul; Foster, Neil

    2012-12-01

    Gram negative sepsis remains a high cause of mortality and places a great burden on public health finance in both the developed and developing world. Treatment of sepsis, using antibiotics, is often ineffective since pathology associated with the disease occurs due to dysregulation of the immune system (failure to return to steady state conditions) which continues after the bacteria, which induced the immune response, have been cleared. Immune modulation is therefore a rational approach to the treatment of sepsis but to date no drug has been developed which is highly effective, cheap and completely safe to use. One potential therapeutic agent is VIP, which is a natural peptide and is highly homologous in all vertebrates. In this review we will discuss the effect of VIP on components of the immune system, relevant to gram negative sepsis, and present data from animal models. Furthermore we will hypothesise on how these studies could be improved in future and speculate on the possible different ways in which VIP could be used in clinical medicine.

  18. Monomicrobial necrotizing fasciitis in a single center: the emergence of Gram-negative bacteria as a common pathogen

    D. Yahav

    2014-11-01

    Conclusions: In our center, 42% of monomicrobial necrotizing fasciitis cases were found to be caused by Gram-negative organisms, mostly E. coli. These infections usually appeared in immunocompromised or postoperative patients, often presented with normal CPK levels, and were associated with high mortality rates.

  19. Defining Multidrug Resistance of Gram-Negative Bacteria in the Dutch-German Border Region-Impact of National Guidelines

    Köck, Robin; Siemer, Philipp; Esser, Jutta; Kampmeier, Stefanie; Berends, Matthijs S; Glasner, Corinna; Arends, Jan P; Becker, Karsten; Friedrich, Alexander W

    2018-01-01

    Preventing the spread of multidrug-resistant Gram-negative bacteria (MDRGNB) is a public health priority. However, the definition of MDRGNB applied for planning infection prevention measures such as barrier precautions differs depending on national guidelines. This is particularly relevant in the

  20. Spread of resistant gram negatives in a Sri Lankan intensive care unit.

    Tissera, Kavinda; Liyanapathirana, Veranja; Dissanayake, Nilanthi; Pinto, Vasanthi; Ekanayake, Asela; Tennakoon, Manjula; Adasooriya, Dinuka; Nanayakkara, Dulmini

    2017-07-11

    Infections with multi drug resistant (MDR) organisms are a major problem in intensive care units (ICUs). Proper infection control procedures are mandatory to combat the spread of resistant organisms within ICUs. Well stablished surveillance programmes will enhance the adherence of the staff to infection control protocols. The study was conducted to assess the feasibility of using basic molecular typing methods and routine hospital data for laboratory surveillance of resistance organisms in resource limited settings. A retrospective study was conducted using consecutive Gram negative isolates obtained from an ICU over a six month period. Antibiotic sensitivity patterns and random amplified polymorphic DNA (RAPD) based typing was performed on the given isolates. Of the seventy isolates included in the study, seven were E.coli. All E.coli were MDRs and Extended Spectrum β lactamse (ESBL) producers carrying bla CTX-M . Fourteen isolates were K.pneumoniae, and all were MDRs and ESBL producers. All K.pneumoniae harboured bla SHV while 13 harboured bla CTX-M . The MDR rate among P.aeruginosa was 13% (n=15) while all acinetobacters (n=30) were MDRs. Predominant clusters were identified within all four types of Gram negatives using RAPD and the ICU stay of patients overlapped temporally. We propose that simple surveillance methods like RAPD based typing and basic hospital data can be used to convince hospital staff to adhere to infection control protocols more effectively, in low and middle income countries.

  1. [Catheter-associated bloodstream infections: implementation of a new consensus protocol].

    Urrea Ayala, M; Rozas Quesada, L

    2009-07-01

    Catheter-associated bloodstream infection is highly prevalent and often associated with fatal complications. Some studies have shown that applying preventive interventions could help to reduce and control this type of infection. To determine whether a new consensus protocol for the manipulation and maintenance of central venous catheters would decrease catheter-associated bloodstream infections (CA-BSIs) in paediatric patients. To evaluate its compliance in intensive care units. Prospective study in the paediatric (PICU) and neonatal (NICU) intensive cares units, haematology, oncology and hospital wards in a Maternal and Paediatric reference Hospital in Barcelona. The study period is divided into two periods: before (first semester) and after the start of the new protocol (second semester) in 2007. The most important changes have been the insertion of the hermetic connection in the proximal and distal site (between the line and the syringe) of the central venous catheter (CVC), the labelling of the medication line and the CVC with the date of placement. A check-list to evaluate compliance was introduced in both intensive care units (paediatrics and neonatal) during the second study period. The rates of bloodstream infection per 1000 catheter-days were assessed. The rate of bloodstream infections per 1000 catheter-days before and after the start of the new protocol was 5.7 and 4.9 in PICU; 24.6 and 18.0 in NICU; 7.6 and 4.6 in haematology-oncology, and 11.9 and 10.3 in hospital wards. As regards compliance to the protocol, we found that proximal sealed connectors were used in more than 95% of the cases and up to 85% of the central venous catheter were labelled with the insertion date in both intensive care units. A consensus protocol for the use and maintenance of central venous catheters and healthcare worker training helped to control the rate of CA-BSIs. We reaffirm the importance of epidemiological surveillance as a measure for controlling nosocomial infections.

  2. The gram-negative bacterial periplasm: Size matters.

    Samuel I Miller

    2018-01-01

    Full Text Available Gram-negative bacteria are surrounded by two membrane bilayers separated by a space termed the periplasm. The periplasm is a multipurpose compartment separate from the cytoplasm whose distinct reducing environment allows more efficient and diverse mechanisms of protein oxidation, folding, and quality control. The periplasm also contains structural elements and important environmental sensing modules, and it allows complex nanomachines to span the cell envelope. Recent work indicates that the size or intermembrane distance of the periplasm is controlled by periplasmic lipoproteins that anchor the outer membrane to the periplasmic peptidoglycan polymer. This periplasm intermembrane distance is critical for sensing outer membrane damage and dictates length of the flagellar periplasmic rotor, which controls motility. These exciting results resolve longstanding debates about whether the periplasmic distance has a biological function and raise the possibility that the mechanisms for maintenance of periplasmic size could be exploited for antibiotic development.

  3. A study of gram-negative bacterial resistance to Aminoglycosides

    Maleknejad P

    1993-05-01

    Full Text Available From hygienic and economical point of view, drug therapy and prophylaxy in infectious diseases are of great importance. After the world war II, a reduction in the efficacy of sulfonamide in the treatment of shigellosis was observed and later on it led to a survey on drug resistance and the way of its transmission. The aim of this survey, during which 100 cases of gram-negative bacteria were identified, is to study the drug resistance of this bacteria against five types of aminoglycosides by antibiotic sensitivity test (disc-diffusion. Out of 100 strains, 47% were resistant to gentamycin, 70% to kanamycin, 82% to streptomycin, 53% to tobramycin, and 8% to amikacin

  4. Transient sensitivity to nisin in cold-shocked Gram negatives.

    Boziaris, I S; Adams, M R

    2000-09-01

    Rapid chilling in the presence of nisin caused a dose-dependent reduction in the populations of several Gram-negative bacteria, despite the fact that appreciable structural injury to the outer membrane was not detected. Pseudomonas aeruginosa was most affected, followed by Pseudomonas fragi, Salmonella enteritidis PT4, PT7 and Escherichia coli, respectively. Addition of nisin after the chilling treatment had no effect. The results are ascribed to a transient susceptibility caused by phase changes in the lipids associated with the outer membrane, which are rapidly reversed when the cells return to higher temperatures. Combinations of chilling shock, nisin and EDTA gave much lower reductions of Salmonella and Pseudomonas on chicken skin in comparison with broths. This is attributed to a buffering of the temperature shock experienced by adherent bacteria and binding of the nisin by food particles.

  5. Outbreak of Serratia marcescens postsurgical bloodstream infection due to contaminated intravenous pain control fluids.

    Chiang, Ping-Cherng; Wu, Tsu-Lan; Kuo, An-Jing; Huang, Yhu-Chering; Chung, Ting-Ying; Lin, Chun-Sui; Leu, Hsieh-Shong; Su, Lin-Hui

    2013-09-01

    Serratia marcescens is an important nosocomial pathogen causing significant outbreaks. Here we report an outbreak of bloodstream infection caused by S. marcescens at a 3500-bed hospital in Taiwan. The effective cooperative efforts of both laboratory personnel and infection control practitioners (ICPs) jointly contributed to the total control of the outbreak. A sudden increase in the isolation of S. marcescens from blood cultures was noted in the Clinical Microbiology Laboratory. The information was passed to the ICPs and an investigation was initiated. Pulsed-field gel electrophoresis was used to study the relationships among the isolates. Pulsotype A was identified in 43 (82.7%) of the 52 blood isolates studied. They were isolated from 52 patients distributed across 22 wards that were surveyed by seven ICPs. All patients had undergone surgery before the infection, and fentanyl-containing intravenous fluids were used for pain control in 43 of them. Isolates from 42 belonged to pulsotype A. Three S. marcescens isolates, all from fentanyl-containing fluids and demonstrating pulsotype A, were identified from 251 environmental cultures. All fentanyl-containing fluids that were in use were withdrawn and the outbreak was stopped. The outbreak of S. marcescens bloodstream infection apparently occurred through the use of fentanyl-containing fluids contaminated by a pulsotype A S. marcescens. Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  6. Is Clostridium difficile infection a risk factor for subsequent bloodstream infection?

    Ulrich, Robert J; Santhosh, Kavitha; Mogle, Jill A; Young, Vincent B; Rao, Krishna

    2017-12-01

    Clostridium difficile infection (CDI) is a common nosocomial diarrheal illness increasingly associated with mortality in United States. The underlying factors and mechanisms behind the recent increases in morbidity from CDI have not been fully elucidated. Murine models suggest a mucosal barrier breakdown leads to bacterial translocation and subsequent bloodstream infection (BSI). This study tests the hypothesis that CDI is associated with subsequent BSI in humans. We conducted a retrospective cohort study on 1132 inpatients hospitalized >72 h with available stool test results for toxigenic C. difficile. The primary outcome was BSI following CDI. Secondary outcomes included 30-day mortality, colectomy, readmission, and ICU admission. Unadjusted and adjusted logistic regression models were developed. CDI occurred in 570 of 1132 patients (50.4%). BSI occurred in 86 (7.6%) patients. Enterococcus (14%) and Klebsiella (14%) species were the most common organisms. Patients with BSI had higher comorbidity scores and were more likely to be male, on immunosuppression, critically ill, and have a central venous catheter in place. Of the patients with BSI, 36 (42%) had CDI. CDI was not associated with subsequent BSI (OR 0.69; 95% CI 0.44-1.08; P = 0.103) in unadjusted analysis. In multivariable modeling, CDI appeared protective against subsequent BSI (OR 0.57; 95% CI 0.34-0.96; P = 0.036). Interaction modeling suggests a complicated relationship among CDI, BSI, antibiotic exposure, and central venous catheter use. In this cohort of inpatients that underwent testing for CDI, CDI was not a risk factor for developing subsequent BSI. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Gram-Negative Bacterial Sensors for Eukaryotic Signal Molecules

    Olivier Lesouhaitier

    2009-09-01

    Full Text Available Ample evidence exists showing that eukaryotic signal molecules synthesized and released by the host can activate the virulence of opportunistic pathogens. The sensitivity of prokaryotes to host signal molecules requires the presence of bacterial sensors. These prokaryotic sensors, or receptors, have a double function: stereospecific recognition in a complex environment and transduction of the message in order to initiate bacterial physiological modifications. As messengers are generally unable to freely cross the bacterial membrane, they require either the presence of sensors anchored in the membrane or transporters allowing direct recognition inside the bacterial cytoplasm. Since the discovery of quorum sensing, it was established that the production of virulence factors by bacteria is tightly growth-phase regulated. It is now obvious that expression of bacterial virulence is also controlled by detection of the eukaryotic messengers released in the micro-environment as endocrine or neuro-endocrine modulators. In the presence of host physiological stress many eukaryotic factors are released and detected by Gram-negative bacteria which in return rapidly adapt their physiology. For instance, Pseudomonas aeruginosa can bind elements of the host immune system such as interferon-γ and dynorphin and then through quorum sensing circuitry enhance its virulence. Escherichia coli sensitivity to the neurohormones of the catecholamines family appears relayed by a recently identified bacterial adrenergic receptor. In the present review, we will describe the mechanisms by which various eukaryotic signal molecules produced by host may activate Gram-negative bacteria virulence. Particular attention will be paid to Pseudomonas, a genus whose representative species, P. aeruginosa, is a common opportunistic pathogen. The discussion will be particularly focused on the pivotal role played by these new types of pathogen sensors from the sensing to the transduction

  8. [Left-sided endocarditis due to gram-negative bacilli: epidemiology and clinical characteristics].

    Noureddine, Mariam; de la Torre, Javier; Ivanova, Radka; Martínez, Francisco José; Lomas, Jose María; Plata, Antonio; Gálvez, Juan; Reguera, Jose María; Ruiz, Josefa; Hidalgo, Carmen; Luque, Rafael; García-López, María Victoria; de Alarcón, Arístides

    2011-04-01

    The aim of this study is to describe the epidemiological, clinical characteristics, and outcome of patients with left-side endocarditis caused by gram-negative bacteria. Prospective multicenter study of left-sided infective endocarditis reported in the Andalusian Cohort for the Study of Cardiovascular Infections between 1984 and 2008. Among the 961 endocarditis, 24 (2.5%) were caused by gram-negative bacilli. The most common pathogens were Escherichia coli, Pseudomonas aeruginosa and Salmonella enterica. Native valves (85.7%) were mainly affected, most of them with previous valve damage (57%). Comorbidity was greater (90% vs 39%; P=.05) than in endocarditis due to other microorganism, the most frequent being, diabetes, hepatic cirrhosis and neoplasm. A previous manipulation was found in 47.6% of the cases, and 37% were considered hospital-acquired. Renal failure (41%), central nervous system involvement (33%) and ventricular dysfunction (45%) were the most frequent complications. Five cases (21%) required cardiac surgery, mostly due to ventricular dysfunction. More than 50% of cases were treated with aminoglycosides, but this did not lead to a better outcome or prognosis. Mortality (10 patients) was higher than that reported with other microorganisms (41% vs 35%; P=.05). Left-sided endocarditis due to gram-negative bacilli is a rare disease, which affects patients with major morbidities and often with a previous history of hospital manipulations. Cardiac, neurological and renal complications are frequent and associated with a high mortality. The association of aminoglycosides in the antimicrobial treatment did not involve a better outcome or prognosis. Copyright © 2010 Elsevier España, S.L. All rights reserved.

  9. Epidemiology and Outcomes of Bloodstream Infections in Patients With Solid Tumors in a Central American Population at Mexico Hospital, San Jose, Costa Rica

    Jorge Calvo-Lon

    2017-12-01

    Full Text Available Purpose: Bloodstream infections (BSIs are an important cause of mortality in patients with solid tumors. We conducted a retrospective study to evaluate the epidemiologic profile and mortality of patients with solid tumors who have BSIs and were admitted to Mexico Hospital. This is the first study in Costa Rica and Central America describing the current epidemiologic situation. Methods: We analyzed the infectious disease database for BSIs in patients with solid tumors admitted to Mexico Hospital from January 2012 to December 2014. Epidemiology and mortality were obtained according to microorganism, antibiotic sensitivity, tumor type, and presence of central venous catheter (CVC. Descriptive statistics were used. Results: A total of 164 BSIs were recorded, the median age was 58 years, 103 patients (63% were males, and 128 cases of infection (78% were the result of gram-negative bacilli (GNB. Klebsiella pneumoniae (21%, Escherichia coli (21%, and Pseudomonas aeruginosa (15% were the most common microorganisms isolated. Gram-positive cocci (GPC were found in 36 patients, with the most frequent microorganisms being Staphylococcus aureus (10% and Staphyloccocus epidermidis (6%. With respect to tumor type, BSIs were more frequent in the GI tract (57% followed by head and neck (9% and genitourinary tract (8%. Regarding antibiotic susceptibility, only 17% (GNB expressed extended-spectrum beta-lactamase and 12% (GPC had methicillin resistance. Patients with CVCs (n = 59 were colonized mainly by GNB (78%. Overall the mortality rate at 30 days was about 30%. Conclusion: GNB are the most frequent cause of BSIs in solid tumors and in patients with CVCs. GI cancers had more BSIs than other sites. Mortality and antibiotic sensitivity remained stable and acceptable during this observational period in this Latin American population.

  10. suPAR remains uninfluenced by surgery in septic patients with bloodstream infection

    Rabensteiner, Jasmin

    2016-07-01

    Full Text Available Surgical trauma induces activation of the immune system and may cause an increase of inflammatory biomarkers tested postoperatively in septic patients treated for bloodstream infection. The aim of this study was to determine the impact of surgical interventions on the novel sepsis biomarker soluble urokinase plasminogen activator receptor (suPAR and to compare results with those of routine laboratory parameters CRP, PCT, and IL-6 in patients with culture-proven bloodstream infection. Forty-six adult patients with positive blood culture undergoing minor or major surgical intervention were investigated, 12 blood culture positive patients served as control group. Blood was collected 24 hours before and after surgical intervention for determination of the sepsis biomarkers suPAR, CRP, PCT, and IL-6. Within the surgical study cohort, a non-significant increase of suPAR, CRP, and PCT was observed postoperatively ( 0.642; 0.773; 0.087. In contrast, a slight decrease of IL-6 ( 0.599 was observed. A significant correlation was calculated for the pre- and postoperative difference of CRP ( 0.028 and PCT and type of surgical intervention received: after minor surgical intervention only PCT decreased significantly (<0.001, while after major surgical interventions no significant differences were observed for all biomarkers evaluated. In the control group, a significant decrease of CRP ( 0.005 and PCT ( 0.005 was observed. In patients treated adequately for bloodstream infections, postoperative suPAR levels remained uninfluenced of the surgical trauma and might therefore be a reliable parameter for postoperative infectious monitoring. After minor surgical intervention, PCT seems to be the most reliable parameter.

  11. Central Venous Catheters and Bloodstream Infection During Induction Therapy in Children With Acute Lymphoblastic Leukemia

    Bergmann, Kristin; Hasle, Henrik; Asdahl, Peter

    2016-01-01

    The purpose of the study was to assess the risk of firsttime bloodstream infection (BSI) according to type of central venous catheter (CVC) during induction therapy in children with acute lymphoblastic leukemia (ALL). Patients eligible for our analysis were all newly diagnosed children with ALL......-negative blood isolates occurred more frequently in patients with a TE, and that lower incidences of BSI were detected in patients older than 9 years with a TE, and in patients with T-ALL. It is concluded that the type of CVC inserted at diagnosis has no impact upon the risk of BSI in patients with ALL...

  12. Clinical and molecular epidemiology of Acinetobacter baumannii bloodstream infections in an endemic setting.

    Marchaim, Dror; Levit, Dana; Zigron, Roy; Gordon, Michal; Lazarovitch, Tsillia; Carrico, Joao A; Chalifa-Caspi, Vered; Moran-Gilad, Jacob

    2017-03-01

    The transmission dynamics of Acinetobacter baumannii in endemic settings, and the relation between microbial properties and patients' clinical outcomes, are yet obscure and hampered by insufficient metadata. Of 20 consecutive patients with A. baumannii bloodstream infection that were thoroughly analyzed at a single center, at least one transmission opportunity was evident for 85% of patients. This implies that patient-to-patient transmission is the major mode of A. baumannii acquisitions in health facilities. Moreover, all patients who died immediately (baumannii ST457 lineage compared with other strains.

  13. Catheter-Related Bloodstream Infections in Adults Receiving Home Parenteral Nutrition

    Tribler, Siri; Brandt, Christopher F; Hvistendahl, Mark

    2018-01-01

    BACKGROUND: A common complication in patients receiving home parenteral nutrition (HPN) is catheter-related bloodstream infections (CRBSIs). The CRBSI incidence has been advocated as an outcome parameter assessing the quality of care. This study aimed to illustrate how the use of different CRBSI......) and European Society for Clinical Nutrition (ESPEN) CRBSI criteria. Employing a catheter-salvaging strategy, 40% of the CRBSI diagnoses were supported by the paired blood culture positivity criteria and only 6% by a positive catheter tip. In 53%, CRBSIs were categorized as a clinical or "probable CRBSI...

  14. The TFPI-2 derived peptide EDC34 improves outcome of gram-negative sepsis.

    Papareddy, Praveen; Kalle, Martina; Sørensen, Ole E; Malmsten, Martin; Mörgelin, Matthias; Schmidtchen, Artur

    2013-01-01

    Sepsis is characterized by a dysregulated host-pathogen response, leading to high cytokine levels, excessive coagulation and failure to eradicate invasive bacteria. Novel therapeutic strategies that address crucial pathogenetic steps during infection are urgently needed. Here, we describe novel bioactive roles and therapeutic anti-infective potential of the peptide EDC34, derived from the C-terminus of tissue factor pathway inhibitor-2 (TFPI-2). This peptide exerted direct bactericidal effects and boosted activation of the classical complement pathway including formation of antimicrobial C3a, but inhibited bacteria-induced activation of the contact system. Correspondingly, in mouse models of severe Escherichia coli and Pseudomonas aeruginosa infection, treatment with EDC34 reduced bacterial levels and lung damage. In combination with the antibiotic ceftazidime, the peptide significantly prolonged survival and reduced mortality in mice. The peptide's boosting effect on bacterial clearance paired with its inhibiting effect on excessive coagulation makes it a promising therapeutic candidate for invasive Gram-negative infections.

  15. Prospects and challenges of developing new agents for tough Gram-negatives.

    Meyer, Annette L

    2005-10-01

    Historically, the medical profession has been successful in treating most bacterial infections in humans with synthetic second- and third-generation antibiotics. Recently, the prospects for continued success have dimmed with the increase in multidrug-resistant stains of bacteria. Infections caused by the Gram-negative bacteria Pseudomonas aeruginosa and Acinetobacter spp. in particular have increased in frequency and severity, and become progressively more difficult to treat. Contributors to disease severity include chronic infections due to mutator strains, persister cells and biofilms. The worst-case scenario of infections susceptible only to toxic polymixins is now a reality. The need to address the treatment of multidrug-resistant pathogens with innovative combination approaches and/or novel antibacterial agents is occurring in the context of reduced investment in antimicrobial drug discovery by the pharmaceutical industry.

  16. Patients with Central Lines — What You Need to Know to Avoid a Bloodstream Infection

    2011-03-01

    This podcast is based on the March, 2011 CDC Vital Signs report which indicates bloodstream infections in patients with central lines are largely preventable when healthcare providers use CDC-recommended infection control steps.  Created: 3/1/2011 by Centers for Disease Control and Prevention (CDC).   Date Released: 3/1/2011.

  17. Bloodstream-To-Eye Infections Are Facilitated by Outer Blood-Retinal Barrier Dysfunction.

    Phillip S Coburn

    Full Text Available The blood-retinal barrier (BRB functions to maintain the immune privilege of the eye, which is necessary for normal vision. The outer BRB is formed by tightly-associated retinal pigment epithelial (RPE cells which limit transport within the retinal environment, maintaining retinal function and viability. Retinal microvascular complications and RPE dysfunction resulting from diabetes and diabetic retinopathy cause permeability changes in the BRB that compromise barrier function. Diabetes is the major predisposing condition underlying endogenous bacterial endophthalmitis (EBE, a blinding intraocular infection resulting from bacterial invasion of the eye from the bloodstream. However, significant numbers of EBE cases occur in non-diabetics. In this work, we hypothesized that dysfunction of the outer BRB may be associated with EBE development. To disrupt the RPE component of the outer BRB in vivo, sodium iodate (NaIO3 was administered to C57BL/6J mice. NaIO3-treated and untreated mice were intravenously injected with 108 colony forming units (cfu of Staphylococcus aureus or Klebsiella pneumoniae. At 4 and 6 days postinfection, EBE was observed in NaIO3-treated mice after infection with K. pneumoniae and S. aureus, although the incidence was higher following S. aureus infection. Invasion of the eye was observed in control mice following S. aureus infection, but not in control mice following K. pneumoniae infection. Immunohistochemistry and FITC-dextran conjugate transmigration assays of human RPE barriers after infection with an exoprotein-deficient agr/sar mutant of S. aureus suggested that S. aureus exoproteins may be required for the loss of the tight junction protein, ZO-1, and for permeability of this in vitro barrier. Our results support the clinical findings that for both pathogens, complications which result in BRB permeability increase the likelihood of bacterial transmigration from the bloodstream into the eye. For S. aureus, however, BRB

  18. Changing trends in the aetiology, treatment and outcomes of bloodstream infection occurring in the first year after solid organ transplantation: a single-centre prospective cohort study.

    Oriol, Isabel; Sabé, Núria; Simonetti, Antonella F; Lladó, Laura; Manonelles, Anna; González, Jose; Tubau, Fe; Carratalà, Jordi

    2017-09-01

    To analyse trends in the aetiology, treatment and outcomes of bloodstream infection (BSI) within the first year post-transplant over the last 10-year period, we prospectively recorded all episodes of BSI occurring in solid organ transplant (SOT) recipients during the first year post-transplant from 2007 to 2016. Trends of factors were analysed by 2-year periods. Of 475 consecutive episodes of BSI, 218 occurred within a year of SOT in 178 SOT recipients. Gram-positive BSI decreased over time (40.5-2.2%). In contrast, there was a steady increase in Gram-negative bacilli (GNB) BSI (54.1-93.3%; P < 0.001), mainly due to Pseudomonas aeruginosa (2.4-20.4%) and Klebsiella pneumoniae (7.1-26.5%). Multidrug-resistant (MDR) GNB (4.8-38.8%; P < 0.001) rose dramatically, especially due to extended-spectrum β-lactamase (ESBL) production (7.1-34.7%). There was a sharp rise in the use of carbapenems, both as empirical (11.9-55.3%; P < 0.001) and as targeted antibiotic treatment (11.9-46.9%; P < 0.001). In conclusion, today, GNB are the leading causative agents of BSI in SOT recipients within the first year after SOT. In addition, MDR GNB have emerged mainly due to ESBL-producing strains. In spite of these changes, length of hospital stay, days of treatment and mortality have remained stable over time. © 2017 Steunstichting ESOT.

  19. Should we use closed or open infusion containers for prevention of bloodstream infections?

    Rangel-Frausto, Manuel S; Higuera-Ramirez, Francisco; Martinez-Soto, Jose; Rosenthal, Victor D

    2010-02-02

    Hospitalized patients in critical care settings are at risk for bloodstream infections (BSI). Most BSIs originate from a central line (CL), and they increase length of stay, cost, and mortality. Open infusion containers may increase the risk of contamination and administration-related (CLAB) because they allow the entry of air into the system, thereby also providing an opportunity for microbial entry. Closed infusion containers were designed to overcome this flaw. However, open infusion containers are still widely used throughout the world.The objective of the study was to determine the effect of switching from open (glass, burettes, and semi-rigid) infusion containers to closed, fully collapsible, plastic infusion containers (Viaflex) on the rate and time to onset of central line-associated bloodstream infections CLABs. An open label, prospective cohort, active healthcare-associated infection surveillance, sequential study was conducted in four ICUs in Mexico. Centers for Disease Control National Nosocomial Infections Surveillance Systems definitions were used to define device-associated infections. A total of 1,096 adult patients who had a central line in place for >24 hours were enrolled. The CLAB rate was significantly higher during the open versus the closed container period (16.1 versus 3.2 CLAB/1000 central line days; RR = 0.20, 95% CI = 0.11-0.36, P container period (1.4% Days 2-4 to 0.5% Days 8-10), but increased in the open container period (4.9% Days 2-4 to 5.4% Days 8-10). The chance of acquiring a CLAB was significantly decreased (81%) in the closed container period (Cox proportional hazard ratio 0.19, P container period (23.4% versus 16.1%; RR = 0.69, 95% CI = 0.54-0.88, P containers significantly reduced CLAB rate, the probability of acquiring CLAB, and mortality.

  20. Resistant gram-negative bacilli and antibiotic consumption in zarqa, jordan

    Bataineh, H.A.; Alrashed, K.M.

    2007-01-01

    To investigate the prevalence of antibiotic resistance among gram-negative bacteria in relation to antibiotic use in Prince Hashem Hospital (PHH), Jordan. One hundred consecutive gram-negative bacterial isolates from different sites were collected from patients admitted to the ICU at PHH. The susceptibilities of the strains to 12 antibiotics were performed and interpreted. The quantities and the numbers of the patients discharged on antibiotics and the quantities consumed were obtained from the hospital pharmacy records. The most common isolate was P. aeruginosa (n=21) The most common site of isolation was the respiratory tract (65%), The highest susceptibility was to piperacillin/ tazobactam(78%), and the lowest was to cefuroxime(34%). The aminoglycosides gentamicin and amikacin were active against 71% and 73% of the isolates respectively, Ciprofloxacin was active against 75% of the isolates. The most frequently used antibiotics were the third-generation cephalosporins ceftriaxone and ceftazidime, followed by imipenem and amikacin. Antibiotic resistance surveillance programs associated with registration of antibiotic consumption are necessary to promote optimal use of antibiotics. Rational prescribing of antibiotics should be encouraged through educational programs, surveillance and audit. Proper infection control measures should be practiced to prevent horizontal transfer of drug-resistant organisms. (author)

  1. Probing the Penetration of Antimicrobial Polymyxin Lipopeptides into Gram-Negative Bacteria

    2015-01-01

    The dry antibiotic development pipeline coupled with the emergence of multidrug resistant Gram-negative ‘superbugs’ has driven the revival of the polymyxin lipopeptide antibiotics. Polymyxin resistance implies a total lack of antibiotics for the treatment of life-threatening infections. The lack of molecular imaging probes that possess native polymyxin-like antibacterial activity is a barrier to understanding the resistance mechanisms and the development of a new generation of polymyxin lipopeptides. Here we report the regioselective modification of the polymyxin B core scaffold at the N-terminus with the dansyl fluorophore to generate an active probe that mimics polymyxin B pharmacologically. Time-lapse laser scanning confocal microscopy imaging of the penetration of probe (1) into Gram-negative bacterial cells revealed that the probe initially accumulates in the outer membrane and subsequently penetrates into the inner membrane and finally the cytoplasm. The implementation of this polymyxin-mimetic probe will advance the development of platforms for the discovery of novel polymyxin lipopeptides with efficacy against polymyxin-resistant strains. PMID:24635310

  2. Antibacterial activity of crude extract of Punica granatum pericarp on pathogenic Gram-negative bacilli.

    Voravuthikunchai, S.

    2005-08-01

    Full Text Available The objective of this study was to investigate the effect of crude extracts of Punica granatum Linn. pericarp with 3 different solvents against pathogenic Gram-negative bacilli. Ethanolic extracts showed the antibacterial activity against all strains tested including enterohaemorrhagic Escherichia coli 4 strains (E. coli O157: H7, E. coli O26: H11, E. coli O111: NM, E. coli O22, Pseudomonas aeruginosa, Shigella boydii and Salmonella london. Inhibition zones ranged from 10.02 to 19.15 mm. Minimum inhibitory concentration (MIC and minimum bactericidal concentration (MBC ranged from 0.09 to 3.13 mg/ml and 3.13 to 25 mg/ml, respectively. Aqueous extract had low antibacterial activity while crude chloroform extracts had no effect on the growth of these strains. Ethyl acetate and n-butanol fractions of P. granatum pericarp demonstrated high activity with the best MIC and MBC values of 0.02 to 0.78 mg/ml and 0.19 to 6.25 mg/ml, respectively. As ethanolic extract of P. granatum was very effective against these pathogenic bacteria, further investigation on this plant species may provide alternative, but bioactive, medicines for the treatment of Gram-negative bacterial infection.

  3. Infectious tenosynovitis with bloodstream infection caused by Erysipelothrix rhusiopathiae, a case report on an occupational pathogen.

    Hofseth, Kristine; Dalen, Håvard; Kibsgaard, Leif; Nebb, Solrun; Kümmel, Angela; Mehl, Arne

    2017-01-05

    Erysipelothrix rhusiopathiae is an established animal pathogen, which may cause infections in humans. It is a gram-positive rod and found in the tonsils or the digestive tracts of animals. The bacterium is occupationally related, as usually only people with frequent animal contacts are infected. We report a case of a patient who was admitted with an infectious tenosynovitis with bloodstream infection due to E. rhusiopathiae, and to our knowledge, this is the first report of a tenosynovitis with systemic manifestation associated with this bacterium. A 52-year old Norwegian man, who worked with transportation of swine cadavers, was admitted to the local hospital with sepsis and unknown focus of infection. A few days earlier he had an injury to the skin of one of his fingers that later proved to be infected with E. rhusiopathiae. There were no other causes for his symptoms than the infectious tenosynovitis with systemic manifestation. The infection resolved on treatment with antibiotics and surgery. A transoesophageal echocardiogram was performed to exclude endocarditis, which may be associated with this pathogen. This case report highlights the importance of clinicians being aware of this bacterium, and we describe risk factors for infection, differences in the clinical manifestations of the disease, challenges with diagnosing the bacterium and adverse effects of immunosuppressive drugs. Recommended treatment is appropriate antibiotic therapy and adequate debridement and surgical drainage of the tendon sheath.

  4. An optimized staining technique for the detection of Gram positive and Gram negative bacteria within tissue.

    Becerra, Sandra C; Roy, Daniel C; Sanchez, Carlos J; Christy, Robert J; Burmeister, David M

    2016-04-12

    Bacterial infections are a common clinical problem in both acute and chronic wounds. With growing concerns over antibiotic resistance, treatment of bacterial infections should only occur after positive diagnosis. Currently, diagnosis is delayed due to lengthy culturing methods which may also fail to identify the presence of bacteria. While newer costly bacterial identification methods are being explored, a simple and inexpensive diagnostic tool would aid in immediate and accurate treatments for bacterial infections. Histologically, hematoxylin and eosin (H&E) and Gram stains have been employed, but are far from optimal when analyzing tissue samples due to non-specific staining. The goal of the current study was to develop a modification of the Gram stain that enhances the contrast between bacteria and host tissue. A modified Gram stain was developed and tested as an alternative to Gram stain that improves the contrast between Gram positive bacteria, Gram negative bacteria and host tissue. Initially, clinically relevant strains of Pseudomonas aeruginosa and Staphylococcus aureus were visualized in vitro and in biopsies of infected, porcine burns using routine Gram stain, and immunohistochemistry techniques involving bacterial strain-specific fluorescent antibodies as validation tools. H&E and Gram stain of serial biopsy sections were then compared to a modification of the Gram stain incorporating a counterstain that highlights collagen found in tissue. The modified Gram stain clearly identified both Gram positive and Gram negative bacteria, and when compared to H&E or Gram stain alone provided excellent contrast between bacteria and non-viable burn eschar. Moreover, when applied to surgical biopsies from patients that underwent burn debridement this technique was able to clearly detect bacterial morphology within host tissue. We describe a modification of the Gram stain that provides improved contrast of Gram positive and Gram negative microorganisms within host

  5. Quorum sensing signal molecules (acylated homoserine lactones) in Gram-negative fish pathogenic bacteria

    Bruhn, Jesper Bartholin; Dalsgaard, Inger; Nielsen, K.F.

    2005-01-01

    The aim of the present study was to investigate the production of quorum sensing signals (specifically acylated homoserine lactones, AHLs) among a selection of strains of Gram-negative fish bacterial pathogens. These signals are involved in the regulation of virulence factors in some human...... salmonicida and Vibrio splendidus were also positive. Aeromonas species produced N-butanoyl homoserine lactone (BHL) and N-hexanoyl homoserine lactone (HHL) and 1 additional product, whereas N-3-oxo-hexanoyl homoserine lactone (OHHL) and HHL were detected in Vibrio salmonicida. N-3-oxo-octanoyl homoserine...... lactone (OOHL) and N-3-octanoyl homoserine lactone (OHL) were detected in Y. ruckeii. AHLs were not detected from strains of Photobacterium damselae, Flavobacterium psychrophilum or Moritella viscosa. AHLs were extracted from fish infected with Y. ruckeri but not from fish infected with A. salmonicida...

  6. Plasmid-Mediated Antibiotic Resistance and Virulence in Gram-negatives: the Klebsiella pneumoniae Paradigm.

    Ramirez, Maria S; Traglia, German M; Lin, David L; Tran, Tung; Tolmasky, Marcelo E

    Plasmids harbor genes coding for specific functions including virulence factors and antibiotic resistance that permit bacteria to survive the hostile environment found in the host and resist treatment. Together with other genetic elements such as integrons and transposons, and using a variety of mechanisms, plasmids participate in the dissemination of these traits resulting in the virtual elimination of barriers among different kinds of bacteria. In this article we review the current information about physiology and role in virulence and antibiotic resistance of plasmids from the gram-negative opportunistic pathogen Klebsiella pneumoniae . This bacterium has acquired multidrug resistance and is the causative agent of serious communityand hospital-acquired infections. It is also included in the recently defined ESKAPE group of bacteria that cause most of US hospital infections.

  7. Coordinated Molecular Cross-Talk between Staphylococcus aureus, Endothelial Cells and Platelets in Bloodstream Infection

    Carolina D. Garciarena

    2015-12-01

    Full Text Available Staphylococcus aureus is an opportunistic pathogen often carried asymptomatically on the human body. Upon entry to the otherwise sterile environment of the cardiovascular system, S. aureus can lead to serious complications resulting in organ failure and death. The success of S. aureus as a pathogen in the bloodstream is due to its ability to express a wide array of cell wall proteins on its surface that recognise host receptors, extracellular matrix proteins and plasma proteins. Endothelial cells and platelets are important cells in the cardiovascular system and are a major target of bloodstream infection. Endothelial cells form the inner lining of a blood vessel and provide an antithrombotic barrier between the vessel wall and blood. Platelets on the other hand travel throughout the cardiovascular system and respond by aggregating around the site of injury and initiating clot formation. Activation of either of these cells leads to functional dysregulation in the cardiovascular system. In this review, we will illustrate how S. aureus establish intimate interactions with both endothelial cells and platelets leading to cardiovascular dysregulation.

  8. Executive summary: Diagnosis and Treatment of Catheter-Related Bloodstream Infection: Clinical Guidelines of the Spanish Society of Clinical Microbiology and Infectious Diseases (SEIMC) and the Spanish Society of Intensive Care Medicine and Coronary Units (SEMICYUC).

    Chaves, Fernando; Garnacho-Montero, José; Del Pozo, José Luis; Bouza, Emilio; Capdevila, José Antonio; de Cueto, Marina; Domínguez, M Ángeles; Esteban, Jaime; Fernández-Hidalgo, Nuria; Fernández Sampedro, Marta; Fortún, Jesús; Guembe, María; Lorente, Leonardo; Paño, Jose Ramón; Ramírez, Paula; Salavert, Miguel; Sánchez, Miguel; Vallés, Jordi

    2018-02-01

    Catheter-related bloodstream infections (CRBSI) constitute an important cause of hospital-acquired infection associated with morbidity, mortality, and cost. The aim of these guidelines is to provide updated recommendations for the diagnosis and management of CRBSI in adults. Prevention of CRBSI is excluded. Experts in the field were designated by the two participating Societies (Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica and the Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias). Short-term peripheral venous catheters, non-tunneled and long-term central venous catheters, tunneled catheters and hemodialysis catheters are covered by these guidelines. The panel identified 39 key topics that were formulated in accordance with the PICO format. The strength of the recommendations and quality of the evidence were graded in accordance with ESCMID guidelines. Recommendations are made for the diagnosis of CRBSI with and without catheter removal and of tunnel infection. The document establishes the clinical situations in which a conservative diagnosis of CRBSI (diagnosis without catheter removal) is feasible. Recommendations are also made regarding empirical therapy, pathogen-specific treatment (coagulase-negative staphylococci, Sthaphylococcus aureus, Enterococcus spp, Gram-negative bacilli, and Candida spp), antibiotic lock therapy, diagnosis and management of suppurative thrombophlebitis and local complications. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  9. Bacillus Cereus catheter related bloodstream infection in a patient in a patient with acute lymphblastic leukemia

    Lütfiye Öksüz

    2012-01-01

    Full Text Available Bacillus cereus infection is rarely associated with actual infection and for this reason single positive blood culture is usually regarded as contamination . However it may cause a number of infections, such catheter-related blood stream infections. Significant catheter-related bloodstream infections (CRBSI caused by Bacillus spp. are mainly due to B.cereus and have been predominantly reported in immunocompromised hosts1 . Catheter removal is generally advised for management of infection. In this report, catheter-related bacteremia caused by B.cereus in a patient with acute lymphoblastıc leukemia (ALL in Istanbul Medical Faculty was presented.A 44-year old man presented with fatigue, weight loss, epistaxis and high fever. A double-lumen Hickman–catheter (Bard 12.0 Fr, Round Dual Lumen was inserted by surgical cut-down to access the right subclavian vein which would be necessary for allogeneic stem cell transplantation. Three weeks later the patient presented with high fever and headache. Bacillus spp. was isolated from the cathether while blood culture obtained from the peripheral vein remained negative. The bacterial identification was confirmed as B.cereus using VITEK identification system It has been reported Bacillus cereus septicemia may be fatal in immunocompromised hosts despite broad-spectrum appropriate treatment10. Catheter removal is essential for prevention of recurrent bacteremia. Long-term cathater salvage should be reserved for appropriate patient group.

  10. Taurolidine lock is superior to heparin lock in the prevention of catheter related bloodstream infections and occlusions.

    Evelyn D Olthof

    Full Text Available Patients on home parenteral nutrition (HPN are at risk for catheter-related complications; mainly infections and occlusions. We have previously shown in HPN patients presenting with catheter sepsis that catheter locking with taurolidine dramatically reduced re-infections when compared with heparin. Our HPN population therefore switched from heparin to taurolidine in 2008. The aim of the present study was to compare long-term effects of this catheter lock strategy on the occurrence of catheter-related bloodstream infections and occlusions in HPN patients.Data of catheter-related complications were retrospectively collected from 212 patients who received HPN between January 2000 and November 2011, comprising 545 and 200 catheters during catheter lock therapy with heparin and taurolidine, respectively. We evaluated catheter-related bloodstream infection and occlusion incidence rates using Poisson-normal regression analysis. Incidence rate ratios were calculated by dividing incidence rates of heparin by those of taurolidine, adjusting for underlying disease, use of anticoagulants or immune suppressives, frequency of HPN/fluid administration, composition of infusion fluids, and duration of HPN/fluid use before catheter creation.Bloodstream infection incidence rates were 1.1/year for heparin and 0.2/year for taurolidine locked catheters. Occlusion incidence rates were 0.2/year for heparin and 0.1/year for taurolidine locked catheters. Adjusted incidence ratios of heparin compared to taurolidine were 5.9 (95% confidence interval, 3.9-8.7 for bloodstream infections and 1.9 (95% confidence interval, 1.1-3.1 for occlusions.Given that no other procedural changes than the catheter lock strategy were implemented during the observation period, these data strongly suggest that taurolidine decreases catheter-related bloodstream infections and occlusions in HPN patients compared with heparin.

  11. The target of daptomycin is absent from Escherichia coli and other gram-negative pathogens.

    Randall, Christopher P; Mariner, Katherine R; Chopra, Ian; O'Neill, Alex J

    2013-01-01

    Antistaphylococcal agents commonly lack activity against Gram-negative bacteria like Escherichia coli owing to the permeability barrier presented by the outer membrane and/or the action of efflux transporters. When these intrinsic resistance mechanisms are artificially compromised, such agents almost invariably demonstrate antibacterial activity against Gram negatives. Here we show that this is not the case for the antibiotic daptomycin, whose target appears to be absent from E. coli and other Gram-negative pathogens.

  12. Community-Onset Bloodstream Infection during the ‘After Hours’ Is not Associated with an increased Risk for Death

    Kevin B Laupland

    2012-01-01

    Full Text Available BACKGROUND/OBJECTIVE: Patients admitted to hospital during the ‘after hours’ (weekends and evenings may be at increased risk for adverse outcome. The objective of the present study was to assess whether community-onset bloodstream infections presenting in the after hours are associated with death.

  13. Taurolidine-citrate-heparin lock reduces catheter-related bloodstream infections in intestinal failure patients dependent on home parenteral support

    Tribler, Siri; Brandt, Christopher F.; Petersen, Anne H.

    2017-01-01

    Background: In patients with intestinal failure who are receiving home parenteral support (HPS), catheter-related bloodstream infections (CRBSIs) inflict health impairment and high costs.Objective: This study investigates the efficacy and safety of the antimicrobial catheter lock solution, taurol...

  14. Clinical and Laboratory Characteristics of Patients with Nontuberculous Mycobacterium Bloodstream Infection in a Tertiary Referral Hospital in Beijing, China

    Sai-Nan Bian

    2016-01-01

    Conclusions: We reported all cases in our hospital diagnosed with bloodstream NTM infection that was rarely reported. In this group of patients, patients usually had a high fever and could have multiple organ involvements. All patients with poor prognosis had underlying diseases.

  15. Metallo- β-lactamases among Multidrug Resistant (MDR Gram Negative Bacteria Isolated from Clinical Specimens during 2009 in Sanandaj, Kurdistan Province

    Himen Salimizand

    2012-08-01

    Full Text Available Background: Today, there are numerous reports about emerging multi drug resistant gram negative bacteria all around the world, especially in ICUs. Rarely, Metallo-β-lactamase (MBL enzymes are responsible for these cases. Study of MBLs for diagnosing and preventing distribution of the origin of infection are critical issues. In addition, we would like to compare the efficacy of Iranian and foreign- made antibiotic disks. Materials and Methods: During 2009 all entered clinical specimens to the laboratory tested for detecting gram negative bacteria. Isolated bacteria were tested by Kirby-Bauer method to antibiotic susceptibility test by Iranian and foreign (MAST disks. For gram negative carbapenem resistant isolates, PCR technique used to detect VIM, GIM, and SIM variants of MBLs.Results: During one year, 17890 clinical specimens referred Besat laboratory. The most specimen was Urine (8172 followed by blood culture (5190 that in which 1110 gram negative and positives isolated. Out of which, 778 (70% of isolates were gram negatives. MDR gram negatives were 157 (20.2%. Imipenem and meropenem were the most efficient antibiotics (all susceptible and ceftriaxone was the least (19 % susceptible. E. coli was the most prevalent isolate. 79 Gram negative isolates (10.1% were resistant to Iranian-made discs but all susceptible for foreign ones. All 79 isolates were tested by PCR for MBL genes, that, all were negative. Besides, Iranian imipenem and cefepime disks have had distinguishable difference in susceptibility of isolates.Conclusion: Fortunately, none of gram negative isolates were MBL producer, which revealed no colonization of MBL producing bacteria. Iranian-made disks appear efficient except for imipenem and cefepime.

  16. Clinical Impact of Pretransplant Multidrug-Resistant Gram-Negative Colonization in Autologous and Allogeneic Hematopoietic Stem Cell Transplantation.

    Forcina, Alessandra; Lorentino, Francesca; Marasco, Vincenzo; Oltolini, Chiara; Marcatti, Magda; Greco, Raffaella; Lupo-Stanghellini, Maria Teresa; Carrabba, Matteo; Bernardi, Massimo; Peccatori, Jacopo; Corti, Consuelo; Ciceri, Fabio

    2018-03-02

    Multidrug-resistant Gram-negative bacteria (MDR-GNB) are an emerging cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Three-hundred forty-eight consecutive patients transplanted at our hospital from July 2012 to January 2016 were screened for a pretransplant MDR-GNB colonization and evaluated for clinical outcomes. A pretransplant MDR-GNB colonization was found in 16.9% of allo-HSCT and in 9.6% of auto-HSCT recipients. Both in auto- and in allo-HSCT, carriers of a MDR-GNB showed no significant differences in overall survival (OS), transplant-related mortality (TRM), or infection-related mortality (IRM) compared with noncarriers. OS at 2 years for carriers compared with noncarriers was 85% versus 81% (P = .262) in auto-HSCT and 50% versus 43% (P = .091) in allo-HSCT. TRM at 2 years was 14% versus 5% (P = .405) in auto-HSCT and 31% versus 25% (P = .301) in allo-HSCT. IRM at 2 years was 14% versus 2% (P = .142) in auto-HSCT and 23% versus 14% (P = .304) in allo-HSCT. In multivariate analysis, only grade III to IV acute graft-versus-host disease was an independent factor for reduced OS (P < .001) and increased TRM (P < .001) and IRM (P < .001). During the first year after transplant, we collected 73 GNB bloodstream infectious (BSI) episodes in 54 patients, 42.4% of which sustained by a MDR-GNB. Rectal swabs positivity associated with the pathogen causing subsequent MDR-GNB BSI episodes in 13 of 31 (41.9%). Overall, OS at 4 months from MDR-GNB BSI episode onset was of 67.9%, with a 14-day attributed mortality of 12.9%, not being significantly different between carriers and noncarriers (P = .207). We conclude that in this extended single-center experience, a pretransplant MDR-GNB colonization did not significantly influence OS, TRM, and IRM both in auto- and allo-HSCT settings and that MDR-GNB attributed mortality can be controlled in carriers when an early pre-emptive antimicrobial therapy is

  17. Molecular diagnosis of bloodstream infections in onco-haematology patients with PCR/ESI-MS technology.

    Jordana-Lluch, Elena; Rivaya, Belén; Marcó, Clara; Giménez, Montserrat; Quesada, Mª Dolores; Escobedo, Agustín; Batlle, Montserrat; Martró, Elisa; Ausina, Vicente

    2017-02-01

    Onco-haematological patients are prone to develop infections, and antibiotic prophylaxis may lead to negative blood cultures. Thus, the microbiological diagnosis and subsequent administration of a targeted antimicrobial therapy is often difficult. The goal of this study was to evaluate the usefulness of IRIDICA (PCR/ESI-MS technology) for the molecular diagnosis of bloodstream infections in this patient group. A total of 463 whole blood specimens from different sepsis episodes in 429 patients were analysed using the PCR/ESI-MS platform, comparing the results with those of blood culture and other clinically relevant information. The sensitivity of PCR/ESI-MS by specimen (excluding polymicrobial infections, n = 25) in comparison with blood culture was 64.3% overall, 69.0% in oncological patients, and 59.3% in haematological patients. When comparing with a clinical infection criterion, overall sensitivity rose to 74.7%, being higher in oncological patients (80.0%) than in haematological patients (67.7%). Thirty-one microorganisms isolated by culture were not detected by IRIDICA, whereas 42 clinically relevant pathogens not isolated by culture were detected moleculary. PCR/ESI-MS offers a reliable identification of pathogens directly from whole blood. While additional studies are needed to confirm our findings, the system showed a lower sensitivity in onco-haematological patients in comparison with previously reported results in patients from the Intensive Care Unit. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  18. High Prevalence of Antimicrobial-resistant Gram-negative Colonization in Hospitalized Cambodian Infants.

    Turner, Paul; Pol, Sreymom; Soeng, Sona; Sar, Poda; Neou, Leakhena; Chea, Phal; Day, Nicholas Pj; Cooper, Ben S; Turner, Claudia

    2016-08-01

    Antimicrobial-resistant Gram-negative infections are a significant cause of mortality in young infants. We aimed to determine characteristics of, and risk factors for, colonization and invasive infection caused by 3rd generation cephalosporin (3GC) or carbapenem-resistant organisms in outborn infants admitted to a neonatal unit (NU) in Cambodia. During the first year of operation, patients admitted to the Angkor Hospital for Children NU, Siem Reap, Cambodia, underwent rectal swabbing on admission and twice weekly until discharge. Swabs were taken also from 7 environmental sites. Swabs were cultured to identify 3GC or carbapenem-resistant Acinetobacter sp., Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. The study included 333 infants with a median age at NU admission of 10 days (range, 0-43). Colonization by ≥1 3GC-resistant organism was detected in 85.9% (286/333). Admission swabs were collected in 289 infants: 61.9% were colonized by a 3GC-resistant organism at the time of admission, and a further 23.2% were colonized during hospitalization, at a median of 4 days [95% confidence interval: 3-5]. Probiotic treatment (hazard ratio: 0.58; 95% confidence interval: 0.35-0.98) was associated with delayed colonization. Colonization by a carbapenem-resistant organism occurred in 25 (7.5%) infants. Six infants had NU-associated K. pneumoniae bacteremia; phenotypically identical colonizing strains were found in 3 infants. Environmental colonization occurred early. Colonization by antimicrobial-resistant Gram-negative organisms occurred early in hospitalized Cambodian infants and was associated with subsequent invasive infection. Trials of potential interventions such as probiotics are needed.

  19. Positive deviance as a strategy to prevent and control bloodstream infections in intensive care

    Francimar Tinoco de Oliveira

    Full Text Available Abstract OBJECTIVE To describe the application of positive deviance as a strategy to prevent and control bloodstream infections. METHOD An intervention study with nursing and medical team members working in an intensive care unit in a university hospital, between June and December 2014. The four steps of the positive defiance methodology were applied: to define, to determine, to discover and to design. RESULTS In 90 days, 188 actions were observed, of these, 36.70% (n=69 were related to catheter dressing. In 81.15% (n=56 of these dressings, the professionals most adhered to the use of flexible sterile cotton-tipped swabs to perform antisepsis at catheter entry sites and fixation dressing. CONCLUSION Positive deviance contributed to the implementation of proposals to improve work processes and team development related to problems identified in central venous catheter care.

  20. [Evaluation of practices for the prevention and control of bloodstream infections in a government hospital].

    Jardim, Jaquelline Maria; Lacerda, Rúbia Aparecida; Soares, Naury de Jesus Danzi; Nunes, Bruna Kosar

    2013-02-01

    The aim of this study was to observe clinical procedures in order to evaluate the practices used for the control and prevention of bloodstream infections associated with short-term central venous catheters (BSI-ACVC). The study data came from 5877 assessments distributed among selected practices. The results revealed the following adherence rates among the practices selected: 91.6% for recording the indication and permanence time of the CVC, 51.5% for adhering to the care and maintenance of the dressing at the CVC insertion site and its devices, 10.7% for hand hygiene practices while performing procedures related to the CVC, and 0.0% for the practices related to the insertion of the central venous catheter (CVC). The results demonstrate the need for further elaboration of strategies that ensure sustainable compliance practices for prevention and control BSI-ACVC in the institution being assessed.

  1. APSIC guide for prevention of Central Line Associated Bloodstream Infections (CLABSI

    Moi Lin Ling

    2016-05-01

    Full Text Available Abstract This document is an executive summary of the APSIC Guide for Prevention of Central Line Associated Bloodstream Infections (CLABSI. It describes key evidence-based care components of the Central Line Insertion and Maintenance Bundles and its implementation using the quality improvement methodology, namely the Plan-Do-Study-Act (PDSA methodology involving multidisciplinary process and stakeholders. Monitoring of improvement over time with timely feedback to stakeholders is a key component to ensure the success of implementing best practices. A surveillance program is recommended to monitor outcomes and adherence to evidence-based central line insertion and maintenance practices (compliance rate and identify quality improvement opportunities and strategically targeting interventions for the reduction of CLABSI.

  2. Impact of universal disinfectant cap implementation on central line-associated bloodstream infections.

    Merrill, Katreena Collette; Sumner, Sharon; Linford, Lorraine; Taylor, Carrie; Macintosh, Christopher

    2014-12-01

    Central line-associated bloodstream infections (CLABSIs) result in increased length of stay, cost, and patient morbidity and mortality. One CLABSI prevention method is disinfection of intravenous access points. The literature suggests that placing disinfectant caps over needleless connectors decreases CLABSI risk. A quasi-experimental intervention study was conducted in a >430-bed trauma I center. In addition to an existing standard central line bundle, a new intervention consisting of a luer-lock disinfectant cap with 70% alcohol was implemented in all intravenous (IV) needleless connectors on patients with peripheral and central lines. Compliance to the disinfectant cap was monitored weekly. A generalized linear model using a Poisson distribution was fit to determine if there were significant relationships between CLABSIs and disinfectant cap use. Impacts on costs were also examined. The rate of CLABSI decreased following implementation of the disinfectant cap. The incidence rate ratios (.577, P = .004) for implementing the disinfectant caps was statistically significant, indicating that the rate of patient infections decreased by >40%. Increased compliance rates were associated with lower infection rates. Disinfectant cap use was associated with an estimated savings of almost $300,000 per year in the hospital studied. Use of a disinfectant cap on IV needleless connectors in addition to an existing standard central line bundle was associated with decreased CLABSI and costs. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  3. Epidemiology and molecular characterization of multidrug-resistant Gram-negative bacteria in Southeast Asia

    Nuntra Suwantarat

    2016-05-01

    Full Text Available Abstract Background Multidrug-resistant Gram-negative bacteria (MDRGN, including extended-spectrum β-lactamases (ESBLs and multidrug-resistant glucose-nonfermenting Gram-negative bacilli (nonfermenters, have emerged and spread throughout Southeast Asia. Methods We reviewed and summarized current critical knowledge on the epidemiology and molecular characterization of MDRGN in Southeast Asia by PubMed searches for publications prior to 10 March 2016 with the term related to “MDRGN definition” combined with specific Southeast Asian country names (Thailand, Singapore, Malaysia, Vietnam, Indonesia, Philippines, Laos, Cambodia, Myanmar, Brunei. Results There were a total of 175 publications from the following countries: Thailand (77, Singapore (35, Malaysia (32, Vietnam (23, Indonesia (6, Philippines (1, Laos (1, and Brunei (1. We did not find any publications on MDRGN from Myanmar and Cambodia. We did not include publications related to Shigella spp., Salmonella spp., and Vibrio spp. and non-human related studies in our review. English language articles and abstracts were included for analysis. After the abstracts were reviewed, data on MDRGN in Southeast Asia from 54 publications were further reviewed and included in this study. Conclusions MDRGNs are a major contributor of antimicrobial-resistant bacteria in Southeast Asia. The high prevalence of ESBLs has been a major problem since 2005 and is possibly related to the development of carbapenem resistant organisms in this region due to the overuse of carbapenem therapy. Carbapenem–resistant Acinetobacter baumannii is the most common pathogen associated with nosocomial infections in this region followed by carbapenem-resistant Pseudomonas aeruginosa. Although Southeast Asia is not an endemic area for carbapenem-resistant Enterobacteriaceae (CRE, recently, the rate of CRE detection has been increasing. Limited infection control measures, lack of antimicrobial control, such as the presence of

  4. Phenotypic and Genotypic Detection of Metallo-beta-lactamases among Imipenem-Resistant Gram Negative Isolates

    Mohammad Mohammadzadeh

    2016-08-01

    Full Text Available Background:   Imipenem-resistant gram negative bacteria, resulting from metallo-beta-lactamase (MBLs-producing strains have been reported to be among the important causes of nosocomial infections and of serious therapeutic problem worldwide. Because of their broad range, potent carbapenemase activity and resistance to inhibitors, these enzymes can confer resistance to almost all beta-lactams. The prevalence of metallo-beta-lactamase among imipenem-resistant Acinetobacter spp., Pseudomonas spp. and Enerobacteriaceae isolates is determined.Methods:   In this descriptive study 864 clinical isolates of Acinetobacter spp., Pseudomonas spp. and Enterobacteriaceae, were initially tested for imipenem susceptibility. The metallo-beta-lactamase production was detected using combined disk diffusion, double disk synergy test, and Hodge test. Then all imipenem resistant isolates were tested by PCR for imp, vim and ndm genes. Results:   Among 864 isolates, 62 (7.17 % were imipenem-resistant. Positive phonetypic test for metallo-beta-lactamase was 40 (64.5%, of which 24 (17.1% and 16 (9.2% isolates were Acinetobacter spp. and Pseudomonas spp., respectively. By PCR method 30 (48.4% of imipenem resistant Acinetobacter, and Pseudomonas isolates were positive for MBL-producing genes. None of the Enterobacteriaceae isolates were positive for metallo-beta-lactamase activity. Conclusion:   The results of this study are indicative of the growing number of nosocomial infections associated with multidrug-resistant gram negative bacteria in this region leading to difficulties in antibiotic therapy. Thereby, using of phenotypic methods can be helpful for management of this problem.

  5. Beta-lactam resistance in the gram negatives: increasing complexity of conditional, composite and multiply resistant phenotypes.

    Iredell, Jon; Thomas, Lee; Espedido, Björn

    2006-12-01

    The greatest impact of microbiology data on clinical care is in the critically ill. Unfortunately, this is also the area in which microbiology laboratories are most often non-contributive. Attempts to move to rapid, culture-independent diagnostics are driven by the need to expedite urgent results. This is difficult in Gram-negative infection because of the complexity of the antibiotic resistance phenotype. Here, we discuss resistance to modern beta-lactams as a case in point. Recent outbreaks of transmissible carbapenem resistance among Gram-negative enteric pathogens in Sydney and Melbourne serve to illustrate the pitfalls of traditional phenotypical approaches. A better understanding of the epidemiology and mosaic nature of antibiotic resistance elements in the microflora is needed for us to move forward.

  6. Bacillus Cereus catheter related bloodstream infection in a patient in a patient with acute lymphblastic leukemia

    Lütfiye Öksüz

    2012-01-01

    Full Text Available

    Bacillus cereus infection is rarely associated with actual infection and for this reason single positive blood culture is usually regarded as contamination . However it may cause a number of infections, such catheter-related blood stream infections. Significant catheter-related bloodstream infections (CRBSI caused by Bacillus spp. are mainly due to B.cereus and have been predominantly reported in immunocompromised hosts1 . Catheter removal is generally advised for management of infection. In this report, catheter-related bacteremia caused by B.cereus in a patient with acute lymphoblastıc leukemia (ALL in Istanbul Medical Faculty was presented.A 44-year old man presented with fatigue, weight loss, epistaxis and high fever. A double-lumen Hickman–catheter (Bard 12.0 Fr, Round Dual Lumen was inserted by surgical cut-down to access the right subclavian vein which would be necessary for allogeneic stem cell transplantation. Three weeks later the patient presented with high fever and headache. Bacillus spp. was isolated from the cathether while blood culture obtained from the peripheral vein remained negative. The bacterial identification was confirmed as B.cereus using VITEK identification system

    It has been reported Bacillus cereus septicemia may be fatal in immunocompromised hosts despite broad-spectrum appropriate treatment10. Catheter removal is essential for prevention of recurrent bacteremia. Long-term cathater salvage should be reserved for appropriate patient group.

  7. Interventional strategies and current clinical experience with carbapenemase-producing Gram-negative bacteria.

    Akova, M; Daikos, G L; Tzouvelekis, L; Carmeli, Y

    2012-05-01

    The wide dissemination of carbapenemase-producing Gram-negatives (CPGNs), including enterobacterial species and non-fermenters, has caused a public health crisis of global dimensions. These organisms cause serious infections in hospitalized patients, and are associated with increased mortality. Cross-transmission is common, and outbreaks may occur in healthcare facilities where the infection control practices are inadequate. CPGNs exhibit extensive drug-resistant phenotypes, complicate therapy, and limit treatment options. Systematic data on therapy are limited. However, regimens combining two or more active agents seem to be more efficacious than monotherapy in carbapenemase-producing Klebsiella pneumoniae infections. Strict infection control measures, including active surveillance for timely detection of colonized patients, separation of carriers from non-carriers, and contact precautions, are of utmost importance, and may be the only effective way of preventing the introduction and transmission of these bacteria in healthcare settings. © 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.

  8. Antimicrobial Susceptibility of Enteric Gram Negative Facultative Anaerobe Bacilli in Aerobic versus Anaerobic Conditions

    Amachawadi, Raghavendra G.; Renter, David G.; Volkova, Victoriya V.

    2016-01-01

    Antimicrobial treatments result in the host’s enteric bacteria being exposed to the antimicrobials. Pharmacodynamic models can describe how this exposure affects the enteric bacteria and their antimicrobial resistance. The models utilize measurements of bacterial antimicrobial susceptibility traditionally obtained in vitro in aerobic conditions. However, in vivo enteric bacteria are exposed to antimicrobials in anaerobic conditions of the lower intestine. Some of enteric bacteria of food animals are potential foodborne pathogens, e.g., Gram-negative bacilli Escherichia coli and Salmonella enterica. These are facultative anaerobes; their physiology and growth rates change in anaerobic conditions. We hypothesized that their antimicrobial susceptibility also changes, and evaluated differences in the susceptibility in aerobic vs. anaerobic conditions of generic E. coli and Salmonella enterica of diverse serovars isolated from cattle feces. Susceptibility of an isolate was evaluated as its minimum inhibitory concentration (MIC) measured by E-Test® following 24 hours of adaptation to the conditions on Mueller-Hinton agar, and on a more complex tryptic soy agar with 5% sheep blood (BAP) media. We considered all major antimicrobial drug classes used in the U.S. to treat cattle: β-lactams (specifically, ampicillin and ceftriaxone E-Test®), aminoglycosides (gentamicin and kanamycin), fluoroquinolones (enrofloxacin), classical macrolides (erythromycin), azalides (azithromycin), sulfanomides (sulfamethoxazole/trimethoprim), and tetracyclines (tetracycline). Statistical analyses were conducted for the isolates (n≥30) interpreted as susceptible to the antimicrobials based on the clinical breakpoint interpretation for human infection. Bacterial susceptibility to every antimicrobial tested was statistically significantly different in anaerobic vs. aerobic conditions on both media, except for no difference in susceptibility to ceftriaxone on BAP agar. A satellite experiment

  9. Pulmonary and systemic inflammatory responses in rabbits with gram-negative pneumonia.

    Fox-Dewhurst, R; Alberts, M K; Kajikawa, O; Caldwell, E; Johnson, M C; Skerrett, S J; Goodman, R B; Ruzinski, J T; Wong, V A; Chi, E Y; Martin, T R

    1997-06-01

    The major goals of this study were to define the relationships between intrapulmonary and systemic inflammatory responses in animals with gram-negative pneumonia. We treated rabbits with intrapulmonary Escherichia coli (1 x 10(7) to 1 x 10(10) cfu/ml), and then measured physiologic, cellular, and molecular events in the lungs and systemic circulation for 24 h. The treatment protocols resulted in groups of animals that mimicked the stages of the septic inflammatory response in humans. Animals treated with low inocula had systemic changes consistent with systemic inflammatory response syndrome and cleared the bacteria and inflammatory products from the lungs. Animals treated with high inocula failed to clear bacteria from the lungs, had severe intrapulmonary inflammatory responses, and developed septic shock. Intrapulmonary leukocyte recruitment was directly related to the size of the bacterial inoculum, but lung protein accumulation was not. Tumor neurosis factor-alpha (TNF-alpha), interleukin-8 (IL-8), and GRO were detectable in lung lavage fluid at 4 h and declined by 24 h in animals that cleared intrapulmonary E. coli. In contrast, lavage TNF-alpha, IL-8, and GRO increased over 24 h in animals that failed to clear intrapulmonary bacteria. MCP-1 increased between 4 h and 24 h in the lungs of all of the animals as the histologic response evolved from neutrophilic to mononuclear cell predominance. Thus, the intensity of systemic inflammatory and physiologic responses to intrapulmonary gram-negative infection depends on the inoculum size and whether the bacteria are cleared from or proliferate in the lungs. The results provide experimental support for the recently proposed classification of septic responses in humans.

  10. Raman Spectroscopy of Xylitol Uptake and Metabolism in Gram-Positive and Gram-Negative Bacteria▿

    Palchaudhuri, Sunil; Rehse, Steven J.; Hamasha, Khozima; Syed, Talha; Kurtovic, Eldar; Kurtovic, Emir; Stenger, James

    2011-01-01

    Visible-wavelength Raman spectroscopy was used to investigate the uptake and metabolism of the five-carbon sugar alcohol xylitol by Gram-positive viridans group streptococcus and the two extensively used strains of Gram-negative Escherichia coli, E. coli C and E. coli K-12. E. coli C, but not E. coli K-12, contains a complete xylitol operon, and the viridans group streptococcus contains an incomplete xylitol operon used to metabolize the xylitol. Raman spectra from xylitol-exposed viridans group streptococcus exhibited significant changes that persisted even in progeny grown from the xylitol-exposed mother cells in a xylitol-free medium for 24 h. This behavior was not observed in the E. coli K-12. In both viridans group streptococcus and the E. coli C derivative HF4714, the metabolic intermediates are stably formed to create an anomaly in bacterial normal survival. The uptake of xylitol by Gram-positive and Gram-negative pathogens occurs even in the presence of other high-calorie sugars, and its stable integration within the bacterial cell wall may discontinue bacterial multiplication. This could be a contributing factor for the known efficacy of xylitol when taken as a prophylactic measure to prevent or reduce occurrences of persistent infection. Specifically, these bacteria are causative agents for several important diseases of children such as pneumonia, otitis media, meningitis, and dental caries. If properly explored, such an inexpensive and harmless sugar-alcohol, alone or used in conjunction with fluoride, would pave the way to an alternative preventive therapy for these childhood diseases when the causative pathogens have become resistant to modern medicines such as antibiotics and vaccine immunotherapy. PMID:21037297

  11. A functionalized surface modification with vanadium nanoparticles of various valences against implant-associated bloodstream infection

    Wang J

    2017-04-01

    Full Text Available Jiaxing Wang,1,* Huaijuan Zhou,2,* Geyong Guo,1 Tao Cheng,1 Xiaochun Peng,1 Xin Mao,1 Jinhua Li,2–4 Xianlong Zhang1 1Department of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Jiao Tong University, 2State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 3Department of Orthopaedics and Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, 4University of Chinese Academy of Sciences, Beijing, China *These authors contributed equally to this work Abstract: Bloodstream infection, especially with implants involved, is an often life-threatening condition with high mortality rates, imposing a heavy burden on patients and medical systems. Herein, we firstly deposited homogeneous vanadium metal, V2O3, VO2, and V2O5 nanofilms on quartz glass by magnetron sputtering. Using these platforms, we further investigated the potential antimicrobial efficiency of these nano-VOx films and the interactions of human erythrocytes and bacteria (methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa with our samples in a novel cell–bacteria coculture model. It was demonstrated that these nano-VOx precipitated favorable antibacterial activity on both bacteria, especially on S. aureus, and this effect increased with higher vanadium valence. A possible mechanism accountable for these results might be elevated levels of vanadium-induced intracellular reactive oxygen species. More importantly, based on hemolysis assays, our nano-VOx films were found to be able to kill prokaryotic cells but were not toxic to mammalian cells, holding the potential for the prevention of implant-related hematogenous infections. As far as we know, this is the first report wherein such nano-VOx films have assisted human erythrocytes to combat bacteria in a valence-dependent manner. Additionally, vanadium

  12. Sustained Reduction in Bloodstream Infections in Infants at a Large Tertiary Care Neonatal Intensive Care Unit

    Neill, Sara; Haithcock, Sarah; Smith, P. Brian; Goldberg, Ronald; Bidegain, Margarita; Tanaka, David; Carriker, Charlene; Ericson, Jessica E.

    2015-01-01

    Purpose Reduction of bloodstream infections (BSI) has emerged as an important patient safety goal. Implementation of central line insertion bundles, standardized line care protocols, and health care provider education programs have reduced BSI in neonatal intensive care units (NICUs) around the country. The ability of large tertiary care centers to decrease nosocomial infections, including BSI, has been demonstrated. However, long-term BSI reductions in infants are not well documented. We sought to demonstrate that a low incidence of BSI can be maintained over time in a tertiary care NICU. Subjects 6,790 infants admitted to a large, tertiary care NICU between 2005 and 2013. Design Retrospective intervention study. Methods A staged, multifaceted infection prevention plan was implemented beginning in October 2007 under nursing leadership. The incidence of BSI was determined annually for 2005-2013. Results Baseline BSI incidence for infants admitted to the NICU was 5.15 and 6.08 episodes per 1,000 infant-days in 2005 and 2006, respectively. After protocol implementation, the incidence of BSI decreased to 2.14/1,000 infant-days and 2.44/1,000 infant-days in 2008 and 2009, respectively. Yearly incidence remained low over the next 4 years and decreased even further to 0.20-0.45 infections/1,000 infant days. This represents a 92% decrease in BSI over a period of >5 years. Conclusions Implementation of a nursing-led comprehensive infection control initiative can effectively produce and maintain a reduction in the incidence of BSI in infants at a large tertiary care NICU. What this study adds Long term reductions in neonatal BSI are possible with implementation of a multidisciplinary team approach and strong nursing leadership. PMID:25915573

  13. Outcomes of single organism peritonitis in peritoneal dialysis: gram negatives versus gram positives in the Network 9 Peritonitis Study.

    Bunke, C M; Brier, M E; Golper, T A

    1997-08-01

    The use of the "peritonitis rate" in the management of patients undergoing peritoneal dialysis is assuming importance in comparing the prowess of facilities, care givers and new innovations. For this to be a meaningful outcome measure, the type of infection (causative pathogen) must have less clinical significance than the number of infections during a time interval. The natural history of Staphylococcus aureus, pseudomonas, and fungal peritonitis would not support that the outcome of an episode of peritonitis is independent of the causative pathogen. Could this concern be extended to other more frequently occurring pathogens? To address this, the Network 9 Peritonitis Study identified 530 episodes of single organism peritonitis caused by a gram positive organism and 136 episodes caused by a single non-pseudomonal gram negative (NPGN) pathogen. Coincidental soft tissue infections (exit site or tunnel) occurred equally in both groups. Outcomes of peritonitis were analyzed by organism classification and by presence or absence of a soft tissue infection. NPGN peritonitis was associated with significantly more frequent catheter loss, hospitalization, and technique failure and was less likely to resolve regardless of the presence or absence of a soft tissue infection. Hospitalization and death tended to occur more frequently with enterococcal peritonitis than with other gram positive peritonitis. The outcomes in the NPGN peritonitis group were significantly worse (resolution, catheter loss, hospitalization, technique failure) compared to coagulase negative staphylococcal or S. aureus peritonitis, regardless of the presence or absence of a coincidental soft tissue infection. Furthermore, for the first time, the poor outcomes of gram negative peritonitis are shown to be independent of pseudomonas or polymicrobial involvement or soft tissue infections. The gram negative organism appears to be the important factor. In addition, the outcome of peritonitis caused by S. aureus

  14. Risk Factors for Bloodstream Infection After Living-donor Liver Transplantation in Children.

    Shoji, Kensuke; Funaki, Takanori; Kasahara, Mureo; Sakamoto, Seisuke; Fukuda, Akinari; Vaida, Florin; Ito, Kenta; Miyairi, Isao; Saitoh, Akihiko

    2015-10-01

    Postoperative bloodstream infection (BSI) is the most important determinant of recipient morbidity and mortality after liver transplantation (LT). Children who underwent LT are at the highest risk of developing BSI because of the significant surgical intervention, use of multiple devices, and administration of immunosuppressive agents. However, information regarding the risk factors for BSI in children after LT is limited. We retrospectively reviewed 210 children who underwent living-donor LT at the largest pediatric LT center in Japan. Patients' characteristics, blood culture results and clinical outcomes were extracted from electronic medical records. Univariate and multivariate analyses were performed to identify the risk factors for BSI. Among the 210 LT recipients, 53 (25%) recipients experienced 86 episodes of BSI during the observational period. The source of the BSI was identified only in 38%: catheter-related BSI (27%) peritonitis (7%), urinary tract infection (2%), pneumonia (1%) and infectious endocarditis (1%). A multivariate analysis demonstrated that body weight (P = 0.03), volume of blood loss during LT (P 24 months), blood loss and pediatric end-stage liver disease/model for end-stage liver disease versus positive CMV antigenemia. The volume of blood loss, postoperative CMV antigenemia positivity and body weight were associated with the development of BSI after LT in pediatric living-donor recipients. To identify the age-specific predictors of BSI in children who underwent LT, age-specific analyses are crucial.

  15. The TFPI-2 derived peptide EDC34 improves outcome of gram-negative sepsis.

    Praveen Papareddy

    Full Text Available Sepsis is characterized by a dysregulated host-pathogen response, leading to high cytokine levels, excessive coagulation and failure to eradicate invasive bacteria. Novel therapeutic strategies that address crucial pathogenetic steps during infection are urgently needed. Here, we describe novel bioactive roles and therapeutic anti-infective potential of the peptide EDC34, derived from the C-terminus of tissue factor pathway inhibitor-2 (TFPI-2. This peptide exerted direct bactericidal effects and boosted activation of the classical complement pathway including formation of antimicrobial C3a, but inhibited bacteria-induced activation of the contact system. Correspondingly, in mouse models of severe Escherichia coli and Pseudomonas aeruginosa infection, treatment with EDC34 reduced bacterial levels and lung damage. In combination with the antibiotic ceftazidime, the peptide significantly prolonged survival and reduced mortality in mice. The peptide's boosting effect on bacterial clearance paired with its inhibiting effect on excessive coagulation makes it a promising therapeutic candidate for invasive Gram-negative infections.

  16. Extended-spectrum beta-lactamase producing gram negative ...

    African Journal of Infectious Diseases ... The rate of nosocomial infections caused by ESBL-producing GNB in Asia Pacific ... Results: In almost all parts of the country, high resistance has been observed, especially in the central part of Iran.

  17. Facilitating central line-associated bloodstream infection prevention: a qualitative study comparing perspectives of infection control professionals and frontline staff.

    McAlearney, Ann Scheck; Hefner, Jennifer L

    2014-10-01

    Infection control professionals (ICPs) play a critical role in implementing and managing healthcare-associated infection reduction interventions, whereas frontline staff are responsible for delivering direct and ongoing patient care. The objective of our study was to determine if ICPs and frontline staff have different perspectives about the facilitators and challenges of central line-associated bloodstream infection (CLABSI) prevention program success. We conducted key informant interviews at 8 hospitals that participated in the Agency for Healthcare Research and Quality CLABSI prevention initiative called "On the CUSP: Stop BSI." We analyzed interview data from 50 frontline nurses and 26 ICPs to identify common themes related to program facilitators and challenges. We identified 4 facilitators of CLABSI program success: education, leadership, data, and consistency. We also identified 3 common challenges: lack of resources, competing priorities, and physician resistance. However, the perspective of ICPs and frontline nurses differed. Whereas ICPs tended to focus on general descriptions, frontline staff noted program specifics and often discussed concrete examples. Our results suggest that ICPs need to take into account the perspectives of staff nurses when implementing infection control and broader quality improvement initiatives. Further, the deliberate inclusion of frontline staff in the implementation of these programs may be critical to program success. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  18. Identification and Whole Genome Sequencing of the First Case of Kosakonia radicincitans Causing a Human Bloodstream Infection

    Bhatti, Micah D.; Kalia, Awdhesh; Sahasrabhojane, Pranoti; Kim, Jiwoong; Greenberg, David E.; Shelburne, Samuel A.

    2017-01-01

    The taxonomy of Enterobacter species is rapidly changing. Herein we report a bloodstream infection isolate originally identified as Enterobacter cloacae by Vitek2 methodology that we found to be Kosakonia radicincitans using genetic means. Comparative whole genome sequencing of our isolate and other published Kosakonia genomes revealed these organisms lack the AmpC β-lactamase present on the chromosome of Enterobacter sp. A fimbriae operon primarily found in Escherichia coli O157:H7 isolates ...

  19. Trends in Nosocomial Bloodstream Infections in a Burn Intensive Care Unit: an Eight-Year Survey

    Zorgani, A.; Franka, R.A.; Zaidi, M.M.; Alshweref, U.M.; Elgmati, M.

    2010-01-01

    Summary This study was designed to evaluate the frequency and profile of bloodstream infection (BSI) in a burn intensive care unit (BICU) in Tripoli, Libya, from 1st January 2000 to 31st December 2007 and to determine the prevalence of different bacteria involved in such infections and their antimicrobial susceptibilities. During the eight-year study period, 995 patients were admitted to the BICU. Blood cultures were collected from each septicaemic case and reviewed for age, sex, total body surface area burned, isolated micro-organisms, and antibiotic sensitivity. There were 430 episodes of BSI among 830 cases; the annual true positive rate varied between 40.0 and 59.4%, the majority (87.9%) being caused by one species only. However, 22% had two or more episodes with different pathogens during hospitalization. The leading isolate was Staphylococcus aureus (40.4%) (methicillinresistant, 55.7%). Pseudomonas spp ranked second (23.9%). Klebsiella spp were third, responsible for 7.4%; the rate of extended spectrum beta lactamase among Klebsiella isolates was 47%. Candida spp were the fourth most common pathogen (6.7%), the majority (55%) being C. albicans. Staphylococci were generally resistant to trimethoprim (91%) and fusidic acid (80%). Pseudomonas spp proved moderately resistant (38-43%) to tobramicin, ciprofloxacin, amikacin, and impenem but remained relatively susceptible to cefepime (72%). Klebsiella isolates demonstrated moderate resistance (46-58%) to most agents tested, and relatively low resistance (19-27%) to meropenem, impenem, and cefepime. We suggest that extra infection control measures should be implemented and antibiotic policy and guidelines introduced to reduce the high resistance rate among isolates such as Pseudomonas, Acinetobacter, and MRSA. PMID:21991204

  20. Klebsiella pneumoniae bloodstream infections in neonates in a hospital in the Kingdom of Saudi Arabia.

    Al-Rabea, A A; Burwen, D R; Eldeen, M A; Fontaine, R E; Tenover, F; Jarvis, W R

    1998-09-01

    To identify risk factors for Klebsiella pneumoniae bloodstream infections (BSI) in neonates in a hospital in the Kingdom of Saudi Arabia (KSA). Two case-control studies among hospitalized neonates during February 15-May 14, 1991, and a procedural and microbiological investigation. Hospital A, a maternity and children's hospital in KSA. Case patients had a blood culture positive for K pneumoniae after >2 days of hospitalization and had no evidence of a nonblood primary site of infection. When the 20 case patients were compared with controls, hospitalization in a critical-care unit (odds ratio [OR], 5.5; 95% confidence interval [CI95], 1.20-51.1; P=.03) was identified as a risk factor. When the case patients were compared with a second set of controls matched by critical-care status, receipt of a particular intravenous fluid (D10%/0.2NS; OR, 11.0; CI95, 1.42-85.2; P=.009) or a blood product (OR undefined; P=.04) were identified as risk factors. Infusates were administered via umbilical catheters for most case and control patients (19/20 vs 15/20, P>.05); catheters were manipulated more frequently in patients in critical-care units. Umbilical catheter tip, skin, or mucus membrane K pneumoniae colonization occurred in 47% and 53% of evaluated case and control patients, respectively. Available K pneumoniae isolates from blood cultures and colonization sites had identical antimicrobial susceptibility patterns. Emphasis on handwashing, careful preparation and administration of infusates, and aseptic technique for catheter insertion, maintenance, and manipulation was temporally associated with resolution of the epidemic. This outbreak was probably due to infusion therapy practices that led to BSI in nursery patients colonized with K pneumoniae. Both catheter-related infections and extrinsic contamination of infusates may have occurred. Hospital personnel should be aware of their potential to spread nosocomial pathogens from person to person and should implement Centers for

  1. Characterising health care-associated bloodstream infections in public hospitals in Queensland, 2008-2012.

    Si, Damin; Runnegar, Naomi; Marquess, John; Rajmokan, Mohana; Playford, Elliott G

    2016-04-18

    To describe the epidemiology and rates of all health care-associated bloodstream infections (HA-BSIs) and of specific HA-BSI subsets in public hospitals in Queensland. Standardised HA-BSI surveillance data were collected in 23 Queensland public hospitals, 2008-2012. HA-BSIs were prospectively classified in terms of place of acquisition (inpatient, non-inpatient); focus of infection (intravascular catheter-associated, organ site focus, neutropenic sepsis, or unknown focus); and causative organisms. Inpatient HA-BSI rates (per 10,000 patient-days) were calculated. There were 8092 HA-BSIs and 9418 causative organisms reported. Inpatient HA-BSIs accounted for 79% of all cases. The focus of infection in 2792 cases (35%) was an organ site, intravascular catheters in 2755 (34%; including 2240 central line catheters), neutropenic sepsis in 1063 (13%), and unknown in 1482 (18%). Five per cent (117 of 2240) of central line-associated BSIs (CLABSIs) were attributable to intensive care units (ICUs). Eight groups of organisms provided 79% of causative agents: coagulase-negative staphylococci (18%), Staphylococcus aureus (15%), Escherichia coli (11%), Pseudomonas species (9%), Klebsiella pneumoniae/oxytoca (8%), Enterococcus species (7%), Enterobacter species (6%), and Candida species (5%). The overall inpatient HA-BSI rate was 6.0 per 10,000 patient-days. The rates for important BSI subsets included: intravascular catheter-associated BSIs, 1.9 per 10,000 patient-days; S. aureus BSIs, 1.0 per 10,000 patient-days; and methicillin-resistant S. aureus BSIs, 0.3 per 10,000 patient-days. The rate of HA-BSIs in Queensland public hospitals is lower than reported by similar studies elsewhere. About one-third of HA-BSIs are attributable to intravascular catheters, predominantly central venous lines, but the vast majority of CLABSIs are contracted outside ICUs. Different sources of HA-BSIs require different prevention strategies.

  2. Antibiotic Resistance Patterns of Common Gram-negative ...

    Background: The resistance of bacteria causing urinary tract infection (UTI) to commonly prescribed antibiotics is increasing both in developing and developed countries. Resistance has emerged even to more potent antimicrobial agents. This study was undertaken to determine the current antibiotic resistance pattern ...

  3. Prevalence and risk factors for CTX-M gram-negative bacteria in hospitalized patients at a tertiary care hospital in Kilimanjaro, Tanzania

    Sonda, Tolbert; Kumburu, Happiness; van Zwetselaar, Marco

    2018-01-01

    Emergence and spread of extended spectrum beta-lactamase (ESBL)-producing gram-negative bacteria, mainly due to CTX-M, is a major global public health problem. Patients infected with ESBL-producing gram-negative bacteria have an increased risk of treatment failure and death. We investigated...... 2015 were fully genome sequenced. The prevalence of ESBL-producing gram-negative bacteria was determined based on the presence of blaCTX-M. The odds ratio (OR) and risk factors for ESBL-producing gram-negative bacteria due to CTX-M were assessed using logistic regression models. The overall CTX......-M prevalence (95% CI) was 13.6% (10.1–18.1). Adjusted for other factors, the OR of CTX-M gram-negative bacteria for patients previously hospitalized was 0.26 (0.08–0.88), p = 0.031; the OR for patients currently on antibiotics was 4.02 (1.29–12.58), p = 0.017; the OR for patients currently on ceftriaxone was 0...

  4. Validity of calendar day-based definitions for community-onset bloodstream infections.

    Laupland, Kevin B; Gregson, Daniel B; Church, Deirdre L

    2015-04-02

    Community-onset (CO) bloodstream infections (BSI) are those BSI where the blood culture is drawn culture draw or hospital admission are not always available. We evaluated the validity of using 2- or 3- calendar day based definitions for CO-BSI by comparing to a "gold standard" 48-hour definition. Among the population-based cohort of 14,106 episodes of BSI studied, 10,543 were classified as CO based on "gold standard" 48-hour criteria. When 2-day and 3-day definitions were applied, 10,396 and 10,707 CO-BSI episodes were ascertained, respectively. All but 147 (1.4%) true CO-BSI cases were included by using the 2-day definition. When the 3-day definition was applied, all cases of CO-BSI were identified but and additional 164 (1.5%) cases of hospital-onset HO-BSI were also included. Thus the sensitivity and specificity of the 2-day definition was 98.6% and 100% and for the 3-day definition was 100% and 98.5%, respectively. Overall, only 311 (2.2%) cases were potentially miss-classifiable using either the 2- or 3-calendar day based definitions. Use of either a 2- or 3-day definition is highly accurate for classifying CO-BSI.

  5. [Candida parapsilosis: a major cause of bloodstream infection in a tertiary care hospital in Costa Rica].

    Villalobos, Juan M; Castro, José A; Avilés, Alvaro; Peláez, M Claudia; Somogyi, Teresita; Sandoval, Lilliana

    2016-04-01

    Invasive Candida bloodstream infections are frequent and display high mortality in clinical practice. There is scarce published on this topic in Central America. To characterize the epidemiology of candidemia in a hospital setting in Costa Rica. 210 cases of nosocomial candidemia were analyzed in patients over 17 years of age, admitted to Hospital Mexico, between 2007 and 2011. Descriptive and temporary analyses were performed and the risk factors associated with C. parapsilosis and survival were evaluated. The incidence rate of candidemia was 1.47 cases per 1,000 admissions. The non-albicans Candida represented 62% of the isolated yeasts. Except for 2009, C. parapsilosis was the most commonly isolated species in four out of the five years reviewed, followed by C. albicans. There was a strong association between C. parapsilosis, the presence of a central venous catheter (OR: 4.8, CI 95%: 1.8-14.6, p < 0.001) and the use of parenteral nutrition (p: 0.008). The 30-day mortality was 50%. Candida albicans displayed the highest mortality and C. parapsilosis the lowest. Patients who did not receive anti-fungal treatment showed a significantly higher probability of death. The high incidence of candidemia from C. parapsilosis is directly related to the use of central venous catheters and parenteral nutrition. There is a need for creating local guidelines addressing the use of central venous catheters and parenteral nutrition, as well as implementing hand hygiene protocols.

  6. A New Take on an Old Remedy: Generating Antibodies against Multidrug-Resistant Gram-Negative Bacteria in a Postantibiotic World.

    Motley, Michael P; Fries, Bettina C

    2017-01-01

    With the problem of multidrug-resistant Gram-negative pathogens becoming increasingly dire, new strategies are needed to protect and treat infected patients. Though abandoned in the past, monoclonal antibody therapy against Gram-negative bacteria remains a potential solution and has potential advantages over the broad-spectrum antibiotics they were once replaced by. This Perspective reviews the prospect of utilizing monoclonal antibody therapy against these pathogens, as well as the challenges of doing so and the current therapy targets under investigation.

  7. Septicemia caused by the gram-negative bacterium CDC IV c-2 in an immunocompromised human.

    Dan, M; Berger, S A; Aderka, D; Levo, Y

    1986-01-01

    A 37-year-old man with plasma cell leukemia developed nonfatal septicemia caused by the gram-negative bacterium CDC IV c-2. Recovery followed appropriate treatment with antibiotics. The biochemical features of this organism are reviewed.

  8. Gram-negative folliculitis. A rare problem or is it underdiagnosed? Case report and literature review

    Sierra-Téllez Daniela, Ponce-Olivera Rosa María, Tirado-Sánchez Andrés

    2011-07-01

    Full Text Available AbstractGram-negative folliculitis may be the result of prolonged antibacterial treatments in patients with acne and rosacea. It is caused by alteration of facial skin flora and the nasal mucous, a decrease of Gram-positive bacteria and a proliferation of Gram-negative bacteria (for example Escherichia coli, Pseudomonas aeruginosa, Serratia marcescens, Klebsiella sp. and Proteus mirabilis. It should be considered in patients with acne who have not had a clinical improvement after 3-6 months of treatment with tetracyclines. The disease is underestimated, probably because bacteriological studies are rarely requested and the increased use of oral isotretinoin for acne management. One of the most effective treatments for Gram-negative folliculitis is oral isotretinoin (0.5-1 mg / kg / day for 4-5 months. We report the case of Gram negative folliculitis successfully treated with oral isotretinoin.

  9. Multifaceted antibiotic treatment analysis of methicillin-sensitive Staphylococcus aureus bloodstream infections.

    Weber, Zhanni; Ariano, Robert; Lagacé-Wiens, Philippe; Zelenitsky, Sheryl

    2016-12-01

    Given the overall prevalence and poor prognosis of Staphylococcus aureus bloodstream infections (BSIs), the study of treatment strategies to improve patient outcomes is important. The aim of this study was to conduct a multifaceted antibiotic treatment analysis of methicillin-sensitive S. aureus (MSSA) BSI and to characterise optimal early antibiotic therapy (within the first 7 days of drawing the index blood culture) for this serious infection. Antibiotic selection was categorised as optimal targeted (intravenous cloxacillin or cefazolin), optimal broad (piperacillin/tazobactam or meropenem), adequate (vancomycin) or inadequate (other antibiotics or oral therapy). A TSE (timing, selection, exposure) score was developed to comprehensively characterise early antibiotic therapy, where higher points corresponded to prompt initiation, optimal antibiotic selection and longer exposure (duration). Amongst 71 cases of complicated MSSA-BSI, end-of-treatment (EOT) response (i.e. clinical cure) was improved when at least adequate antibiotic therapy was initiated within 24 h [71.7% (33/46) vs. 48.0% (12/25); P = 0.047]. Clinical cure was also more likely when therapy included ≥4 days of optimal targeted antibiotics within the first 7 days [74.4% (29/39) vs. 50.0% (16/32); P = 0.03]. The TSE score was an informative index of early antibiotic therapy, with EOT cure documented in 72.0% (36/50) compared with 42.9% (9/21) of cases with scores above and below 15.2, respectively (P = 0.02). In multivariable analysis, lower Charlson comorbidity index, presence of BSI on admission, and optimising early antibiotic therapy, as described above, were associated with clinical cure in patients with MSSA-BSI. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  10. Case-crossover study of Burkholderia cepacia complex bloodstream infection associated with contaminated intravenous bromopride.

    Martins, Ianick Souto; Pellegrino, Flávia Lúcia Piffano Costa; Freitas, Andrea d'Avila; Santos, Marisa da Silva; Ferraiuoli, Giovanna Ianini d'Alemeida; Vasques, Márcia Regina Guimarães; Amorim, Efigenia Lourdes Teixeira; Oliveira, Sandra; Nouér, Simone Aranha; Cardoso, Fernando Luiz Lopes; Mascarenhas, Luiz Affonso; Magalhães, Ana Cristina Gouveia; Cleinman, Isabella Barbosa; Figueiredo, Agnes Marie Sá; Moreira, Beatriz Meurer

    2010-05-01

    To investigate an outbreak of healthcare-associated Burkholderia cepacia complex (BCC) primary bloodstream infections (BCC-BSI). Case-crossover study in a public hospital, a university hospital and a private hospital in Rio de Janeiro, Brazil, from March 2006 to May 2006. Twenty-five patients with BCC-BSI. After determining the date BCC-BSI symptoms started for each patient, 3 time intervals of data collection were defined, each one with a duration of 3 days: the case period, starting just before BCC-BSI symptoms onset; the control period, starting 6 days before BCC-BSI symptoms onset; and the washout period, comprising the 3 days between the case period and the control period. Exposures evaluated were intravascular solutions and invasive devices and procedures. Potential risk factors were identified by using the McNemar chi(2) adjusted test. Cultures of samples of potentially contaminated solutions were performed. BCC strain typing was performed by pulsed-field gel electrophoresis using SpeI. The statistical analysis revealed that the use of bromopride and dipyrone was associated with BCC-BSI. A total of 21 clinical isolates from 17 (68%) of the 25 patients and an isolate obtained from the bromopride vial were available for strain typing. Six pulsotypes were detected. A predominant pulsotype (A) accounted for 11 isolates obtained from 11 patients (65%) in the 3 study hospitals. Our investigation, using a case-crossover design, of an outbreak of BCC-BSI infections concluded it was polyclonal but likely caused by infusion of contaminated bromopride. The epidemiological finding was validated by microbiological analysis. After recall of contaminated bromopride vials by the manufacturer, the outbreak was controlled.

  11. Outbreak of Serratia marcescens bloodstream infections in patients receiving parenteral nutrition prepared by a compounding pharmacy.

    Gupta, Neil; Hocevar, Susan N; Moulton-Meissner, Heather A; Stevens, Kelly M; McIntyre, Mary G; Jensen, Bette; Kuhar, David T; Noble-Wang, Judith A; Schnatz, Rick G; Becker, Shawn C; Kastango, Eric S; Shehab, Nadine; Kallen, Alexander J

    2014-07-01

    Compounding pharmacies often prepare parenteral nutrition (PN) and must adhere to rigorous standards to avoid contamination of the sterile preparation. In March 2011, Serratia marcescens bloodstream infections (BSIs) were identified in 5 patients receiving PN from a single compounding pharmacy. An investigation was conducted to identify potential sources of contamination and prevent further infections. Cases were defined as S. marcescens BSIs in patients receiving PN from the pharmacy between January and March 2011. We reviewed case patients' clinical records, evaluated pharmacy compounding practices, and obtained epidemiologically directed environmental cultures. Molecular relatedness of available Serratia isolates was determined by pulsed-field gel electrophoresis (PFGE). Nineteen case patients were identified; 9 died. The attack rate for patients receiving PN in March was 35%. No case patients were younger than 18 years. In October 2010, the pharmacy began compounding and filter-sterilizing amino acid solution for adult PN using nonsterile amino acids due to a national manufacturer shortage. Review of this process identified breaches in mixing, filtration, and sterility testing practices. S. marcescens was identified from a pharmacy water faucet, mixing container, and opened amino acid powder. These isolates were indistinguishable from the outbreak strain by PFGE. Compounding of nonsterile amino acid components of PN was initiated due to a manufacturer shortage. Failure to follow recommended compounding standards contributed to an outbreak of S. marcescens BSIs. Improved adherence to sterile compounding standards, critical examination of standards for sterile compounding from nonsterile ingredients, and more rigorous oversight of compounding pharmacies is needed to prevent future outbreaks. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public

  12. Validation of a Sampling Method to Collect Exposure Data for Central-Line-Associated Bloodstream Infections.

    Hammami, Naïma; Mertens, Karl; Overholser, Rosanna; Goetghebeur, Els; Catry, Boudewijn; Lambert, Marie-Laurence

    2016-05-01

    Surveillance of central-line-associated bloodstream infections requires the labor-intensive counting of central-line days (CLDs). This workload could be reduced by sampling. Our objective was to evaluate the accuracy of various sampling strategies in the estimation of CLDs in intensive care units (ICUs) and to establish a set of rules to identify optimal sampling strategies depending on ICU characteristics. Analyses of existing data collected according to the European protocol for patient-based surveillance of ICU-acquired infections in Belgium between 2004 and 2012. CLD data were reported by 56 ICUs in 39 hospitals during 364 trimesters. We compared estimated CLD data obtained from weekly and monthly sampling schemes with the observed exhaustive CLD data over the trimester by assessing the CLD percentage error (ie, observed CLDs - estimated CLDs/observed CLDs). We identified predictors of improved accuracy using linear mixed models. When sampling once per week or 3 times per month, 80% of ICU trimesters had a CLD percentage error within 10%. When sampling twice per week, this was >90% of ICU trimesters. Sampling on Tuesdays provided the best estimations. In the linear mixed model, the observed CLD count was the best predictor for a smaller percentage error. The following sampling strategies provided an estimate within 10% of the actual CLD for 97% of the ICU trimesters with 90% confidence: 3 times per month in an ICU with >650 CLDs per trimester or each Tuesday in an ICU with >480 CLDs per trimester. Sampling of CLDs provides an acceptable alternative to daily collection of CLD data.

  13. Tigecycline activity tested against 26,474 bloodstream infection isolates: a collection from 6 continents.

    Sader, Helio S; Jones, Ronald N; Stilwell, Matthew G; Dowzicky, Michael J; Fritsche, Thomas R

    2005-07-01

    The activity of tigecycline (formerly GAR936), a novel glycylcycline, was tested against recent bloodstream infection (BSI) pathogen isolates from 6 continents. Frequency of clinical occurrence of these pathogens was determined and their antibiograms assessed using reference broth microdilution methods. A total of 26474 strains were tested for tigecycline susceptibility according to the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) by the M7-A6 guidelines with interpretations from M100-S15 and the package insert. The rank order of pathogens was Staphylococcus aureus (33.1%), Escherichia coli (14.0%), coagulase-negative staphylococci (13.5%), Enterococcus spp. (12.3%), Klebsiella spp. (5.7%), Pseudomonas aeruginosa (4.2%), Enterobacter spp. (3.0%), beta-hemolytic streptococci (2.9%), Streptococcus pneumoniae (2.3%), and viridans group streptococci (1.4%). Tigecycline exhibited a broader spectrum of activity against BSI isolates when compared to ciprofloxacin, tetracycline, aminoglycosides, and many beta-lactams (imipenem). Tigecycline was highly active against most pathogens tested, including staphylococci (MIC(90), 0.5 microg/mL), enterococci (MIC90, 0.25 microg/mL), streptococci (MIC(90), < or =0.12 microg/mL), Escherichia coli (MIC90, 0.25 microg/mL), Klebsiella spp. (MIC90, 1 mmicrog/mL), and Enterobacter spp. (MIC(90), 2 mmicrog/mL), but showed limited inhibition of Pseudomonas aeruginosa (MIC90, 16 microg/mL) and indole-positive or indole-negative Proteae (MIC90, 4-8 microg/mL). In summary, tigecycline exhibited a wide spectrum of antimicrobial potency versus BSI isolates collected worldwide. Serious infections in nosocomial environments should benefit from tigecycline use among the investigational phase 3 agents focused toward resistant strains.

  14. Infection and colonization by Gram-negative bacilli in neonates hospitalized in High Risk Nursery at Uberlandia Federal University Hospital: etiology, resistant phenotypes and risk factors Infecção e colonização por bacilos Gram-negativos em neonatos internados em Berçário de Alto Risco do Hospital da Universidade Federal de Uberlândia: etiologia, fenótipos de resistência e fatores de risco

    Renata Cristina Cezário

    2004-09-01

    Full Text Available The aims of this study were to determine endemic and epidemic infection due to Gram-negative bacilli, risk factors associated with colonization and infection by these organisms and the resistance phenotypes (ESBL, AmpC in neonates admitted in a High Risk Nursery. The study was conducted during a 21 month period and included: a prospective study to evaluate the neonates with hospital infection and the use of third-generation cephalosporins; a case-control study to determine the risk factors associated with colonization/infection. Rectal and oropharynx cultures were also performed in four opportunities (September and November 2001, February and August 2002. The isolates for which the resistance of ceftazidime was 2 mg/mL were suspected of producing ESBL or AmpC b-lactamases. The incidence of infection by Gram-negative bacilli was 2.4% (89/3.708 neonates, and sepsis (35.9% and conjunctivitis (31.4% were the most common infections. The endemic infections were more prevalent (73.9% and usually associated with Enterobacteriaceae (95.5%, being these organisms also related to colonization, corresponding mainly to isolates of Enterobacter spp. and Klebsiella spp. Two outbreaks of Pseudomonas aeruginosa (n=10 and Acinetobacter baumannii (n=11 were identified during the survey. Univariate analysis showed that risk factors for Gram-negative bacilli infection considered significant included: the length of stay before infection/colonization, exposure to antimicrobial agents, mechanical ventilation, central venous catheters, parenteral nutrition and surgery. The majority of resistance to ceftazidime among Enterobacteriaceae isolates (80.9% was from ESBL phenotype. Administration of third-generation cephalosporins (ceftriaxone led to the emergence of these multiresistant Gram-negative bacilli in the neonatal unit.Os objetivos deste estudo foram determinar infecções endêmicas e epidêmicas por bacilos Gram-negativos, fatores de risco associados a coloniza

  15. Widespread Fosfomycin Resistance in Gram-Negative Bacteria Attributable to the Chromosomal fosA Gene

    Ryota Ito

    2017-08-01

    Full Text Available Fosfomycin is a decades-old antibiotic which is being revisited because of its perceived activity against many extensively drug-resistant Gram-negative pathogens. FosA proteins are Mn2+ and K+-dependent glutathione S-transferases which confer fosfomycin resistance in Gram-negative bacteria by conjugation of glutathione to the antibiotic. Plasmid-borne fosA variants have been reported in fosfomycin-resistant Escherichia coli strains. However, the prevalence and distribution of fosA in other Gram-negative bacteria are not known. We systematically surveyed the presence of fosA in Gram-negative bacteria in over 18,000 published genomes from 18 Gram-negative species and investigated their contribution to fosfomycin resistance. We show that FosA homologues are present in the majority of genomes in some species (e.g., Klebsiella spp., Enterobacter spp., Serratia marcescens, and Pseudomonas aeruginosa, whereas they are largely absent in others (e.g., E. coli, Acinetobacter baumannii, and Burkholderia cepacia. FosA proteins in different bacterial pathogens are highly divergent, but key amino acid residues in the active site are conserved. Chromosomal fosA genes conferred high-level fosfomycin resistance when expressed in E. coli, and deletion of chromosomal fosA in S. marcescens eliminated fosfomycin resistance. Our results indicate that FosA is encoded by clinically relevant Gram-negative species and contributes to intrinsic fosfomycin resistance.

  16. Screening of the novel colicinogenic gram-negative rods against pathogenic Escherichia coli O157:H7

    H Mushtaq

    2015-01-01

    Full Text Available Purpose: Escherichia coli (E. coli O157:H7 is gram-negative enteric pathogen producing different types of Shiga toxin. This bacterium is the most corporate cause of haemorrhagic colitis in human. Administration of antibiotics (particularly sulfa drugs against this pathogen is a debatable topic as this may increase the risk of uremic syndrome; especially in children and aged people. Around the world, microbiologists are in search of alternative therapeutic methods specially probiotics against this pathogen. In the present study, we have focused on the investigation of alternate bio-therapeutics (probiotics for the treatment of patients infected with E. coli O157:H7. This study is based on the identification of colicin-producing gram-negative bacteria (particularly enterobacteriaceae which can competently exclude E. coli O157:H7 from the gut of the infected individual. Materials and Methods: Hundred samples from human, animal faeces and septic tank water were analysed for nonpathogenic gram-negative rods (GNRs. Results: Out of these samples, 175 isolates of GNRs were checked for their activity against E. coli O157:H7. Only 47 isolates inhibited the growth of E. coli O157:H7, among which majority were identified as E. coli. These E. coli strains were found to be the efficient producers of colicin. Some of the closely related species i. e., Citrobacter sp, Pantoea sp. and Kluyvera sp. also showed considerable colicinogenic activity. Moreover, colicinogenic species were found to be nonhaemolytic, tolerant to acidic environment (pH 3 and sensitive to commonly used antibiotics. Conclusion: Nonhaemolytic, acid tolerant and sensitive to antibiotics suggests the possible use of these circulating endothelial cells (CEC as inexpensive and inoffensive therapeutic agent (probiotics in E. coli O157:H7 infections.

  17. Comparison of the systemic inflammatory response syndrome between monomicrobial and polymicrobial Pseudomonas aeruginosa nosocomial bloodstream infections

    Wenzel Richard P

    2005-10-01

    Full Text Available Abstract Background Some studies of nosocomial bloodstream infection (nBSI have demonstrated a higher mortality for polymicrobial bacteremia when compared to monomicrobial nBSI. The purpose of this study was to compare differences in systemic inflammatory response and mortality between monomicrobial and polymicrobial nBSI with Pseudomonas aeruginosa. Methods We performed a historical cohort study on 98 adults with P. aeruginosa (Pa nBSI. SIRS scores were determined 2 days prior to the first positive blood culture through 14 days afterwards. Monomicrobial (n = 77 and polymicrobial BSIs (n = 21 were compared. Results 78.6% of BSIs were caused by monomicrobial P. aeruginosa infection (MPa and 21.4% by polymicrobial P. aeruginosa infection (PPa. Median APACHE II score on the day of BSI was 22 for MPa and 23 for PPa BSIs. Septic shock occurred in 33.3% of PPa and in 39.0% of MPa (p = 0.64. Progression to septic shock was associated with death more frequently in PPa (OR 38.5, CI95 2.9–508.5 than MPa (OR 4.5, CI95 1.7–12.1. Maximal SIR (severe sepsis, septic shock or death was seen on day 0 for PPa BSI vs. day 1 for MPa. No significant difference was noted in the incidence of organ failure, 7-day or overall mortality between the two groups. Univariate analysis revealed that APACHE II score ≥20 at BSI onset, Charlson weighted comorbidity index ≥3, burn injury and respiratory, cardiovascular, renal and hematologic failure were associated with death, while age, malignant disease, diabetes mellitus, hepatic failure, gastrointestinal complications, inappropriate antimicrobial therapy, infection with imipenem resistant P. aeruginosa and polymicrobial nBSI were not. Multivariate analysis revealed that hematologic failure (p Conclusion In this historical cohort study of nBSI with P. aeruginosa, the incidence of septic shock and organ failure was high in both groups. Additionally, patients with PPa BSI were not more acutely ill, as judged by APACHE II

  18. Detection of extra-cellular enzymes of anaerobic gram-negative bacteria from clinically diseased and healthy sites

    Nagmoti J

    2008-01-01

    Full Text Available Anaerobic gram-negative bacteria (AGNB produce enzymes that play a significant role in the development of disease. We tested 50 AGNB isolates, 25 each from clinically diseased and healthy human sites for in vitro production of caseinase, collagenase, etc. Majority of the isolates were Bacteroides fragilis and Porphyromonas gingivalis, which more commonly produced collagenase and haemolysin. Comparatively larger number of clinical AGNB produced collagenase (P = 0.004. No such difference was observed with other enzymes. Hence, collagenase is probably one of the key virulence markers of pathogenic AGNB, and the inhibitors targeting collagenases might help in the therapy of anaerobic infections.

  19. Central line-associated bloodstream infections and catheter dwell-time: A theoretical foundation for a rule of thumb.

    Voets, Philip J G M

    2018-05-14

    Many clinicians know from experience and medical epidemiological literature that the risk of central line-associated bloodstream infections (CLABSI) increases rapidly with a prolonged catheter dwell-time, but how this infection risk increases over time remains obscure. In this manuscript, a clinically useful rule of thumb is derived, stating that the risk of CLABSI increases in a quadratic fashion with the increase in catheter dwell-time. The proposed rule of thumb could be considered a quick and effortless clinical tool to rationally predict the pattern of CLABSI risk with an increasing catheter dwell-time. Copyright © 2018. Published by Elsevier Ltd.

  20. Implementing a multifaceted intervention to decrease central line-associated bloodstream infections in SEHA (Abu Dhabi Health Services Company) intensive care units: the Abu Dhabi experience.

    Latif, Asad; Kelly, Bernadette; Edrees, Hanan; Kent, Paula S; Weaver, Sallie J; Jovanovic, Branislava; Attallah, Hadeel; de Grouchy, Kristin K; Al-Obaidli, Ali; Goeschel, Christine A; Berenholtz, Sean M

    2015-07-01

    OBJECTIVE To determine whether implementation of a multifaceted intervention would significantly reduce the incidence of central line-associated bloodstream infections. DESIGN Prospective cohort collaborative. SETTING AND PARTICIPANTS Intensive care units of the Abu Dhabi Health Services Company hospitals in the Emirate of Abu Dhabi. INTERVENTIONS A bundled intervention consisting of 3 components was implemented as part of the program. It consisted of a multifaceted approach that targeted clinician use of evidence-based infection prevention recommendations, tools that supported the identification of local barriers to these practices, and implementation ideas to help ensure patients received the practices. Comprehensive unit-based safety teams were created to improve safety culture and teamwork. Finally, the measurement and feedback of monthly infection rate data to safety teams, senior leaders, and staff in participating intensive care units was encouraged. The main outcome measure was the quarterly rate of central line-associated bloodstream infections. RESULTS Eighteen intensive care units from 7 hospitals in Abu Dhabi implemented the program and achieved an overall 38% reduction in their central line-associated bloodstream infection rate, adjusted at the hospital and unit level. The number of units with a quarterly central line-associated bloodstream infection rate of less than 1 infection per 1,000 catheter-days increased by almost 40% between the baseline and postintervention periods. CONCLUSION A significant reduction in the global morbidity and mortality associated with central line-associated bloodstream infections is possible across intensive care units in disparate settings using a multifaceted intervention.

  1. Second-Generation central venous catheter in the prevention of bloodstream infection: a systematic review.

    Stocco, Janislei Gislei Dorociaki; Hoers, Hellen; Pott, Franciele Soares; Crozeta, Karla; Barbosa, Dulce Aparecida; Meier, Marineli Joaquim

    2016-08-08

    to evaluate the effectiveness and safety in the use of second-generation central venous catheters impregnated in clorhexidine and silver sulfadiazine when compared with other catheters, being them impregnated or not, in order to prevent the bloodstream infection prevention. systematic review with meta-analysis. Databases searched: MEDLINE, EMBASE, CINAHL, LILACS/SciELO, Cochrane CENTRAL; search in Congress Proceedings and records from Clinical Trials. 1.235 studies were identified, 97 were pre-selected and 4 were included. In catheter-related bloodstream infection, there was no statistical significance between second-generation impregnated catheter compared with the non-impregnated ones, absolute relative risk 1,5% confidence interval 95% (3%-1%), relative risk 0,68 (confidence interval 95%, 0,40-1,15) and number needed to treat 66. In the sensitivity analysis, there was less bloodstream infection in impregnated catheters (relative risk 0,50, confidence interval 95%, 0,26-0,96). Lower colonization, absolute relative risk 9,6% (confidence interval 95%, 10% to 4%), relative risk 0,51 (confidence interval 95% from 0,38-0,85) and number needed to treat 5. the use of second-generation catheters was effective in reducing the catheter colonization and infection when a sensitivity analysis is performed. Future clinical trials are suggested to evaluate sepsis rates, mortality and adverse effects. evaluar la efectividad y seguridad del uso de catéteres venosos centrales de segunda generación, impregnados en clorhexidina y sulfadiazina de plata, comparados con otros catéteres impregnados o no impregnados, para prevención de infección de la corriente sanguínea. revisión sistemática con metaanálisis. La búsqueda fue realizada en las bases: MEDLINE, EMBASE, CINAHL, LILACS/SciELO, Cochrane CENTRAL; fueron consultados anales de congresos y registros de ensayos clínicos. fueron identificados 1.235 estudios, 97 preseleccionados y cuatro incluidos. En la infección de la

  2. Long-term survival and function after suspected gram-negative sepsis.

    Perl, T M; Dvorak, L; Hwang, T; Wenzel, R P

    1995-07-26

    To determine the long-term (> 3 months) survival of septic patients, to develop mathematical models that predict patients likely to survive long-term, and to measure the health and functional status of surviving patients. A large tertiary care university hospital and an associated Veterans Affairs Medical Center. From December 1986 to December 1990, a total of 103 patients with suspected gram-negative sepsis entered a double-blind, placebo-controlled efficacy trial of monoclonal antiendotoxin antibody. Of these, we followed up 100 patients for 7667 patient-months. Beginning in May 1992, we reviewed hospital records and contacted all known survivors. We measured the health status of all surviving patients. The determinants of long-term survival (up to 6 years) were identified through two Cox proportional hazard regression models: one that included patient characteristics identified at the time of sepsis (bedside model) and another that included bedside, infection-related, and treatment characteristics (overall model). Of the 60 patients in the cohort who died at a median interval of 30.5 days after sepsis, 32 died within the first month of the septic episode, seven died within 3 months, and four more died within 6 months. In the bedside multivariate model constructed to predict long-term survival, large hazard ratios (HRs) were associated with severity of underlying illness as classified by McCabe and Jackson criteria (for rapidly fatal disease, HR = 30.4, P respiratory distress syndrome (HR = 2.3; P = .02) predicted patients most likely to die. The Acute Physiology and Chronic Health Evaluation II score was not a significant predictor of outcome when either model included the simpler McCabe and Jackson classification of underlying disease severity. We compared the health status scores with norms for the general population and found that patients with resolved sepsis reported more physical dysfunction (P bedridden), suggesting that the patients' physical function

  3. Staphylococcus species and their Methicillin-Resistance in 7424 Blood Cultures for Suspected Bloodstream Infections

    Ariana ALMAŞ

    2011-06-01

    Full Text Available Objectives: The aim of this study was to evaluate the distribution of Staphylococcus species in bloodstream infections and to assess their susceptibility to methicillin. Material and Methods: Between January 1st 2008 - December 31st 2010, 7424 blood culture sets were submitted to the Laboratory Department of the Hospital for Clinical Infectious Diseases in Cluj-Napoca, Romania. The blood cultures were performed using BacT/Alert until January 2010 and BacT/Alert 3D automated system (bioMérieux after that date. The blood culture bottles were incubated at 37°C in a continuously monitoring system for up to 7 days. The strain identifications were performed by conventional methods, ApiStaph galleries and Vitek 2 Compact system. Susceptibility to methicillin was determined by disk diffusion method with cefoxitin disk and by using Vitek 2 Compact system. Results: From the total number of performed blood cultures, 568 were positive with Staphylococcus species. From 168 bacteriemic episodes 103 were with Staphylococcus aureus. Among 65 coagulase-negative staphylococci isolates, Staphylococcus epidermidis was the most frequently isolated species (34, followed by Staphylococcus hominis (15, Staphylococcus haemolyticus (8, Staphylococcus saprophyticus (3, Staphylococcus cohnii (1, Staphylococcus auricularis (1, and 3 strains that were not identified at species level. Methicillin resistance was encountered in 53.40% of Staphylococcus aureus strains and in 80% of coagulase-negative staphylococci. Conclusions: An important percentage of blood cultures were contaminated with Staphylococcus species. The main species identified in true bacteriemia cases were Staphylococcus aureus and Staphylococcus epidermidis. The percentage of methicillin-resistance, proved to be high not only for coagulase-negative staphylococci but also for Staphylococcus aureus.

  4. Risk factors and mortality for nosocomial bloodstream infections in elderly patients.

    Reunes, S; Rombaut, V; Vogelaers, D; Brusselaers, N; Lizy, C; Cankurtaran, M; Labeau, S; Petrovic, M; Blot, S

    2011-10-01

    To determine risk factors for nosocomial bloodstream infection (BSI) and associated mortality in geriatric patients in geriatric and internal medicine wards at a university hospital. Single-center retrospective (1992-2007), pairwise-matched (1:1-ratio) cohort study. Geriatric patients with nosocomial BSI were matched with controls without BSI on year of admission and length of hospitalization before onset of BSI. Demographic, microbiological, and clinical data are collected. One-hundred forty-two BSI occurred in 129 patients. Predominant microorganisms were Escherichia coli (23.2%), coagulase-negative Staphylococci (19.4%), Pseudomonas aeruginosa (8.4%), Staphylococcus aureus (7.1%), Klebsiella pneumoniae (5.8%) and Candida spp. (5.8%). Matching was successful for 109 cases. Compared to matched control subjects, cases were more frequently female, suffered more frequently from arthrosis, angina pectoris and pressure ulcers, had worse Activities of Daily Living-scores, had more often an intravenous or bladder catheter, and were more often bedridden. Logistic regression demonstrated presence of an intravenous catheter (odds ratio [OR] 7.5, 95% confidence interval [CI] 2.5-22.9) and being bedridden (OR 2.9, 95% CI 1.6-5.3) as independent risk factors for BSI. In univariate analysis nosocomial BSI was associated with increased mortality (22.0% vs. 11.0%; P=0.029). After adjustment for confounding co-variates, however, nosocomial BSI was not associated with mortality (hazard ratio 1.3, 95% CI 0.6-2.6). Being bedridden and increasing age were independent risk factors for death. Intravenous catheters and being bedridden are the main risk factors for nosocomial BSI. Although associated with higher mortality, this infectious complication seems not to be an independent risk factor for death in geriatric patients. Copyright © 2011 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  5. Neonatal Escherichia coli Bloodstream Infections: Clinical Outcomes and Impact of Initial Antibiotic Therapy.

    Bergin, Stephen P; Thaden, Joshua T; Ericson, Jessica E; Cross, Heather; Messina, Julia; Clark, Reese H; Fowler, Vance G; Benjamin, Daniel K; Hornik, Christoph P; Smith, P Brian

    2015-09-01

    Escherichia coli is a common cause of bloodstream infections (BSIs) in infants and is associated with high mortality and morbidity among survivors. The clinical significance of antibiotic resistance and timing of appropriate antimicrobial therapy in this population is poorly understood. We identified all infants with E. coli BSIs discharged from 77 neonatal intensive care units managed by the Pediatrix Medical Group in 2012. We used multivariable logistic regression to evaluate the association between 30-day mortality and ampicillin-resistant E. coli BSI, as well as the number of active empiric antimicrobial agents administered, controlling for gestational age, small-for-gestational age status, early-onset versus late-onset BSI, oxygen requirement, ventilator support and inotropic support on the day of the first positive blood culture. We identified 258 episodes of E. coli BSI, including 123 (48%) ampicillin-resistant isolates. Unadjusted 30-day mortality did not significantly differ between infants with ampicillin-resistant versus ampicillin-susceptible E. coli BSI [11 of 123 (9%) vs. 7 of 135 (5%); P = 0.33; adjusted odds ratio = 1.37 (95% confidence interval: 0.39, 4.77)]. Among ampicillin-resistant E. coli BSIs, 30-day mortality was not significantly lower for infants treated with at least one empiric antimicrobial active against ampicillin-resistant E. coli versus infants receiving no active empiric agent [adjusted odds ratio = 1.50 (0.07, 33.6)]. In this population of infants with E. coli BSI, ampicillin resistance was not associated with significantly increased mortality. Among the subset of infants with ampicillin-resistant E. coli, appropriate empirical antibiotic therapy was not associated with lower mortality.

  6. Non-oral gram-negative facultative rods in chronic periodontitis microbiota.

    van Winkelhoff, Arie J; Rurenga, Patrick; Wekema-Mulder, Gepke J; Singadji, Zadrach M; Rams, Thomas E

    2016-05-01

    The subgingival prevalence of gram-negative facultative rods not usually inhabiting or indigenous to the oral cavity (non-oral GNFR), as well as selected periodontal bacterial pathogens, were evaluated by culture in untreated and treated chronic periodontitis patients. Subgingival biofilm specimens from 102 untreated and 101 recently treated adults with chronic periodontitis in the Netherlands were plated onto MacConkey III and Dentaid selective media with air-5% CO2 incubation for isolation of non-oral GNFR, and onto enriched Oxoid blood agar with anaerobic incubation for recovery of selected periodontal bacterial pathogens. Suspected non-oral GNFR clinical isolates were identified to a species level with the VITEK 2 automated system. A total of 87 (42.9%) out of 203 patients yielded subgingival non-oral GNFR. Patients recently treated with periodontal mechanical debridement therapy demonstrated a greater prevalence of non-oral GNFR (57.4% vs 28.4%, P chronic periodontitis patients yielded cultivable non-oral GNFR in periodontal pockets, particularly among those recently treated with periodontal mechanical debridement therapy. Since non-oral GNFR species may resist mechanical debridement from periodontal pockets, and are often not susceptible to many antibiotics frequently used in periodontal practice, their subgingival presence may complicate periodontal treatment in species-positive patients and increase risk of potentially dangerous GNFR infections developing at other body sites. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Biofilms Formed by Gram-Negative Bacteria Undergo Increased Lipid A Palmitoylation, Enhancing In Vivo Survival

    Chalabaev, Sabina; Chauhan, Ashwini; Novikov, Alexey; Iyer, Pavithra; Szczesny, Magdalena; Beloin, Christophe; Caroff, Martine

    2014-01-01

    ABSTRACT Bacterial biofilm communities are associated with profound physiological changes that lead to novel properties compared to the properties of individual (planktonic) bacteria. The study of biofilm-associated phenotypes is an essential step toward control of deleterious effects of pathogenic biofilms. Here we investigated lipopolysaccharide (LPS) structural modifications in Escherichia coli biofilm bacteria, and we showed that all tested commensal and pathogenic E. coli biofilm bacteria display LPS modifications corresponding to an increased level of incorporation of palmitate acyl chain (palmitoylation) into lipid A compared to planktonic bacteria. Genetic analysis showed that lipid A palmitoylation in biofilms is mediated by the PagP enzyme, which is regulated by the histone-like protein repressor H-NS and the SlyA regulator. While lipid A palmitoylation does not influence bacterial adhesion, it weakens inflammatory response and enhances resistance to some antimicrobial peptides. Moreover, we showed that lipid A palmitoylation increases in vivo survival of biofilm bacteria in a clinically relevant model of catheter infection, potentially contributing to biofilm tolerance to host immune defenses. The widespread occurrence of increased lipid A palmitoylation in biofilms formed by all tested bacteria suggests that it constitutes a new biofilm-associated phenotype in Gram-negative bacteria. PMID:25139899

  8. Development of Quorum-Based Anti-Virulence Therapeutics Targeting Gram-Negative Bacterial Pathogens

    Wen Shan Yew

    2013-08-01

    Full Text Available Quorum sensing is a cell density-dependent signaling phenomenon used by bacteria for coordination of population-wide phenotypes, such as expression of virulence genes, antibiotic resistance and biofilm formation. Lately, disruption of bacterial communication has emerged as an anti-virulence strategy with enormous therapeutic potential given the increasing incidences of drug resistance in pathogenic bacteria. The quorum quenching therapeutic approach promises a lower risk of resistance development, since interference with virulence generally does not affect the growth and fitness of the bacteria and, hence, does not exert an associated selection pressure for drug-resistant strains. With better understanding of bacterial communication networks and mechanisms, many quorum quenching methods have been developed against various clinically significant bacterial pathogens. In particular, Gram-negative bacteria are an important group of pathogens, because, collectively, they are responsible for the majority of hospital-acquired infections. Here, we discuss the current understanding of existing quorum sensing mechanisms and present important inhibitory strategies that have been developed against this group of pathogenic bacteria.

  9. Detection of AmpC β lactamases in gram-negative bacteria

    Gunjan Gupta

    2014-01-01

    Full Text Available Amp C β-lactamases are clinically important cephalosporinases encoded on the chromosomes of many Enterobacteriaceae and a few other organisms, where they mediate resistance to cephalothin, cefazolin, cefoxitin, most penicillins, and β-lactamase inhibitor/β-lactam combinations. The increase in antibiotic resistance among Gram-negative bacteria is a notable example of how bacteria can procure, maintain and express new genetic information that can confer resistance to one or several antibiotics. Detection of organisms producing these enzymes can be difficult, because their presence does not always produce a resistant phenotype on conventional disc diffusion or automated susceptibility testing methods. These enzymes are often associated with potentially fatal laboratory reports of false susceptibility to β-lactams phenotypically. With the world-wide increase in the occurrence, types and rate of dissemination of these enzymes, their early detection is critical. AmpC β-lactamases show tremendous variation in geographic distribution. Thus, their accurate detection and characterization are important from epidemiological, clinical, laboratory, and infection control point of view. This document describes the methods for detection for AmpC β-lactamases, which can be adopted by routine diagnostic laboratories.

  10. Update on the taxonomy and the clinical and laboratory characteristics of pigmented anaerobic gram-negative rods.

    Jousimies-Somer, H R

    1995-06-01

    Pigmented anaerobic gram-negative rods are currently categorized as 17 species distributed in three genera: Prevotella, Porphyromonas, and Bacteroides. These organisms are often encountered in clinical specimens but are also found as part of the indigenous flora on various mucosal surfaces. Several studies are presently assessing the association of individual species with health and disease. For example, Porphyromonas gingivalis and Porphyromonas endodontalis are key putative pathogens in adult periodontitis and root canal infections, respectively. Porphyromonas asaccharolytica is prevalent in extraoral infections. The Porphyromonas species of animal origin have been isolated from infected bite wounds in humans. Isolates closely resembling Bacteroides levii have been recovered from various types of human infections. According to preliminary reports, Prevotella intermedia tends to be associated more often with periodontal disease than with a healthy oral cavity. In the laboratory, enzyme profiling facilitates the identification of these pigmented rods. Beta-Lactamase production is more common among prevotella species (30%-50%) than among Porphyromonas species (< 10%).

  11. The warmer the weather, the more gram-negative bacteria - impact of temperature on clinical isolates in intensive care units.

    Frank Schwab

    Full Text Available BACKGROUND: We investigated the relationship between average monthly temperature and the most common clinical pathogens causing infections in intensive care patients. METHODS: A prospective unit-based study in 73 German intensive care units located in 41 different hospitals and 31 different cities with total 188,949 pathogen isolates (102,377 Gram-positives and 86,572 Gram-negatives from 2001 to 2012. We estimated the relationship between the number of clinical pathogens per month and the average temperature in the month of isolation and in the month prior to isolation while adjusting for confounders and long-term trends using time series analysis. Adjusted incidence rate ratios for temperature parameters were estimated based on generalized estimating equation models which account for clustering effects. RESULTS: The incidence density of Gram-negative pathogens was 15% (IRR 1.15, 95%CI 1.10-1.21 higher at temperatures ≥ 20°C than at temperatures below 5°C. E. cloacae occurred 43% (IRR=1.43; 95%CI 1.31-1.56 more frequently at high temperatures, A. baumannii 37% (IRR=1.37; 95%CI 1.11-1.69, S. maltophilia 32% (IRR=1.32; 95%CI 1.12-1.57, K. pneumoniae 26% (IRR=1.26; 95%CI 1.13-1.39, Citrobacter spp. 19% (IRR=1.19; 95%CI 0.99-1.44 and coagulase-negative staphylococci 13% (IRR=1.13; 95%CI 1.04-1.22. By contrast, S. pneumoniae 35% (IRR=0.65; 95%CI 0.50-0.84 less frequently isolated at high temperatures. For each 5°C increase, we observed a 3% (IRR=1.03; 95%CI 1.02-1.04 increase of Gram-negative pathogens. This increase was highest for A. baumannii with 8% (IRR=1.08; 95%CI 1.05-1.12 followed by K. pneumoniae, Citrobacter spp. and E. cloacae with 7%. CONCLUSION: Clinical pathogens vary by incidence density with temperature. Significant higher incidence densities of Gram-negative pathogens were observed during summer whereas S. pneumoniae peaked in winter. There is increasing evidence that different seasonality due to physiologic changes underlies

  12. The warmer the weather, the more gram-negative bacteria - impact of temperature on clinical isolates in intensive care units.

    Schwab, Frank; Gastmeier, Petra; Meyer, Elisabeth

    2014-01-01

    We investigated the relationship between average monthly temperature and the most common clinical pathogens causing infections in intensive care patients. A prospective unit-based study in 73 German intensive care units located in 41 different hospitals and 31 different cities with total 188,949 pathogen isolates (102,377 Gram-positives and 86,572 Gram-negatives) from 2001 to 2012. We estimated the relationship between the number of clinical pathogens per month and the average temperature in the month of isolation and in the month prior to isolation while adjusting for confounders and long-term trends using time series analysis. Adjusted incidence rate ratios for temperature parameters were estimated based on generalized estimating equation models which account for clustering effects. The incidence density of Gram-negative pathogens was 15% (IRR 1.15, 95%CI 1.10-1.21) higher at temperatures ≥ 20°C than at temperatures below 5°C. E. cloacae occurred 43% (IRR=1.43; 95%CI 1.31-1.56) more frequently at high temperatures, A. baumannii 37% (IRR=1.37; 95%CI 1.11-1.69), S. maltophilia 32% (IRR=1.32; 95%CI 1.12-1.57), K. pneumoniae 26% (IRR=1.26; 95%CI 1.13-1.39), Citrobacter spp. 19% (IRR=1.19; 95%CI 0.99-1.44) and coagulase-negative staphylococci 13% (IRR=1.13; 95%CI 1.04-1.22). By contrast, S. pneumoniae 35% (IRR=0.65; 95%CI 0.50-0.84) less frequently isolated at high temperatures. For each 5°C increase, we observed a 3% (IRR=1.03; 95%CI 1.02-1.04) increase of Gram-negative pathogens. This increase was highest for A. baumannii with 8% (IRR=1.08; 95%CI 1.05-1.12) followed by K. pneumoniae, Citrobacter spp. and E. cloacae with 7%. Clinical pathogens vary by incidence density with temperature. Significant higher incidence densities of Gram-negative pathogens were observed during summer whereas S. pneumoniae peaked in winter. There is increasing evidence that different seasonality due to physiologic changes underlies host susceptibility to different bacterial pathogens

  13. A resurgence of β-lactamase inhibitor combinations effective against multidrug-resistant Gram-negative pathogens.

    Bush, Karen

    2015-11-01

    β-Lactamase inhibitors (BLIs) have played an important role in combatting β-lactam resistance in Gram-negative bacteria, but their effectiveness has diminished with the evolution of diverse and deleterious varieties of β-lactamases. In this review, a new generation of BLIs and inhibitor combinations is presented, describing epidemiological information, pharmacodynamic studies, resistance identification and current clinical status. Novel serine BLIs of major interest include the non-β-lactams of the diazabicyclo[3.2.1]octanone (DBO) series. The DBOs avibactam, relebactam and RG6080 inhibit most class A and class C β-lactamases, with selected inhibition of class D enzymes by avibactam. The novel boronic acid inhibitor RPX7009 has a similar inhibitory profile. All of these inhibitors are being developed in combinations that are targeting primarily carbapenemase-producing Gram-negative pathogens. Two BLI combinations (ceftolozane/tazobactam and ceftazidime/avibactam) were recently approved by the US Food and Drug Administration (FDA) under the designation of a Qualified Infectious Disease Product (QIDP). Other inhibitor combinations that have at least completed phase 1 clinical trials are ceftaroline fosamil/avibactam, aztreonam/avibactam, imipenem/relebactam, meropenem/RPX7009 and cefepime/AAI101. Although effective inhibitor combinations are in development for the treatment of infections caused by Gram-negative bacteria with serine carbapenemases, better options are still necessary for pathogens that produce metallo-β-lactamases (MBLs). The aztreonam/avibactam combination demonstrates inhibitory activity against MBL-producing enteric bacteria owing to the stability of the monobactam to these enzymes, but resistance is still an issue for MBL-producing non-fermentative bacteria. Because all of the inhibitor combinations are being developed as parenteral drugs, an orally bioavailable combination would also be of interest. Copyright © 2015 Elsevier B.V. and the

  14. Antibiofilm effect of Nocardiopsis sp. GRG 1 (KT235640) compound against biofilm forming Gram negative bacteria on UTIs.

    Rajivgandhi, Govindan; Vijayan, Ramachandran; Maruthupandy, Muthuchamy; Vaseeharan, Baskaralingam; Manoharan, Natesan

    2018-05-01

    Urinary tract infections (UTIs) are diverse public health complication and caused by range of pathogens, however mostly Gram negative bacteria cause significant life threatening risks to different populations. The prevalence rate and antimicrobial resistance among the Gram negative uropathogens alarmed significantly heighten the economic burden of these infections. In this study, we investigated the antibiofilm efficiency of Pyrrolo [1,2-a] pyrazine-1,4-dione,hexahydro-3-(2-methylpropyl) extracted from endophytic actinomycetes Nocardiopsis sp. GRG 1 (KT235640) against P. mirabilis and E. coli. The extracted compound was characterized through TLC, HPLC, GC-MS, LC-MS and confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM). The compound, Pyrrolo [1,2-a] pyrazine-1, 4-dione, hexahydro-3-(2-methylpropyl) inhibits both bacterial biofilm formation as well as reduces the viability of preformed biofilms. Furthermore, CLSM image shows cell shrinkage, disorganized cell membrane and loss of viability. The SEM result also confirms the cell wall degradation in treated cells of the bacteria. Hence, the Pyrrolo [1,2-a]pyrazine-1,4-dione, hexahydro-3-(2-methylpropyl) is active against P. mirabilis and E. coli. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Comparison of flomoxef with latamoxef in the treatment of sepsis and/or Gram-negative bacteremia in adult patients.

    Chen, Y C; Hung, C C; Lin, S F; Chang, S C; Hsieh, W C

    1996-05-01

    The safety and efficacy of flomoxef and latamoxef were compared in the treatment of hospitalized patients with sepsis and/or Gram-negative bacteremia in a prospective, open-labelled clinical trial. Patients were randomized to receive 1 to 2 g intravenous doses of either flomoxef every 6 to 12 h, or latamoxef every 8 to 12 h. Data from 21 patients given flomoxef and 23 patients given latamoxef were included in the evaluation of efficacy. Flomoxef produced clinical cure and satisfactory microbiological responses in 85.7% and 100% of patients, respectively. These results were similar to those obtained with latamoxef (87% and 100%, respectively). In addition, no significant difference was found in mean age, sex, severity of infection, distribution of pathogens and focus of infection between the two groups. However, the flomoxef group included more patients with ultimately fatal diseases. Six patients given flomoxef and two patients given latamoxef developed superinfections caused by yeast, enterococci and Pseudomonas aeruginosa in the urinary tract. Mild and reversible adverse reactions probably related to flomoxef and latamoxef were noted in 14.3% and 13% of patients, respectively. The results of this study demonstrated that flomoxef is a safe and effective antimicrobial agent in the treatment of patients with sepsis and/or Gram-negative bacteremia.

  16. Defining Multidrug Resistance of Gram-Negative Bacteria in the Dutch–German Border Region—Impact of National Guidelines

    Robin Köck

    2018-01-01

    Full Text Available Preventing the spread of multidrug-resistant Gram-negative bacteria (MDRGNB is a public health priority. However, the definition of MDRGNB applied for planning infection prevention measures such as barrier precautions differs depending on national guidelines. This is particularly relevant in the Dutch–German border region, where patients are transferred between healthcare facilities located in the two different countries, because clinicians and infection control personnel must understand antibiograms indicating MDRGNB from both sides of the border and using both national guidelines. This retrospective study aimed to compare antibiograms of Gram-negative bacteria and classify them using the Dutch and German national standards for MDRGNB definition. A total of 31,787 antibiograms from six Dutch and four German hospitals were classified. Overall, 73.7% were no MDRGNB according to both guidelines. According to the Dutch and German guideline, 7772/31,787 (24.5% and 4586/31,787 (12.9% were MDRGNB, respectively (p < 0.0001. Major divergent classifications were observed for extended-spectrum β-lactamase (ESBL -producing Enterobacteriaceae, non-carbapenemase-producing carbapenem-resistant Enterobacteriaceae, Pseudomonas aeruginosa and Stenotrophomonas maltophilia. The observed differences show that medical staff must carefully check previous diagnostic findings when patients are transferred across the Dutch–German border, as it cannot be assumed that MDRGNB requiring special hygiene precautions are marked in the transferred antibiograms in accordance with both national guidelines.

  17. Defining Multidrug Resistance of Gram-Negative Bacteria in the Dutch-German Border Region-Impact of National Guidelines.

    Köck, Robin; Siemer, Philipp; Esser, Jutta; Kampmeier, Stefanie; Berends, Matthijs S; Glasner, Corinna; Arends, Jan P; Becker, Karsten; Friedrich, Alexander W

    2018-01-26

    Preventing the spread of multidrug-resistant Gram-negative bacteria (MDRGNB) is a public health priority. However, the definition of MDRGNB applied for planning infection prevention measures such as barrier precautions differs depending on national guidelines. This is particularly relevant in the Dutch-German border region, where patients are transferred between healthcare facilities located in the two different countries, because clinicians and infection control personnel must understand antibiograms indicating MDRGNB from both sides of the border and using both national guidelines. This retrospective study aimed to compare antibiograms of Gram-negative bacteria and classify them using the Dutch and German national standards for MDRGNB definition. A total of 31,787 antibiograms from six Dutch and four German hospitals were classified. Overall, 73.7% were no MDRGNB according to both guidelines. According to the Dutch and German guideline, 7772/31,787 (24.5%) and 4586/31,787 (12.9%) were MDRGNB, respectively ( p Dutch-German border, as it cannot be assumed that MDRGNB requiring special hygiene precautions are marked in the transferred antibiograms in accordance with both national guidelines.

  18. Incidence of bloodstream infections in small bowel transplant recipients receiving selective decontamination of the digestive tract: A single-center experience.

    Galloway, David; Danziger-Isakov, Lara; Goldschmidt, Monique; Hemmelgarn, Trina; Courter, Joshua; Nathan, Jaimie D; Alonso, Maria; Tiao, Greg; Fei, Lin; Kocoshis, Samuel

    2015-11-01

    Pediatric patients undergoing small bowel transplantation are susceptible to postoperative CLABSI. SDD directed against enteric microbes is a strategy for reducing CLABSI. We hypothesized that SDD reduces the frequency of CLABSI, infections outside the bloodstream, and allograft rejection during the first 30 days following transplant. A retrospective chart review of 38 pediatric small bowel transplant recipients at CCHMC from 2003 to 2011 was conducted. SDD antimicrobials were oral colistin, tobramycin, and amphotericin B. The incidence of CLABSI, infections outside the bloodstream, and rejection episodes were compared between study periods. The incidence of CLABSI did not differ between study periods (6.9 CLABSI vs. 4.6 CLABSI per 1000 catheter days; p = 0.727), but gram positives and Candida predominated in the first 30 days. Incidence of bacterial infections outside the bloodstream did not differ (p = 0.227). Rejection occurred more frequently during the first month following transplant (p = 0.302). SDD does not alter the incidence of CLABSI, bacterial infections outside the bloodstream, or allograft rejection in the immediate 30 days post-transplantation. However, SDD does influence CLABSI organism types (favoring gram positives and Candida) and Candidal infections outside the bloodstream. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Positive deviance as a strategy to prevent and control bloodstream infections in intensive care.

    Oliveira, Francimar Tinoco de; Ferreira, Maria Manuela Frederico; Araújo, Silvia Teresa Carvalho de; Bessa, Amanda Trindade Teixeira de; Moraes, Advi Catarina Barbachan; Stipp, Marluci Andrade Conceição

    2017-04-03

    To describe the application of positive deviance as a strategy to prevent and control bloodstream infections. An intervention study with nursing and medical team members working in an intensive care unit in a university hospital, between June and December 2014. The four steps of the positive defiance methodology were applied: to define, to determine, to discover and to design. In 90 days, 188 actions were observed, of these, 36.70% (n=69) were related to catheter dressing. In 81.15% (n=56) of these dressings, the professionals most adhered to the use of flexible sterile cotton-tipped swabs to perform antisepsis at catheter entry sites and fixation dressing. Positive deviance contributed to the implementation of proposals to improve work processes and team development related to problems identified in central venous catheter care. Descrever a aplicação do Positive Deviance como estratégia na prevenção e no controle da infecção de corrente sanguínea. Estudo de intervenção realizado na Unidade de Terapia Intensiva de um hospital universitário, com os membros das equipes de enfermagem e médica, de junho a dezembro de 2014. Foram aplicados os quatro passos da metodologia Positive Deviance: Definir, Determinar, Descobrir e Desenhar. Em 90 dias 188 ações foram observadas, destas, 36,70% (n=69) estavam relacionadas aos curativos dos cateteres. Em 81,15% (n=56) desses curativos, o uso da haste flexível estéril para realização da antissepsia do local de inserção do cateter e de sua placa de fixação foi a ação de maior adesão. O Positive Deviance auxiliou na implementação de propostas de melhorias de processo de trabalho e no desenvolvimento da equipe para os problemas identificados no cuidado com o cateter venoso central.

  20. The structures of lipopolysaccharides from plant-associated gram-negative bacteria

    Molinaro, Antonio; Newman, Mari-Anne; Lanzetta, Rosa

    2009-01-01

    Gram-negative bacterial lipopolysaccharides (LPSs) have multiple roles in plant-microbe interactions. LPSs contribute to the low permeabilities of bacterial outer membranes, which act as barriers to protect bacteria from plant-derived antimicrobial substances. Conversely, perception of LPSs...... is an important prerequisite for any further understanding of the biological processes in plant-microbe interactions. Moreover, the LPSs from Gram-negative bacteria - especially those originating from plant-associated bacteria - are a great source of novel monosaccharides with unusual and occasionally astounding...

  1. Emerging Gram negative resistance to last-line antimicrobial agents fosfomycin, colistin and ceftazidime-avibactam - epidemiology, laboratory detection and treatment implications.

    Sherry, Norelle; Howden, Benjamin

    2018-04-01

    Multidrug-resistant (MDR) and extensively-drug-resistant (XDR) Gram-negative bacteria have emerged as a major threat to human health globally. This has resulted in the 're-discovery' of some older antimicrobials and development of new agents, however resistance has also rapidly emerged to these agents. Areas covered: Here we describe recent developments in resistance to three of the most important last-line antimicrobials for treatment of MDR and XDR Gram negatives: fosfomycin, colistin and ceftazidime-avibactam. Expert commentary: A key challenge for microbiologists and clinicians using these agents for treating patients with MDR and XDR Gram negative infections is the need to ensure appropriate reference methods are being used to test susceptibility to these agents, especially colistin and fosfomycin. These methods are not available in all laboratories meaning accurate results are either delayed, or potentially inaccurate as non-reference methods are employed. Combination therapy for MDR and XDR Gram negatives is likely to become more common, and future studies should focus on the clinical effects of monotherapy vs combination therapy, as well as validation of synergy testing methods. Effective national and international surveillance systems to detect and respond to resistance to these last line agents are also critical.

  2. Emergence in Taiwan of novel imipenem-resistant Acinetobacter baumannii ST455 causing bloodstream infection in critical patients.

    Lee, Hao-Yuan; Huang, Chih-Wei; Chen, Chyi-Liang; Wang, Yi-Hsin; Chang, Chee-Jen; Chiu, Cheng-Hsun

    2015-12-01

    Acinetobacter baumannii is one of the most important nosocomial pathogens worldwide. This study aimed to use multilocus sequence typing (MLST) for the epidemiological surveillance of A. baumannii isolates in Taiwan and analyze the clinical presentations and patients' outcome. MLST according to both Bartual's PubMLST and Pasteur's MLST schemes was applied to characterize bloodstream imipenem-resistant A. baumannii (IRAB) infection in intensive care units in a medical center. A total of 39 clinical IRAB bloodstream isolates in 2010 were enrolled. We also collected 13 imipenem-susceptible A. baumannii (ISAB) bloodstream isolates and 30 clinical sputum isolates (24 IRAB and 6 ISAB) for comparison. Clinical presentations and outcome of the patients were analyzed. We found that infection by ST455(B)/ST2(P) and inappropriate initial therapy were statistically significant risk factors for mortality. More than one-third of the IRAB isolates belonged to ST455(B)/ST2(P). Most ST455(B)/ST2(P) (80%) carried ISAba1-blaOXA-23, including 10 (66.7%) with Tn2006 (ISAba1-blaOXA-23-ISAba1) in an AbaR4-type resistance island. ST455(B)/ST2(P) appears to evolve from ST208(B)/ST2(P) of clonal complex (CC) 92(B)/CC2(P). In this hospital-based study, A. baumannii ST455 accounted for 38.5% of IRAB bacteremia, with a high mortality of 86.7%. Approximately 85% of ST455(B)/ST2(P)bacteremia had a primary source of ventilation-associated pneumonia. We report the emergence in Taiwan of IRAB ST455(B)/ST2(P), which is the current predominant clone of IRAB in our hospital and has been causing bacteremia with high mortality in critical patients. Copyright © 2015. Published by Elsevier B.V.

  3. Role of blood culture systems in the evaluation of epidemiological features of coagulase-negative staphylococcal bloodstream infection in critically ill patients.

    Oud, L; Krimerman, S; Salam, N; Srugo, I

    1999-12-01

    The impact of blood culture systems on the detection of coagulase-negative staphylococcal bloodstream infections in critically ill patients prior to and following the introduction of the Bactec 9240 blood culture system (Becton Dickinson Diagnostic Instrument Systems, USA), which replaced the Bactec NR 730 (Becton Dickinson Diagnostic Instrument Systems), was investigated over a 3-year period. Following the introduction of the new culture system, the incidence of bloodstream infections doubled (P<0.001). Patient demographics, severity of illness, and mortality remained unchanged, while the annual standardized mortality ratio decreased significantly. These data suggest that blood culture systems may have a major impact on the perceived incidence of coagulase-negative staphylococcal bloodstream infections in this population.

  4. Glycosaminoglycans are involved in pathogen adherence to corneal epithelial cells differently for Gram-positive and Gram-negative bacteria

    Beatriz García

    2016-11-01

    Full Text Available The epithelium of the cornea is continuously exposed to pathogens, and adhesion to epithelial cells is regarded as an essential first step in bacterial pathogenesis. In this article, the involvement of glycosaminoglycans in the adhesion of various pathogenic bacteria to corneal epithelial cells is analyzed. All microorganisms use glycosaminoglycans as receptors, but arranged in different patterns depending on the Gram-type of the bacterium. The heparan sulfate chains of syndecans are the main receptors, though other molecular species also seem to be involved, particularly in Gram-negative bacteria. Adherence is inhibited differentially by peptides, including heparin binding sequences, indicating the participation of various groups of Gram-positive and -negative adhesins. The length of the saccharides produces a major effect, and low molecular weight chains inhibit the binding of Gram-negative microorganisms but increase the adherence of Gram-positives. Pathogen adhesion appears to occur preferentially through sulfated domains, and is very dependent on N- and 6-O-sulfation of the glucosamine residue and, to a lesser extent, 2-O sulfation of uronic acid. These data show the differential use of corneal receptors, which could facilitate the development of new anti-infective strategies.

  5. The resveratrol tetramer (--hopeaphenol inhibits type III secretion in the gram-negative pathogens Yersinia pseudotuberculosis and Pseudomonas aeruginosa.

    Caroline E Zetterström

    Full Text Available Society faces huge challenges, as a large number of bacteria have developed resistance towards many or all of the antibiotics currently available. Novel strategies that can help solve this problem are urgently needed. One such strategy is to target bacterial virulence, the ability to cause disease e.g., by inhibition of type III secretion systems (T3SSs utilized by many clinically relevant gram-negative pathogens. Many of the antibiotics used today originate from natural sources. In contrast, most virulence-blocking compounds towards the T3SS identified so far are small organic molecules. A recent high-throughput screening of a prefractionated natural product library identified the resveratrol tetramer (--hopeaphenol as an inhibitor of the T3SS in Yersinia pseudotuberculosis. In this study we have investigated the virulence blocking properties of (--hopeaphenol in three different gram-negative bacteria. (--Hopeaphenol was found to have micromolar activity towards the T3SSs in Yersinia pseudotuberculosis and Pseudomonas aeruginosa in cell-based infection models. In addition (--hopeaphenol reduced cell entry and subsequent intracellular growth of Chlamydia trachomatis.

  6. Different Use of Cell Surface Glycosaminoglycans As Adherence Receptors to Corneal Cells by Gram Positive and Gram Negative Pathogens

    García, Beatriz; Merayo-Lloves, Jesús; Rodríguez, David; Alcalde, Ignacio; García-Suárez, Olivia; Alfonso, José F.; Baamonde, Begoña; Fernández-Vega, Andrés; Vazquez, Fernando; Quirós, Luis M.

    2016-01-01

    The epithelium of the cornea is continuously exposed to pathogens, and adhesion to epithelial cells is regarded as an essential first step in bacterial pathogenesis. In this article, the involvement of glycosaminoglycans in the adhesion of various pathogenic bacteria to corneal epithelial cells is analyzed. All microorganisms use glycosaminoglycans as receptors, but arranged in different patterns depending on the Gram-type of the bacterium. The heparan sulfate chains of syndecans are the main receptors, though other molecular species also seem to be involved, particularly in Gram-negative bacteria. Adherence is inhibited differentially by peptides, including heparin binding sequences, indicating the participation of various groups of Gram-positive, and -negative adhesins. The length of the saccharides produces a major effect, and low molecular weight chains inhibit the binding of Gram-negative microorganisms but increase the adherence of Gram-positives. Pathogen adhesion appears to occur preferentially through sulfated domains, and is very dependent on N- and 6-O-sulfation of the glucosamine residue and, to a lesser extent, 2-O sulfation of uronic acid. These data show the differential use of corneal receptors, which could facilitate the development of new anti-infective strategies. PMID:27965938

  7. Evaluation of an expanded microarray for detecting antibiotic resistance genes in a broad range of gram-negative bacterial pathogens.

    Card, Roderick; Zhang, Jiancheng; Das, Priya; Cook, Charlotte; Woodford, Neil; Anjum, Muna F

    2013-01-01

    A microarray capable of detecting genes for resistance to 75 clinically relevant antibiotics encompassing 19 different antimicrobial classes was tested on 132 Gram-negative bacteria. Microarray-positive results correlated >91% with antimicrobial resistance phenotypes, assessed using British Society for Antimicrobial Chemotherapy clinical breakpoints; the overall test specificity was >83%. Microarray-positive results without a corresponding resistance phenotype matched 94% with PCR results, indicating accurate detection of genes present in the respective bacteria by microarray when expression was low or absent and, hence, undetectable by susceptibility testing. The low sensitivity and negative predictive values of the microarray results for identifying resistance to some antimicrobial resistance classes are likely due to the limited number of resistance genes present on the current microarray for those antimicrobial agents or to mutation-based resistance mechanisms. With regular updates, this microarray can be used for clinical diagnostics to help accurate therapeutic options to be taken following infection with multiple-antibiotic-resistant Gram-negative bacteria and prevent treatment failure.

  8. Rapid membrane permeabilization and inhibition of vital functions of gram-negative bacteria by bactenecins.

    Skerlavaj, B; Romeo, D; Gennaro, R

    1990-11-01

    Bactenecins are a class of arginine-rich antibacterial peptides of bovine neutrophil granules. Two bactenecins with approximate molecular weights of 5,000 and 7,000 designated Bac5 and Bac7, respectively, exert in vitro a potent bactericidal activity toward several gram-negative bacteria (R. Gennaro, B. Skerlavaj, and D. Romeo, Infect. Immun. 57:3142-3146, 1989). We have now found that this activity shows an inverse relationship to the ionic strength of the medium and is inhibited by divalent cations and greatly potentiated by lactoferrin. Under conditions supporting marked bactericidal activity, the two peptides cause a rapid increase in the permeability of both the outer and inner membranes of Escherichia coli, as shown by unmasking of periplasmic beta-lactamase and of cytoplasmic beta-galactosidase. In addition, the two bactenecins inhibit the respiration of E. coli and Klebsiella pneumoniae but not of Bac5- and Bac7-resistant Staphylococcus aureus. Furthermore, they induce a drop in ATP content in E. coli, K. pneumoniae, and Salmonella typhimurium and a marked decrease in the rates of transport and incorporation of [3H]leucine and [3H]uridine into E. coli protein and RNA, respectively. In general, all these effects become evident within 1 to 2 min and reach their maximal expression within about 5 min. Overall, these data strongly suggest that the decrease in bacterial viability is causally related to the increase in membrane permeability and the subsequent fall in respiration-linked proton motive force, with the attendant loss of cellular metabolites and macromolecular biosynthesis ability.

  9. Changes in healthcare-associated Staphylococcus aureus bloodstream infections after the introduction of a national hand hygiene initiative.

    Barnett, Adrian G; Page, Katie; Campbell, Megan; Brain, David; Martin, Elizabeth; Rashleigh-Rolls, Rebecca; Halton, Kate; Hall, Lisa; Jimmieson, Nerina; White, Katherine; Paterson, David; Graves, Nicholas

    2014-08-01

    Interventions that prevent healthcare-associated infection should lead to fewer deaths and shorter hospital stays. Cleaning hands (with soap or alcohol) is an effective way to prevent the transmission of organisms, but rates of compliance with hand hygiene are sometimes disappointingly low. The National Hand Hygiene Initiative in Australia aimed to improve hand hygiene compliance among healthcare workers, with the goal of reducing rates of healthcare-associated infection. We examined whether the introduction of the National Hand Hygiene Initiative was associated with a change in infection rates. Monthly infection rates for healthcare-associated Staphylococcus aureus bloodstream infections were examined in 38 Australian hospitals across 6 states. We used Poisson regression and examined 12 possible patterns of change, with the best fitting pattern chosen using the Akaike information criterion. Monthly bed-days were included to control for increased hospital use over time. The National Hand Hygiene Initiative was associated with a reduction in infection rates in 4 of the 6 states studied. Two states showed an immediate reduction in rates of 17% and 28%, 2 states showed a linear decrease in rates of 8% and 11% per year, and 2 showed no change in infection rates. The intervention was associated with reduced infection rates in most states. The failure in 2 states may have been because those states already had effective initiatives before the national initiative's introduction or because infection rates were already low and could not be further reduced.

  10. Cost Analysis of Implementing Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry Plus Real-Time Antimicrobial Stewardship Intervention for Bloodstream Infections.

    Patel, Twisha S; Kaakeh, Rola; Nagel, Jerod L; Newton, Duane W; Stevenson, James G

    2017-01-01

    Studies evaluating rapid diagnostic testing plus stewardship intervention have consistently demonstrated improved clinical outcomes for patients with bloodstream infections. However, the cost of implementing new rapid diagnostic testing can be significant, and such testing usually does not generate additional revenue. There are minimal data evaluating the impact of adding matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for rapid organism identification and dedicating pharmacy stewardship personnel time on the total hospital costs. A cost analysis was performed utilizing patient data generated from the hospital cost accounting system and included additional costs of MALDI-TOF equipment, supplies and personnel, and dedicated pharmacist time for blood culture review and of making interventions to antimicrobial therapy. The cost analysis was performed from a hospital perspective for 3-month blocks before and after implementation of MALDI-TOF plus stewardship intervention. A total of 480 patients with bloodstream infections were included in the analysis: 247 in the preintervention group and 233 in the intervention group. Thirty-day mortality was significantly improved in the intervention group (12% versus 21%, P cost per bloodstream infection was lower in the intervention group ($42,580 versus $45,019). Intensive care unit cost per bloodstream infection accounted for the largest share of the total costs in each group and was also lower in the intervention group ($10,833 versus $13,727). Implementing MALDI-TOF plus stewardship review and intervention decreased mortality for patients with bloodstream infections. Despite the additional costs of implementing MALDI-TOF and of dedicating pharmacy stewardship personnel time to interventions, the total hospital costs decreased by $2,439 per bloodstream infection, for an approximate annual cost savings of $2.34 million. Copyright © 2016 American Society for Microbiology.

  11. Candidatus Renichlamydia lutjani, a Gram-negative bacterium in internal organs of blue striped snapper Lutjanus kasmira from Hawaii

    Corsaro, Daniele; Work, Thierry M.

    2012-01-01

    The blue-striped snapper Lutjanus kasmira (Perciformes, Lutjanidae) are cosmopolitan in the Indo-Pacific but were introduced into Oahu, Hawaii, USA, in the 1950s and have since colonized most of the archipelago. Studies of microparasites in blue-striped snappers from Hawaii revealed chlamydia-like organisms (CLO) infecting the spleen and kidney, characterized by intracellular basophilic granular inclusions containing Gram-negative and Gimenez-positive bacteria similar in appearance to epitheliocysts when seen under light microscopy. We provide molecular evidence that CLO are a new member of Chlamydiae, i.e. Candidatus Renichlamydia lutjani, that represents the first reported case of chlamydial infection in organs other than the gill in fishes.

  12. In vitro susceptibility of gram-negative bacterial isolates to chlorhexidine gluconate.

    Mengistu, Y; Erge, W; Bellete, B

    1999-05-01

    To investigate the susceptibility of clinical isolates of gram-negative bacteria to chlorhexidine gluconate. Prospective laboratory study. Tikur Anbessa Hospital, Addis Ababa, Ethiopia. Clinical specimens from 443 hospital patients. Significant number of gram negative bacteria were not inhibited by chlorhexidine gluconate (0.02-0.05%) used for antisepsis. Four hundred and forty three strains of gram-negative bacteria were isolated from Tikur Anbessa Hospital patients. Escherichia coli (31.6%) and Klebsiella pneumoniae (23%) were the most frequently isolated bacteria followed by Proteus species (13.3%), Pseudomonas species (9.2%), and Citrobacter species (6.1%). Each organism was tested to chlorhexidine gluconate (CHG), minimum inhibitory concentration (MIC) ranging from 0.0001% to 1%w/v. All Salmonella species and E. coli were inhibited by CHG, MIC or = 0.1%). Our results showed that a significant number of the gram-negative bacterial isolates were not inhibited by CHG at the concentration used for disinfection of wounds or instruments (MIC 0.02-0.05% w/v). It is therefore important to select appropriate concentration of this disinfectant and rationally use it for disinfection and hospital hygiene. Continuing follow up and surveillance is also needed to detect resistant bacteria to chlorhexidine or other disinfectants in time.

  13. Activation of toll-like receptors 2 and 4 by gram-negative periodontal bacteria

    Kikkert, R.; Laine, M. L.; Aarden, L. A.; van Winkelhoff, A. J.

    2007-01-01

    BACKGROUND/AIMS: Periodontitis is a chronic infectious disease associated with a gram-negative subgingival microflora. Bacterial components stimulate, among other receptors, Toll-like receptor (TLR) 2 and/or TLR4. Accumulating evidence indicates that both qualitatively and quantitatively distinct

  14. Antibiotic-Resistant Gram Negative Bacilli in Meals Delivered at a General Hospital, Italy

    Maria Rosa Anna Plano

    2009-01-01

    Full Text Available This study aimed at detecting the presence of antibiotic-resistant Gram-negatives in samples of meals delivered at the University General Hospital of Palermo, Italy. Antibiotic resistant Gram negatives were isolated in July—September 2007 ffrom cold dishes and food contact surfaces and utensils. Bacterial strains were submitted to susceptibility test and subtyped by random amplification of polymorphic DNA (RAPD. Forty-six of 55 (83.6% food samples and 14 of 17 (82.3% environmental swabs were culture positive for Gram negative bacilli resistant to at least one group of antibacterial drugs. A total of 134 antibiotic resistant strains, 51 fermenters and 83 non-fermenters, were recovered. Fermenters and non-fermenters showed frequencies as high as 97.8% of resistance to two or more groups of antibiotics and non fermenters were 28.9% resistant to more than three groups. Molecular typing detected 34 different profiles among the fermenters and 68 among the non-fermenters. Antibiotic resistance was very common among both fermenters and non-fermenters. However, the wide heterogeneity of RAPD patterns seems to support a prominent role of cross-contamination rather than a clonal expansion of a few resistant isolates. A contribution of commensal Gram negatives colonizing foods to a common bacterial resistance pool should not been overlooked.

  15. Protamine-induced permeabilization of cell envelopes of gram-positive and gram-negative bacteria

    Johansen, Charlotte; Verheul, A.; Gram, Lone

    1997-01-01

    carboxyfluorescein and ATP after 2 to 5 min. Maximum antibacterial activity was reached at alkaline pH and in the absence of divalent cations. The efficient permeabilization of cell envelopes of both gram-positive and gram-negative bacteria suggests that protamine causes a general disruption of the cell envelope...

  16. Antibiotic-resistant gram negative bacilli in meals delivered at a general hospital, Italy.

    Plano, Maria Rosa Anna; Di Noto, Anna Maria; Firenze, Alberto; Sciortino, Sonia; Mammina, Caterina

    2009-01-01

    This study aimed at detecting the presence of antibiotic-resistant Gram-negatives in samples of meals delivered at the University General Hospital of Palermo, Italy. Antibiotic resistant Gram negatives were isolated in July-September 2007 ffrom cold dishes and food contact surfaces and utensils. Bacterial strains were submitted to susceptibility test and subtyped by random amplification of polymorphic DNA (RAPD). Forty-six of 55 (83.6%) food samples and 14 of 17 (82.3%) environmental swabs were culture positive for Gram negative bacilli resistant to at least one group of antibacterial drugs. A total of 134 antibiotic resistant strains, 51 fermenters and 83 non-fermenters, were recovered. Fermenters and non-fermenters showed frequencies as high as 97.8% of resistance to two or more groups of antibiotics and non fermenters were 28.9% resistant to more than three groups. Molecular typing detected 34 different profiles among the fermenters and 68 among the non-fermenters. Antibiotic resistance was very common among both fermenters and non-fermenters. However, the wide heterogeneity of RAPD patterns seems to support a prominent role of cross-contamination rather than a clonal expansion of a few resistant isolates. A contribution of commensal Gram negatives colonizing foods to a common bacterial resistance pool should not been overlooked.

  17. Antimicrobial Resistance in Gram-Negative Rods Causing Bacteremia in Hematopoietic Stem Cell Transplant Recipients

    Averbuch, Diana; Tridello, Gloria; Hoek, Jennifer

    2017-01-01

    Background: This intercontinental study aimed to study gram-negative rod (GNR) resistance in hematopoietic stem cell transplantation (HSCT). Methods: GNR bacteremias occurring during 6 months post-HSCT (February 2014-May 2015) were prospectively collected, and analyzed for rates and risk factors...

  18. Non-oral gram-negative facultative rods in chronic periodontitis microbiota

    van Winkelhoff, Arie J; Rurenga, Patrick; Wekema-Mulder, Gepke J; Singadji, Zadnach; Rams, Thomas E

    OBJECTIVE: The subgingival prevalence of gram-negative facultative rods not usually inhabiting or indigenous to the oral cavity (non-oral GNFR), as well as selected periodontal bacterial pathogens, were evaluated by culture in untreated and treated chronic periodontitis patients. METHODS:

  19. Gram-negative and -positive bacteria differentiation in blood culture samples by headspace volatile compound analysis.

    Dolch, Michael E; Janitza, Silke; Boulesteix, Anne-Laure; Graßmann-Lichtenauer, Carola; Praun, Siegfried; Denzer, Wolfgang; Schelling, Gustav; Schubert, Sören

    2016-12-01

    Identification of microorganisms in positive blood cultures still relies on standard techniques such as Gram staining followed by culturing with definite microorganism identification. Alternatively, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry or the analysis of headspace volatile compound (VC) composition produced by cultures can help to differentiate between microorganisms under experimental conditions. This study assessed the efficacy of volatile compound based microorganism differentiation into Gram-negatives and -positives in unselected positive blood culture samples from patients. Headspace gas samples of positive blood culture samples were transferred to sterilized, sealed, and evacuated 20 ml glass vials and stored at -30 °C until batch analysis. Headspace gas VC content analysis was carried out via an auto sampler connected to an ion-molecule reaction mass spectrometer (IMR-MS). Measurements covered a mass range from 16 to 135 u including CO2, H2, N2, and O2. Prediction rules for microorganism identification based on VC composition were derived using a training data set and evaluated using a validation data set within a random split validation procedure. One-hundred-fifty-two aerobic samples growing 27 Gram-negatives, 106 Gram-positives, and 19 fungi and 130 anaerobic samples growing 37 Gram-negatives, 91 Gram-positives, and two fungi were analysed. In anaerobic samples, ten discriminators were identified by the random forest method allowing for bacteria differentiation into Gram-negative and -positive (error rate: 16.7 % in validation data set). For aerobic samples the error rate was not better than random. In anaerobic blood culture samples of patients IMR-MS based headspace VC composition analysis facilitates bacteria differentiation into Gram-negative and -positive.

  20. Incidence of colonization and bloodstream infection with carbapenem-resistant Enterobacteriaceae in children receiving antineoplastic chemotherapy in Italy.

    Caselli, Desiree; Cesaro, Simone; Fagioli, Franca; Carraro, Francesca; Ziino, Ottavio; Zanazzo, Giulio; Meazza, Cristina; Colombini, Antonella; Castagnola, Elio

    2016-02-01

    Few data are available on the incidence of carbapenemase-producing Enterobacteriaceae (CPE) infection or colonization in children receiving anticancer chemotherapy. We performed a nationwide survey among centers participating in the pediatric hematology-oncology cooperative study group (Associazione Italiana Ematologia Oncologia Pediatrica, AIEOP). During a 2-year observation period, we observed a threefold increase in the colonization rate, and a fourfold increase of bloodstream infection episodes, caused by CPE, with a 90-day mortality of 14%. This first nationwide Italian pediatric survey shows that the circulation of CPE strains in the pediatric hematology-oncology environment is increasing. Given the mortality rate, which is higher than for other bacterial strains, specific monitoring should be applied and the results should have implications for health-care practice in pediatric hematology-oncology.

  1. Gram-negative, but not Gram-positive, bacteria elicit strong PGE2 production in human monocytes.

    Hessle, Christina C; Andersson, Bengt; Wold, Agnes E

    2003-12-01

    Gram-positive and Gram-negative bacteria induce different cytokine patterns in human mononuclear cells. We have seen that Gram-positives preferentially induce IL-12 and TNF-alpha, whereas Gram-negatives induce more IL-10, IL-6, and IL-8. In this study, we compared the capacity of these two groups of bacteria to induce PGE2. Monocytes stimulated with Gram-negative bacterial species induced much more PGE2 than did Gram-positive bacteria (5600 +/- 330 vs. 1700 +/- 670 pg/mL, p Gram-positive and Gram-negative bacteria. We suggest that Gram-positive and Gram-negative bacteria may stimulate different innate effector functions; Gram-positive bacteria promoting cell-mediated effector functions whereas Gram-negative bacteria inducing mediators inhibiting the same.

  2. Evidence-based measures to prevent central line-associated bloodstream infections: a systematic review.

    Perin, Daniele Cristina; Erdmann, Alacoque Lorenzini; Higashi, Giovana Dorneles Callegaro; Sasso, Grace Teresinha Marcon Dal

    2016-09-01

    to identify evidence-based care to prevent CLABSI among adult patients hospitalized in ICUs. systematic review conducted in the following databases: PubMed, Scopus, Cinahl, Web of Science, Lilacs, Bdenf and Cochrane Studies addressing care and maintenance of central venous catheters, published from January 2011 to July 2014 were searched. The 34 studies identified were organized in an instrument and assessed by using the classification provided by the Joanna Briggs Institute. the studies presented care bundles including elements such as hand hygiene and maximal barrier precautions; multidimensional programs and strategies such as impregnated catheters and bandages and the involvement of facilities in and commitment of staff to preventing infections. care bundles coupled with education and the commitment of both staff and institutions is a strategy that can contribute to decreased rates of central line-associated bloodstream infections among adult patients hospitalized in intensive care units. identificar evidências de cuidados para prevenção de infecção de corrente sanguínea relacionada a cateter venoso central em pacientes adultos em Unidades de Terapia Intensiva. revisão Sistemática realizada por meio de busca nas bases de dados Pubmed, Scopus, Cinahl, Web of Science, Lilacs, Bdenf e Cochrane. Foram buscadas pesquisas com cuidados com a cateterização e manutenção do cateter venoso central, publicados de janeiro de 2011 a julho de 2014. Os 34 estudos incluídos foram organizados em um instrumento e avaliados por meio da classificação do The Joanna Briggs Institute. os estudos apresentaram bundles de cuidados com elementos como a higiene das mãos e precauções máximas de barreira; programas multidimensionais e estratégias como cateteres e curativos impregnados e o envolvimento da instituição e engajamento da equipe nos esforços para prevenção de infecção. os cuidados no formato de bundles aliados com a educação e engajamento da equipe e

  3. Central line-associated bloodstream infections in adult hematology patients with febrile neutropenia: an evaluation of surveillance definitions using differential time to blood culture positivity.

    Freeman, Joshua T; Elinder-Camburn, Anna; McClymont, Catherine; Anderson, Deverick J; Bilkey, Mary; Williamson, Deborah A; Berkahn, Leanne; Roberts, Sally A

    2013-01-01

    We used differential time to positivity between central and peripheral blood cultures to evaluate the positive predictive value (PPV) of the National Healthcare Safety Network central line-associated bloodstream infection (CLABSI) surveillance definition among hematology patients with febrile neutropenia. The PPV was 27.7%, which suggests that, when the definition is applied to this population, CLABSI rates will be substantially overestimated.

  4. Beyond the bundle: a survey of central line-associated bloodstream infection prevention practices used in US and Canadian pediatric hospitals.

    Klieger, Sarah B; Potter-Bynoe, Gail; Quach, Caroline; Sandora, Thomas J; Coffin, Susan E

    2013-11-01

    We surveyed US and Canadian pediatric hospitals about their use of central line-associated bloodstream infection (CLABSI) prevention strategies beyond typical insertion and maintenance bundles. We found wide variation in supplemental strategies across hospitals and in their penetration within hospitals. Future studies should assess specific adjunctive prevention strategies and CLABSI rates.

  5. Sequential hand hygiene promotion contributes to a reduced nosocomial bloodstream infection rate among very low-birth weight infants: An interrupted time series over a 10-year period

    Helder, O.K.; Brug, J.; van Goudoever, J.B.; Looman, C.W.N.; Reiss, I.K.M.; Kornelisse, R.F.

    2014-01-01

    Background Sustained high compliance with hand hygiene (HH) is needed to reduce nosocomial bloodstream infections (NBSIs). However, over time, a wash out effect often occurs. We studied the long-term effect of sequential HH-promoting interventions. Methods An observational study with an interrupted

  6. Sequential hand hygiene promotion contributes to a reduced nosocomial bloodstream infection rate among very low-birth weight infants: an interrupted time series over a 10-year period

    Helder, Onno K.; Brug, Johannes; van Goudoever, Johannes B.; Looman, Caspar W. N.; Reiss, Irwin K. M.; Kornelisse, René F.

    2014-01-01

    Sustained high compliance with hand hygiene (HH) is needed to reduce nosocomial bloodstream infections (NBSIs). However, over time, a wash out effect often occurs. We studied the long-term effect of sequential HH-promoting interventions. An observational study with an interrupted time series

  7. Detection of mcr-1 encoding plasmid-mediated colistin-resistant Escherichia coli isolates from human bloodstream infection and imported chicken meat, Denmark 2015

    Hasman, H.; Hammerum, A. M.; Hansen, F.

    2015-01-01

    The plasmid-mediated colistin resistance gene, mcr-1, was detected in an Escherichia coli isolate from a Danish patient with bloodstream infection and in five E. coli isolates from imported chicken meat. One isolate from chicken meat belonged to the epidemic spreading sequence type ST131...

  8. Trojan Horse Antibiotics-A Novel Way to Circumvent Gram-Negative Bacterial Resistance?

    Tillotson, Glenn S

    2016-01-01

    Antibiotic resistance has been emerged as a major global health problem. In particular, gram-negative species pose a significant clinical challenge as bacteria develop or acquire more resistance mechanisms. Often, these bacteria possess multiple resistance mechanisms, thus nullifying most of the major classes of drugs. Novel approaches to this issue are urgently required. However, the challenges of developing new agents are immense. Introducing novel agents is fraught with hurdles, thus adapting known antibiotic classes by altering their chemical structure could be a way forward. A chemical addition to existing antibiotics known as a siderophore could be a solution to the gram-negative resistance issue. Siderophore molecules rely on the bacterial innate need for iron ions and thus can utilize a Trojan Horse approach to gain access to the bacterial cell. The current approaches to using this potential method are reviewed.

  9. Lipopolysaccharide biogenesis and transport at the outer membrane of Gram-negative bacteria.

    Sperandeo, Paola; Martorana, Alessandra M; Polissi, Alessandra

    2017-11-01

    The outer membrane (OM) of Gram-negative bacteria is an asymmetric lipid bilayer containing a unique glycolipid, lipopolysaccharide (LPS) in its outer leaflet. LPS molecules confer to the OM peculiar permeability barrier properties enabling Gram-negative bacteria to exclude many toxic compounds, including clinically useful antibiotics, and to survive harsh environments. Transport of LPS poses several problems to the cells due to the amphipatic nature of this molecule. In this review we summarize the current knowledge on the LPS transport machinery, discuss the challenges associated with this process and present the solutions that bacterial cells have evolved to address the problem of LPS transport and assembly at the cell surface. Finally, we discuss how knowledge on LPS biogenesis can be translated for the development of novel antimicrobial therapies. This article is part of a Special Issue entitled: Bacterial Lipids edited by Russell E. Bishop. Copyright © 2016. Published by Elsevier B.V.

  10. Surface-Exposed Lipoproteins: An Emerging Secretion Phenomenon in Gram-Negative Bacteria.

    Wilson, Marlena M; Bernstein, Harris D

    2016-03-01

    Bacterial lipoproteins are hydrophilic proteins that are anchored to a cell membrane by N-terminally linked fatty acids. It is widely believed that nearly all lipoproteins produced by Gram-negative bacteria are either retained in the inner membrane (IM) or transferred to the inner leaflet of the outer membrane (OM). Lipoproteins that are exposed on the cell surface have also been reported but are generally considered to be rare. Results from a variety of recent studies, however, now suggest that the prevalence of surface-exposed lipoproteins has been underestimated. In this review we describe the evidence that the surface exposure of lipoproteins in Gram-negative bacteria is a widespread phenomenon and discuss possible mechanisms by which these proteins might be transported across the OM. Published by Elsevier Ltd.

  11. Rapid, highly sensitive detection of Gram-negative bacteria with lipopolysaccharide based disposable aptasensor.

    Zhang, Jian; Oueslati, Rania; Cheng, Cheng; Zhao, Ling; Chen, Jiangang; Almeida, Raul; Wu, Jayne

    2018-07-30

    Gram-negative bacteria are one of the most common microorganisms in the environment. Their differential detection and recognition from Gram-positive bacteria has been attracting much attention over the years. Using Escherichia coli (E. coli) as a model, we demonstrated on-site detection of Gram-negative bacteria by an AC electrokinetics-based capacitive sensing method using commercial microelectrodes functionalized with an aptamer specific to lipopolysaccharides. Dielectrophoresis effect was utilized to enrich viable bacteria to the microelectrodes rapidly, achieving a detection limit of 10 2 cells/mL within a 30 s' response time. The sensor showed a negligible response to Staphylococcus aureus (S. aureus), a Gram-positive species. The developed sensor showed significant advantages in sensitivity, selectivity, cost, operation simplicity, and response time. Therefore, this sensing method has shown great application potential for environmental monitoring, food safety, and real-time diagnosis. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. WGS-based surveillance of third-generation cephalosporin-resistant Escherichia coli from bloodstream infections in Denmark

    Roer, Louise; Hansen, Frank; Thomsen, Martin Christen Frølund

    2017-01-01

    clone, here observed for the first time in Denmark. Additionally, the analysis revealed three individual cases with possible persistence of closely related clones collected more than 13 months apart. Continuous WGS-based national surveillance of 3GC-R Ec , in combination with more detailed......-genome sequenced and characterized by using the batch uploader from the Center for Genomic Epidemiology (CGE) and automatically analysed using the CGE tools according to resistance profile, MLST, serotype and fimH subtype. Additionally, the phylogenetic relationship of the isolates was analysed by SNP analysis......To evaluate a genome-based surveillance of all Danish third-generation cephalosporin-resistant Escherichia coli (3GC-R Ec ) from bloodstream infections between 2014 and 2015, focusing on horizontally transferable resistance mechanisms. A collection of 552 3GC-R Ec isolates were whole...

  13. Combinatorial events of insertion sequences and ICE in Gram-negative bacteria.

    Toleman, Mark A; Walsh, Timothy R

    2011-09-01

    The emergence of antibiotic and antimicrobial resistance in Gram-negative bacteria is incremental and linked to genetic elements that function in a so-called 'one-ended transposition' manner, including ISEcp1, ISCR elements and Tn3-like transposons. The power of these elements lies in their inability to consistently recognize one of their own terminal sequences, while recognizing more genetically distant surrogate sequences. This has the effect of mobilizing the DNA sequence found adjacent to their initial location. In general, resistance in Gram-negatives is closely linked to a few one-off events. These include the capture of the class 1 integron by a Tn5090-like transposon; the formation of the 3' conserved segment (3'-CS); and the fusion of the ISCR1 element to the 3'-CS. The structures formed by these rare events have been massively amplified and disseminated in Gram-negative bacteria, but hitherto, are rarely found in Gram-positives. Such events dominate current resistance gene acquisition and are instrumental in the construction of large resistance gene islands on chromosomes and plasmids. Similar combinatorial events appear to have occurred between conjugative plasmids and phages constructing hybrid elements called integrative and conjugative elements or conjugative transposons. These elements are beginning to be closely linked to some of the more powerful resistance mechanisms such as the extended spectrum β-lactamases, metallo- and AmpC type β-lactamases. Antibiotic resistance in Gram-negative bacteria is dominated by unusual combinatorial mistakes of Insertion sequences and gene fusions which have been selected and amplified by antibiotic pressure enabling the formation of extended resistance islands. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  14. Surveillance of Candida spp bloodstream infections: epidemiological trends and risk factors of death in two Mexican tertiary care hospitals.

    Dora E Corzo-Leon

    Full Text Available Larger populations at risk, broader use of antibiotics and longer hospital stays have impacted on the incidence of Candida sp. bloodstream infections (CBSI.To determine clinical and epidemiologic characteristics of patients with CBSI in two tertiary care reference medical institutions in Mexico City.Prospective and observational laboratory-based surveillance study conducted from 07/2008 to 06/2010.All patients with CBSI were included. Identification and antifungal susceptibility were performed using CLSI M27-A3 standard procedures. Frequencies, Mann-Whitney U test or T test were used as needed. Risk factors were determined with multivariable analysis and binary logistic regression analysis.CBSI represented 3.8% of nosocomial bloodstream infections. Cumulative incidence was 2.8 per 1000 discharges (incidence rate: 0.38 per 1000 patient-days. C. albicans was the predominant species (46%, followed by C. tropicalis (26%. C. glabrata was isolated from patients with diabetes (50%, and elderly patients. Sixty-four patients (86% received antifungals. Amphotericin-B deoxycholate (AmBD was the most commonly used agent (66%. Overall mortality rate reached 46%, and risk factors for death were APACHE II score ≥ 16 (OR = 6.94, CI95% = 2.34-20.58, p<0.0001, and liver disease (OR = 186.11, CI95% = 7.61-4550.20, p = 0.001. Full susceptibility to fluconazole, AmBD and echinocandins among C. albicans, C. tropicalis, and C. parapsilosis was observed.The cumulative incidence rate in these centers was higher than other reports from tertiary care hospitals from Latin America. Knowledge of local epidemiologic patterns permits the design of more specific strategies for prevention and preemptive therapy of CBSI.

  15. Surveillance of Candida spp Bloodstream Infections: Epidemiological Trends and Risk Factors of Death in Two Mexican Tertiary Care Hospitals

    Corzo-Leon, Dora E.; Alvarado-Matute, Tito; Colombo, Arnaldo L.; Cornejo-Juarez, Patricia; Cortes, Jorge; Echevarria, Juan I.; Guzman-Blanco, Manuel; Macias, Alejandro E.; Nucci, Marcio; Ostrosky-Zeichner, Luis; Ponce-de-Leon, Alfredo; Queiroz-Telles, Flavio; Santolaya, Maria E.; Thompson-Moya, Luis; Tiraboschi, Iris N.; Zurita, Jeannete; Sifuentes-Osornio, Jose

    2014-01-01

    Introduction Larger populations at risk, broader use of antibiotics and longer hospital stays have impacted on the incidence of Candida sp. bloodstream infections (CBSI). Objective To determine clinical and epidemiologic characteristics of patients with CBSI in two tertiary care reference medical institutions in Mexico City. Design Prospective and observational laboratory-based surveillance study conducted from 07/2008 to 06/2010. Methods All patients with CBSI were included. Identification and antifungal susceptibility were performed using CLSI M27-A3 standard procedures. Frequencies, Mann-Whitney U test or T test were used as needed. Risk factors were determined with multivariable analysis and binary logistic regression analysis. Results CBSI represented 3.8% of nosocomial bloodstream infections. Cumulative incidence was 2.8 per 1000 discharges (incidence rate: 0.38 per 1000 patient-days). C. albicans was the predominant species (46%), followed by C. tropicalis (26%). C. glabrata was isolated from patients with diabetes (50%), and elderly patients. Sixty-four patients (86%) received antifungals. Amphotericin-B deoxycholate (AmBD) was the most commonly used agent (66%). Overall mortality rate reached 46%, and risk factors for death were APACHE II score ≥16 (OR = 6.94, CI95% = 2.34–20.58, p<0.0001), and liver disease (OR = 186.11, CI95% = 7.61–4550.20, p = 0.001). Full susceptibility to fluconazole, AmBD and echinocandins among C. albicans, C. tropicalis, and C. parapsilosis was observed. Conclusions The cumulative incidence rate in these centers was higher than other reports from tertiary care hospitals from Latin America. Knowledge of local epidemiologic patterns permits the design of more specific strategies for prevention and preemptive therapy of CBSI. PMID:24830654

  16. Bloodstream infections caused by multi-drug resistant Proteus mirabilis: Epidemiology, risk factors and impact of multi-drug resistance.

    Korytny, Alexander; Riesenberg, Klaris; Saidel-Odes, Lisa; Schlaeffer, Fransisc; Borer, Abraham

    2016-01-01

    The prevalence of antimicrobial co-resistance among ESBL-producing Enterobactereaceae is extremely high in Israel. Multidrug-resistant Proteus mirabilis strains (MDR-PM), resistant to almost all antibiotic classes have been described. The aim was to determine the risk factors for bloodstream infections caused by MDR-PM and clinical outcomes. A retrospective case-control study. Adult patients with PM bacteremia during 7 years were identified retrospectively and their files reviewed for demographics, underlying diseases, Charlson Comorbidity Index, treatment and outcome. One hundred and eighty patients with PM-bloodstream infection (BSI) were included; 90 cases with MDR-PM and 90 controls with sensitive PM (S-PM). Compared to controls, cases more frequently were from nursing homes, had recurrent hospital admissions in the past year and received antibiotic therapy in the previous 3 months, were bedridden and suffered from peripheral vascular disease and peptic ulcer disease (p < 0.001). Two-thirds of the MDR-PM isolates were ESBL-producers vs 4.4% of S-PM isolates (p < 0.001, OR = 47.6, 95% CI = 15.9-142.6). In-hospital crude mortality rate of patients with MDR-PM BSI was 37.7% vs 23.3% in those with S-PM BSI (p = 0.0359, OR = 2, 95% CI = 1.4-3.81). PM bacteremia in elderly and functionally-dependent patients is likely to be caused by nearly pan-resistant PM strains in the institution; 51.8% of the patients received inappropriate empiric antibiotic treatment. The crude mortality rate of patients with MDR-PM BSI was significantly higher than that of patients with S-PM BSI.

  17. Gram positive and Gram negative bacteria differ in their sensitivity to cold plasma

    Mai-Prochnow, Anne; Clauson, Maryse; Hong, Jungmi; Murphy, Anthony B.

    2016-12-01

    Cold atmospheric-pressure plasma (CAP) is a relatively new method being investigated for antimicrobial activity. However, the exact mode of action is still being explored. Here we report that CAP efficacy is directly correlated to bacterial cell wall thickness in several species. Biofilms of Gram positive Bacillus subtilis, possessing a 55.4 nm cell wall, showed the highest resistance to CAP, with less than one log10 reduction after 10 min treatment. In contrast, biofilms of Gram negative Pseudomonas aeruginosa, possessing only a 2.4 nm cell wall, were almost completely eradicated using the same treatment conditions. Planktonic cultures of Gram negative Pseudomonas libanensis also had a higher log10 reduction than Gram positive Staphylococcus epidermidis. Mixed species biofilms of P. aeruginosa and S. epidermidis showed a similar trend of Gram positive bacteria being more resistant to CAP treatment. However, when grown in co-culture, Gram negative P. aeruginosa was more resistant to CAP overall than as a mono-species biofilm. Emission spectra indicated OH and O, capable of structural cell wall bond breakage, were present in the plasma. This study indicates that cell wall thickness correlates with CAP inactivation times of bacteria, but cell membranes and biofilm matrix are also likely to play a role.

  18. DMPD: Gram-negative endotoxin: an extraordinary lipid with profound effects oneukaryotic signal transduction. [Dynamic Macrophage Pathway CSML Database

    Full Text Available 1916089 Gram-negative endotoxin: an extraordinary lipid with profound effects oneuk...ep;5(12):2652-60. (.png) (.svg) (.html) (.csml) Show Gram-negative endotoxin: an extraordinary lipid with profound effects...tive endotoxin: an extraordinary lipid with profound effects oneukaryotic signal transduction. Authors Raetz

  19. A randomized clinical trial on the effectiveness of a symbiotic product to decolonize patients harboring multidrug-resistant Gram-negative bacilli

    Mariana Correa Coelho Salomão

    Full Text Available Abstract INTRODUCTION: We aimed to evaluate the effectiveness of a symbiotic product to decolonize the intestinal tract of patients harboring multidrug-resistant (MDR Gram-negative bacilli and to prevent nosocomial infections. METHODS: This was a randomized, double blind, placebo-controlled clinical trial, conducted in a tertiary-care university hospital. All adult hospitalized patients with a positive clinical culture and a positive rectal swab for any MDR Gram-negative bacilli were potentially eligible. Exclusion criteria were pregnancy, immunosuppression, and bowel obstruction/perforation. The intervention consisted of administering a symbiotic product (Lactobacillus bulgaricus, Lactobacillus rhamnosus, and fructo-oligosaccharides twice a day for seven days via the oral/enteral route. RESULTS: Between August 1, 2012 and December 22, 2013, 116 of 275 eligible patients were allocated to treatment (n=57 and placebo (n=59. Overall, 101 patients received at least four doses of the study products and were included in the modified intention-to-treat analysis. The primary study outcome, a negative rectal swab for MDR Gram-negative bacilli after treatment, was identified in 16.7% (8/48 and 20.7% (11/53 of patients in the experimental and placebo group, respectively (p=0.60. The secondary outcome, the combined incidence of nosocomial respiratory and urinary tract infections, was 37.5% (18/48 in the experimental group versus 22.6% (12/53 in the control group (adjusted odds ratio: 1.95, 95% confidence interval: 0.69-5.50, p=0.21. Length of stay after the beginning of the intervention, incidence of adverse events, and in-hospital mortality rates were similar in both study groups. CONCLUSIONS: Under the present study conditions, symbiotic administration was not effective for decolonizing hospitalized patients harboring MDR Gram-negative bacilli.

  20. A Randomized Trial of the Amikacin Fosfomycin Inhalation System for the Adjunctive Therapy of Gram-Negative Ventilator-Associated Pneumonia: IASIS Trial.

    Kollef, Marin H; Ricard, Jean-Damien; Roux, Damien; Francois, Bruno; Ischaki, Eleni; Rozgonyi, Zsolt; Boulain, Thierry; Ivanyi, Zsolt; János, Gál; Garot, Denis; Koura, Firas; Zakynthinos, Epaminondas; Dimopoulos, George; Torres, Antonio; Danker, Wayne; Montgomery, A Bruce

    2017-06-01

    Clinical failures in ventilator-associated pneumonia (VAP) caused by gram-negative bacteria are common and associated with substantial morbidity, mortality, and resource utilization. We assessed the safety and efficacy of the amikacin fosfomycin inhalation system (AFIS) for the treatment of gram-negative bacterial VAP in a randomized double-blind, placebo-controlled, parallel group, phase 2 study between May 2013 and March 2016. We compared standard of care in each arm plus 300 mg amikacin/120 mg fosfomycin or placebo (saline), delivered by aerosol twice daily for 10 days (or to extubation if < 10 days) via the investigational eFlow Inline System (PARI GmbH). The primary efficacy end point was change from baseline in the Clinical Pulmonary Infection Score (CPIS) during the randomized course of AFIS/placebo, using the subset of patients with microbiologically proven baseline infections with gram-negative bacteria. There were 143 patients randomized: 71 to the AFIS group, and 72 to the placebo group. Comparison of CPIS change from baseline between treatment groups was not different (P = .70). The secondary hierarchical end point of no mortality and clinical cure at day 14 or earlier was also not significant (P = .68) nor was the hierarchical end point of no mortality and ventilator-free days (P = .06). The number of deaths in the AFIS group was 17 (24%) and 12 (17%) in the placebo group (P = .32). The AFIS group had significantly fewer positive tracheal cultures on days 3 and 7 than placebo. In this trial of adjunctive aerosol therapy compared with standard of care IV antibiotics in patients with gram-negative VAP, the AFIS was ineffective in improving clinical outcomes despite reducing bacterial burden. ClinicalTrials.gov; No.: NCT01969799; URL: www.clinicaltrials.gov. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  1. A Web-Based, Hospital-Wide Health Care-Associated Bloodstream Infection Surveillance and Classification System: Development and Evaluation.

    Tseng, Yi-Ju; Wu, Jung-Hsuan; Lin, Hui-Chi; Chen, Ming-Yuan; Ping, Xiao-Ou; Sun, Chun-Chuan; Shang, Rung-Ji; Sheng, Wang-Huei; Chen, Yee-Chun; Lai, Feipei; Chang, Shan-Chwen

    2015-09-21

    Surveillance of health care-associated infections is an essential component of infection prevention programs, but conventional systems are labor intensive and performance dependent. To develop an automatic surveillance and classification system for health care-associated bloodstream infection (HABSI), and to evaluate its performance by comparing it with a conventional infection control personnel (ICP)-based surveillance system. We developed a Web-based system that was integrated into the medical information system of a 2200-bed teaching hospital in Taiwan. The system automatically detects and classifies HABSIs. In this study, the number of computer-detected HABSIs correlated closely with the number of HABSIs detected by ICP by department (n=20; r=.999 Psystem performed excellently with regard to sensitivity (98.16%), specificity (99.96%), positive predictive value (95.81%), and negative predictive value (99.98%). The system enabled decreasing the delay in confirmation of HABSI cases, on average, by 29 days. This system provides reliable and objective HABSI data for quality indicators, improving the delay caused by a conventional surveillance system.

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

    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.

  3. Rationalizing the permeation of polar antibiotics into Gram-negative bacteria

    Scorciapino, Mariano Andrea; Acosta-Gutierrez, Silvia; Benkerrou, Dehbia; D’Agostino, Tommaso; Malloci, Giuliano; Samanta, Susruta; Bodrenko, Igor; Ceccarelli, Matteo

    2017-01-01

    The increasing level of antibiotic resistance in Gram-negative bacteria, together with the lack of new potential drug scaffolds in the pipeline, make the problem of infectious diseases a global challenge for modern medicine. The main reason that Gram-negative bacteria are particularly challenging is the presence of an outer cell-protecting membrane, which is not present in Gram-positive species. Such an asymmetric bilayer is a highly effective barrier for polar molecules. Several protein systems are expressed in the outer membrane to control the internal concentration of both nutrients and noxious species, in particular: (i) water-filled channels that modulate the permeation of polar molecules and ions according to concentration gradients, and (ii) efflux pumps to actively expel toxic compounds. Thus, besides expressing specific enzymes for drugs degradation, Gram-negative bacteria can also resist by modulating the influx and efflux of antibiotics, keeping the internal concentration low. However, there are no direct and robust experimental methods capable of measuring the permeability of small molecules, thus severely limiting our knowledge of the molecular mechanisms that ultimately control the permeation of antibiotics through the outer membrane. This is the innovation gap to be filled for Gram-negative bacteria. This review is focused on the permeation of small molecules through porins, considered the main path for the entry of polar antibiotics into Gram-negative bacteria. A fundamental understanding of how these proteins are able to filter small molecules is a prerequisite to design/optimize antibacterials with improved permeation. The level of sophistication of modern molecular modeling algorithms and the advances in new computer hardware has made the simulation of such complex processes possible at the molecular level. In this work we aim to share our experience and perspectives in the context of a multidisciplinary extended collaboration within the IMI

  4. Rationalizing the permeation of polar antibiotics into Gram-negative bacteria

    Scorciapino, Mariano Andrea; Acosta-Gutierrez, Silvia; Benkerrou, Dehbia; D'Agostino, Tommaso; Malloci, Giuliano; Samanta, Susruta; Bodrenko, Igor; Ceccarelli, Matteo

    2017-03-01

    The increasing level of antibiotic resistance in Gram-negative bacteria, together with the lack of new potential drug scaffolds in the pipeline, make the problem of infectious diseases a global challenge for modern medicine. The main reason that Gram-negative bacteria are particularly challenging is the presence of an outer cell-protecting membrane, which is not present in Gram-positive species. Such an asymmetric bilayer is a highly effective barrier for polar molecules. Several protein systems are expressed in the outer membrane to control the internal concentration of both nutrients and noxious species, in particular: (i) water-filled channels that modulate the permeation of polar molecules and ions according to concentration gradients, and (ii) efflux pumps to actively expel toxic compounds. Thus, besides expressing specific enzymes for drugs degradation, Gram-negative bacteria can also resist by modulating the influx and efflux of antibiotics, keeping the internal concentration low. However, there are no direct and robust experimental methods capable of measuring the permeability of small molecules, thus severely limiting our knowledge of the molecular mechanisms that ultimately control the permeation of antibiotics through the outer membrane. This is the innovation gap to be filled for Gram-negative bacteria. This review is focused on the permeation of small molecules through porins, considered the main path for the entry of polar antibiotics into Gram-negative bacteria. A fundamental understanding of how these proteins are able to filter small molecules is a prerequisite to design/optimize antibacterials with improved permeation. The level of sophistication of modern molecular modeling algorithms and the advances in new computer hardware has made the simulation of such complex processes possible at the molecular level. In this work we aim to share our experience and perspectives in the context of a multidisciplinary extended collaboration within the IMI

  5. The Influence of Efflux Pump Inhibitors on the Activity of Non-Antibiotic NSAIDS against Gram-Negative Rods.

    Agnieszka E Laudy

    Full Text Available Most patients with bacterial infections suffer from fever and various pains that require complex treatments with antibiotics, antipyretics, and analgaesics. The most common drugs used to relieve these symptoms are non-steroidal anti-inflammatory drugs (NSAIDs, which are not typically considered antibiotics. Here, we investigate the effects of NSAIDs on bacterial susceptibility to antibiotics and the modulation of bacterial efflux pumps.The activity of 12 NSAID active substances, paracetamol (acetaminophen, and eight relevant medicinal products was analyzed with or without pump inhibitors against 89 strains of Gram-negative rods by determining the MICs. Furthermore, the effects of NSAIDs on the susceptibility of clinical strains to antimicrobial agents with or without PAβN (Phe-Arg-β-naphtylamide were measured.The MICs of diclofenac, mefenamic acid, ibuprofen, and naproxen, in the presence of PAβN, were significantly (≥4-fold reduced, decreasing to 25-1600 mg/L, against the majority of the studied strains. In the case of acetylsalicylic acid only for 5 and 7 out of 12 strains of P. mirabilis and E. coli, respectively, a 4-fold increase in susceptibility in the presence of PAβN was observed. The presence of Aspirin resulted in a 4-fold increase in the MIC of ofloxacin against only two strains of E. coli among 48 tested clinical strains, which included species such as E. coli, K. pneumoniae, P. aeruginosa, and S. maltophilia. Besides, the medicinal products containing the following NSAIDs, diclofenac, mefenamic acid, ibuprofen, and naproxen, did not cause the decrease of clinical strains' susceptibility to antibiotics.The effects of PAβN on the susceptibility of bacteria to NSAIDs indicate that some NSAIDs are substrates for efflux pumps in Gram-negative rods. Morever, Aspirin probably induced efflux-mediated resistance to fluoroquinolones in a few E. coli strains.

  6. Organo-Selenium Coatings Inhibit Gram-Negative and Gram-Positive Bacterial Attachment to Ophthalmic Scleral Buckle Material.

    Tran, Phat; Arnett, Avery; Jarvis, Courtney; Mosley, Thomas; Tran, Khien; Hanes, Rob; Webster, Dan; Mitchell, Kelly; Dominguez, Leo; Hamood, Abdul; Reid, Ted W

    2017-09-01

    Biofilm formation is a problem for solid and sponge-type scleral buckles. This can lead to complications that require removal of the buckle, and result in vision loss due to related ocular morbidity, primarily infection, or recurrent retinal detachment. We investigate the ability of a covalent organo-selenium coating to inhibit biofilm formation on a scleral buckle. Sponge and solid Labtican brand scleral buckles were coated with organo-selenium coupled to a silyation reagent. Staphylococcus aureus biofilm formation was monitored by a standard colony-forming unit assay and the confocal laser scanning microscopy, while Pseudomonas aeruginosa biofilm formation was examined by scanning electron microscopy. Stability studies were done, by soaking in phosphate buffer saline (PBS) at room temperature for 2 months. Toxicity against human corneal epithelial cell was examined by growing the cells in the presence of organo-selenium-coated scleral buckles. The organo-selenium coating inhibited biofilm formation by gram-negative and gram-positive bacteria. The buckle coatings also were shown to be fully active after soaking in PBS for 2 months. The organo-selenium coatings had no effect on the viability of human corneal epithelial cells. Organo-selenium can be used to covalently coat a scleral buckle, which is stable and inhibits biofilm formation for gram-negative and gram-positive bacteria. The organo-selenium buckle coating was stable and nontoxic to cell culture. This technology provides a means to inhibit bacterial attachment to devices attached to the eye, without damage to ocular cells.

  7. In vitro activity of potential old and new drugs against multidrug-resistant gram-negatives.

    Rizek, Camila; Ferraz, Juliana Rosa; van der Heijden, Inneke Marie; Giudice, Mauro; Mostachio, Anna Karina; Paez, Jorge; Carrilho, Claudia; Levin, Anna Sara; Costa, Silvia F

    2015-02-01

    The aim of this study was to evaluate the in vitro susceptibility of MDR gram-negatives bacteria to old drugs such as polymyxin B, minocycline and fosfomycin and new drugs such as tigecycline. One hundred and fifty-three isolates from 4 Brazilian hospitals were evaluated. Forty-seven Acinetobacter baumannii resistant to carbapenens harboring adeB, blaOxA23, blaOxA51, blaOxA143 and blaIMP genes, 48 Stenotrophomonas maltophilia including isolates resistant to levofloxacin and/or trimethoprim-sulfamethoxazole harboring sul-1, sul-2 and qnrMR and 8 Serratia marcescens and 50 Klebsiella pneumoniae resistant to carbapenens harboring blaKPC-2 were tested to determine their minimum inhibitory concentrations (MICs) by microdilution to the following drugs: minocycline, ampicillin-sulbactam, tigecycline, and polymyxin B and by agar dilution to fosfomycin according with breakpoint criteria of CLSI and EUCAST (fosfomycin). In addition, EUCAST fosfomycin breakpoint for Pseudomonas spp. was applied for Acinetobacter spp and S. maltophilia, the FDA criteria for tigecycline was used for Acinetobacter spp and S. maltophilia and the Pseudomonas spp polymyxin B CLSI criterion was used for S. maltophilia. Tigecycline showed the best in vitro activity against the MDR gram-negative evaluated, followed by polymyxin B and fosfomycin. Polymyxin B resistance among K. pneumoniae was detected in 6 isolates, using the breakpoint of MIC > 8 ug/mL. Two of these isolates were resistant to tigecycline. Minocycline was tested only against S. maltophilia and A. baumannii and showed excellent activity against both. Fosfomycin seems to not be an option to treat infections due to the A. baumannii and S. maltophilia isolates according with EUCAST breakpoint, on the other hand, showed excellent activity against S. marcescens and K. pneumoniae. Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  8. Overexpression of the endothelial protein C receptor is detrimental during pneumonia-derived gram-negative sepsis (Melioidosis.

    Liesbeth M Kager

    Full Text Available The endothelial protein C receptor (EPCR enhances anticoagulation by accelerating activation of protein C to activated protein C (APC and mediates anti-inflammatory effects by facilitating APC-mediated signaling via protease activated receptor-1. We studied the role of EPCR in the host response during pneumonia-derived sepsis instigated by Burkholderia (B. pseudomallei, the causative agent of melioidosis, a common form of community-acquired Gram-negative (pneumosepsis in South-East Asia.Soluble EPCR was measured in plasma of patients with septic culture-proven melioidosis and healthy controls. Experimental melioidosis was induced by intranasal inoculation of B. pseudomallei in wild-type (WT mice and mice with either EPCR-overexpression (Tie2-EPCR or EPCR-deficiency (EPCR(-/-. Mice were sacrificed after 24, 48 or 72 hours. Organs and plasma were harvested to measure colony forming units, cellular influxes, cytokine levels and coagulation parameters. Plasma EPCR-levels were higher in melioidosis patients than in healthy controls and associated with an increased mortality. Tie2-EPCR mice demonstrated enhanced bacterial growth and dissemination to distant organs during experimental melioidosis, accompanied by increased lung damage, neutrophil influx and cytokine production, and attenuated coagulation activation. EPCR(-/- mice had an unremarkable response to B. pseudomallei infection as compared to WT mice, except for a difference in coagulation activation in plasma.Increased EPCR-levels correlate with accelerated mortality in patients with melioidosis. In mice, transgenic overexpression of EPCR aggravates outcome during Gram-negative pneumonia-derived sepsis caused by B. pseudomallei, while endogenous EPCR does not impact on the host response. These results add to a better understanding of the regulation of coagulation during severe (pneumosepsis.

  9. Use of organs from donors with bloodstream infection, pneumonia, and influenza: Results of a survey of infectious diseases practitioners.

    Mehta, Sanjay R; Logan, Cathy; Kotton, Camille N; Kumar, Deepali; Aslam, Saima

    2017-02-01

    Potential organ donors may be admitted with an infection to an intensive care unit, or contract a nosocomial infection during their stay, increasing the risk of potential transmission to the recipient. Because of a lack of practice guidelines and large-scale data on this topic, we undertook a survey to assess the willingness of transplant infectious diseases (ID) physicians to accept such organs. We performed a 10-question survey of ID providers from the American Society of Transplantation Infectious Disease Community of Practice to determine the scope of practice regarding acceptance of organs from donors with bloodstream infection, pneumonia, and influenza prior to organ procurement, as well as management of such infections following transplantation. Among 60 respondents to our survey, a majority indicated that organs would be accepted from donors bacteremic with streptococci (76%) or Enterobacteriaceae (73%) without evidence of drug resistance. Acceptance rates varied based on infecting organism, type of organ, and center size. Ten percent of respondents would accept an organ from a donor bacteremic with a carbapenem-resistant organism. Over 90% of respondents would accept an organ other than a lung from a donor with influenza on treatment, compared with 52% that would accept a lung in the same setting. This study is the first to our knowledge to survey transplant ID providers regarding acceptance of organs based on specific infections in the donor. These decisions are often based on limited published data and experience. Better characterization of the outcomes from donors with specific types of infection could lead to liberalization of organ acceptance practices across centers. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Leadership line care rounds: Application of the engage, educate, execute, and evaluate improvement model for the prevention of central line-associated bloodstream infections in children with cancer.

    Owings, Angie; Graves, JoBeth; Johnson, Sherry; Gilliam, Craig; Gipson, Mike; Hakim, Hana

    2018-02-01

    To prevent central line-associated bloodstream infections (CLABSIs), leadership line care rounds (LLCRs) used the engage, educate, execute, and evaluate improvement model to audit compliance, identify barriers and opportunities, empower patients and families, and engage leadership. Findings of excellence and improvement opportunities were communicated to unit staff and managers. LLCRs contributed to compliance with CLABSI prevention interventions. Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  11. Antiseptic barrier cap effective in reducing central line-associated bloodstream infections: A systematic review and meta-analysis.

    Voor In 't Holt, Anne F; Helder, Onno K; Vos, Margreet C; Schafthuizen, Laura; Sülz, Sandra; van den Hoogen, Agnes; Ista, Erwin

    2017-04-01

    Microorganisms can intraluminally access a central venous catheter via the catheter hub. The catheter hub should be appropriately disinfected to prevent central line-associated bloodstream infections (CLABSIs). However, compliance with the time-consuming manual disinfection process is low. An alternative is the use of an antiseptic barrier cap, which cleans the catheter hub by continuous passive disinfection. To compare the effects of antiseptic barrier cap use and manual disinfection on the incidence of CLABSIs. Systematic review and meta-analysis. We systematically searched Embase, Medline Ovid, Web-of-science, CINAHL EBSCO, Cochrane Library, PubMed Publisher and Google Scholar until May 10, 2016. The primary outcome, reduction in CLABSIs per 1000 catheter-days, expressed as an incidence rate ratio (IRR), was analyzed with a random effects meta-analysis. Studies were included if 1) conducted in a hospital setting, 2) used antiseptic barrier caps on hubs of central lines with access to the bloodstream and 3) reported the number of CLABSIs per 1000 catheter-days when using the barrier cap and when using manual disinfection. A total of 1537 articles were identified as potentially relevant and after exclusion of duplicates, 953 articles were screened based on title and abstract; 18 articles were read full text. Eventually, nine studies were included in the systematic review, and seven of these nine in the random effects meta-analysis. The pooled IRR showed that use of the antiseptic barrier cap was effective in reducing CLABSIs (IRR=0.59, 95% CI=0.45-0.77, Pantiseptic barrier cap is associated with a lower incidence CLABSIs and is an intervention worth adding to central-line maintenance bundles. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Regional variations in fluoroquinolone non-susceptibility among Escherichia coli bloodstream infections within the Veterans Healthcare Administration

    Daniel J. Livorsi

    2016-10-01

    Full Text Available Abstract Objectives We sought to define regional variations in fluoroquinolone non-susceptibility (FQ-NS among bloodstream isolates of Escherichia coli across the Veterans Health Administration (VHA in the United States. Methods We analyzed a retrospective cohort of patients managed at 136 VHA hospitals who had a blood culture positive for E.coli between 2003 and 2013. Hospitals were classified based on US Census Divisions, and regional variations in FQ-NS were analyzed. Results Twenty-four thousand five hundred twenty-three unique E.coli bloodstream infections (BSIs were identified between 2003 and 2013. 53.9 % of these were community-acquired, 30.7 % were healthcare-associated, and 15.4 % were hospital-onset BSIs. The proportion of E.coli BSIs with FQ-NS significantly varied across US Census Divisions (p < 0.001. During 2003–2013, the proportion of E.coli BSIs with FQ-NS was highest in the West South-Central Division (32.7 % and lowest in the Mountain Division (20.0 %. Multivariable analysis showed that there were universal secular trends towards higher FQ-NS rates (p < 0.001 with significant variability of slopes across US Census Divisions (p < 0.001. Conclusion There has been a universal increase in FQ-NS among E.coli BSIs within VHA, but the rate of increase has significantly varied across Census Divisions. The reasons for this variability are unclear. These findings reinforce the importance of using local data to develop and update local antibiograms and antibiotic-prescribing guidelines.

  13. Implementation of central line-associated bloodstream infection prevention bundles in a surgical intensive care unit using peer tutoring.

    Park, Sang-Won; Ko, Suhui; An, Hye-Sun; Bang, Ji Hwan; Chung, Woo-Young

    2017-01-01

    Central line-associated bloodstream infections (CLABSIs) can be prevented through well-coordinated, multifaceted programs. However, implementation of CLABSI prevention programs requires individualized strategies for different institutional situations, and the best strategy in resource-limited settings is uncertain. Peer tutoring may be an efficient and effective method that is applicable in such settings. A prospective intervention was performed to reduce CLABSIs in a surgical intensive care unit (SICU) at a tertiary hospital. The core interventions consisted of implementation of insertion and maintenance bundles for CLABSI prevention. The overall interventions were guided and coordinated by active educational programs using peer tutoring. The CLABSI rates were compared for 9 months pre-intervention, 6 months during the intervention and 9 months post-intervention. The CLABSI rate was further observed for three years after the intervention. The rate of CLABSIs per 1000 catheter-days decreased from 6.9 infections in the pre-intervention period to 2.4 and 1.8 in the intervention (6 m; P  = 0.102) and post-intervention (9 m; P  = 0.036) periods, respectively. A regression model showed a significantly decreasing trend in the infection rate from the pre-intervention period ( P  tutoring in a resource-limited setting was useful and effectively reduced CLABSIs. However, maintaining the reduced CLABSI rate will require further strategies.

  14. Dose-Dependent Antimicrobial Activity of Silver Nanoparticles on Polycaprolactone Fibers against Gram-Positive and Gram-Negative Bacteria

    Erick Pazos-Ortiz

    2017-01-01

    Full Text Available The adhesion ability and adaptability of bacteria, coupled with constant use of the same bactericides, have made the increase in the diversity of treatments against infections necessary. Nanotechnology has played an important role in the search for new ways to prevent and treat infections, including the use of metallic nanoparticles with antibacterial properties. In this study, we worked on the design of a composite of silver nanoparticles (AgNPS embedded in poly-epsilon-caprolactone nanofibers and evaluated its antimicrobial properties against various Gram-positive and Gram-negative microorganisms associated with drug-resistant infections. Polycaprolactone-silver composites (PCL-AgNPs were prepared in two steps. The first step consisted in the reduction in situ of Ag+ ions using N,N-dimethylformamide (DMF in tetrahydrofuran (THF solution, and the second step involved the simple addition of polycaprolactone before electrospinning process. Antibacterial activity of PCL-AgNPs nanofibers against E. coli, S. mutans, K. pneumoniae, S. aureus, P. aeruginosa, and B. subtilis was evaluated. Results showed sensibility of E. coli, K. pneumoniae, S. aureus, and P. aeruginosa, but not for B. subtilis and S. mutans. This antimicrobial activity of PCL-AgNPs showed significant positive correlations associated with the dose-dependent effect. The antibacterial property of the PCL/Ag nanofibers might have high potential medical applications in drug-resistant infections.

  15. Detection and Antibiotic Susceptibility Pattern of Biofilm Producing Gram Positive and Gram Negative Bacteria Isolated From a Tertiary Care Hospital of Pakistan

    Iqbal, M.

    2011-01-01

    Full Text Available Microorganisms adhere to non-living material or living tissue, and form biofilms made up of extracellular polymers/slime. Biofilm-associated microorganisms behave differently from free-floating bacteria with respect to growth rates and ability to resist antimicrobial treatments and therefore pose a public health problem. The objective of this study is to detect the prevalence of biofilm producers among Gram positive and Gram negative bacteria isolated from clinical specimens, and to study their antimicrobial susceptibility pattern. The study was carried out from October 2009 to March 2010, at the Department of Microbiology, Army Medical College/ National University of Sciences and Technology (NUST, Rawalpindi, Pakistan. Clinical specimens were received from various wards of a tertiary care hospital. These were dealt by standard microbiological procedures. Gram positive and Gram negative bacteria isolated were subjected to biofilm detection by congo red agar method (CRA. Antimicrobial susceptibility testing of those isolates, which showed positive results (slime production, was done according to the Kirby-Bauer disc diffusion technique. A total of 150 isolates were tested for the production of biofilm/slime. Among them, 81 isolates showed positive results. From these 81, 51 were Gram positive and 30 were Gram negative. All the 81(54% slime producers showed reduced susceptibility to majority of antibiotics. Bacterial biofilms are an important virulence factor associated with chronic nosocomial infection. Detection of biofilm forming organisms can help in appropriate antibiotic choice.

  16. Macrophage migration inhibitory factor deficiency is associated with impaired killing of gram-negative bacteria by macrophages and increased susceptibility to Klebsiella pneumoniae sepsis.

    Roger, Thierry; Delaloye, Julie; Chanson, Anne-Laure; Giddey, Marlyse; Le Roy, Didier; Calandra, Thierry

    2013-01-15

    The cytokine macrophage migration inhibitory factor (MIF) is an important component of the early proinflammatory response of the innate immune system. However, the antimicrobial defense mechanisms mediated by MIF remain fairly mysterious. In the present study, we examined whether MIF controls bacterial uptake and clearance by professional phagocytes, using wild-type and MIF-deficient macrophages. MIF deficiency did not affect bacterial phagocytosis, but it strongly impaired the killing of gram-negative bacteria by macrophages and host defenses against gram-negative bacterial infection, as shown by increased mortality in a Klebsiella pneumonia model. Consistent with MIF's regulatory role of Toll-like 4 expression in macrophages, MIF-deficient cells stimulated with lipopolysaccharide or Escherichia coli exhibited reduced nuclear factor κB activity and tumor necrosis factor (TNF) production. Addition of recombinant MIF or TNF corrected the killing defect of MIF-deficient macrophages. Together, these data show that MIF is a key mediator of host responses against gram-negative bacteria, acting in part via a modulation of bacterial killing by macrophages.

  17. Gram-positive and gram-negative bacteria induce different patterns of cytokine production in human mononuclear cells irrespective of taxonomic relatedness.

    Skovbjerg, Susann; Martner, Anna; Hynsjö, Lars; Hessle, Christina; Olsen, Ingar; Dewhirst, Floyd E; Tham, Wilhelm; Wold, Agnes E

    2010-01-01

    Upon bacterial stimulation, tissue macrophages produce a variety of cytokines that orchestrate the immune response that clears the infection. We have shown that Gram-positives induce higher levels of interleukin-12 (IL-12), interferon-gamma (IFN-gamma), and tumor necrosis factor (TNF) from human peripheral blood mononuclear cells (PBMCs) than do Gram-negatives, which instead induce more of IL-6, IL-8, and IL-10. Here, we study whether these patterns follows or crosses taxonomic borders. PBMCs from blood donors were incubated with UV-inactivated bacteria representing 37 species from five phyla. IL-12, TNF, IL-1beta, IL-6, IL-8, and IL-10 were measured in the supernatants after 24 h and IFN-gamma after 5 days. Irrespective of phylogenetic position, Gram-positive bacteria induced much more IL-12 (nine times more on average) and IFN-gamma (seven times), more TNF (three times), and slightly more IL-1beta (1.5 times) than did Gram-negatives, which instead induced more IL-6 (1.5 times), IL-8 (1.9 times), and IL-10 (3.3 times) than did Gram-positives. A notable exception was the Gram-positive Listeria monocytogenes, which induced very little IL-12, IFN-gamma, and TNF. The results confirm the fundamental difference in innate immune responses to Gram-positive and Gram-negative bacteria, which crosses taxonomic borders and probably reflects differences in cell wall structure.

  18. [Identification of anaerobic gram-negative bacilli isolated from various clinical specimens and determination of antibiotic resistance profiles with E-test methods].

    Demir, Cengiz; Keşli, Recep

    2018-01-01

    The aim of this study was to identify gram-negative anaerobic bacilli isolated from various clinical specimens that were obtained from patients with suspected anaerobic infections and to determine the antibiotic resistance profiles by using the antibiotic concentration gradient method. The study was performed in Afyon Kocatepe University Ahmet Necdet Sezer Research and Practice Hospital, Medical Microbiology Laboratory between 1 November 2014 and 30 October 2015. Two hundred and seventyeight clinical specimens accepted for anaerobic culture were enrolled in the study. All the samples were cultivated anaerobically by using Schaedler agar with 5% defibrinated sheep blood and Schaedler broth. The isolated anaerobic gram-negative bacilli were identified by using both the conventional methods and automated identification system (VITEK 2, bioMerieux, France). Antibiotic susceptibility tests were performed with antibiotic concentration gradient method (E-test, bioMerieux, France); against penicillin G, clindamycin, cefoxitin, metronidazole, moxifloxacin, imipenem, meropenem, ertapenem and doripenem for each isolate. Of the 28 isolated anaerobic gram-negative bacilli; 14 were identified as Bacteroides fragilis group, 9 were Prevotella spp., and 5 were Fusobacterium spp. The highest resistance rate was found against penicillin (78.5%) and resistance rates against clindamycin and cefoxitin were found as 17.8% and 21.4%, respectively. No resistance was found against metronidazole, moxifloxacin, imipenem, meropenem, ertapenem and doripenem. As a result, isolation and identification of anaerobic bacteria are difficult, time-consuming and more expensive when compared with the cost of aerobic culture. The rate of anaerobic bacteria isolation may be increased by obtaining the appropriate clinical specimen and appropriate transportation of these specimens. We believe that the data obtained from the study in our center may offer benefits for the follow up and treatment of infections

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

    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. Mid-infrared spectroscopic assessment of nanotoxicity in gram-negative vs. gram-positive bacteria.

    Heys, Kelly A; Riding, Matthew J; Strong, Rebecca J; Shore, Richard F; Pereira, M Glória; Jones, Kevin C; Semple, Kirk T; Martin, Francis L

    2014-03-07

    Nanoparticles appear to induce toxic effects through a variety of mechanisms including generation of reactive oxygen species (ROS), physical contact with the cell membrane and indirect catalysis due to remnants from manufacture. The development and subsequent increasing usage of nanomaterials has highlighted a growing need to characterize and assess the toxicity of nanoparticles, particularly those that may have detrimental health effects such as carbon-based nanomaterials (CBNs). Due to interactions of nanoparticles with some reagents, many traditional toxicity tests are unsuitable for use with CBNs. Infrared (IR) spectroscopy is a non-destructive, high throughput technique, which is unhindered by such problems. We explored the application of IR spectroscopy to investigate the effects of CBNs on Gram-negative (Pseudomonas fluorescens) and Gram-positive (Mycobacterium vanbaalenii PYR-1) bacteria. Two types of IR spectroscopy were compared: attenuated total reflection Fourier-transform infrared (ATR-FTIR) and synchrotron radiation-based FTIR (SR-FTIR) spectroscopy. This showed that Gram-positive and Gram-negative bacteria exhibit differing alterations when exposed to CBNs. Gram-positive bacteria appear more resistant to these agents and this may be due to the protection afforded by their more sturdy cell wall. Markers of exposure also vary according to Gram status; Amide II was consistently altered in Gram-negative bacteria and carbohydrate altered in Gram-positive bacteria. ATR-FTIR and SR-FTIR spectroscopy could both be applied to extract biochemical alterations induced by each CBN that were consistent across the two bacterial species; these may represent potential biomarkers of nanoparticle-induced alterations. Vibrational spectroscopy approaches may provide a novel means of fingerprinting the effects of CBNs in target cells.

  1. Low antibiotic resistance among anaerobic Gram-negative bacteria in periodontitis 5 years following metronidazole therapy.

    Dahlen, G; Preus, H R

    2017-02-01

    The objective of this study was to assess antibiotic susceptibility among predominant Gram-negative anaerobic bacteria isolated from periodontitis patients who 5 years prior had been subject to mechanical therapy with or without adjunctive metronidazole. One pooled sample was taken from the 5 deepest sites of each of 161 patients that completed the 5 year follow-up after therapy. The samples were analyzed by culture. A total number of 85 anaerobic strains were isolated from the predominant subgingival flora of 65/161 patient samples, identified, and tested for antibiotic susceptibility by MIC determination. E-tests against metronidazole, penicillin, amoxicillin, amoxicillin + clavulanic acid and clindamycin were employed. The 73/85 strains were Gram-negative rods (21 Porphyromonas spp., 22 Prevotella/Bacteroides spp., 23 Fusobacterium/Filifactor spp., 3 Campylobacter spp. and 4 Tannerella forsythia). These were all isolated from the treated patients irrespective of therapy procedures (+/-metronidazole) 5 years prior. Three strains (Bifidobacterium spp., Propionibacterium propionicum, Parvimonas micra) showed MIC values for metronidazole over the European Committee on Antimicrobial Susceptibility Testing break point of >4 μg/mL. All Porphyromonas and Tannerella strains were highly susceptible. Metronidazole resistant Gram-negative strains were not found, while a few showed resistance against beta-lactam antibiotics. In this population of 161 patients who had been subject to mechanical periodontal therapy with or without adjunct metronidazole 5 years prior, no cultivable antibiotic resistant anaerobes were found in the predominant subgingival microbiota. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Cefepime restriction improves gram-negative overall resistance patterns in neonatal intensive care unit

    Orlei Ribeiro de Araujo

    Full Text Available Antibiotic restriction can be useful in maintaining bacterial susceptibility. The objective of this study was verify if restriction of cefepime, the most frequently used cephalosporin in our neonatal intensive care unit (NICU, would ameliorate broad-spectrum susceptibility of Gram-negative isolates. Nine hundred and ninety-five premature and term newborns were divided into 3 cohorts, according to the prevalence of cefepime use in the unit: Group 1 (n=396 comprised patients admitted from January 2002 to December 2003, period in which cefepime was the most used broad-spectrum antibiotic. Patients in Group 2 (n=349 were admitted when piperacillin/tazobactam replaced cefepime (January to December 2004 and in Group 3 (n=250 when cefepime was reintroduced (January to September 2005. Meropenem was the alternative third-line antibiotic for all groups. Multiresistance was defined as resistance to 2 or more unrelated antibiotics, including necessarily a third or fourth generation cephalosporin, piperacillin/tazobactam or meropenem. Statistics involved Kruskal-Wallis, Mann-Whitney and logrank tests, Kaplan-Meier analysis. Groups were comparable in length of stay, time of mechanical ventilation, gestational age and birth weight. Ninety-eight Gram-negative isolates were analyzed. Patients were more likely to remain free of multiresistant isolates by Kaplan-Meier analysis in Group 2 when compared to Group 1 (p=0.017 and Group 3 (p=0.003. There was also a significant difference in meropenem resistance rates. Cefepime has a greater propensity to select multiresistant Gram-negative pathogens than piperacillin/tazobactam and should not be used extensively in neonatal intensive care.

  3. In Vitro Antibacterial Activity of Several Plant Extracts and Oils against Some Gram-Negative Bacteria

    Ayman Al-Mariri

    2014-01-01

    Full Text Available Background: Medicinal plants are considered new resources for producing agents that could act as alternatives to antibiotics in the treatment of antibiotic-resistant bacteria. The aim of this study was to evaluate the antibacterial activity of 28 plant extracts and oils against four Gram-negative bacterial species. Methods: Experimental, in vitro, evaluation of the activities of 28 plant extracts and oils as well as some antibiotics against E. coli O157:H7, Yersinia enterocolitica O9, Proteus spp., and Klebsiella pneumoniae was performed. The activity against 15 isolates of each bacterium was determined by disc diffusion method at a concentration of 5%. Microdilution susceptibility assay was used in order to determine the minimal inhibitory concentrations (MICs of the plant extracts, oils, and antibiotics. Results: Among the evaluated herbs, only Origanum syriacum L., Thymus syriacus Boiss., Syzygium aromaticum L., Juniperus foetidissima Wild, Allium sativum L., Myristica fragrans Houtt, and Cinnamomum zeylanicum L. essential oils and Laurus nobilis L. plant extract showed anti-bacterial activity. The MIC50 values of these products against the Gram-negative organisms varied from 1.5 (Proteus spp. and K. pneumoniae( and 6.25 µl/ml (Yersinia enterocolitica O9 to 12.5 µl/ml (E. coli O:157. Conclusion: Among the studied essential oils, O. syriacum L., T. syriacus Boiss., C. zeylanicum L., and S. aromaticum L. essential oils were the most effective. Moreover, Cephalosporin and Ciprofloxacin were the most effective antibiotics against almost all the studied bacteria. Therefore, O. syriacum L., T. syriacus Boiss., C. zeylanicum L., and S. aromaticum L. could act as bactericidal agents against Gram-negative bacteria.

  4. The Causes of Post-Operative Meningitis: The Comparison Of Gram-Negative and Gram-Positive Pathogens.

    Kurtaran, Behice; Kuscu, Ferit; Ulu, Aslihan; Inal, Ayse Seza; Komur, Suheyla; Kibar, Filiz; Cetinalp, Nuri Eralp; Ozsoy, Kerem Mazhar; Arslan, Yusuf Kemal; Aksu, Hasan Salih; Tasova, Yesim

    2017-06-20

    In this study, we aim to determine the microbiological etiology in critically ill neurosurgical patients with nosocomial meningitis (NM) and show the impact of Gram-negative rods and differences of patient's characteristics, clinical and prognostic measures between Gram-negative and Gram-positive meningitis. In this prospective, one center study we reviewed all adult patients hospitalized during a 12-year period and identified pathogens isolated from post-neurosurgical cases of NM. Demographic, clinical, and treatment characteristics were noted from the medical records. Of the 134 bacterial NM patients, 78 were male and 56 were female, with a mean age of 46±15.9 and median age of 50 (18-80) years. 141 strains isolated; 82 (58.2%) were Gram negative, 59 (41.8%) were Gram positive. Most common isolated microorganism was Acinetobacter baumannii (%34.8). In comparison of mortality data shows that the patients who have meningitis with Gram-negative pathogens have higher mortality than with Gram positives (p=0.034). The duration between surgery and meningitis was shorter in Gram negative meningitis cases compared to others (p=0.045) but the duration between the diagnosis and death was shorter in Gram-positive meningitis cases compared to Gram negatives (p= 0.017). CSF protein and lactate level were higher and glucose level was lower in cases of NM with Gram negatives (p value were respectively, 0.022, 0.039 and 0.049). As conclusions; in NM, Gram-negative pathogens were seen more frequently; A.baumanni was the predominant pathogen; and NM caused by Gram negatives had worse clinical and laboratory characteristic and prognostic outcome than Gram positives.

  5. Studies on tridecaptin B(1), a lipopeptide with activity against multidrug resistant Gram-negative bacteria.

    Cochrane, Stephen A; Lohans, Christopher T; van Belkum, Marco J; Bels, Manon A; Vederas, John C

    2015-06-07

    Previously other groups had reported that Paenibacillus polymyxa NRRL B-30507 produces SRCAM 37, a type IIA bacteriocin with antimicrobial activity against Campylobacter jejuni. Genome sequencing and isolation of antimicrobial compounds from this P. polymyxa strain show that the antimicrobial activity is due to polymyxins and tridecaptin B1. The complete structural assignment, synthesis, and antimicrobial profile of tridecaptin B1 is reported, as well as the putative gene cluster responsible for its biosynthesis. This peptide displays strong activity against multidrug resistant Gram-negative bacteria, a finding that is timely to the current problem of antibiotic resistance.

  6. The Changing Role of the Clinical Microbiology Laboratory in Defining Resistance in Gram-negatives.

    Endimiani, Andrea; Jacobs, Michael R

    2016-06-01

    The evolution of resistance in Gram-negatives has challenged the clinical microbiology laboratory to implement new methods for their detection. Multidrug-resistant strains present major challenges to conventional and new detection methods. More rapid pathogen identification and antimicrobial susceptibility testing have been developed for use directly on specimens, including fluorescence in situ hybridization tests, automated polymerase chain reaction systems, microarrays, mass spectroscopy, next-generation sequencing, and microfluidics. Review of these methods shows the advances that have been made in rapid detection of resistance in cultures, but limited progress in direct detection from specimens. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. O-antigen protects gram-negative bacteria from histone killing.

    Catherine Chaput

    Full Text Available Beyond their traditional role of wrapping DNA, histones display antibacterial activity to Gram-negative and -positive bacteria. To identify bacterial components that allow survival to a histone challenge, we selected resistant bacteria from homologous Escherichia coli libraries that harbor plasmids carrying pieces of the chromosome in different sizes. We identified genes required for exopolysaccharide production and for the synthesis of the polysaccharide domain of the lipopolysaccharide, called O-antigen. Indeed, O-antigen and exopolysaccharide conferred further resistance to histones. Notably, O-antigen also conferred resistance to histones in the pathogens Shigella flexneri and Klebsiella pneumoniae.

  8. Surveillance of bloodstream infections in pediatric cancer centers – what have we learned and how do we move on?

    Simon, Arne

    2016-05-01

    Full Text Available Pediatric patients receiving conventional chemotherapy for malignant disease face an increased risk of bloodstream infection (BSI. Since BSI may represent an acute life-threatening event in patients with profound immunosuppression, and show further negative impact on quality of life and anticancer treatment, the prevention of BSI is of paramount importance to improve and guarantee patients’ safety during intensive treatment. The great majority of all pediatric cancer patients (about 85% have a long-term central venous access catheter in use (type Broviac or Port; CVAD. Referring to the current surveillance definitions a significant proportion of all BSI in pediatric patients with febrile neutropenia is categorized as CVAD- BSI. This state of the art review summarizes the epidemiology and the distinct pathogen profile of BSI in pediatric cancer patients from the perspective of infection surveillance. Problems in executing the current surveillance definition in this patient population are discussed and a new concept for the surveillance of BSI in pediatric cancer patients is outlined.

  9. Surveillance of bloodstream infections in pediatric cancer centers – what have we learned and how do we move on?

    Simon, Arne; Furtwängler, Rhoikos; Graf, Norbert; Laws, Hans Jürgen; Voigt, Sebastian; Piening, Brar; Geffers, Christine; Agyeman, Philipp; Ammann, Roland A.

    2016-01-01

    Pediatric patients receiving conventional chemotherapy for malignant disease face an increased risk of bloodstream infection (BSI). Since BSI may represent an acute life-threatening event in patients with profound immunosuppression, and show further negative impact on quality of life and anticancer treatment, the prevention of BSI is of paramount importance to improve and guarantee patients’ safety during intensive treatment. The great majority of all pediatric cancer patients (about 85%) have a long-term central venous access catheter in use (type Broviac or Port; CVAD). Referring to the current surveillance definitions a significant proportion of all BSI in pediatric patients with febrile neutropenia is categorized as CVAD-associated BSI. This state of the art review summarizes the epidemiology and the distinct pathogen profile of BSI in pediatric cancer patients from the perspective of infection surveillance. Problems in executing the current surveillance definition in this patient population are discussed and a new concept for the surveillance of BSI in pediatric cancer patients is outlined. PMID:27274442

  10. Nanomechanical sensor applied to blood culture pellets: a fast approach to determine the antibiotic susceptibility against agents of bloodstream infections.

    Stupar, P; Opota, O; Longo, G; Prod'hom, G; Dietler, G; Greub, G; Kasas, S

    2017-06-01

    The management of bloodstream infection, a life-threatening disease, largely relies on early detection of infecting microorganisms and accurate determination of their antibiotic susceptibility to reduce both mortality and morbidity. Recently we developed a new technique based on atomic force microscopy capable of detecting movements of biologic samples at the nanoscale. Such sensor is able to monitor the response of bacteria to antibiotic's pressure, allowing a fast and versatile susceptibility test. Furthermore, rapid preparation of a bacterial pellet from a positive blood culture can improve downstream characterization of the recovered pathogen as a result of the increased bacterial concentration obtained. Using artificially inoculated blood cultures, we combined these two innovative procedures and validated them in double-blind experiments to determine the susceptibility and resistance of Escherichia coli strains (ATCC 25933 as susceptible and a characterized clinical isolate as resistant strain) towards a selection of antibiotics commonly used in clinical settings. On the basis of the variance of the sensor movements, we were able to positively discriminate the resistant from the susceptible E. coli strains in 16 of 17 blindly investigated cases. Furthermore, we defined a variance change threshold of 60% that discriminates susceptible from resistant strains. By combining the nanomotion sensor with the rapid preparation method of blood culture pellets, we obtained an innovative, rapid and relatively accurate method for antibiotic susceptibility test directly from positive blood culture bottles, without the need for bacterial subculture. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Rapid and reliable MALDI-TOF mass spectrometry identification of Candida non-albicans isolates from bloodstream infections.

    Pulcrano, Giovanna; Iula, Dora Vita; Vollaro, Antonio; Tucci, Alessandra; Cerullo, Monica; Esposito, Matilde; Rossano, Fabio; Catania, Maria Rosaria

    2013-09-01

    Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) fingerprinting has recently become an effective instrument for rapid microbiological diagnostics and in particular for identification of micro-organisms directly in a positive blood culture. The aim of the study was to evaluate a collection of 82 stored yeast isolates from bloodstream infection, by MALDI-TOF MS; 21 isolates were identified also directly from positive blood cultures and in the presence of other co-infecting micro-organisms. Of the 82 isolates grown on plates, 64 (76%) were correctly identified by the Vitek II system and 82 (100%) by MALDI-TOF MS; when the two methods gave different results, the isolate was identified by PCR. MALDI-TOF MS was unreliable in identifying two isolates (Candida glabrata and Candida parapsilosis) directly from blood culture; however, direct analysis from positive blood culture samples was fast and effective for the identification of yeast, which is of great importance for early and adequate treatment. © 2013. Published by Elsevier B.V. All rights reserved.

  12. High resistance rate against 15 different antibiotics in aerobic gram-negative bacteria isolates of cardiology intensive care unit patients

    Küçükates E

    2002-01-01

    Full Text Available Aerobic gram negative bacteria were isolated and examined microbiologically from various clinical samples of 602 patients hospitalized between January 1997 and December 2000 in surgical and coronary intensive care units (ICUs. A total of 827 isolates were obtained from 602 patients. The majority of microorganisms were isolated from the respiratory tract (50.3% and blood (39.9%. Pseudomonas spp. were the most frequently isolated gram negative species (32.7%, followed by Acinetobacter spp. (24.0% and Klebsiella pneumoniae (19.4%. High resistance rates to all antibiotics studied were observed. Imipenem and meropenem were the most effective antibiotics against gram negatives.

  13. Procalcitonin as a diagnostic biomarker for septic shock and bloodstream infection in burn patients from the Formosa Fun Coast dust explosion

    Rui-Xin Wu

    2017-12-01

    Full Text Available Background/Purpose: Infection is the most common cause of death following burn injury. The study was conducted to compare the diagnostic value of serum procalcitonin (PCT with the other current benchmarks as early predictors of septic shock and bloodstream infection in burn patients. Methods: We included 24 patients admitted to the Burn Unit of a medical center from June 2015 to December 2015 from the Formosa Fun Coast dust explosion. We categorized all patients at initial admission into either sepsis or septic shock groups. Laboratory tests including the worst PCT and C-reactive protein (CRP levels, platelet (PLT, and white blood cell (WBC count were performed at <48 h after admission. Patients were also classified in two groups with subsequent bacteremia and non-bacteremia groups during hospitalization. Results: Significantly higher PCT levels were observed among participants with septic shock compared to those with sepsis (47.19 vs. 1.18 ng/mL, respectively; p < 0.001. Patients with bacteremia had significantly elevated PCT levels compared to patients without bacteremia (29.54 versus 1.81 ng/mL, respectively, p < 0.05. No significant differences were found in CRP levels, PLT, and WBC count between the two groups. PCT levels showed reasonable discriminative power (cut-off: 5.12 ng/mL; p = 0.01 in predicting of bloodstream infection in burn patients and the area under receiver operating curves was 0.92. Conclusions: PCT levels can be helpful in determining the septic shock and bloodstream infection in burn patients but CRP levels, PLT, and WBC count were of little diagnostic value. Keywords: Procalcitonin, Septic shock, Bloodstream infection, Burn patient, Formosa fun coast dust explosion

  14. A Prospective, Holistic, Multicenter Approach to Tracking and Understanding Bloodstream Infections in Pediatric Hematology-Oncology Patients.

    Gaur, Aditya H; Bundy, David G; Werner, Eric J; Hord, Jeffrey D; Miller, Marlene R; Tang, Li; Lawlor, John P; Billett, Amy L

    2017-06-01

    OBJECTIVE To assess the burden of bloodstream infections (BSIs) among pediatric hematology-oncology (PHO) inpatients, to propose a comprehensive, all-BSI tracking approach, and to discuss how such an approach helps better inform within-center and across-center differences in CLABSI rate DESIGN Prospective cohort study SETTING US multicenter, quality-improvement, BSI prevention network PARTICIPANTS PHO centers across the United States who agreed to follow a standardized central-line-maintenance care bundle and track all BSI events and central-line days every month. METHODS Infections were categorized as CLABSI (stratified by mucosal barrier injury-related, laboratory-confirmed BSI [MBI-LCBI] versus non-MBI-LCBI) and secondary BSI, using National Healthcare Safety Network (NHSN) definitions. Single positive blood cultures (SPBCs) with NHSN defined common commensals were also tracked. RESULTS Between 2013 and 2015, 34 PHO centers reported 1,110 BSIs. Among them, 708 (63.8%) were CLABSIs, 170 (15.3%) were secondary BSIs, and 232 (20.9%) were SPBCs. Most SPBCs (75%) occurred in patients with profound neutropenia; 22% of SPBCs were viridans group streptococci. Among the CLABSIs, 51% were MBI-LCBI. Excluding SPBCs, CLABSI rates were higher (88% vs 77%) and secondary BSI rates were lower (12% vs 23%) after the NHSN updated the definition of secondary BSI (Papproach that could help better assess across-center and within-center differences in infection rates, including CLABSI. This approach enables informed decision making by healthcare providers, payors, and the public. Infect Control Hosp Epidemiol 2017;38:690-696.

  15. Common TNF-alpha, IL-1 beta, PAI-1, uPA, CD14 and TLR4 polymorphisms are not associated with disease severity or outcome from Gram negative sepsis

    Jessen, Kirstine Marie; Lindboe, Sarah Bjerre; Petersen, Anncatrine Luisa

    2007-01-01

    consecutive adult patients with culture proven Gram negative bacteremia admitted to a Danish hospital between 2000 and 2002. Analysis for commonly described SNPs of tumor necrosis-alpha, (TNF-alpha), interleukin-1 beta (IL-1 beta), plasminogen activator-1 (PAI-1), urokinase plasminogen activator (uPA), CD14...... hazard regression analysis, increasing age, polymicrobial infection and haemoglobin levels were associated with in-hospital mortality. CONCLUSION: We did not find any association between TNF-alpha, IL-1 beta, PAI-1, uPA, CD14 and TLR4 polymorphisms and outcome of Gram negative sepsis. Other host factors...... appear to be more important than the genotypes studied here in determining the severity and outcome of Gram negative sepsis....

  16. Protein secretion and membrane insertion systems in gram-negative bacteria.

    Saier, Milton H

    2006-01-01

    In contrast to other organisms, gram-negative bacteria have evolved numerous systems for protein export. Eight types are known that mediate export across or insertion into the cytoplasmic membrane, while eight specifically mediate export across or insertion into the outer membrane. Three of the former secretory pathway (SP) systems, type I SP (ISP, ABC), IIISP (Fla/Path) and IVSP (Conj/Vir), can export proteins across both membranes in a single energy-coupled step. A fourth generalized mechanism for exporting proteins across the two-membrane envelope in two distinct steps (which we here refer to as type II secretory pathways [IISP]) utilizes either the general secretory pathway (GSP or Sec) or the twin-arginine targeting translocase for translocation across the inner membrane, and either the main terminal branch or one of several protein-specific export systems for translocation across the outer membrane. We here survey the various well-characterized protein translocation systems found in living organisms and then focus on the systems present in gram-negative bacteria. Comparisons between these systems suggest specific biogenic, mechanistic and evolutionary similarities as well as major differences.

  17. Bioengineered nisin A derivatives with enhanced activity against both Gram positive and Gram negative pathogens.

    Des Field

    Full Text Available Nisin is a bacteriocin widely utilized in more than 50 countries as a safe and natural antibacterial food preservative. It is the most extensively studied bacteriocin, having undergone decades of bioengineering with a view to improving function and physicochemical properties. The discovery of novel nisin variants with enhanced activity against clinical and foodborne pathogens has recently been described. We screened a randomized bank of nisin A producers and identified a variant with a serine to glycine change at position 29 (S29G, with enhanced efficacy against S. aureus SA113. Using a site-saturation mutagenesis approach we generated three more derivatives (S29A, S29D and S29E with enhanced activity against a range of Gram positive drug resistant clinical, veterinary and food pathogens. In addition, a number of the nisin S29 derivatives displayed superior antimicrobial activity to nisin A when assessed against a range of Gram negative food-associated pathogens, including E. coli, Salmonella enterica serovar Typhimurium and Cronobacter sakazakii. This is the first report of derivatives of nisin, or indeed any lantibiotic, with enhanced antimicrobial activity against both Gram positive and Gram negative bacteria.

  18. [Detection of endotoxins of Gram-negative bacteria on the basis of electromagnetic radiation frequency spectrum].

    Likhoded, V G; Kuleshova, N V; Sergieva, N V; Konev, Iu V; Trubnikova, I A; Sudzhian, E V

    2007-01-01

    Method of Gram-negative bacteria endotoxins detection on the basis of their own spectrum of electromagnetic radiation frequency was developed. Frequency spectrum typical for chemotype Re glycolipid, which is a part of lypopolysaccharides in the majority of Gram-negative bacteria, was used. Two devices--"Mini- Expert-DT" (manufactured by IMEDIS, Moscow) and "Bicom" (manufactured by Regumed, Germany)--were used as generators of electromagnetic radiation. Detection of endotoxin using these devices was performed by electropuncture vegetative resonance test. Immunoenzyme reaction with antibodies to chemotype Re glycolipid was used during analysis of preparations for assessment of resonance-frequency method specificity. The study showed that resonance-frequency method can detect lypopolysaccharides of different enterobacteria in quantities up to 0.1 pg as well as bacteria which contain lypopolysaccharides. At the same time, this method does not detect such bacteria as Staphylococcus aureus, Bifidobacterium spp., Lactobacillus spp., and Candida albicans. The method does not require preliminary processing of blood samples and can be used for diagnostics of endotoxinemia, and detection of endotoxins in blood samples or injection solutions.

  19. Imipenem-resistant Gram-negative bacterial isolates carried by persons upon medical examination in Korea.

    Kim, So Yeon; Shin, Sang Yop; Rhee, Ji-Young; Ko, Kwan Soo

    2017-08-01

    Carbapenem-resistant Gram-negative bacteria (CR-GNB) have emerged and disseminated worldwide, become a great concern worldwide including Korea. The prevalence of fecal carriage of imipenem-resistant Gram-negative bacteria (IR-GNB) in persons in Korea was investigated. Stool samples were collected from 300 persons upon medical examination. Samples were screened for IR-GNB by using MacConkey agar with 2 μl/ml imipenem. Species were identified by 16S rRNA gene sequence analysis, and antimicrobial susceptibility was determined by the broth microdilution method. In total, 82 IR-GNB bacterial isolates were obtained from 79 (26.3%) out of 300 healthy persons. Multilocus sequence typing analysis showed very high diversity among IR P. aeruginosa, S. maltophilia, and E. cloacae isolates, and pulsed-field gel electrophoresis revealed five main pulsotypes of IR P. mirabilis. As for the presence of metallo-β-lactamases (MBLs), only one IMP-25-producing S. marcescens isolate was identified. Although only one carbapenemase-producing isolate was identified, the high colonization rates with IR-GNB isolates in this study is notable because carriers may be a reservoir for the dissemination of resistant pathogens within the community as well as in health care institutions.

  20. Mechanistic antimicrobial approach of extracellularly synthesized silver nanoparticles against gram positive and gram negative bacteria

    Tamboli, Dhawal P.; Lee, Dae Sung, E-mail: daesung@knu.ac.kr

    2013-09-15

    Highlights: • Bacterial extracelluar enzymes stabilized the silver nanoparticles (AgNPs). • AgNPs formation was characterized by analytical techniques such as UV–vis, TEM, and FTIR. • AgNPs showed obvious antimicrobial activity against both gram positive and gram negative microorganisms. • A mechanism of AgNPs’ antimicrobial activity was proposed. -- Abstract: The development of eco-friendly and reliable processes for the synthesis of nanoparticles has attracted considerable interest in nanotechnology. In this study, an extracellular enzyme system of a newly isolated microorganism, Exiguobacterium sp. KNU1, was used for the reduction of AgNO{sub 3} solutions to silver nanoparticles (AgNPs). The extracellularly biosynthesized AgNPs were characterized by UV–vis spectroscopy, Fourier transform infra-red spectroscopy and transmission electron microscopy. The AgNPs were approximately 30 nm (range 5–50 nm) in size, well-dispersed and spherical. The AgNPs were evaluated for their antimicrobial effects on different gram negative and gram positive bacteria using the minimum inhibitory concentration method. Reasonable antimicrobial activity against Salmonella typhimurium, Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus was observed. The morphological changes occurred in all the microorganisms tested. In particular, E. coli exhibited DNA fragmentation after being treated with the AgNPs. Finally, the mechanism for their bactericidal activity was proposed according to the results of scanning electron microscopy and single cell gel electrophoresis.

  1. Mechanistic antimicrobial approach of extracellularly synthesized silver nanoparticles against gram positive and gram negative bacteria

    Tamboli, Dhawal P.; Lee, Dae Sung

    2013-01-01

    Highlights: • Bacterial extracelluar enzymes stabilized the silver nanoparticles (AgNPs). • AgNPs formation was characterized by analytical techniques such as UV–vis, TEM, and FTIR. • AgNPs showed obvious antimicrobial activity against both gram positive and gram negative microorganisms. • A mechanism of AgNPs’ antimicrobial activity was proposed. -- Abstract: The development of eco-friendly and reliable processes for the synthesis of nanoparticles has attracted considerable interest in nanotechnology. In this study, an extracellular enzyme system of a newly isolated microorganism, Exiguobacterium sp. KNU1, was used for the reduction of AgNO 3 solutions to silver nanoparticles (AgNPs). The extracellularly biosynthesized AgNPs were characterized by UV–vis spectroscopy, Fourier transform infra-red spectroscopy and transmission electron microscopy. The AgNPs were approximately 30 nm (range 5–50 nm) in size, well-dispersed and spherical. The AgNPs were evaluated for their antimicrobial effects on different gram negative and gram positive bacteria using the minimum inhibitory concentration method. Reasonable antimicrobial activity against Salmonella typhimurium, Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus was observed. The morphological changes occurred in all the microorganisms tested. In particular, E. coli exhibited DNA fragmentation after being treated with the AgNPs. Finally, the mechanism for their bactericidal activity was proposed according to the results of scanning electron microscopy and single cell gel electrophoresis

  2. Bioengineered Nisin A Derivatives with Enhanced Activity against Both Gram Positive and Gram Negative Pathogens

    Field, Des; Begley, Maire; O’Connor, Paula M.; Daly, Karen M.; Hugenholtz, Floor; Cotter, Paul D.; Hill, Colin; Ross, R. Paul

    2012-01-01

    Nisin is a bacteriocin widely utilized in more than 50 countries as a safe and natural antibacterial food preservative. It is the most extensively studied bacteriocin, having undergone decades of bioengineering with a view to improving function and physicochemical properties. The discovery of novel nisin variants with enhanced activity against clinical and foodborne pathogens has recently been described. We screened a randomized bank of nisin A producers and identified a variant with a serine to glycine change at position 29 (S29G), with enhanced efficacy against S. aureus SA113. Using a site-saturation mutagenesis approach we generated three more derivatives (S29A, S29D and S29E) with enhanced activity against a range of Gram positive drug resistant clinical, veterinary and food pathogens. In addition, a number of the nisin S29 derivatives displayed superior antimicrobial activity to nisin A when assessed against a range of Gram negative food-associated pathogens, including E. coli, Salmonella enterica serovar Typhimurium and Cronobacter sakazakii. This is the first report of derivatives of nisin, or indeed any lantibiotic, with enhanced antimicrobial activity against both Gram positive and Gram negative bacteria. PMID:23056510

  3. Survival and detection of coliforms, Enterobacteriaceae, and gram-negative bacteria in Greek yogurt.

    Hervert, C J; Martin, N H; Boor, K J; Wiedmann, M

    2017-02-01

    Despite the widespread use of coliforms as indicator bacteria, increasing evidence suggests that the Enterobacteriaceae (EB) and total gram-negative groups more accurately reflect the hygienic status of high-temperature, short-time pasteurized milk and processing environments. If introduced into milk as postpasteurization contamination, these bacteria may grow to high levels and produce a wide range of sensory-related defects. However, limited information is available on the use and survival of bacterial hygiene indicators in dairy products outside of pasteurized fluid milk and cheese. The goal of this study was to (1) provide information on the survival of a diverse set of bacterial hygiene indicators in the low pH environment of Greek yogurt, (2) compare traditional and alternative detection methods for their ability to detect bacterial hygiene indicators in Greek yogurt, and (3) offer insight into optimal hygiene indicator groups for use in low-pH fermented dairy products. To this end, we screened 64 bacterial isolates, representing 24 dairy-relevant genera, for survival and detection in Greek yogurt using 5 testing methods. Before testing, isolates were inoculated into plain, 0% fat Greek yogurt (pH 4.35 to 4.65), followed by a 12-h hold period at 4 ± 1°C. Yogurts were subsequently tested using Coliform Petrifilm (3M, St. Paul, MN) to detect coliforms; Enterobacteriaceae Petrifilm (3M), violet red bile glucose agar and the D-Count (bioMérieux, Marcy-l'Étoile, France) to detect EB; and crystal violet tetrazolium agar (CVTA) to detect total gram-negative bacteria. Overall, the non-EB gram-negative isolates showed significantly larger log reductions 12 h after inoculation into Greek yogurt (based on bacterial numbers recovered on CVTA) compared with the coliform and noncoliform EB isolates tested. The methods evaluated varied in their ability to detect different microbial hygiene indicators in Greek yogurt. Crystal violet tetrazolium agar detected the highest

  4. Effectiveness of oral hygiene interventions against oral and oropharyngeal reservoirs of aerobic and facultatively anaerobic gram-negative bacilli.

    Lam, Otto L T; McGrath, Colman; Li, Leonard S W; Samaranayake, Lakshman P

    2012-03-01

    Aerobic and facultatively anaerobic gram-negative bacilli (AGNB) are opportunistic pathogens and continue to cause a large number of hospital-acquired infections. AGNB residing in the oral cavity and oropharynx have been linked to nosocomial pneumonia and septicemia. Although AGNB are not considered members of the normal oral and oropharyngeal flora, medically compromised patients have been demonstrated to be susceptible to AGNB colonization. A literature search was conducted to retrieve articles that evaluated the effectiveness of oral hygiene interventions in reducing the oral and oropharyngeal carriage of AGNB in medically compromised patients. Few studies have documented the use of mechanical oral hygiene interventions alone against AGNB. Although a number of studies have employed oral hygiene interventions complemented by antiseptic agents such as chlorhexidine and povidone iodine, there appears to be a discrepancy between their in vitro and in vivo effectiveness. With the recognition of the oral cavity and oropharynx as a reservoir of AGNB and the recent emergence of multidrug and pandrug resistance in hospital settings, there is a pressing need for additional high-quality randomized controlled trials to determine which oral hygiene interventions or combination of interventions are most effective in eliminating or reducing AGNB carriage. Copyright © 2012 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

  5. Activities of doripenem against nosocomial bacteremic drug-resistant Gram-negative bacteria in a medical center in Taiwan.

    Dong, Shao-Xing; Wang, Jann-Tay; Chang, Shan-Chwen

    2012-12-01

    The majority of nosocomial infections in Taiwan hospitals are caused by drug-resistant Gram-negative bacteria (GNB), including Pseudomonas aeruginosa, Acinetobacter baumannii, and various species of Enterobacteriaceae. Carbapenems are important agents for treating infections caused by these GNB. Recently, doripenem was approved for use in Taiwan in August 2009. However, data on its in vitro activity against nosocomial GNB isolated from Taiwan remain limited. The study was designed to look into this clinical issue. A total of 400 nonduplicated nosocomial blood isolates isolated in 2009, inclusive of P. aeruginosa (n = 100), A. baumannii (n = 100), and Enterobacteriaceae (n = 200), were randomly selected from the bacterial bank preserved at National Taiwan University Hospital. Susceptibilities of these 400 isolates to various antibiotics, including doripenem, imipenem, meropenem, ceftazidime, amikacin, ciprofloxacin, colistin, and tigecycline were determined by using Etest. Doripenem demonstrated similar in vitro activity to imipenem and meropenem against P. aeruginosa (87%, vs. 85% and 89%), A. baumannii (56%, vs. 60% and 60%), and Enterobacteriaceae (100%, vs. 98.5% and 99.5%). The prevalence of carbapenem-resistant (any one of three tested carbapenems) P. aeruginosa, A. baumannii, and Enterobacteriaceae isolates was 15%, 44%, and 0.5%, respectively. Doripenem was as effective as imipenem and meropenem in our study. However, there was a significant proportion of carbapenem resistance among the tested isolates. Hence, longitudinal surveillance is necessary to monitor the resistance trend. Copyright © 2012. Published by Elsevier B.V.

  6. Nanoparticle targeting of Gram-positive and Gram-negative bacteria for magnetic-based separations of bacterial pathogens

    Lu, Hoang D.; Yang, Shirley S.; Wilson, Brian K.; McManus, Simon A.; Chen, Christopher V. H.-H.; Prud'homme, Robert K.

    2017-04-01

    Antimicrobial resistance is a healthcare problem of increasing significance, and there is increasing interest in developing new tools to address bacterial infections. Bacteria-targeting nanoparticles hold promise to improve drug efficacy, compliance, and safety. In addition, nanoparticles can also be used for novel applications, such as bacterial imaging or bioseperations. We here present the use of a scalable block-copolymer-directed self-assembly process, Flash NanoPrecipitation, to form zinc(II)-bis(dipicolylamine) modified nanoparticles that bind to both Gram-positive and Gram-negative bacteria with specificity. Particles have tunable surface ligand densities that change particle avidity and binding efficacy. A variety of materials can be encapsulated into the core of the particles, such as optical dyes or iron oxide colloids, to produce imageable and magnetically active bacterial targeting constructs. As a proof-of-concept, these particles are used to bind and separate bacteria from solution in a magnetic column. Magnetic manipulation and separation would translate to a platform for pathogen identification or removal. These magnetic and targeted nanoparticles enable new methods to address bacterial infections.

  7. Effect of extended infusion of meropenem and nebulized amikacin on Gram-negative multidrug-resistant ventilator-associated pneumonia

    Mona Ahmed Ammar

    2018-01-01

    Conclusions: Adding nebulized amikacin to systemic antibiotics in patients with VAP caused by Gram-negative MDRO may offer efficacy benefits, and the use of extended infusions of meropenem could improve the clinical outcomes in critically ill populations.

  8. Rapid identification of carbapenemase genes in gram-negative bacteria with an oligonucleotide microarray-based assay.

    Sascha D Braun

    Full Text Available Rapid molecular identification of carbapenemase genes in Gram-negative bacteria is crucial for infection control and prevention, surveillance and for epidemiological purposes. Furthermore, it may have a significant impact upon determining the appropriate initial treatment and greatly benefit for critically ill patients. A novel oligonucleotide microarray-based assay was developed to simultaneously detect genes encoding clinically important carbapenemases as well as selected extended (ESBL and narrow spectrum (NSBL beta-lactamases directly from clonal culture material within few hours. Additionally, a panel of species specific markers was included to identify Escherichia coli, Pseudomonas aeruginosa, Citrobacter freundii/braakii, Klebsiella pneumoniae and Acinetobacter baumannii. The assay was tested using a panel of 117 isolates collected from urinary, blood and stool samples. For these isolates, phenotypic identifications and susceptibility tests were available. An independent detection of carbapenemase, ESBL and NSBL genes was carried out by various external reference laboratories using PCR methods. In direct comparison, the microarray correctly identified 98.2% of the covered carbapenemase genes. This included blaVIM (13 out of 13, blaGIM (2/2, blaKPC (27/27, blaNDM (5/5, blaIMP-2/4/7/8/13/14/15/16/31 (10/10, blaOXA-23 (12/13, blaOXA-40-group (7/7, blaOXA-48-group (32/33, blaOXA-51 (1/1 and blaOXA-58 (1/1. Furthermore, the test correctly identified additional beta-lactamases [blaOXA-1 (16/16, blaOXA-2 (4/4, blaOXA-9 (33/33, OXA-10 (3/3, blaOXA-51 (25/25, blaOXA-58 (2/2, CTX-M1/M15 (17/17 and blaVIM (1/1]. In direct comparison to phenotypical identification obtained by VITEK or MALDI-TOF systems, 114 of 117 (97.4% isolates, including Acinetobacter baumannii (28/28, Enterobacter spec. (5/5, Escherichia coli (4/4, Klebsiella pneumoniae (62/63, Klebsiella oxytoca (0/2, Pseudomonas aeruginosa (12/12, Citrobacter freundii (1/1 and Citrobacter

  9. Catheter-free Period Over 2 Days Is Associated with Better Outcome in Catheter-related Bloodstream Infection due to Candida

    Matsuo, Takahiro; Mori, Nobuyoshi; Hoshino, Eri; Sakurai, Aki; Furukawa, Keiichi

    2017-01-01

    Abstract Background Regardless of active antifungal drugs, mortality of candidemia remains high. Although it is well-known that central venous catheter (CVC) is one of the most important risk factors of candidemia and should be removed immediately, little is known about optimal timing of CVC replacement after removal. Here, we analyzed contributing risk factors associated with 30-day mortality for catheter-related bloodstream infection (CRBSI) due to candida and optimal timing of CVC replacem...

  10. Timing of positive blood samples does not differentiate pathogens causing healthcare-associated from community-acquired bloodstream infections in children in England: a linked retrospective cohort study

    HENDERSON, K. L.; M?LLER-PEBODY, B.; WADE, A.; SHARLAND, M.; MINAJI, M.; JOHNSON, A. P.; GILBERT, R

    2014-01-01

    SUMMARY Paediatricians recognize that using the time-dependent community-acquired vs. hospital-acquired bloodstream infection (BSI) dichotomy to guide empirical treatment no longer distinguishes between causative pathogens due to the emergence of healthcare-associated BSIs. However, paediatric epidemiological evidence of the aetiology of BSIs in relation to hospital admission in England is lacking. For 12 common BSI-causing pathogens in England, timing of laboratory reports of positive paedia...

  11. Incidence of bloodstream infections in small bowel transplant recipients receiving selective decontamination of the digestive tract: A single-center experience

    Galloway, David; Danziger-Isakov, Lara; Goldschmidt, Monique; Hemmelgarn, Trina; Courter, Joshua; Nathan, Jaimie D.; Alonso, Maria; Tiao, Greg; Fei, Lin; Kocoshis, Samuel

    2015-01-01

    Pediatric patients undergoing small bowel transplantation are susceptible to postoperative CLABSI. SDD directed against enteric microbes is a strategy for reducing CLABSI. We hypothesized that SDD reduces the frequency of CLABSI, infections outside the bloodstream, and allograft rejection during the first 30 days following transplant. A retrospective chart review of 38 pediatric small bowel transplant recipients at CCHMC from 2003 to 2011 was conducted. SDD antimicrobials were oral colistin, ...

  12. Epidemiology, clinical characteristics and treatment outcomes of healthcare- associated methicillin-resistant Staphylococcus aureus BLOODSTREAM infections at Chiang Mai University Hospital: a retrospective study.

    Chaiwarith, Romanee; Pacharasupal, Phongsathon; Sirisanthana, Thira

    2014-07-01

    The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) varies widely by region and healthcare setting. The prevalence of MRSA among S. aureus bloodstream infections increased from 23% in 2007 to 43% in 2011 at our hospital. We conducted this retrospective study among patients with MRSA to determine mortality rate of MRSA bloodstream infections (BSIs) and the risk factors for death in those patients at Chiang Mai University Hospital from January 1, 2007 to December 31, 2011. One hundred seventy-nine patients with 184 episodes of MRSA BSIs were enrolled. Ninety-eight patients (54.8%) were male and the mean age was 53.4±25.3 years. The median length of time from admission to diagnosis was 27.5 days (IQR 15, 43.5). One-hundred six patients had BSI with other sites of infection: pneumonia (78 episodes, 42.4%), skin and soft tissue infections (15 episodes, 8.2%), urinary tract infections (13 episodes, 7.1%) and infective endocarditis (4 episodes, 2.2%). The mortality rate was 53.1% (95 patients). Risk factors for death on multivariate analysis were: concurrent pulmonary infection (OR 2.65; 95% CI: 1.27-5.51, p=0.009), having a central venous catheter (OR 8.85; 95% CI: 2.31-33.88, p=0.001), having a urinary catheter (OR 8.52; 95% CI: 2.60-27.89, p < 0.001) and having a prothrombin time longer than 1.5 times the upper limit of normal (OR 3.85; 95% CI: 1.68-8.81, p=0.001). MRSA bloodstream infections caused significant mortality particularly among those patients with concurrent pulmonary infections.

  13. Characterization and Clinical Impact of Bloodstream Infection Caused by Carbapenemase-Producing Enterobacteriaceae in Seven Latin American Countries.

    Villegas, Maria Virginia; Pallares, Christian J; Escandón-Vargas, Kevin; Hernández-Gómez, Cristhian; Correa, Adriana; Álvarez, Carlos; Rosso, Fernando; Matta, Lorena; Luna, Carlos; Zurita, Jeannete; Mejía-Villatoro, Carlos; Rodríguez-Noriega, Eduardo; Seas, Carlos; Cortesía, Manuel; Guzmán-Suárez, Alfonso; Guzmán-Blanco, Manuel

    2016-01-01

    Infections caused by carbapenem-resistant Enterobacteriaceae are a public health problem associated with higher mortality rates, longer hospitalization and increased healthcare costs. We carried out a study to describe the characteristics of patients with carbapenemase-producing Enterobacteriaceae (CPE) and non-CPE bloodstream infection (BSI) from Latin American hospitals and to determine the clinical impact in terms of mortality and antibiotic therapy. Between July 2013 and November 2014, we conducted a multicenter observational study in 11 hospitals from 7 Latin American countries (Argentina, Colombia, Ecuador, Guatemala, Mexico, Peru, Venezuela). Patients with BSI caused by Enterobacteriaceae were included and classified either as CPE or non-CPE based on detection of blaKPC, blaVIM, blaIMP, blaNDM and blaOXA-48 by polymerase chain reaction. Enrolled subjects were followed until discharge or death. Demographic, microbiological and clinical characteristics were collected from medical records. Both descriptive and inferential statistics were used to analyze the information. A total of 255 patients with Enterobacteriaceae BSI were included; CPE were identified in 53 of them. In vitro non-susceptibility to all screened antibiotics was higher in the patients with CPE BSI, remaining colistin, tigecycline and amikacin as the most active drugs. Combination therapy was significantly more frequent in the CPE BSI group (p mortality was 37% (94/255). Overall and attributable mortality were significantly higher in patients with CPE BSI (p mortality. After multivariate adjustment, CPE BSI (adjusted odds ratio [aOR] 4; 95% confidence interval [CI] 1.7-9.5; p = 0.002) and critical illness (aOR 6.5; 95% CI 3.1-13.7; p mortality. This study provides valuable data on the clinical characteristics and mortality risk factors in patients with CPE BSI. We determined that CPE infection is an independent mortality predictor and thus Latin American hospitals should perform campaigns on

  14. Characterization of Third-Generation Cephalosporin-Resistant Escherichia coli from Bloodstream Infections in Denmark

    Hansen, Frank; Olsen, Stefan S; Heltberg, Ole

    2014-01-01

    The aim of the study was to investigate the molecular epidemiology of 87 third-generation cephalosporin-resistant Escherichia coli (3GC-R Ec) from bloodstream infections in Denmark from 2009. Sixty-eight of the 87 isolates were extended-spectrum beta-lactamase (ESBL) producers, whereas 17 isolates...... featured AmpC mutations only (without a coexpressed ESBL enzyme) and 2 isolates were producing CMY-22. The majority (82%) of the ESBL-producing isolates in our study were CTX-M-15 producers and primarily belonged to phylogroup B2 (54.4%) or D (23.5%). Further, one of the two CMY-22-producing isolates...... belonged to B2, whereas only few of the other AmpCs isolates belonged to B2 and D. Pulsed-field gel electrophoresis revealed that both clonal and nonclonal spread of 3GC-R Ec occurred. ST131 was detected in 50% of ESBL-producing isolates. The remaining ESBL-producing isolates belonged to 17 other sequence...

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

    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

  16. Prevalence, virulence factors and antifungal susceptibility of Candida spp. isolated from bloodstream infections in a tertiary care hospital in Brazil.

    Canela, Heliara Maria Spina; Cardoso, Bárbara; Vitali, Lucia Helena; Coelho, Harnoldo Colares; Martinez, Roberto; Ferreira, Márcia Eliana da Silva

    2018-01-01

    Candida spp. are responsible for 80% of all systemic fungal infections and are associated with high mortality rates. This study characterised 79 bloodstream isolates of C. albicans, C. glabrata, C. orthopsilosis, C. parapsilosis and C. tropicalis from patients in a Brazilian hospital. The susceptibility to amphotericin B, caspofungin, fluconazole and voriconazole was determined; virulence factor production was assessed based on haemolysin, phospholipase and proteinase activities, and the patients' clinical characteristics were analysed. C. albicans was the predominant species (44%), followed by C. glabrata (19%), C. tropicalis (19%), C. parapsilosis (14%) and C. orthopsilosis (4%). The candidemia incidence was 1.52 per 1000 admissions, and the crude mortality rate was 52%. One C. albicans isolate was resistant to fluconazole and voriconazole. Moreover, 20.2%, 2.5% and 3.8% of the isolates exhibited dose-dependent susceptibility to fluconazole, voriconazole and caspofungin, respectively. In conclusion, although the C. glabrata incidence was higher than that usually described in Brazil, its increase was previously observed in studies conducted worldwide. Furthermore, the azole resistance of the C. albicans isolate could be due to previous exposure to these antifungals. These results highlight the importance of epidemiological studies and will facilitate an improved understanding of candidemia in the studied hospital. © 2017 Blackwell Verlag GmbH.

  17. POLYCLONAL OUTBREAK OF BLOODSTREAM INFECTIONS CAUSED BY Burkholderia cepacia COMPLEX IN HEMATOLOGY AND BONE MARROW TRANSPLANT OUTPATIENT UNITS

    Icaro Boszczowski

    2014-01-01

    Full Text Available Aim: The objective was to describe an outbreak of bloodstream infections by Burkholderia cepacia complex (Bcc in bone marrow transplant and hematology outpatients. Methods: On February 15, 2008 a Bcc outbreak was suspected. 24 cases were identified. Demographic and clinical data were evaluated. Environment and healthcare workers' (HCW hands were cultured. Species were determined and typed. Reinforcement of hand hygiene, central venous catheter (CVC care, infusion therapy, and maintenance of laminar flow cabinet were undertaken. 16 different HCWs had cared for the CVCs. Multi-dose heparin and saline were prepared on counter common to both units. Findings: 14 patients had B. multivorans (one patient had also B. cenopacia, six non-multivorans Bcc and one did not belong to Bcc. Clone A B. multivorans occurred in 12 patients (from Hematology; in 10 their CVC had been used on February 11/12. Environmental and HCW cultures were negative. All patients were treated with meropenem, and ceftazidime lock-therapy. Eight patients (30% were hospitalized. No deaths occurred. After control measures (multidose vial for single patient; CVC lock with ceftazidime; cleaning of laminar flow cabinet; hand hygiene improvement; use of cabinet to store prepared medication, no new cases occurred. Conclusions: This polyclonal outbreak may be explained by a common source containing multiple species of Bcc, maybe the laminar flow cabinet common to both units. There may have been contamination by B. multivorans (clone A of multi-dose vials.

  18. Characterization of carbapenem-resistant Gram-negative bacteria from Tamil Nadu.

    Nachimuthu, Ramesh; Subramani, Ramkumar; Maray, Suresh; Gothandam, K M; Sivamangala, Karthikeyan; Manohar, Prasanth; Bozdogan, Bülent

    2016-10-01

    Carbapenem resistance is disseminating worldwide among Gram-negative bacteria. The aim of this study was to identify carbapenem-resistance level and to determine the mechanism of carbapenem resistance among clinical isolates from two centres in Tamil Nadu. In the present study, a total of 93 Gram-negative isolates, which is found to be resistant to carbapenem by disk diffusion test in two centres, were included. All isolates are identified at species level by 16S rRNA sequencing. Minimal inhibitory concentrations (MICs) of isolates for Meropenem were tested by agar dilution method. Presence of blaOXA, blaNDM, blaVIM, blaIMP and blaKPC genes was tested by PCR in all isolates. Amplicons were sequenced for confirmation of the genes. Among 93 isolates, 48 (%52) were Escherichia coli, 10 (%11) Klebsiella pneumoniae, nine (%10) Pseudomonas aeruginosa. Minimal inhibitory concentration results showed that of 93 suspected carbapenem-resistant isolates, 27 had meropenem MICs ≥ 2 μg/ml. The MIC range, MIC50 and MIC90 were 128 μg/ml, 0.12 and 16 μg/ml, respectively. Fig. 1 . Among meropenem-resistant isolates, E. coli were the most common (9/48, 22%), followed by K. pneumoniae (7/9, 77%), P. aeruginosa (6/10, 60%), Acinetobacter baumannii (2/2, 100%), Enterobacter hormaechei (2/3, 67%) and one Providencia rettgeri (1/1, 100%). PCR results showed that 16 of 93 carried blaNDM, three oxa181, and one imp4. Among blaNDM carriers, nine were E. coli, four Klebsiella pneumoniae, two E. hormaechei and one P. rettgeri. Three K. pneumoniae were OXA-181 carriers. The only imp4 carrier was P. aeruginosa. A total of seven carbapenem-resistant isolates were negatives by PCR for the genes studied. All carbapenem-resistance gene-positive isolates had meropenem MICs >2 μg/ml. Our results confirm the dissemination of NDM and emergence of OXA-181 beta-lactamase among Gram-negative bacteria in South India. This study showed the emergence of NDM producer in clinical isolates of E

  19. Engaging Frontline Staff in Central Line-Associated Bloodstream Infection Prevention Practice in the Wake of Superstorm Sandy.

    Rosenberg, Rebecca E; Devins, Lea; Geraghty, Gail; Bock, Steven; Dugan, Christina A; Transou, Marjorie; Phillips, Michael; Lighter-Fisher, Jennifer

    2015-10-01

    Central venous catheters are crucial devices in the care of hospitalized children, both in and out of critical care units, but the concomitant risk of central line-associated bloodstream infection (CLABSI) affects 15,000 Americans annually. In 2012, CLABSI rates varied among units from 6.8/1,000 to 1.0/1,000 in a 109-bed children's service within NYU Langone Medical Center (NYULMC; New York City), a 1,069-bed tertiary care academic medical center. In response to variation in central line-related practices and infection prevention rates, a CLABSI Prevention Core Team began an effort to standardize central venous catheter (CVC) care across all pediatric units (ICU and non-ICU). Momentum in this quality improvement (QI) work was interrupted when Superstorm Sandy shuttered the flagship hospital, but the relatively decreased clinical load provided a "downtime" opportunity to address CLABSI prevention. The first phase of the collaborative effort, Booster 1, Planning/Initial Phase: Development of a Pediatric Central Venous Catheter Working Group, was followed by Booster 2, Maintenance/Sustaining Phase: Transitioning for Sustainability and Adopting Model for Improvement. Data in the subsequent 21 months after the temporary closure of the facility (January 2013-September 2014) showed an increase in maintenance bundle reliability. The inpatient CLABSI rate for patients<18 years decreased from an annual rate of 2.7/1,000 line days (2012) to 0.6/1,000 line days (2013) to 0.5/1,000 line days as of August 2014. There was a decrease in pediatric CLABSI events and no significant change in line days. Key elements contributing to initial success with evolving QI capacity and resources were likely multi-factorial, including staff and leadership engagement, culture change, consistent guidelines, and accountability by individuals and by our multidisciplinary core team.

  20. Motuporamine Derivatives as Antimicrobial Agents and Antibiotic Enhancers against Resistant Gram-Negative Bacteria.

    Borselli, Diane; Blanchet, Marine; Bolla, Jean-Michel; Muth, Aaron; Skruber, Kristen; Phanstiel, Otto; Brunel, Jean Michel

    2017-02-01

    Dihydromotuporamine C and its derivatives were evaluated for their in vitro antimicrobial activities and antibiotic enhancement properties against Gram-negative bacteria and clinical isolates. The mechanism of action of one of these derivatives, MOTU-N44, was investigated against Enterobacter aerogenes by using fluorescent dyes to evaluate outer-membrane depolarization and permeabilization. Its efficiency correlated with inhibition of dye transport, thus suggesting that these molecules inhibit drug transporters by de-energization of the efflux pump rather than by direct interaction of the molecule with the pump. This suggests that depowering the efflux pump provides another strategy to address antibiotic resistance. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  1. DNA/Ag Nanoparticles as Antibacterial Agents against Gram-Negative Bacteria

    Tomomi Takeshima

    2015-03-01

    Full Text Available Silver (Ag nanoparticles were produced using DNA extracted from salmon milt as templates. Particles spherical in shape with an average diameter smaller than 10 nm were obtained. The nanoparticles consisted of Ag as the core with an outermost thin layer of DNA. The DNA/Ag hybrid nanoparticles were immobilized over the surface of cotton based fabrics and their antibacterial efficiency was evaluated using E. coli as the typical Gram-negative bacteria. The antibacterial experiments were performed according to the Antibacterial Standard of Japanese Association for the Functional Evaluation of Textiles. The fabrics modified with DNA/Ag nanoparticles showed a high enough inhibitory and killing efficiency against E. coli at a concentration of Ag ≥ 10 ppm.

  2. Subcellular localization for Gram positive and Gram negative bacterial proteins using linear interpolation smoothing model.

    Saini, Harsh; Raicar, Gaurav; Dehzangi, Abdollah; Lal, Sunil; Sharma, Alok

    2015-12-07

    Protein subcellular localization is an important topic in proteomics since it is related to a protein׳s overall function, helps in the understanding of metabolic pathways, and in drug design and discovery. In this paper, a basic approximation technique from natural language processing called the linear interpolation smoothing model is applied for predicting protein subcellular localizations. The proposed approach extracts features from syntactical information in protein sequences to build probabilistic profiles using dependency models, which are used in linear interpolation to determine how likely is a sequence to belong to a particular subcellular location. This technique builds a statistical model based on maximum likelihood. It is able to deal effectively with high dimensionality that hinders other traditional classifiers such as Support Vector Machines or k-Nearest Neighbours without sacrificing performance. This approach has been evaluated by predicting subcellular localizations of Gram positive and Gram negative bacterial proteins. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Antimicrobial compounds targeting Gram-negative bacteria in food: Their mode of action and combinational effects

    Hyldgaard, Morten

    2015-01-01

    compromising food shelf-life or safety. Natural antimicrobial compounds have therefore gained increased interest as a label-friendly alternative that can be added directly to food products. Although natural antimicrobials constitute an interesting source of compounds, it is often not understood how...... they interact with bacterial cells to exert their mechanism of inhibition or killing. Furthermore, natural antimicrobials are often not potent enough as single compounds, and may cause unwanted sensory side-effects, which limit the quantities that can be applied to food. These problems might be circumvented...... by combining antimicrobials to decrease the concentrations needed without compromising their antimicrobial activity. The work described in this dissertation presents two projects concerning the mechanism of action of selected natural antimicrobial compounds primarily against Gram-negative bacteria, and two...

  4. Temperature shock, injury and transient sensitivity to nisin in Gram negatives.

    Boziaris, I S; Adams, M R

    2001-10-01

    The effect of thermal stresses on survival, injury and nisin sensitivity was investigated in Salmonella Enteritidis PT4, PT7 and Pseudomonas aeruginosa. Heating at 55 degrees C, rapid chilling to 0.5 degrees C or freezing at -20 degrees C produced transient sensitivity to nisin. Cells were only sensitive if nisin was present during stress. Resistance recovered rapidly afterwards, though some cells displayed residual injury. Injury was assessed by SDS sensitivity, hydrophobicity changes, lipopolysaccharide release and NPN uptake. LPS release and hydrophobicity were not always associated with transient nisin sensitivity. Uptake of NPN correlated better but persisted longer after treatment. Thermal shocks produce transient injury to the outer membrane, allowing nisin access. After treatment, the permeability barrier is rapidly restored by a process apparently involving reorganization rather than biosynthetic repair. Inclusion of nisin during food treatments that impose sub-lethal stress on Gram negatives could increase process lethality, enhancing microbiological safety and stability.

  5. Cell wall elongation mode in Gram-negative bacteria is determined by peptidoglycan architecture.

    Turner, Robert D; Hurd, Alexander F; Cadby, Ashley; Hobbs, Jamie K; Foster, Simon J

    2013-01-01

    Cellular integrity and morphology of most bacteria is maintained by cell wall peptidoglycan, the target of antibiotics essential in modern healthcare. It consists of glycan strands, cross-linked by peptides, whose arrangement determines cell shape, prevents lysis due to turgor pressure and yet remains dynamic to allow insertion of new material, and hence growth. The cellular architecture and insertion pattern of peptidoglycan have remained elusive. Here we determine the peptidoglycan architecture and dynamics during growth in rod-shaped Gram-negative bacteria. Peptidoglycan is made up of circumferentially oriented bands of material interspersed with a more porous network. Super-resolution fluorescence microscopy reveals an unexpected discontinuous, patchy synthesis pattern. We present a consolidated model of growth via architecture-regulated insertion, where we propose only the more porous regions of the peptidoglycan network that are permissive for synthesis.

  6. Bloodstream infections by Malassezia and Candida species in critical care patients.

    Iatta, R.; Cafarchia, C.; Cuna, T.; Montagna, M.T.; Laforgia, N.; Gentile, O.; Rizzo, A.; Boekhout, T.; Otranto, D.

    2013-01-01

    Despite being considered an emerging yeast related to immunocompromised individuals, severe infections by Malassezia furfur have not been evaluated. During a one-year survey on yeasts fungemia, 290 neonatal and 17 pediatric patients with intravascular catheters, lipid parenteral nutrition, prolonged

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

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

    2014-08-01

    There is evidence that meticillin-resistant Staphylococcus aureus (MRSA) bacteraemia can be reduced with improved infection control and antibiotic stewardship. To survey infection control and antibiotic stewardship practices within European hospitals and to identify initiatives that correlate with reduced MRSA prevalence. Online questionnaires were sent to European hospitals about their surveillance, hand hygiene, intravenous device management, admission screening, isolation, antibiotic prescribing, hospital demographics and MRSA blood culture isolates during 2010. In all, 269 replies were received from hospitals in 29 European countries. Lower MRSA prevalence showed significant association with presence of incidence surveillance, performance of root cause analysis, mandatory training requirements for hand hygiene, accountability measures for persistent non-compliance, and multi-stakeholder teamwork in antibiotic prescribing. Presence of policies on intravenous catheter insertion and management showed no variation between different MRSA prevalence groups. However, low-prevalence hospitals reported more competency assessment programmes in insertion and maintenance of peripheral and central venous catheters. Hospitals from the UK and Ireland reported the highest uptake of infection control and antibiotic stewardship practices that were significantly associated with low MRSA prevalence, whereas Southern European hospitals exhibited the lowest. In multiple regression analysis, isolation of high-risk patients, performance of root cause analysis, obligatory training for nurses in hand hygiene, and undertaking joint ward rounds including microbiologists and infectious disease physicians remained significantly associated with lower MRSA prevalence. Proactive infection control and antibiotic stewardship initiatives that instilled accountability, ownership, teamwork, and validated competence among healthcare workers were associated with improved MRSA outcomes. Copyright

  8. New transposon tools tailored for metabolic engineering of Gram-negative microbial cell factories

    Esteban eMartínez-García

    2014-10-01

    Full Text Available Re-programming microorganisms to modify their existing functions and/or to bestow bacteria with entirely new-to-Nature tasks have largely relied so far on specialized molecular biology tools. Such endeavors are not only relevant in the burgeoning metabolic engineering arena, but also instrumental to explore the functioning of complex regulatory networks from a fundamental point of view. À la carte modification of bacterial genomes thus calls for novel tools to make genetic manipulations easier. We propose the use of a series of new broad-host-range mini-Tn5 vectors, termed pBAMDs, for the delivery of gene(s into the chromosome of Gram-negative bacteria and for generating saturated mutagenesis libraries in gene function studies. These delivery vectors endow the user with the possibility of easy cloning and subsequent insertion of functional cargoes with three different antibiotic resistance markers (kanamycin, streptomycin, and gentamicin. After validating the pBAMD vectors in the environmental bacterium Pseudomonas putida KT2440, their use was also illustrated by inserting the entire poly(3-hydroxybutyrate (PHB synthesis pathway from Cupriavidus necator in the chromosome of a phosphotransacetylase mutant of Escherichia coli. PHB is a completely biodegradable polyester with a number of industrial applications that make it attractive as a potential replacement of oil-based plastics. The non-selective nature of chromosomal insertions of the biosynthetic genes was evidenced by a large landscape of PHB synthesis levels in independent clones. One clone was selected and further characterized as a microbial cell factory for PHB accumulation, and it achieved polymer accumulation levels comparable to those of a plasmid-bearing recombinant. Taken together, our results demonstrate that the new mini-Tn5 vectors can be used to confer interesting phenotypes in Gram-negative bacteria that would be very difficult to engineer through direct manipulation of the

  9. New Transposon Tools Tailored for Metabolic Engineering of Gram-Negative Microbial Cell Factories

    Martínez-García, Esteban; Aparicio, Tomás; Lorenzo, Víctor de; Nikel, Pablo I.

    2014-01-01

    Re-programming microorganisms to modify their existing functions and/or to bestow bacteria with entirely new-to-Nature tasks have largely relied so far on specialized molecular biology tools. Such endeavors are not only relevant in the burgeoning metabolic engineering arena but also instrumental to explore the functioning of complex regulatory networks from a fundamental point of view. À la carte modification of bacterial genomes thus calls for novel tools to make genetic manipulations easier. We propose the use of a series of new broad-host-range mini-Tn5-vectors, termed pBAMDs, for the delivery of gene(s) into the chromosome of Gram-negative bacteria and for generating saturated mutagenesis libraries in gene function studies. These delivery vectors endow the user with the possibility of easy cloning and subsequent insertion of functional cargoes with three different antibiotic-resistance markers (kanamycin, streptomycin, and gentamicin). After validating the pBAMD vectors in the environmental bacterium Pseudomonas putida KT2440, their use was also illustrated by inserting the entire poly(3-hydroxybutyrate) (PHB) synthesis pathway from Cupriavidus necator in the chromosome of a phosphotransacetylase mutant of Escherichia coli. PHB is a completely biodegradable polyester with a number of industrial applications that make it attractive as a potential replacement of oil-based plastics. The non-selective nature of chromosomal insertions of the biosynthetic genes was evidenced by a large landscape of PHB synthesis levels in independent clones. One clone was selected and further characterized as a microbial cell factory for PHB accumulation, and it achieved polymer accumulation levels comparable to those of a plasmid-bearing recombinant. Taken together, our results demonstrate that the new mini-Tn5-vectors can be used to confer interesting phenotypes in Gram-negative bacteria that would be very difficult to engineer through direct manipulation of the structural genes.

  10. Intrathecal or intraventricular therapy for post-neurosurgical Gram-negative meningitis: matched cohort study.

    Shofty, B; Neuberger, A; Naffaa, M E; Binawi, T; Babitch, T; Rappaport, Z H; Zaaroor, M; Sviri, G; Paul, M

    2016-01-01

    Gram-negative post-operative meningitis due to carbapenem-resistant bacteria (CR-GNPOM) is a dire complication of neurosurgical procedures. We performed a nested propensity-matched historical cohort study aimed at examining the possible benefit of intrathecal or intraventricular (IT/IV) antibiotic treatment for CR-GNPOM. We included consecutive adults with GNPOM in two centres between 2005 and 2014. Patients receiving combined systemic and IT/IV treatment were matched to patients receiving systemic treatment only. Matching was done based on the propensity of the patients to receive IT/IV treatment. We compared patient groups with 30-day mortality defined as the primary outcome. The cohort included 95 patients with GNPOM. Of them, 37 received IT/IV therapy in addition to systemic treatment (22 with colistin and 15 with amikacin), mostly as initial therapy, through indwelling cerebrospinal fluid drains. Variables associated with IT/IV therapy in the propensity score included no previous neurosurgery, time from admission to meningitis, presence of a urinary catheter and GNPOM caused by carbapenem-resistant Gram-negative bacteria. Following propensity matching, 23 patients given IT/IV therapy and 27 controls were analysed. Mortality was significantly lower with IT/IV therapy: 2/23 (8.7%) versus 9/27 (33.3%), propensity-adjusted OR 0.19, 95% CI 0.04-0.99. Death or neurological deterioration at 30 days, 14-day and in-hospital mortality were lower with IT/IV therapy (OR <0.4 for all) without statistically significant differences. Among patients discharged alive, those receiving IT/IV therapy did not experience more neurological deterioration. Serious adverse events with IT/IV therapy were not documented. Our results support the early use of IT antibiotic treatment for CR-GNPOM when a delivery method is available. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  11. Structural modifications of bacterial lipopolysaccharide that facilitate Gram-negative bacteria evasion of host innate immunity

    Motohiro eMatsuura

    2013-05-01

    Full Text Available Bacterial lipopolysaccharide (LPS, a cell wall component characteristic of Gram-negative bacteria, is a representative pathogen-associated molecular pattern that allows mammalian cells to recognize bacterial invasion and trigger innate immune responses. The polysaccharide moiety of LPS primary plays protective roles for bacteria such as prevention from complement attacks or camouflage with common host carbohydrate residues. The lipid moiety, termed lipid A, is recognized by the Toll-like receptor 4 (TLR4/MD-2 complex, which transduces signals for activation of host innate immunity. The basic structure of lipid A is a glucosamine disaccharide substituted by phosphate groups and acyl groups. Lipid A with 6 acyl groups (hexa-acylated form has been indicated to be a strong stimulator of the TLR4/MD-2 complex. This type of lipid A is conserved among a wide variety of Gram-negative bacteria, and those bacteria are easily recognized by host cells for activation of defensive innate immune responses. Modifications of the lipid A structure to less-acylated forms have been observed in some bacterial species, and those forms are poor stimulators of the TLR4/MD-2 complex. Such modifications are thought to facilitate bacterial evasion of host innate immunity, thereby enhancing pathogenicity. This hypothesis is supported by studies of Yersinia pestis LPS, which contains hexa-acylated lipid A when the bacterium grows at 27ºC (the temperature of the vector flea, and shifts to contain less-acylated forms when grown at the human body temperature of 37ºC. This alteration of lipid A forms following transmission of Y. pestis from fleas to humans contributes predominantly to the virulence of this bacterium over other virulence factors. A similar role for less-acylated lipid A forms has been indicated in some other bacterial species, such as Francisella tularensis, Helicobacter pylori, and Porphyromonas gingivalis, and further studies to explore this concept are

  12. New Transposon Tools Tailored for Metabolic Engineering of Gram-Negative Microbial Cell Factories

    Martínez-García, Esteban; Aparicio, Tomás; Lorenzo, Víctor de; Nikel, Pablo I., E-mail: pablo.nikel@cnb.csic.es [Systems and Synthetic Biology Program, Centro Nacional de Biotecnología (CNB-CSIC), Madrid (Spain)

    2014-10-28

    Re-programming microorganisms to modify their existing functions and/or to bestow bacteria with entirely new-to-Nature tasks have largely relied so far on specialized molecular biology tools. Such endeavors are not only relevant in the burgeoning metabolic engineering arena but also instrumental to explore the functioning of complex regulatory networks from a fundamental point of view. À la carte modification of bacterial genomes thus calls for novel tools to make genetic manipulations easier. We propose the use of a series of new broad-host-range mini-Tn5-vectors, termed pBAMDs, for the delivery of gene(s) into the chromosome of Gram-negative bacteria and for generating saturated mutagenesis libraries in gene function studies. These delivery vectors endow the user with the possibility of easy cloning and subsequent insertion of functional cargoes with three different antibiotic-resistance markers (kanamycin, streptomycin, and gentamicin). After validating the pBAMD vectors in the environmental bacterium Pseudomonas putida KT2440, their use was also illustrated by inserting the entire poly(3-hydroxybutyrate) (PHB) synthesis pathway from Cupriavidus necator in the chromosome of a phosphotransacetylase mutant of Escherichia coli. PHB is a completely biodegradable polyester with a number of industrial applications that make it attractive as a potential replacement of oil-based plastics. The non-selective nature of chromosomal insertions of the biosynthetic genes was evidenced by a large landscape of PHB synthesis levels in independent clones. One clone was selected and further characterized as a microbial cell factory for PHB accumulation, and it achieved polymer accumulation levels comparable to those of a plasmid-bearing recombinant. Taken together, our results demonstrate that the new mini-Tn5-vectors can be used to confer interesting phenotypes in Gram-negative bacteria that would be very difficult to engineer through direct manipulation of the structural genes.

  13. Silver resistance in Gram-negative bacteria: a dissection of endogenous and exogenous mechanisms.

    Randall, Christopher P; Gupta, Arya; Jackson, Nicole; Busse, David; O'Neill, Alex J

    2015-04-01

    To gain a more detailed understanding of endogenous (mutational) and exogenous (horizontally acquired) resistance to silver in Gram-negative pathogens, with an emphasis on clarifying the genetic bases for resistance. A suite of microbiological and molecular genetic techniques was employed to select and characterize endogenous and exogenous silver resistance in several Gram-negative species. In Escherichia coli, endogenous resistance arose after 6 days of exposure to silver, a consequence of two point mutations that were both necessary and sufficient for the phenotype. These mutations, in ompR and cusS, respectively conferred loss of the OmpC/F porins and derepression of the CusCFBA efflux transporter, both phenotypic changes previously linked to reduced intracellular accumulation of silver. Exogenous resistance involved derepression of the SilCFBA efflux transporter as a consequence of mutation in silS, but was additionally contingent on expression of the periplasmic silver-sequestration protein SilE. Silver resistance could be selected at high frequency (>10(-9)) from Enterobacteriaceae lacking OmpC/F porins or harbouring the sil operon and both endogenous and exogenous resistance were associated with modest fitness costs in vitro. Both endogenous and exogenous silver resistance are dependent on the derepressed expression of closely related efflux transporters and are therefore mechanistically similar phenotypes. The ease with which silver resistance can become selected in some bacterial pathogens in vitro suggests that there would be benefit in improved surveillance for silver-resistant isolates in the clinic, along with greater control over use of silver-containing products, in order to best preserve the clinical utility of silver. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

  14. Multiparametric Profiling for Identification of Chemosensitizers against Gram-Negative Bacteria

    Vincent Lôme

    2018-02-01

    Full Text Available Antibiotic resistance is now a worldwide therapeutic problem. Since the beginning of anti-infectious treatment bacteria have rapidly shown an incredible ability to develop and transfer resistance mechanisms. In the last decades, the design variation of pioneer bioactive molecules has strongly improved their activity and the pharmaceutical companies partly won the race against the clock. Since the 1980s, the new classes of antibiotics that emerged were mainly directed to Gram-positive bacteria. Thus, we are now facing to multidrug-resistant Gram-negative bacteria, with no therapeutic options to deal with them. These bacteria are mainly resistant because of their double membrane that conjointly impairs antibiotic accumulation and extrudes these molecules when entered. The main challenge is to allow antibiotics to cross the impermeable envelope and reach their targets. One promising solution would be to associate, in a combination therapy, a usual antibiotic with a non-antibiotic chemosensitizer. Nevertheless, for effective drug discovery, there is a prominent lack of tools required to understand the rules of permeation and accumulation into Gram-negative bacteria. By the use of a multidrug-resistant enterobacteria, we introduce a high-content screening procedure for chemosensitizers discovery by quantitative assessment of drug accumulation, alteration of barriers, and deduction of their activity profile. We assembled and analyzed a control chemicals library to perform the proof of concept. The analysis was based on real-time monitoring of the efflux alteration and measure of the influx increase in the presence of studied compounds in an automatized bio-assay. Then, synergistic activity of compounds with an antibiotic was studied and kinetic data reduction was performed which led to the calculation of a score for each barrier to be altered.

  15. Multidrug-resistant gram-negative bacteria colonization of healthy US military personnel in the US and Afghanistan.

    Vento, Todd J; Cole, David W; Mende, Katrin; Calvano, Tatjana P; Rini, Elizabeth A; Tully, Charla C; Zera, Wendy C; Guymon, Charles H; Yu, Xin; Cheatle, Kristelle A; Akers, Kevin S; Beckius, Miriam L; Landrum, Michael L; Murray, Clinton K

    2013-02-05

    The US military has seen steady increases in multidrug-resistant (MDR) gram-negative bacteria (GNB) infections in casualties from Iraq and Afghanistan. This study evaluates the prevalence of MDR GNB colonization in US military personnel. GNB colonization surveillance of healthy, asymptomatic military personnel (101 in the US and 100 in Afghanistan) was performed by swabbing 7 anatomical sites. US-based personnel had received no antibiotics within 30 days of specimen collection, and Afghanistan-based personnel were receiving doxycycline for malaria chemoprophylaxis at time of specimen collection. Isolates underwent genotypic and phenotypic characterization. The only colonizing MDR GNB recovered in both populations was Escherichia coli (p=0.01), which was seen in 2% of US-based personnel (all perirectal) and 11% of Afghanistan-based personnel (10 perirectal, 1 foot+groin). Individuals with higher off-base exposures in Afghanistan did not show a difference in overall GNB colonization or MDR E. coli colonization, compared with those with limited off-base exposures. Healthy US- and Afghanistan-based military personnel have community onset-MDR E. coli colonization, with Afghanistan-based personnel showing a 5.5-fold higher prevalence. The association of doxycycline prophylaxis or other exposures with antimicrobial resistance and increased rates of MDR E. coli colonization needs further evaluation.

  16. Antibacterial activity of sphingoid bases and fatty acids against Gram-positive and Gram-negative bacteria.

    Fischer, Carol L; Drake, David R; Dawson, Deborah V; Blanchette, Derek R; Brogden, Kim A; Wertz, Philip W

    2012-03-01

    There is growing evidence that the role of lipids in innate immunity is more important than previously realized. How lipids interact with bacteria to achieve a level of protection, however, is still poorly understood. To begin to address the mechanisms of antibacterial activity, we determined MICs and minimum bactericidal concentrations (MBCs) of lipids common to the skin and oral cavity--the sphingoid bases D-sphingosine, phytosphingosine, and dihydrosphingosine and the fatty acids sapienic acid and lauric acid--against four Gram-negative bacteria and seven Gram-positive bacteria. Exact Kruskal-Wallis tests of these values showed differences among lipid treatments (P 500 μg/ml). Sapienic acid (MBC range, 31.3 to 375.0 μg/ml) was active against Streptococcus sanguinis, Streptococcus mitis, and Fusobacterium nucleatum but not active against Escherichia coli, Staphylococcus aureus, S. marcescens, P. aeruginosa, Corynebacterium bovis, Corynebacterium striatum, and Corynebacterium jeikeium (MBC > 500 μg/ml). Lauric acid (MBC range, 6.8 to 375.0 μg/ml) was active against all bacteria except E. coli, S. marcescens, and P. aeruginosa (MBC > 500 μg/ml). Complete killing was achieved as early as 0.5 h for some lipids but took as long as 24 h for others. Hence, sphingoid bases and fatty acids have different antibacterial activities and may have potential for prophylactic or therapeutic intervention in infection.

  17. Blood culture gram stain, acridine orange stain and direct sensitivity-based antimicrobial therapy of bloodstream infection in patients with trauma.

    Behera, B; Mathur, P; Gupta, B

    2010-01-01

    The purpose of this study was to ascertain if the simple practice of Gram stain, acridine orange stain and direct sensitivity determination of positive blood culture bottles could be used to guide early and appropriate treatment in trauma patients with clinical suspicion of sepsis. The study also aimed to evaluate the error in interpreting antimicrobial sensitivity by direct method when compared to standard method and find out if specific antibiotic-organism combination had more discrepancies. Findings from consecutive episodes of blood stream infection at an Apex Trauma centre over a 12-month period are summarized. A total of 509 consecutive positive blood cultures were subjected to Gram staining. AO staining was done in BacT/ALERT-positive Gram-stain negative blood cultures. Direct sensitivity was performed from 369 blood culture broths, showing single type of growth in Gram and acridine orange staining. Results of direct sensitivity were compared to conventional sensitivity for errors. No 'very major' discrepancy was found in this study. About 5.2 and 1.8% minor error rates were noted in gram-positive and gram-negative bacteria, respectively, while comparing the two methods. Most of the discrepancies in gram-negative bacteria were noted in beta lactam - beta lactamase inhibitor combinations. Direct sensitivity testing was not reliable for reporting of methicillin and vancomycin resistance in Staphylococci. Gram stain result together with direct sensitivity testing is required for optimizing initial antimicrobial therapy in trauma patients with clinical suspicion of sepsis. Gram staining and AO staining proved particularly helpful in the early detection of candidaemia.

  18. Bloodstream and endovascular infections due to Abiotrophia defectiva and Granulicatella species

    Bille Jacques

    2006-01-01

    Full Text Available Abstract Background Abiotrophia and Granulicatella species, previously referred to as nutritionally variant streptococci (NVS, are significant causative agents of endocarditis and bacteraemia. In this study, we reviewed the clinical manifestations of infections due to A. defectiva and Granulicatella species that occurred at our institution between 1998 and 2004. Methods The analysis included all strains of NVS that were isolated from blood cultures or vascular graft specimens. All strains were identified by 16S rRNA sequence analysis. Patients' medical charts were reviewed for each case of infection. Results Eleven strains of NVS were isolated during the 6-year period. Identification of the strains by 16S rRNA showed 2 genogroups: Abiotrophia defectiva (3 and Granulicatella adiacens (6 or "para-adiacens" (2. The three A. defectiva strains were isolated from immunocompetent patients with endovascular infections, whereas 7 of 8 Granulicatella spp. strains were isolated from immunosuppressed patients, mainly febrile neutropenic patients. We report the first case of "G. para-adiacens" bacteraemia in the setting of febrile neutropenia. Conclusion We propose that Granulicatella spp. be considered as a possible agent of bacteraemia in neutropenic patients.

  19. Implementation of central line-associated bloodstream infection prevention bundles in a surgical intensive care unit using peer tutoring

    Sang-Won Park

    2017-10-01

    Full Text Available Abstract Background Central line-associated bloodstream infections (CLABSIs can be prevented through well-coordinated, multifaceted programs. However, implementation of CLABSI prevention programs requires individualized strategies for different institutional situations, and the best strategy in resource-limited settings is uncertain. Peer tutoring may be an efficient and effective method that is applicable in such settings. Methods A prospective intervention was performed to reduce CLABSIs in a surgical intensive care unit (SICU at a tertiary hospital. The core interventions consisted of implementation of insertion and maintenance bundles for CLABSI prevention. The overall interventions were guided and coordinated by active educational programs using peer tutoring. The CLABSI rates were compared for 9 months pre-intervention, 6 months during the intervention and 9 months post-intervention. The CLABSI rate was further observed for three years after the intervention. Results The rate of CLABSIs per 1000 catheter-days decreased from 6.9 infections in the pre-intervention period to 2.4 and 1.8 in the intervention (6 m; P = 0.102 and post-intervention (9 m; P = 0.036 periods, respectively. A regression model showed a significantly decreasing trend in the infection rate from the pre-intervention period (P < 0.001, with incidence-rate ratios of 0.348 (95% confidence interval [CI], 0.98–1.23 in the intervention period and 0.257 (95% CI, 0.07–0.91 in the post-intervention period. However, after the 9-month post-intervention period, the yearly CLABSI rates reverted to 3.0–5.4 infections per 1000 catheter-days over 3 years. Conclusions Implementation of CLABSI prevention bundles using peer tutoring in a resource-limited setting was useful and effectively reduced CLABSIs. However, maintaining the reduced CLABSI rate will require further strategies.

  20. The Toll pathway underlies host sexual dimorphism in resistance to both Gram-negative and Gram-positive bacteria in mated Drosophila.

    Duneau, David F; Kondolf, Hannah C; Im, Joo Hyun; Ortiz, Gerardo A; Chow, Christopher; Fox, Michael A; Eugénio, Ana T; Revah, J; Buchon, Nicolas; Lazzaro, Brian P

    2017-12-21

    Host sexual dimorphism is being increasingly recognized to generate strong differences in the outcome of infectious disease, but the mechanisms underlying immunological differences between males and females remain poorly characterized. Here, we used Drosophila melanogaster to assess and dissect sexual dimorphism in the innate response to systemic bacterial infection. We demonstrated sexual dimorphism in susceptibility to infection by a broad spectrum of Gram-positive and Gram-negative bacteria. We found that both virgin and mated females are more susceptible than mated males to most, but not all, infections. We investigated in more detail the lower resistance of females to infection with Providencia rettgeri, a Gram-negative bacterium that naturally infects D. melanogaster. We found that females have a higher number of phagocytes than males and that ablation of hemocytes does not eliminate the dimorphism in resistance to P. rettgeri, so the observed dimorphism does not stem from differences in the cellular response. The Imd pathway is critical for the production of antimicrobial peptides in response to Gram-negative bacteria, but mutants for Imd signaling continued to exhibit dimorphism even though both sexes showed strongly reduced resistance. Instead, we found that the Toll pathway is responsible for the dimorphism in resistance. The Toll pathway is dimorphic in genome-wide constitutive gene expression and in induced response to infection. Toll signaling is dimorphic in both constitutive signaling and in induced activation in response to P. rettgeri infection. The dimorphism in pathway activation can be specifically attributed to Persephone-mediated immune stimulation, by which the Toll pathway is triggered in response to pathogen-derived virulence factors. We additionally found that, in absence of Toll signaling, males become more susceptible than females to the Gram-positive Enterococcus faecalis. This reversal in susceptibility between male and female Toll

  1. Bloodstream Infections and Clinical Significance of Healthcare-associated Bacteremia: A Multicenter Surveillance Study in Korean Hospitals

    Son, Jun Seong; Ko, Kwan Soo; Yeom, Joon Sup; Ki, Hyun Kyun; Kim, Shin-Woo; Chang, Hyun-Ha; Ryu, Seong Yeol; Kim, Yeon-Sook; Jung, Sook-In; Shin, Sang Yop; Oh, Hee Bok; Lee, Yeong Seon; Chung, Doo Ryeon; Lee, Nam Yong; Peck, Kyong Ran

    2010-01-01

    Recent changes in healthcare systems have changed the epidemiologic paradigms in many infectious fields including bloodstream infection (BSI). We compared clinical characteristics of community-acquired (CA), hospital-acquired (HA), and healthcare-associated (HCA) BSI. We performed a prospective nationwide multicenter surveillance study from 9 university hospitals in Korea. Total 1,605 blood isolates were collected from 2006 to 2007, and 1,144 isolates were considered true pathogens. HA-BSI accounted for 48.8%, CA-BSI for 33.2%, and HCA-BSI for 18.0%. HA-BSI and HCA-BSI were more likely to have severe comorbidities. Escherichia coli was the most common isolate in CA-BSI (47.1%) and HCA-BSI (27.2%). In contrast, Staphylococcus aureus (15.2%), coagulase-negative Staphylococcus (15.1%) were the common isolates in HA-BSI. The rate of appropriate empiric antimicrobial therapy was the highest in CA-BSI (89.0%) followed by HCA-BSI (76.4%), and HA-BSI (75.0%). The 30-day mortality rate was the highest in HA-BSI (23.0%) followed by HCA-BSI (18.4%), and CA-BSI (10.2%). High Pitt score and inappropriate empirical antibiotic therapy were the independent risk factors for mortality by multivariate analysis. In conclusion, the present data suggest that clinical features, outcome, and microbiologic features of causative pathogens vary by origin of BSI. Especially, HCA-BSI shows unique clinical characteristics, which should be considered a distinct category for more appropriate antibiotic treatment. PMID:20592888

  2. A case-control study to identify risk factors for totally implantable central venous port-related bloodstream infection.

    Lee, Guk Jin; Hong, Sook Hee; Roh, Sang Young; Park, Sa Rah; Lee, Myung Ah; Chun, Hoo Geun; Hong, Young Seon; Kang, Jin Hyoung; Kim, Sang Il; Kim, Youn Jeong; Chun, Ho Jong; Oh, Jung Suk

    2014-07-01

    To date, the risk factors for central venous port-related bloodstream infection (CVPBSI) in solid cancer patients have not been fully elucidated. We conducted this study in order to determine the risk factors for CVP-BSI in patients with solid cancer. A total of 1,642 patients with solid cancer received an implantable central venous port for delivery of chemotherapy between October 2008 and December 2011 in a single center. CVP-BSI was diagnosed in 66 patients (4%). We selected a control group of 130 patients, who were individually matched with respect to age, sex, and catheter insertion time. CVP-BSI occurred most frequently between September and November (37.9%). The most common pathogen was gram-positive cocci (n=35, 53.0%), followed by fungus (n=14, 21.2%). Multivariate analysis identified monthly catheter-stay as a risk factor for CVP-BSI (p=0.000), however, its risk was lower in primary gastrointestinal cancer than in other cancer (p=0.002). Initial metastatic disease and long catheter-stay were statistically significant factors affecting catheter life span (p=0.005 and p=0.000). Results of multivariate analysis showed that recent transfusion was a risk factor for mortality in patients with CVP-BSI (p=0.047). In analysis of the results with respect to risk factors, prolonged catheter-stay should be avoided as much as possible. It is necessary to be cautious of CVP-BSI in metastatic solid cancer, especially non-gastrointestinal cancer. In addition, avoidance of unnecessary transfusion is essential in order to reduce the mortality of CVP-BSI. Finally, considering the fact that confounding factors may have affected the results, conduct of a well-designed prospective controlled study is warranted.

  3. Comparison of pathogen DNA isolation methods from large volumes of whole blood to improve molecular diagnosis of bloodstream infections.

    Anne J M Loonen

    Full Text Available For patients suffering from bloodstream infections (BSI molecular diagnostics from whole blood holds promise to provide fast and adequate treatment. However, this approach is hampered by the need of large blood volumes. Three methods for pathogen DNA isolation from whole blood were compared, i.e. an enzymatic method (MolYsis, 1-5 ml, the novel non-enzymatic procedure (Polaris, 1-5 ml, and a method that does not entail removal of human DNA (Triton-Tris-EDTA EasyMAG, 200 µl. These methods were evaluated by processing blood spiked with 0-1000 CFU/ml of Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans. Downstream detection was performed with real-time PCR assays. Polaris and MolYsis processing followed by real-time PCRs enabled pathogen detection at clinically relevant concentrations of 1-10 CFU/ml blood. By increasing sample volumes, concurrent lower cycle threshold (Ct values were obtained at clinically relevant pathogen concentrations, demonstrating the benefit of using larger blood volumes. A 100% detection rate at a concentration of 10 CFU/ml for all tested pathogens was obtained with the Polaris enrichment, whereas comparatively lower detection rates were measured for MolYsis (50-67% and EasyMAG (58-79%. For the samples with a concentration of 1 CFU/ml Polaris resulted in most optimal detection rates of 70-75% (MolYsis 17-50% and TTE-EasyMAG 20-36%. The Polaris method was more reproducible, less labour intensive, and faster (45 minutes (including Qiagen DNA extraction vs. 2 hours (MolYsis. In conclusion, Polaris and MolYsis enrichment followed by DNA isolation and real-time PCR enables reliable and sensitive detection of bacteria and fungi from 5 ml blood. With Polaris results are available within 3 hours, showing potential for improved BSI diagnostics.

  4. Characterization and Clinical Impact of Bloodstream Infection Caused by Carbapenemase-Producing Enterobacteriaceae in Seven Latin American Countries.

    Maria Virginia Villegas

    Full Text Available Infections caused by carbapenem-resistant Enterobacteriaceae are a public health problem associated with higher mortality rates, longer hospitalization and increased healthcare costs. We carried out a study to describe the characteristics of patients with carbapenemase-producing Enterobacteriaceae (CPE and non-CPE bloodstream infection (BSI from Latin American hospitals and to determine the clinical impact in terms of mortality and antibiotic therapy.Between July 2013 and November 2014, we conducted a multicenter observational study in 11 hospitals from 7 Latin American countries (Argentina, Colombia, Ecuador, Guatemala, Mexico, Peru, Venezuela. Patients with BSI caused by Enterobacteriaceae were included and classified either as CPE or non-CPE based on detection of blaKPC, blaVIM, blaIMP, blaNDM and blaOXA-48 by polymerase chain reaction. Enrolled subjects were followed until discharge or death. Demographic, microbiological and clinical characteristics were collected from medical records. Both descriptive and inferential statistics were used to analyze the information.A total of 255 patients with Enterobacteriaceae BSI were included; CPE were identified in 53 of them. In vitro non-susceptibility to all screened antibiotics was higher in the patients with CPE BSI, remaining colistin, tigecycline and amikacin as the most active drugs. Combination therapy was significantly more frequent in the CPE BSI group (p < 0.001. The most common regimen was carbapenem + colistin or polymyxin B. The overall mortality was 37% (94/255. Overall and attributable mortality were significantly higher in patients with CPE BSI (p < 0.001; however, we found that patients with CPE BSI who received combination therapy and those who received monotherapy had similar mortality. After multivariate adjustment, CPE BSI (adjusted odds ratio [aOR] 4; 95% confidence interval [CI] 1.7-9.5; p = 0.002 and critical illness (aOR 6.5; 95% CI 3.1-13.7; p < 0.001 were independently

  5. Incidence, risk factors, microbiology of venous catheter associated bloodstream infections - A prospective study from a tertiary care hospital

    M Kaur

    2015-01-01

    Full Text Available Purpose : Central venous catheters (CVCs though indispensable in current medical and intensive care treatment, also puts patients at risk of catheter related infection (CRI resulting in increased morbidity and mortality. We analysed the incidence, risk factors, bacteriological profile and antimicrobial susceptibility pattern of the isolates in central venous catheter associated bloodstream infection (CVC-BSI in the intensive care unit (ICU patients and studied the formation of biofilm in CVCs. Materials and Methods: The following case control study included 115 patients with CVC in situ. Quantitative blood cultures (QBC and catheter tip cultures were performed for the diagnoses. Direct catheter staining was done for an early diagnosis by acridine orange (AO and Gram staining methods. Biofilm production in catheters was detected by ′tissue culture plate′ (TCP method. The results were analysed using the computer-based program statistical package for the social sciences (SPSS. Results : In 25/115 patients, definite diagnosis of CVC-BSI was made. The mean age was 48.44 ± 17.34 years (cases vs 40.10 ± 18.24 years (controls and the mean duration of catheterisation was 25.72 ± 8.73 days (cases vs 11.89 ± 6.38 days (controls. Local signs of infection (erythema, tenderness and oozing were found more significantly in CVC-BSI cases. The AO staining was more sensitive and Gram staining of catheters showed higher specificity. Staphylococcus aureus followed by Pseudomonas aeruginosa and non-albicans Candida were common CVC-BSI pathogens. Multidrug-resistant (MDR strains were isolated in bacterial agents of CVC-BSI. Non-albicans Candida and Enterococcus faecalis showed strong biofilm production. Conclusion : The incidence of CVC-BSI was 21.73% and the rate was 14.59 per 1000 catheter days. Prolonged ICU stay and longer catheterisation were major risk factors. S. aureus was isolated most commonly in CVC-BSI cases. The menace of multidrug resistance and

  6. Characterization and Clinical Impact of Bloodstream Infection Caused by Carbapenemase-Producing Enterobacteriaceae in Seven Latin American Countries

    Villegas, Maria Virginia; Pallares, Christian J.; Hernández-Gómez, Cristhian; Correa, Adriana; Álvarez, Carlos; Rosso, Fernando; Matta, Lorena; Luna, Carlos; Zurita, Jeannete; Mejía-Villatoro, Carlos; Rodríguez-Noriega, Eduardo; Seas, Carlos; Cortesía, Manuel; Guzmán-Suárez, Alfonso; Guzmán-Blanco, Manuel

    2016-01-01

    Introduction Infections caused by carbapenem-resistant Enterobacteriaceae are a public health problem associated with higher mortality rates, longer hospitalization and increased healthcare costs. We carried out a study to describe the characteristics of patients with carbapenemase-producing Enterobacteriaceae (CPE) and non-CPE bloodstream infection (BSI) from Latin American hospitals and to determine the clinical impact in terms of mortality and antibiotic therapy. Methods Between July 2013 and November 2014, we conducted a multicenter observational study in 11 hospitals from 7 Latin American countries (Argentina, Colombia, Ecuador, Guatemala, Mexico, Peru, Venezuela). Patients with BSI caused by Enterobacteriaceae were included and classified either as CPE or non-CPE based on detection of blaKPC, blaVIM, blaIMP, blaNDM and blaOXA-48 by polymerase chain reaction. Enrolled subjects were followed until discharge or death. Demographic, microbiological and clinical characteristics were collected from medical records. Both descriptive and inferential statistics were used to analyze the information. Results A total of 255 patients with Enterobacteriaceae BSI were included; CPE were identified in 53 of them. In vitro non-susceptibility to all screened antibiotics was higher in the patients with CPE BSI, remaining colistin, tigecycline and amikacin as the most active drugs. Combination therapy was significantly more frequent in the CPE BSI group (p < 0.001). The most common regimen was carbapenem + colistin or polymyxin B. The overall mortality was 37% (94/255). Overall and attributable mortality were significantly higher in patients with CPE BSI (p < 0.001); however, we found that patients with CPE BSI who received combination therapy and those who received monotherapy had similar mortality. After multivariate adjustment, CPE BSI (adjusted odds ratio [aOR] 4; 95% confidence interval [CI] 1.7–9.5; p = 0.002) and critical illness (aOR 6.5; 95% CI 3.1–13.7; p < 0

  7. Central Venous Catheter-Related Bloodstream Infection with Kocuria kristinae in a Patient with Propionic Acidemia.

    Kimura, Masato; Kawai, Eichiro; Yaoita, Hisao; Ichinoi, Natsuko; Sakamoto, Osamu; Kure, Shigeo

    2017-01-01

    Kocuria kristinae is a catalase-positive, coagulase-negative, Gram-positive coccus found in the environment and in normal skin and mucosa in humans; however, it is rarely isolated from clinical specimens and is considered a nonpathogenic bacterium. We describe a case of catheter-related bacteremia due to K. kristinae in a young adult with propionic acidemia undergoing periodic hemodialysis. The patient had a central venous catheter implanted for total parenteral nutrition approximately 6 months prior to the onset of symptoms because of repeated acute pancreatitis. K. kristinae was isolated from two sets of blood cultures collected from the catheter. Vancomycin followed by cefazolin for 16 days and 5-day ethanol lock therapy successfully eradicated the K. kristinae bacteremia. Although human infections with this organism appear to be rare and are sometimes considered to result from contamination, physicians should not underestimate its significance when it is isolated in clinical specimens.

  8. Central Venous Catheter-Related Bloodstream Infection with Kocuria kristinae in a Patient with Propionic Acidemia

    Masato Kimura

    2017-01-01

    Full Text Available Kocuria kristinae is a catalase-positive, coagulase-negative, Gram-positive coccus found in the environment and in normal skin and mucosa in humans; however, it is rarely isolated from clinical specimens and is considered a nonpathogenic bacterium. We describe a case of catheter-related bacteremia due to K. kristinae in a young adult with propionic acidemia undergoing periodic hemodialysis. The patient had a central venous catheter implanted for total parenteral nutrition approximately 6 months prior to the onset of symptoms because of repeated acute pancreatitis. K. kristinae was isolated from two sets of blood cultures collected from the catheter. Vancomycin followed by cefazolin for 16 days and 5-day ethanol lock therapy successfully eradicated the K. kristinae bacteremia. Although human infections with this organism appear to be rare and are sometimes considered to result from contamination, physicians should not underestimate its significance when it is isolated in clinical specimens.

  9. A coagulase-negative and non-haemolytic strain of Staphylococcus aureus for investigating the roles of SrtA in a murine model of bloodstream infection.

    Wang, Lin; Bi, Chongwei; Wang, Tiedong; Xiang, Hua; Chen, Fuguang; Hu, Jinping; Liu, Bingrun; Cai, Hongjun; Zhong, Xiaobo; Deng, Xuming; Wang, Dacheng

    2015-08-01

    Sortase A (SrtA) is a cysteine transpeptidase and virulence factor from Staphylococcus aureus (S. aureus) that catalyses the attachment and display of surface proteins on the cell wall, thereby mediating bacterial adhesion to host tissues, host-cell entry and evasion of the immune response. As a result, SrtA has become an important target in the development of therapies for S. aureus infections. In this study, we used the new reference strain S. aureus Newman D2C to investigate the role of SrtA in a murine model of bloodstream infection, when the impact of coagulase and haemolysin is excluded. The results suggested that deletion of SrtA reduced the bacterial burden on the heart, liver and kidneys by blunting the host proinflammatory cytokine response at an early point in infection. Kidneys, but not heart or liver, formed abscesses on the sixth day following non-lethal infection, and this effect was diminished by SrtA mutation. These findings indicate that SrtA is a determining virulence factor in lethality and formation of renal abscesses in mice followed by S. aureus bloodstream infection. We have thus established a convenient in vitro and mouse model for developing SrtA-targeted therapeutic strategies. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Biomarkers and Molecular Analysis to Improve Bloodstream Infection Diagnostics in an Emergency Care Unit

    Loonen, Anne J. M.; de Jager, Cornelis P. C.; Tosserams, Janna; Kusters, Ron; Hilbink, Mirrian; Wever, Peter C.; van den Brule, Adriaan J. C.

    2014-01-01

    Molecular pathogen detection from blood is still expensive and the exact clinical value remains to be determined. The use of biomarkers may assist in preselecting patients for immediate molecular testing besides blood culture. In this study, 140 patients with ≥ 2 SIRS criteria and clinical signs of infection presenting at the emergency department of our hospital were included. C-reactive protein (CRP), neutrophil-lymphocyte count ratio (NLCR), procalcitonin (PCT) and soluble urokinase plasminogen activator receptor (suPAR) levels were determined. One ml EDTA blood was obtained and selective pathogen DNA isolation was performed with MolYsis (Molzym). DNA samples were analysed for the presence of pathogens, using both the MagicPlex Sepsis Test (Seegene) and SepsiTest (Molzym), and results were compared to blood cultures. Fifteen patients had to be excluded from the study, leaving 125 patients for further analysis. Of the 125 patient samples analysed, 27 presented with positive blood cultures of which 7 were considered to be contaminants. suPAR, PCT, and NLCR values were significantly higher in patients with positive blood cultures compared to patients without (p molecular assays perform poorly when one ml whole blood is used from emergency care unit patients. NLCR is a cheap, fast, easy to determine, and rapidly available biomarker, and therefore seems most promising in differentiating BSI from non-BSI patients for subsequent pathogen identification using molecular diagnostics. PMID:24475269

  11. Emergence of Livestock-Associated Methicillin-Resistant Staphylococcus aureus Bloodstream Infections in Denmark

    Larsen, Jesper; Petersen, Andreas; Larsen, Anders R.

    2017-01-01

    infections (BSIs) has not been well studied. Methods: We investigated the clinical epidemiology of all human cases of LA-MRSA CC398 BSI during 2010-2015. Cases of LA-MRSA CC398 BSI were compared to cases of BSI caused by other types of MRSA and cases of SSTI caused by LA-MRSA CC398. Whole-genome sequence...... analysis was used to assess the phylogenetic relationship among LA-MRSA CC398 isolates from Danish pigs and cases of BSI and SSTI. Results: The number of LA-MRSA CC398 BSIs and SSTIs increased over the years, peaking in 2014, when LA-MRSA CC398 accounted for 16% (7/44) and 21% (211/985) of all MRSA BSIs...... and SSTIs, corresponding to 1.2 and 37.4 cases of BSI and SSTI per 1 000 000 person-years, respectively. Most patients with LA-MRSA CC398 BSI had no contact to livestock, although they tended to live in rural areas. LA-MRSA CC398 caused 24.3 BSIs per 1000 SSTIs among people with no livestock contact, which...

  12. Procalcitonin as a diagnostic biomarker for septic shock and bloodstream infection in burn patients from the Formosa Fun Coast dust explosion.

    Wu, Rui-Xin; Chiu, Chih-Chien; Lin, Tzu-Chao; Yang, Ya-Sung; Lee, Yi; Lin, Jung-Chung; Chang, Feng-Yee

    2017-12-01

    Infection is the most common cause of death following burn injury. The study was conducted to compare the diagnostic value of serum procalcitonin (PCT) with the other current benchmarks as early predictors of septic shock and bloodstream infection in burn patients. We included 24 patients admitted to the Burn Unit of a medical center from June 2015 to December 2015 from the Formosa Fun Coast dust explosion. We categorized all patients at initial admission into either sepsis or septic shock groups. Laboratory tests including the worst PCT and C-reactive protein (CRP) levels, platelet (PLT), and white blood cell (WBC) count were performed at <48 h after admission. Patients were also classified in two groups with subsequent bacteremia and non-bacteremia groups during hospitalization. Significantly higher PCT levels were observed among participants with septic shock compared to those with sepsis (47.19 vs. 1.18 ng/mL, respectively; p < 0.001). Patients with bacteremia had significantly elevated PCT levels compared to patients without bacteremia (29.54 versus 1.81 ng/mL, respectively, p < 0.05). No significant differences were found in CRP levels, PLT, and WBC count between the two groups. PCT levels showed reasonable discriminative power (cut-off: 5.12 ng/mL; p = 0.01) in predicting of bloodstream infection in burn patients and the area under receiver operating curves was 0.92. PCT levels can be helpful in determining the septic shock and bloodstream infection in burn patients but CRP levels, PLT, and WBC count were of little diagnostic value. Copyright © 2017. Published by Elsevier B.V.

  13. Resistance Markers and Genetic Diversity in Acinetobacter baumannii Strains Recovered from Nosocomial Bloodstream Infections

    Hanoch S. I. Martins

    2014-01-01

    Full Text Available In this study, phenotypic and genotypic methods were used to detect metallo-β-lactamases, cephalosporinases and oxacillinases and to assess genetic diversity among 64 multiresistant Acinetobacter baumannii strains recovered from blood cultures in five different hospitals in Brazil from December 2008 to June 2009. High rates of resistance to imipenem (93.75% and polymyxin B (39.06% were observed using the disk diffusion (DD method and by determining the minimum inhibitory concentration (MIC. Using the disk approximation method, thirty-nine strains (60.9% were phenotypically positive for class D enzymes, and 51 strains (79.6% were positive for cephalosporinase (AmpC. Using the E-test, 60 strains (93.75% were positive for metallo-β-lactamases (MβLs. All strains were positive for at least one of the 10 studied genes; 59 (92.1% contained blaVIM-1, 79.6% contained blaAmpC, 93.7% contained blaOXA23 and 84.3% contained blaOXA51. Enterobacteria Repetitive Intergenic Consensus (ERIC-PCR analysis revealed a predominance of certain clones that differed from each other. However, the same band pattern was observed in samples from the different hospitals studied, demonstrating correlation between the genotypic and phenotypic results. Thus, ERIC-PCR is an appropriate method for rapidly clustering genetically related isolates. These results suggest that defined clonal clusters are circulating within the studied hospitals. These results also show that the prevalence of MDR A. baumannii may vary among clones disseminated in specific hospitals, and they emphasize the importance of adhering to appropriate infection control measures.

  14. Gram-negative bacteria account for main differences between faecal microbiota from patients with ulcerative colitis and healthy controls

    Vigsnæs, Louise Kristine; Brynskov, J.; Steenholdt, C.

    2012-01-01

    process of the gut mucosa. The aim of this study was to investigate the faecal microbiota in patients either with UC in remission (n=6) or with active disease (n=6), and in healthy controls (n=6). The composition of Gram-negative bacteria and Gram-positive bacteria was examined. Antigenic structures...... of Gram-negative bacteria such as lipopolysaccharides have been related to the inflammatory responses and pathogenesis of inflammatory bowel disease. Dice cluster analysis and principal component analysis of faecal microbiota profiles obtained by denaturing gradient gel electrophoresis and quantitative...... PCR, respectively, revealed that the composition of faecal bacteria from UC patients with active disease differed from the healthy controls and that this difference should be ascribed to Gram-negative bacteria. The analysis did not show any clear grouping of UC patients in remission. Even...

  15. Bloodstream infection rates in outpatient hemodialysis facilities participating in a collaborative prevention effort: a quality improvement report.

    Patel, Priti R; Yi, Sarah H; Booth, Stephanie; Bren, Virginia; Downham, Gemma; Hess, Sally; Kelley, Karen; Lincoln, Mary; Morrissette, Kathy; Lindberg, Curt; Jernigan, John A; Kallen, Alexander J

    2013-08-01

    Bloodstream infections (BSIs) cause substantial morbidity in hemodialysis patients. In 2009, the US Centers for Disease Control and Prevention (CDC) sponsored a collaborative project to prevent BSIs in outpatient hemodialysis facilities. We sought to assess the impact of a set of interventions on BSI and access-related BSI rates in participating facilities using data reported to the CDC's National Healthcare Safety Network (NHSN). Quality improvement project. Patients in 17 outpatient hemodialysis facilities that volunteered to participate. Facilities reported monthly event and denominator data to NHSN, received guidance from the CDC, and implemented an evidence-based intervention package that included chlorhexidine use for catheter exit-site care, staff training and competency assessments focused on catheter care and aseptic technique, hand hygiene and vascular access care audits, and feedback of infection and adherence rates to staff. Crude and modeled BSI and access-related BSI rates. Up to 12 months of preintervention (January 2009 through December 2009) and 15 months of intervention period (January 2010 through March 2011) data from participating centers were analyzed. Segmented regression analysis was used to assess changes in BSI and access-related BSI rates during the preintervention and intervention periods. Most (65%) participating facilities were hospital based. Pooled mean BSI and access-related BSI rates were 1.09 and 0.73 events per 100 patient-months during the preintervention period and 0.89 and 0.42 events per 100 patient-months during the intervention period, respectively. Modeled rates decreased 32% (P = 0.01) for BSIs and 54% (P facilities were not representative of all outpatient hemodialysis centers nationally. There was no control arm to this quality improvement project. Facilities participating in a collaborative successfully decreased their BSI and access-related BSI rates. The decreased rates appeared to be maintained in the intervention

  16. Risk factors for carbapenem resistant bacteraemia and mortality due to gram negative bacteraemia in a developing country

    Kalam, K.; Kumar, S.; Ali, S.; Baqi, S.; Qamar, F.

    2014-01-01

    Objective: To identify the risk factors for carbapenem resistant bacteraemia and mortality due to gram negative bacteraemia in a developing country. Methods: A prospective cohort study was conducted at the Sindh Institute of Urology and Transplantation (SIUT) from June to October 2012. Hospitalized patients > 15 years of age with gram negative bacteraemia were included and followed for a period of 2 weeks for in hospital mortality. Data was collected and analyzed for 243 subjects. Multivariate analysis was used to determine the risk factors for carbapenem resistant bacteraemia and mortality due to gram negative bacteraemia. Crude and adjusted odds ratio and 95% CI are reported. Results: A total of 729 out of 1535 (47.5%) cultures were positive for gram negative isolates. Out of 243 subjects, 117 (48%) had an MDR isolate. Having an MDR isolate on culture (AOR, 2.33; 95% CI, 1.35 -4.0), having multiple positive cultures (AOR, 1.8; 95% CI, 0.94 -3.4) and stay in ICU >48 hours (AOR, 2.0 ; 95% CI, 1.12 -3.78) were identified as significant risk factors for mortality due to gram negative organisms. Risk factors for carbapenem resistant bacteraemia were age >50 years (AOR, 1.83; 95% CI, 1.0-3.5), septic shock on presentation (AOR 2.53; 95% CI, 1.03 -6.2) , ICU stay of >72 hours (AOR 2.40; 95% CI, 1.14-5.0) and receiving immunosuppressant medications (AOR 2.23; 95% CI, 0.74 - 6.7). Conclusion: There is a high burden of MDR and carbapenem resistant gram negative bacteraemia, with a high mortality rate. (author)

  17. Antimicrobial Activity of Carbon Nanoparticles Isolated from Natural Sources against Pathogenic Gram-Negative and Gram-Positive Bacteria

    Varghese, S.; Jose, S.; Varghese, S.; Kuriakose, S.; Jose, S.

    2013-01-01

    This paper describes the isolation of carbon nanoparticles (CNPs) from kitchen soot, characterization of the CNPs by UV/visible spectroscopy, SEM and XRD, and their antimicrobial action. The antibacterial activity of the isolated carbon nanoparticles was tested against various pathogenic bacterial strains such as Gram-negative Proteus refrigere and Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus and Streptococcus haemolyticus. The inhibition zones were measured, and it was found that the carbon nanoparticles isolated from natural sources are active against these Gram-negative and Gram-positive bacterial strains

  18. Evaluation of pyrrolidonyl arylamidase for the identification of nonfermenting Gram-negative rods.

    Bombicino, Karina A; Almuzara, Marisa N; Famiglietti, Angela M R; Vay, Carlos

    2007-01-01

    To evaluate the activity of pyrrolidonyl arylamidase (PYR) for the differentiation and identification of nonfermenting gram negative rods (NFGNR), 293 isolates were tested. A 24 h culture of each test organism was prepared. From this a 108-109 cfu/mL suspension was added to 0.25 mL of sterile physiologic solution. A PYR disk was then added and the test was incubated for 30 minutes at 35-37 degrees C, at environmental atmosphere. Reading was done by adding 1 drop of cinnamaldehyde reagent. Strains of Acinetobacter baumannii, Acinetobacter haemolyticus, Alcaligenes faecalis, Bergeyella zoohelcum, Bordetella bronchiseptica, Bordetella hinzii, Brevundimonas diminuta, Brevundimonas vesicularis, Brucella ovis, Brucella spp., Brucella suis, Burkholderia cepacia complex, Moraxella catarrhalis, Moraxella lacunata, Moraxella nonliquefaciens, Moraxella osloensis, Oligella ureolytica, Pseudomonas alcaligenes, Pseudomonas mendocina, Pseudomonas pseudoalcaligenes, Pseudomonas putida, Pseudomonas stutzeri, Pseudomonas Vb3, Psychrobacter phenylpyruvicus, and Stenotrophomonas maltophilia were PYR negative. On the other hand Achromobacter piechaudii, Achromobacter denitrificans, Achromobacter xylosoxidans, Burkholderia gladioli, Chryseobacterium gleum-indologenes, Comamonas testosroni, Cupriavidus pauculus, Delftia acidovorans, Elizabethkingia meningoseptica, Myroides spp., Ochrobactrum anthropi, Pseudomonas oryzihabitans, Ralstonia pickettii, Rhizobium radiobacter, Shewanella spp., Sphingobacterium multivorum, Sphingobacterium spiritivorum, and Weeksella virosa were PYR positive. Finally, Acinetobacter lwoffii, Pseudomonas aeruginosa, Pseudomonas fluorescens, Roseomonas spp., and Sphingomonas paucimobilis-parapaucimobilis were PYR variable. PYR testing should be considered as a useful tool to facilitate the identification of NFGNR.

  19. Trends of 9,416 multidrug-resistant Gram-negative bacteria

    Viviane Decicera Colombo Oliveira

    2015-06-01

    Full Text Available Summary Objective: a resistance of hospital-acquired bacteria to multiple antibiotics is a major concern worldwide. The objective of this study was to investigate multidrugresistant (MDR bacteria, clinical specimens, origin of specimen and trends, and correlate these with bacterial sensitivity and consumption of antimicrobials. Methods: 9,416 bacteria of nosocomial origin were evaluated in a tertiary hospital, from 1999 to 2008. MDR was defined for Gram-negative bacteria (GNB as resistance to two or more classes/groups of antibiotics. Results: GNB MDR increased by 3.7 times over the study period (p<0.001. Acinetobacter baumannii was the most prevalent (36.2%. Over the study period, there were significant 4.8-fold and 14.6-fold increases for A. baumannii and K. pneumoniae (p<0.001, respectively. Sixty-seven percent of isolates of MDR GNB were isolated in intensive care units. The resistance of A. baumannii to carbapenems increased from 7.4 to 57.5% during the study period and concomitant with an increased consumption. Conclusion: that decade showed prevalence of GNB and a gradual increase in MDR GNB. There was an increase in carbapenem resistance of 50.1% during the study.

  20. Bio sorption of some Rare Earth Elements and Yttrium by Gram Positive and Gram Negative Bacteria

    Ibrahim, H.A.

    2012-01-01

    The separate bio sorption of the REEs La, Sm, Eu and Dy together with yttrium upon the Gram positive bacteria Bacillus subtilis (B.subtilis) and Bacillus Licheniformis (B. Licheniformis),the Gram negative bacterium Escherichia coli (E. coli ) and Saccharomyces cervisiae (Yeast) was studied. The revelant factors of ph 1-6, contact time (30-180 min), the initial rare earth concentration (50-200 mg/l) have been studied. The amount of the accumulated element was strongly affected by its concentration.In addition, bio sorptive fractionation of Y and the studied REEs from a solution containing a mixture of these elements was also studied. From the obtained data, it was found that Langmuir isotherm model for both B.licheniformis and E.coli gives a best fit for the studied elements over the working range of concentration (50-200 mg/I). Transmission electron microscopy exhibited accumulation throughout the bacterial cell with some granular deposits in both the cell periphery and cytoplasm

  1. Functional characterization of Gram-negative bacteria from different genera as multiplex cadmium biosensors.

    Bereza-Malcolm, Lara; Aracic, Sanja; Kannan, Ruban; Mann, Gülay; Franks, Ashley E

    2017-08-15

    Widespread presence of cadmium in soil and water systems is a consequence of industrial and agricultural processes. Subsequent accumulation of cadmium in food and drinking water can result in accidental consumption of dangerous concentrations. As such, cadmium environmental contamination poses a significant threat to human health. Development of microbial biosensors, as a novel alternative method for in situ cadmium detection, may reduce human exposure by complementing traditional analytical methods. In this study, a multiplex cadmium biosensing construct was assembled by cloning a single-output cadmium biosensor element, cadRgfp, and a constitutively expressed mrfp1 onto a broad-host range vector. Incorporation of the duplex fluorescent output [green and red fluorescence proteins] allowed measurement of biosensor functionality and viability. The biosensor construct was tested in several Gram-negative bacteria including Pseudomonas, Shewanella and Enterobacter. The multiplex cadmium biosensors were responsive to cadmium concentrations ranging from 0.01 to 10µgml -1 , as well as several other heavy metals, including arsenic, mercury and lead at similar concentrations. The biosensors were also responsive within 20-40min following exposure to 3µgml -1 cadmium. This study highlights the importance of testing biosensor constructs, developed using synthetic biology principles, in different bacterial genera. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. RND-type Drug Efflux Pumps from Gram-negative bacteria: Molecular Mechanism and Inhibition

    Henrietta eVenter

    2015-04-01

    Full Text Available Drug efflux protein complexes confer multidrug resistance on bacteria by transporting a wide spectrum of structurally diverse antibiotics. Moreover, organisms can only acquire resistance in the presence of an active efflux pump. The substrate range of drug efflux pumps is not limited to antibiotics, but it also includes toxins, dyes, detergents, lipids and molecules involved in quorum sensing; hence efflux pumps are also associated with virulence and biofilm formation. Inhibitors of efflux pumps are therefore attractive compounds to reverse multidrug resistance and to prevent the development of resistance in clinically relevant bacterial pathogens. Recent successes on the structure determination and functional analysis of the AcrB and MexB components of the AcrAB-TolC and MexAB-OprM drug efflux systems as well as the structure of the fully assembled, functional triparted AcrAB-TolC complex significantly contributed to our understanding of the mechanism of substrate transport and the options for inhibition of efflux. These data, combined with the well-developed methodologies for measuring efflux pump inhibition, could allow the rational design and subsequent experimental verification of potential efflux pump inhibitors. In this review we will explore how the available biochemical and structural information can be translated into the discovery and development of new compounds that could reverse drug resistance in Gram-negative pathogens. The current literature on efflux pump inhibitors will also be analysed and the reasons why no compounds have yet progressed into clinical use will be explored.

  3. Induction of gram-negative bacterial growth by neurochemical containing banana (Musa x paradisiaca) extracts.

    Lyte, M

    1997-09-15

    Bananas contain large quantities of neurochemicals. Extracts from the peel and pulp of bananas in increasing stages of ripening were prepared and evaluated for their ability to modulate the growth of non-pathogenic and pathogenic bacteria. Extracts from the peel, and to a much lesser degree the pulp, increased the growth of Gram-negative bacterial strains Escherichia coli O157:H7, Shigella flexneri, Enterobacter cloacae and Salmonella typhimurium, as well as two non-pathogenic E. coli strains, in direct relation to the content of norepinephrine and dopamine, but not serotonin. The growth of Gram-positive bacteria was not altered by any of the extracts. Supplementation of vehicle and pulp cultures with norepinephrine or dopamine yielded growth equivalent to peel cultures. Total organic analysis of extracts further demonstrated that the differential effects of peel and pulp on bacterial growth was not nutritionally based, but due to norepinephrine and dopamine. These results suggest that neurochemicals contained within foodstuffs may influence the growth of pathogenic and indigenous bacteria through direct neurochemical-bacterial interactions.

  4. Small-Molecule Inhibitors of Gram-Negative Lipoprotein Trafficking Discovered by Phenotypic Screening

    Fleming, Paul R.; MacCormack, Kathleen; McLaughlin, Robert E.; Whiteaker, James D.; Narita, Shin-ichiro; Mori, Makiko; Tokuda, Hajime; Miller, Alita A.

    2015-01-01

    In Gram-negative bacteria, lipoproteins are transported to the outer membrane by the Lol system. In this process, lipoproteins are released from the inner membrane by the ABC transporter LolCDE and passed to LolA, a diffusible periplasmic molecular chaperone. Lipoproteins are then transferred to the outer membrane receptor protein, LolB, for insertion in the outer membrane. Here we describe the discovery and characterization of novel pyridineimidazole compounds that inhibit this process. Escherichia coli mutants resistant to the pyridineimidazoles show no cross-resistance to other classes of antibiotics and map to either the LolC or LolE protein of the LolCDE transporter complex. The pyridineimidazoles were shown to inhibit the LolA-dependent release of the lipoprotein Lpp from E. coli spheroplasts. These results combined with bacterial cytological profiling are consistent with LolCDE-mediated disruption of lipoprotein targeting to the outer membrane as the mode of action of these pyridineimidazoles. The pyridineimidazoles are the first reported inhibitors of the LolCDE complex, a target which has never been exploited for therapeutic intervention. These compounds open the door to further interrogation of the outer membrane lipoprotein transport pathway as a target for antimicrobial therapy. PMID:25583975

  5. Multidrug-resistant Gram-negative bacteria: a product of globalization.

    Hawkey, P M

    2015-04-01

    Global trade and mobility of people has increased rapidly over the last 20 years. This has had profound consequences for the evolution and the movement of antibiotic resistance genes. There is increasing exposure of populations all around the world to resistant bacteria arising in the emerging economies. Arguably the most important development of the last two decades in the field of antibiotic resistance is the emergence and spread of extended-spectrum β-lactamases (ESBLs) of the CTX-M group. A consequence of the very high rates of ESBL production among Enterobacteriaceae in Asian countries is that there is a substantial use of carbapenem antibiotics, resulting in the emergence of plasmid-mediated resistance to carbapenems. This article reviews the emergence and spread of multidrug-resistant Gram-negative bacteria, focuses on three particular carbapenemases--imipenem carbapenemases, Klebsiella pneumoniae carbapenemase, and New Delhi metallo-β-lactamase--and highlights the importance of control of antibiotic use. Copyright © 2015. Published by Elsevier Ltd.

  6. Molecular Structure of Endotoxins from Gram-negative Marine Bacteria: An Update

    Antonio Molinaro

    2007-09-01

    Full Text Available Marine bacteria are microrganisms that have adapted, through millions of years, to survival in environments often characterized by one or more extreme physical or chemical parameters, namely pressure, temperature and salinity. The main interest in the research on marine bacteria is due to their ability to produce several biologically active molecules, such as antibiotics, toxins and antitoxins, antitumor and antimicrobial agents. Nonetheless, lipopolysaccharides (LPSs, or their portions, from Gram-negative marine bacteria, have often shown low virulence, and represent potential candidates in the development of drugs to prevent septic shock. Besides, the molecular architecture of such molecules is related to the possibility of thriving in marine habitats, shielding the cell from the disrupting action of natural stress factors. Over the last few years, the depiction of a variety of structures of lipids A, core oligosaccharides and O-specific polysaccharides from LPSs of marine microrganisms has been given. In particular, here we will examine the most recently encountered structures for bacteria belonging to the genera Shewanella, Pseudoalteromonas and Alteromonas, of the γ-Proteobacteria phylum, and to the genera Flavobacterium, Cellulophaga, Arenibacter and Chryseobacterium, of the Cytophaga- Flavobacterium-Bacteroides phylum. Particular attention will be paid to the chemical features expressed by these structures (characteristic monosaccharides, non-glycidic appendages, phosphate groups, to the typifying traits of LPSs from marine bacteria and to the possible correlation existing between such features and the adaptation, over years, of bacteria to marine environments.

  7. Small-molecule inhibitors of gram-negative lipoprotein trafficking discovered by phenotypic screening.

    McLeod, Sarah M; Fleming, Paul R; MacCormack, Kathleen; McLaughlin, Robert E; Whiteaker, James D; Narita, Shin-Ichiro; Mori, Makiko; Tokuda, Hajime; Miller, Alita A

    2015-03-01

    In Gram-negative bacteria, lipoproteins are transported to the outer membrane by the Lol system. In this process, lipoproteins are released from the inner membrane by the ABC transporter LolCDE and passed to LolA, a diffusible periplasmic molecular chaperone. Lipoproteins are then transferred to the outer membrane receptor protein, LolB, for insertion in the outer membrane. Here we describe the discovery and characterization of novel pyridineimidazole compounds that inhibit this process. Escherichia coli mutants resistant to the pyridineimidazoles show no cross-resistance to other classes of antibiotics and map to either the LolC or LolE protein of the LolCDE transporter complex. The pyridineimidazoles were shown to inhibit the LolA-dependent release of the lipoprotein Lpp from E. coli spheroplasts. These results combined with bacterial cytological profiling are consistent with LolCDE-mediated disruption of lipoprotein targeting to the outer membrane as the mode of action of these pyridineimidazoles. The pyridineimidazoles are the first reported inhibitors of the LolCDE complex, a target which has never been exploited for therapeutic intervention. These compounds open the door to further interrogation of the outer membrane lipoprotein transport pathway as a target for antimicrobial therapy. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  8. The attenuation effect of UVc radiation doses in gram-negative bacteria (Brucella, Yersinia, Escherichia coli)

    Al-Mariri, A.

    2007-01-01

    The gram-negative bacteria Yersinia enterocolitica sero group O:3 and O:9, and Brucella (Melitensis and abortus) together with Escherichia coli (O:157, DH5alpha-pEt15b), were investigated to evaluate their susceptibility to UV radiation at 254 nm. If the dose of UVc was 18.7 mW/cm2, the time required for inactivation of Y. enterocolitica and E. coli DH5alpha-pEt15b and O:157 was 240s and 360s in the dark and light respectively. Where if the dose was 19.5 mW/cm2, the time required was 60s in the dark and 120s in light respectively. The time required for inactivation of Brucella strains (melitensis and abortus) if the dose was 18.7 mW/cm2 was 240s in both dark and light, whereas it was 120s (dark) and 240s (light) respectively, when the dose was 19.5 mW/cm2. Using E. coli O:157 as control, it appears that Y. enterocolitica sero group O:3 and O:9 and vaccinal strains of Brucella (Rev. 1 and S19) are more sensitive to UV than wild Brucella strains. No relation was found between the sensitivity of Y. enterocolitica to UV and the presence or absence of a pYV+ virulence plasmid. (author)

  9. In vitro susceptibility pattern of extended spectrum ?-lactamase producing gram negative bacilli against tetracyclines

    Gill, M.M.

    2015-01-01

    Extended Spectrum beta-lactamases (ESBLs) are emerging as common nosocomial pathogens and important cause of mortality and morbidity, if not treated properly. The need of the hour is to find effective treatment options for dealing with ESBL producing organisms. This study was aimed to evaluate in vitro susceptibility pattern of extended spectrum beta-lactamase producers against tetracyclines. Methods: This descriptive cross-sectional study was carried out in the department of Microbiology, Army Medical College, Rawalpindi, National University of Sciences and Technology over a period of 6 months. Seventy eight non-duplicate isolates were included in the study. ESBL detection was done using Jarlier et al method. In vitro susceptibility of tetracyclines like tetracycline, doxycycline, minocycline and tigecycline was then tested using Modified Kirby Bauer disc diffusion method. The zones of inhibition were measured after completion of incubation period and interpreted as per CLSI and FDA guidelines. Results: Approximately 56.4% of the isolates were Escherichia coli, 28.2% were Klebsiella pneumoniae, 10.26% were Enterobacter species, and 2.6% were each Klebsiella oxytoca and Acinetobacter species. ESBLs were found to be most sensitive to tigecycline, intermediate in susceptibility to minocycline while least sensitive to doxycycline and tetracycline. Conclusion: Among tetracyclines, tigecycline has best in vitro susceptibility against ESBL producing Gram negative rods. (author)

  10. Effect of chelators and nisin produced in situ on inhibition and inactivation of gram negatives.

    Boziaris, I S; Adams, M R

    1999-12-15

    The ability of chelators and nisin generated in situ to inhibit and inactivate E. coli and other gram negatives in a model substrate was investigated. The effect of various chelators and different concentrations of exogenous nisin on inhibition of E. coli in broth medium showed that only EDTA and pyrophosphates were able to cause appreciable inhibition of E. coli by nisin. In a broth where L. lactis NCFB 497 produced nisin in a concentration of 250-300 IU/ml, pyrophosphates were unable to inactivate E. coli. Under the same conditions, addition of EDTA led to inactivation of E. coli at neutral and slightly acidic pH only. A cocktail of strains of E. coli was less sensitive than E. coli ATCC 25922 alone. Pseudomonas aeruginosa was more sensitive and salmonellae more resistant. EDTA also caused a slight reduction in the L. lactis population and its biochemical activity as regards pH drop and acid production. Some of the inhibition of E. coli could be ascribed to the physical presence of Lactococcus cells rather than their metabolites excreted into the medium. Failure to observe any inhibition in fermented broths at their natural pH (4.0) was ascribed to the poor chelating power of EDTA under acid conditions.

  11. Cytokine profile in severe gram-positive and gram-negative abdominal sepsis

    Surbatovic, Maja; Popovic, Nada; Vojvodic, Danilo; Milosevic, Ivan; Acimovic, Gordana; Stojicic, Milan; Veljovic, Milic; Jevdjic, Jasna; Djordjevic, Dragan; Radakovic, Sonja

    2015-01-01

    Sepsis is a principal cause of death in critical care units worldwide and consumes considerable healthcare resources. The aim of our study was to determine whether the early cytokine profile can discriminate between Gram-positive and Gram-negative bacteraemia (GPB and GNB, respectively) and to assess the prognostic value regarding outcome in critically ill patients with severe abdominal sepsis. The outcome measure was hospital mortality. Blood samples were obtained from 165 adult patients with confirmed severe abdominal sepsis. Levels of the proinflammatory mediators TNF-α, IL-8, IL-12 and IFN-γ and the anti-inflammatory mediators IL-1ra, IL-4, IL-10 and TGF-β1 were determined and correlated with the nature of the bacteria isolated from the blood culture and outcome. The cytokine profile in our study indicated that the TNF-α levels were 2-fold, IL-8 were 3.3-fold, IFN-γ were 13-fold, IL-1ra were 1.05-fold, IL-4 were 1.4-fold and IL-10 were 1.83-fold higher in the GNB group compared with the GPB group. The TNF-α levels were 4.7-fold, IL-8 were 4.6-fold, IL-1ra were 1.5-fold and IL-10 were 3.3-fold higher in the non-survivors compared with the survivors. PMID:26079127

  12. RNA degradation in Archaea and Gram-negative bacteria different from Escherichia coli.

    Evguenieva-Hackenberg, Elena; Klug, Gabriele

    2009-01-01

    Exoribonucleolytic and endoribonucleolytic activities are important for controlled degradation of RNA and contribute to the regulation of gene expression at the posttranscriptional level by influencing the half-lives of specific messenger RNAs. The RNA half-lives are determined by the characteristics of the RNA substrates and by the availability and the properties of the involved proteins-ribonucleases and assisting polypeptides. Much is known about RNA degradation in Eukarya and Bacteria, but there is limited information about RNA-degrading enzymes and RNA destabilizing or stabilizing elements in the domain of the Archaea. The recent progress in the understanding of the structure and function of the archaeal exosome, a protein complex with RNA-degrading and RNA-tailing capabilities, has given some first insights into the mechanisms of RNA degradation in the third domain of life and into the evolution of RNA-degrading enzymes. Moreover, other archaeal RNases with degrading potential have been described and a new mechanism for protection of the 5'-end of RNA in Archaea was discovered. Here, we summarize the current knowledge on RNA degradation in the Archaea. Additionally, RNA degradation mechanisms in Rhodobacter capsulatus and Pseudomonas syringae are compared to those in the major model organism for Gram-negatives, Escherichia coli, which dominates our view on RNA degradation in Bacteria.

  13. Sorption of lead onto two gram-negative marine bacteria in seawater

    Harvey, Ronald W.; Leckie, James O.

    1985-01-01

    Laboratory adsorption experiments performed at environmentally significant lead (Pb) and cell concentrations indicate that the marine bacteria examined have significant binding capacities for Pb. However, the behavior governing Pb sorption onto gram-negative bacteria in seawater may be quite complex. The sorption kinetics appear to involve two distinct phases, i.e., a rapid removal of Pb from solution within the first few minutes, followed by a slow but nearly constant removal over many hours. Also, the average binding coefficient, calculated for Pb sorption onto bacteria and a measure of binding intensity, increases with decreasing sorption density (amounts of bacteria-associated Pb per unit bacterial surface) at low cell concentrations (105 cells ml−1), but decreases with decreasing sorption density at higher cell concentrations (107 cells ml−1). The latter effect is apparently due to the production of significant amounts of extra-cellular organics at high cell concentrations that compete directly with bacterial surfaces for available lead. Lead toxicity and active uptake by marine bacteria did not appear significant at the Pb concentrations used.

  14. Re-Factoring Glycolytic Genes for Targeted Engineering of Catabolism in Gram-Negative Bacteria.

    Sánchez-Pascuala, Alberto; Nikel, Pablo I; de Lorenzo, Víctor

    2018-01-01

    The Embden-Meyerhof-Parnas (EMP) pathway is widely accepted to be the biochemical standard of glucose catabolism. The well-characterized glycolytic route of Escherichia coli, based on the EMP catabolism, is an example of an intricate pathway in terms of genomic organization of the genes involved and patterns of gene expression and regulation. This intrinsic genetic and metabolic complexity renders it difficult to engineer glycolytic activities and transfer them onto other microbial cell factories, thus limiting the biotechnological potential of bacterial hosts that lack the route. Taking into account the potential applications of such a portable tool for targeted pathway engineering, in the present protocol we describe how the genes encoding all the enzymes of the linear EMP route have been individually recruited from the genome of E. coli K-12, edited in silico to remove their endogenous regulatory signals, and synthesized de novo following a standard (i.e., GlucoBrick) that facilitates their grouping in the form of functional modules that can be combined at the user's will. This novel genetic tool allows for the à la carte implementation or boosting of EMP pathway activities into different Gram-negative bacteria. The potential of the GlucoBrick platform is further illustrated by engineering novel glycolytic activities in the most representative members of the Pseudomonas genus (Pseudomonas putida and Pseudomonas aeruginosa).

  15. In vitro antimicrobial activity of five essential oils on multidrug resistant Gram-negative clinical isolates.

    Sakkas, Hercules; Gousia, Panagiota; Economou, Vangelis; Sakkas, Vassilios; Petsios, Stefanos; Papadopoulou, Chrissanthy

    2016-01-01

    The emergence of drug-resistant pathogens has drawn attention on medicinal plants for potential antimicrobial properties. The objective of the present study was the investigation of the antimicrobial activity of five plant essential oils on multidrug resistant Gram-negative bacteria. Basil, chamomile blue, origanum, thyme, and tea tree oil were tested against clinical isolates of Acinetobacter baumannii (n = 6), Escherichia coli (n = 4), Klebsiella pneumoniae (n = 7), and Pseudomonas aeruginosa (n = 5) using the broth macrodilution method. The tested essential oils produced variable antibacterial effect, while Chamomile blue oil demonstrated no antibacterial activity. Origanum, Thyme, and Basil oils were ineffective on P. aeruginosa isolates. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration values ranged from 0.12% to 1.50% (v/v) for tea tree oil, 0.25-4% (v/v) for origanum and thyme oil, 0.50% to >4% for basil oil and >4% for chamomile blue oil. Compared to literature data on reference strains, the reported MIC values were different by 2SD, denoting less successful antimicrobial activity against multidrug resistant isolates. The antimicrobial activities of the essential oils are influenced by the strain origin (wild, reference, drug sensitive, or resistant) and it should be taken into consideration whenever investigating the plants' potential for developing new antimicrobials.

  16. The attenuation effect of UVc radiation doses in gram-negative bacteria (Brucella, Yersinia, Escherichia coli)

    Al-Mariri, A.

    2006-06-01

    The gram-negative bacteria Yersinia enterocolitica sero group O:3 and O:9, and Brucella (Melitensis and abortus) together with Escherichia coli (O:157, DH5α-pEt15b), were investigated to evaluate their susceptibility to UV radiation at 254 nm. If the dose of UVc was 18.7 mW/cm 2 , the time required for inactivation of Y. enterocolitica and E. coli DH5α-pEt15b and O:157 was 240s and 360s in the dark and light respectively; where if the dose was 19.5 mW/cm 2 , the time required was 60s in the dark and 120s in light respectively. The time required for inactivation of Brucella strains (melitensis and abortus) if the dose was 18.7 mW/cm 2 was 240s in both dark and light, whereas it was 120s(dark) and 240s (light) respectively, when the dose was 19.5 mW/cm 2 . Using E. coli O:157 as control, it appears that Y. enterocolitica sero group O:3 and O:9 and vaccinal strains of Brucella (Rev. 1 and S19) are more sensitive to UV than wild Brucella strains. No relation was found between the sensitivity of Y. enterocolitica to UV and the presence or absence of a pYV + virulence plasmid. (author)

  17. Mucosal barrier injury laboratory-confirmed bloodstream infection: results from a field test of a new National Healthcare Safety Network definition.

    See, Isaac; Iwamoto, Martha; Allen-Bridson, Kathy; Horan, Teresa; Magill, Shelley S; Thompson, Nicola D

    2013-08-01

    To assess challenges to implementation of a new National Healthcare Safety Network (NHSN) surveillance definition, mucosal barrier injury laboratory-confirmed bloodstream infection (MBI-LCBI). Multicenter field test. Selected locations of acute care hospitals participating in NHSN central line-associated bloodstream infection (CLABSI) surveillance. Hospital staff augmented their CLABSI surveillance for 2 months to incorporate MBI-LCBI: a primary bloodstream infection due to a selected group of organisms in patients with either neutropenia or an allogeneic hematopoietic stem cell transplant with gastrointestinal graft-versus-host disease or diarrhea. Centers for Disease Control and Prevention (CDC) staff reviewed submitted data to verify whether CLABSIs met MBI-LCBI criteria and summarized the descriptive epidemiology of cases reported. Eight cancer, 2 pediatric, and 28 general acute care hospitals including 193 inpatient units (49% oncology/bone marrow transplant [BMT], 21% adult ward, 20% adult critical care, 6% pediatric, 4% step-down) conducted field testing. Among 906 positive blood cultures reviewed, 282 CLABSIs were identified. Of the 103 CLABSIs that also met MBI-LCBI criteria, 100 (97%) were reported from oncology/BMT locations. Agreement between hospital staff and CDC classification of reported CLABSIs as meeting the MBI-LCBI definition was high (90%; κ = 0.82). Most MBI-LCBIs (91%) occurred in patients meeting neutropenia criteria. Some hospitals indicated that their laboratories' methods of reporting cell counts prevented application of neutropenia criteria; revised neutropenia criteria were created using data from field testing. Hospital staff applied the MBI-LCBI definition accurately. Field testing informed modifications for the January 2013 implementation of MBI-LCBI in the NHSN.

  18. Use of Six Sigma strategies to pull the line on central line-associated bloodstream infections in a neurotrauma intensive care unit.

    Loftus, Kelli; Tilley, Terry; Hoffman, Jason; Bradburn, Eric; Harvey, Ellen

    2015-01-01

    The creation of a consistent culture of safety and quality in an intensive care unit is challenging. We applied the Six Sigma Define-Measure-Analyze-Improve-Control (DMAIC) model for quality improvement (QI) to develop a long-term solution to improve outcomes in a high-risk neurotrauma intensive care unit. We sought to reduce central line utilization as a cornerstone in preventing central line-associated bloodstream infections (CLABSIs). This study describes the successful application of the DMAIC model in the creation and implementation of evidence-based quality improvement designed to reduce CLABSIs to below national benchmarks.

  19. Direct maldi-tof mass spectrometry assay of blood culture broths for rapid identification of Candida species causing bloodstream infections: an observational study in two large microbiology laboratories.

    Spanu, Teresa; Posteraro, Brunella; Fiori, Barbara; D'Inzeo, Tiziana; Campoli, Serena; Ruggeri, Alberto; Tumbarello, Mario; Canu, Giulia; Trecarichi, Enrico Maria; Parisi, Gabriella; Tronci, Mirella; Sanguinetti, Maurizio; Fadda, Giovanni

    2012-01-01

    We evaluated the reliability of the Bruker Daltonik's MALDI Biotyper system in species-level identification of yeasts directly from blood culture bottles. Identification results were concordant with those of the conventional culture-based method for 95.9% of Candida albicans (187/195) and 86.5% of non-albicans Candida species (128/148). Results were available in 30 min (median), suggesting that this approach is a reliable, time-saving tool for routine identification of Candida species causing bloodstream infection.

  20. A Descriptive Study of Nosocomial Infections in an Adult Intensive Care Unit in Fiji: 2011-12

    Keshni Naidu

    2014-01-01

    Full Text Available Nosocomial infections in an intensive care unit (ICU are common and associated with a high mortality but there are no published data from the Oceania region. A retrospective study in Fiji’s largest ICU (2011-12 reported that 114 of a total 663 adult ICU admissions had bacteriological culture-confirmed nosocomial infection. The commonest sites of infection were respiratory and bloodstream. Gram negative bacteria were the commonest pathogens isolated, especially Klebsiella pneumoniae (extended-spectrum β-Lactamase-producing, Acinetobacter, and Pseudomonas species. Mortality for those with a known outcome was 33%. Improved surveillance and implementation of effective preventive interventions are needed.

  1. Clinical study of carbapenem sensitive and resistant Gram-negative bacteremia in neutropenic and nonneutropenic patients: The first series from India.

    Ghafur, A K; Vidyalakshmi, P R; Kannaian, P; Balasubramaniam, R

    2014-01-01

    Carbapenem resistance is a growing global concern. There is a lack of published clinical studies on the topic from Indian subcontinent. Aim of this study was to analyze clinical profile of patients with carbapenem sensitive and resistant bacteremia among neutropenic and nonneutropenic patients. Retrospective analysis of 141 patients who had carbapenem resistant or sensitive Gram-negative bacteremia, identified over a period of 1-year was done by medical records review, in Apollo Specialty Hospital, a 300-bedded tertiary care Oncology, neurosurgical and orthopedic center in South India. Of the total 141 patients with Gram-negative bacteremia, 44 had carbapenem resistant ones. Of these 44 patients, 17 were neutropenics (resistant neutropenic group) and 27 nonneutropenic patients (resistant nonneutropenic group). Of the 97 patients with carbapenem sensitive bacteremia, 43 were neutropenic (sensitive neutropenic group) and 54 nonneutropenics (sensitive nonneutropenic group). The 28 days mortality was significantly higher in carbapenem resistant bacteremic group compared to the sensitive one (P = 0.008). This is the first study from India comparing clinical features of patients with carbapenem sensitive and resistant blood stream infections. Patients with carbapenem resistant bacteremia had higher mortality compared to patients with sensitive bacteremia.

  2. Novel pharmacotherapy for the treatment of hospital-acquired and ventilator-associated pneumonia caused by resistant gram-negative bacteria.

    Kidd, James M; Kuti, Joseph L; Nicolau, David P

    2018-03-01

    Hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) are among the most prevalent infections in hospitalized patients, particularly those in the intensive care unit. Importantly, the frequency of multidrug resistant (MDR) Gram-negative (GN) bacteria as the bacteriologic cause of HABP/VABP is increasing. These include MDR Pseudomonas aeruginosa, Acinetobacter baumannii, and carbapenem resistant Enterobacteriaceae (CRE). Few antibiotics are currently available when such MDR Gram-negatives are encountered and older agents such as polymyxin B, colistin (polymyxin E), and tigecycline have typically performed poorly in HABP/VABP. Areas covered: In this review, the authors summarize novel antibiotics which have reached phase 3 clinical trials including patients with HABP/VABP. For each agent, the spectrum of activity, pertinent pharmacological characteristics, clinical trial data, and potential utility in the treatment of MDR-GN HABP/VABP is discussed. Expert opinion: Novel antibiotics currently available, and those soon to be, will expand opportunities to treat HABP/VABP caused by MDR-GN organisms and minimize the use of more toxic, less effective drugs. However, with sparse clinical data available, defining the appropriate role for each of the new agents is challenging. In order to maximize the utility of these antibiotics, combination therapy and the role of therapeutic drug monitoring should be investigated.

  3. In vitro activity of XF-73, a novel antibacterial agent, against antibiotic-sensitive and -resistant Gram-positive and Gram-negative bacterial species.

    Farrell, David J; Robbins, Marion; Rhys-Williams, William; Love, William G

    2010-06-01

    The antibacterial activity of XF-73, a dicationic porphyrin drug, was investigated against a range of Gram-positive and Gram-negative bacteria with known antibiotic resistance profiles, including resistance to cell wall synthesis, protein synthesis, and DNA and RNA synthesis inhibitors as well as cell membrane-active antibiotics. Antibiotic-sensitive strains for each of the bacterial species tested were also included for comparison purposes. XF-73 was active [minimum inhibitory concentration (MIC) 0.25-4 mg/L] against all of the Gram-positive bacteria tested, irrespective of the antibiotic resistance profile of the isolates, suggesting that the mechanism of action of XF-73 is unique compared with the major antibiotic classes. Gram-negative activity was lower (MIC 1 mg/L to > 64 mg/L). Minimum bactericidal concentration data confirmed that the activity of XF-73 was bactericidal. Time-kill kinetics against healthcare-associated and community-associated meticillin-resistant Staphylococcus aureus isolates demonstrated that XF-73 was rapidly bactericidal, with > 5 log(10) kill obtained after 15 min at 2 x MIC, the earliest time point sampled. The post-antibiotic effect (PAE) for XF-73 under conditions where the PAE for vancomycin was 5.4 h. XF-73 represents a novel broad-spectrum Gram-positive antibacterial drug with potentially beneficial characteristics for the treatment and prevention of Gram-positive bacterial infections. 2010. Published by Elsevier B.V.

  4. Rectal carriage of extended-spectrum beta-lactamase-producing gram-negative bacilli in community settings in Madagascar.

    Perlinot Herindrainy

    Full Text Available BACKGROUND: Extended-spectrum ß-lactamase-producing Enterobacteria (ESBL-PE emerged at the end of the 1980s, causing nosocomial outbreaks and/or hyperendemic situations in hospitals and long-term care facilities. In recent years, community-acquired infections due to ESBL-PE have spread worldwide, especially across developing countries including Madagascar. OBJECTIVES: This study aimed to determine the prevalence and risk factors of intestinal carriage of ESBL-PE in the community of Antananarivo. METHODS: Non-hospitalized patients were recruited in three health centers in different socio economic settings. Fresh stool collected were immediately plated on Drigalski agar containing 3 mg/liter of ceftriaxone. Gram-negative bacilli species were identified and ESBL production was tested by a double disk diffusion (cefotaxime and ceftazidime +/- clavulanate assay. Characterization of ESBLs were perfomed by PCR and direct sequencing. Molecular epidemiology was analysed by Rep-PCR and ERIC-PCR. RESULTS: 484 patients were screened (sex ratio  =  1.03, median age 28 years. 53 ESBL-PE were isolated from 49 patients (carrier rate 10.1%. The isolates included Escherichia coli (31, Klebsiella pneumoniae (14, Enterobacter cloacae (3, Citrobacter freundii (3, Kluyvera spp. (1 and Pantoae sp. (1. In multivariate analysis, only the socioeconomic status of the head of household was independently associated with ESBL-PE carriage, poverty being the predominant risk factor. CONCLUSIONS: The prevalence of carriage of ESBL in the community of Antananarivo is one of the highest reported worldwide. This alarming spread of resistance genes should be stopped urgently by improving hygiene and streamlining the distribution and consumption of antibiotics.

  5. Multi-scale model of drug induced adaptive resistance of Gram-negative bacteria to polymyxin B.

    Wojciech Krzyzanski

    Full Text Available The purpose of this report is to apply multi-scale modeling using the theory of physiologically structured populations (PSP to develop a mathematical model for antimicrobial resistance based on a heterogeneous distribution of receptors and affinities among bacterial cells. The theory has been tested on data obtained from an in vitro static time-kill infection model analyzing the pharmacodynamics of polymyxin B against Gram-negative bacteria. The drug binding parameter KD (dissociation equilibrium constant is assumed to vary between the bacterial cells. The PSP model describes the time course of the density distribution of KD upon exposure to cytotoxic drug concentrations. The drug increases the hazard of cell death as a function of receptor occupancy. The initial distribution of KD is described by the Weibull function. Time-kill data were used for model qualification. In vitro static time-kill experiments to evaluate the rate and extent of killing due to polymyxin B against two Klebsiella pneumoniae clinical isolates with differing susceptibilities to polymyxin B were performed over 48 h. The time-kill kinetics data of bacterial load cfu (colony forming units/mL was used for model qualification. The resistant bacterial population is determined by the balance between growth rate and hazard of cell death controlled by polymyxin B concentrations. There exists a critical KD value below which cells continue to grow. Estimates of shape parameters for distributions of KD yielded unimodal distributions with the modes at 0 nM and the right tails containing approximately 25% of the bacteria. Our findings support a hypothesis that resistance of Klebsiella pneumoniae to polymyxin B can be at least partially attributed to a drug-induced selection of a subpopulation due to heterogeneity of polymyxin B receptor binding in the bacterial population.

  6. Bacteremia and resistant gram-negative pathogens among under-fives in Tanzania.

    Christopher, Alexandra; Mshana, Stephen E; Kidenya, Benson R; Hokororo, Aldofineh; Morona, Domenica

    2013-05-08

    Antibiotic resistance is one of the most serious public health concerns worldwide and is increasing at an alarming rate, making daily treatment decisions more challenging. This study is aimed at identifying local bacterial isolates and their antimicrobial susceptibility patterns to avoid irrational antibiotic use, especially in settings where unguided management occurs and febrile illnesses are predominant. A hospital-based prospective cross-sectional study was conducted from September 2011 to February 2012. Febrile children were serially recruited and demographic and clinical data were collected using a standardized data collection tool. A blood culture was performed and identification of the isolates was undertaken using in-house biochemical tests. Susceptibility to common antibiotics was investigated using the disc diffusion methods. Of the 1081 children admitted during the study period, 317 (29.3%) met the inclusion criteria and were recruited, of whom 195 (61.5%) and 122 (38.5%) were male and female respectively. The median age was 18 months with an interquartile range of 9 to 36 months. Of the 317 children, 251 (79.2%) were below or equal to 36 months of age. The prevalence of bacteremia was 6.6%. A higher prevalence of bacteraemia was observed in children below 36 months than in those ≥ 36 months (7.5% vs. 3.0%, p = 0.001). Predictors of bacteraemia were an axillary temperature of >38.5 °C (OR =7, 95% CI = 2.2 - 14.8, p-value = 0.0001), a positive malaria slide (OR =5, 95% CI = 3.0 - 21.2, p-value = 0.0001) and a high neutrophils' count (OR =21 95% CI = 5.6 - 84, p-value = 0.0001). Escherichia coli and Klebsiella pneumoniae accounted for 7 (33.3%) and 6 (28.6%) of all the isolates respectively. Others gram-negatives bacteria were Citrobacter spp 2 (9.5%), Enterobacter spp 1 (4.25%), Pseudomonas spp 2 (9.5%), Proteus spp 1 (4.25%) and Salmonella spp 1 (4.25%). These isolates were highly resistant to ampicillin (95%), co

  7. Complete Genome Sequence of Bacillus velezensis CN026 Exhibiting Antagonistic Activity against Gram-Negative Foodborne Pathogens.

    Nannan, Catherine; Gillis, Annika; Caulier, Simon; Mahillon, Jacques

    2018-01-25

    We report here the complete genome sequence of Bacillus velezensis strain CN026, a member of the B. subtilis group, which is known for its many industrial applications. The genome contains 3,995,812 bp and displays six gene clusters potentially involved in strain CN026's activity against Gram-negative foodborne pathogens. Copyright © 2018 Nannan et al.

  8. Complete Genome Sequence of Bacillus velezensis CN026 Exhibiting Antagonistic Activity against Gram-Negative Foodborne Pathogens

    Nannan, Catherine; Gillis, Annika; Caulier, Simon; Mahillon, Jacques

    2018-01-01

    ABSTRACT We report here the complete genome sequence of Bacillus velezensis strain CN026, a member of the B. subtilis group, which is known for its many industrial applications. The genome contains 3,995,812 bp and displays six gene clusters potentially involved in strain CN026’s activity against Gram-negative foodborne pathogens.

  9. Antibacterial Activity of Silver-Graphene Quantum Dots Nanocomposites Against Gram-Positive and Gram-Negative Bacteria

    Habiba, Khaled (Inventor); Makarov, Vladimir (Inventor); Weiner, Brad R (Inventor); Morell, Gerardo (Inventor)

    2018-01-01

    The invention provides a composite of silver nanoparticles decorated with graphene quantum dots (Ag-GQDs) using pulsed laser synthesis. The nanocomposites were functionalized with polyethylene glycol (PEG). A concentration of 150 .mu.g/mL of Ag-GQDs, a non-toxic level for human cells, exhibits strong antibacterial activity against both Gram-Positive and Gram-Negative Bacteria.

  10. Viruses and Gram-negative bacilli dominate the etiology of community-acquired pneumonia in Indonesia, a cohort study

    Helmia Farida

    2015-09-01

    Conclusions: Viruses and Gram-negative bacilli are dominant causes of CAP in this region, more so than S. pneumoniae. Most of the bacteria have wild type susceptibility to antimicrobial agents. Patients with severe disease and those with unknown etiology have a higher mortality risk.

  11. Detection of Extended Spectrum Beta-Lactamases Among Gram Negative Bacilli Recovered from Cattle Feces In Benin City, Nigeria

    Helen Oroboghae OGEFERE

    2017-06-01

    Full Text Available This study was carried out to determine the prevalence of extended spectrum beta-lactamase (ESBL among Gram negative bacteria isolated from cattle feces in Benin City, Nigeria. A total of 250 Gram negative bacteria isolates were recovered from cattle feces and were processed microbiologically using standard techniques. Emergent colonies were identified and antibacterial susceptibility tests were determined using Kirby-Bauer disk diffusion method. All bacterial isolates were screened for the presence of ESBL using the double-disc synergy method. A total of 37 (14.8% isolates were positive for ESBL, with 33 (13.2% indicated by ceftazidime, while only 4 (1.6% were indicated by both ceftazidime and cefotaxime (P < 0.0001. Of the Gram negative bacterial isolates recovered, Salmonella species was the most prevalent ESBL-producer with 55.0% prevalence (P = 0.0092, while no isolate of Pseudomonas aeruginosa produced ESBL. ESBL-positive isolates showed poor susceptibility to the tested antibacterial agents in comparison with non-ESBL-producers and imipenem was the most active antibiotic. The prevalence of ESBL among Gram negative bacilli recovered from cattle feces was 14.8%. The study advises prudent use of antibiotics in the treatment of cattle and harps on improved hygiene in managing cattle, as they are potential reservoirs of ESBL-producing organisms.

  12. In vitro Efficacy of Meropenem, Colistin and Tigecycline Against the Extended Spectrum Beta-Lactamase Producing Gram Negative Bacilli

    Gill, M. M.; Usman, J.; Hassan, A.; Kaleem, F.; Anjum, R.

    2015-01-01

    Objective:To compare the in vitroefficacy of meropenem, colistin and tigecycline against extended spectrum Betalactamase producing Gram negative bacilli by minimal inhibitory concentration. Study Design:Cross-sectional descriptive study. Place and Duration of Study: Department of Microbiology, Army Medical College, National University of Sciences and Technology, Rawalpindi, from June to December 2010. Methodology: Routine clinical specimens were subjected to standard microbiological procedures and the isolates were identified to species level. Extended spectrum beta-lactamase producing Gram negative bacilli were detected by Jarlier disc synergy method and confirmed by ceftazidime and ceftazidime-clavulanate Etest. Minimum Inhibitory Concentration (MIC90) of meropenem, colistin and tigecycline was determined by Etest (AB BIOMERIUX) and the results were interpreted according to the manufacturer's instructions and Clinical and Laboratory Standards Institute guidelines and Food and Drug Authority recommendations. Results were analyzed by using Statistical Package for the Social Sciences version 20. Results: A total of 52 non-duplicate extended spectrum Beta-lactamase-producing Gram negative bacilli were included in the study. The MIC90 of tigecycline (0.75 micro g/ml) was lowest as compared to the meropenem (2 micro g/ml) and colistin (3 micro g/ml). Conclusion: Tigecycline is superior in efficacy against the extended spectrum Beta-lactamase producing Gram negative bacilli as compared to colistin and meropenem. (author)

  13. Dustborne and airborne gram-positive and gram-negative bacteria in high versus low ERMI homes

    The study aimed at investigating Gram-positive and Gram-negative bacteria in moldy and non-moldy homes, as defined by the home's Environmental Relative Moldiness Index (ERMI) value. The ERMI values were determined from floor dust samples in 2010 and 2011 and homes were classified...

  14. Metabolic and process engineering for biodesulfurization in Gram-negative bacteria.

    Martínez, I; El-Said Mohamed, M; Santos, V E; García, J L; García-Ochoa, F; Díaz, E

    2017-11-20

    Microbial desulfurization or biodesulfurization (BDS) is an attractive low-cost and environmentally friendly complementary technology to the hydrotreating chemical process based on the potential of certain bacteria to specifically remove sulfur from S-heterocyclic compounds of crude fuels that are recalcitrant to the chemical treatments. The 4S or Dsz sulfur specific pathway for dibenzothiophene (DBT) and alkyl-substituted DBTs, widely used as model S-heterocyclic compounds, has been extensively studied at the physiological, biochemical and genetic levels mainly in Gram-positive bacteria. Nevertheless, several Gram-negative bacteria have been also used in BDS because they are endowed with some properties, e.g., broad metabolic versatility and easy genetic and genomic manipulation, that make them suitable chassis for systems metabolic engineering strategies. A high number of recombinant bacteria, many of which are Pseudomonas strains, have been constructed to overcome the major bottlenecks of the desulfurization process, i.e., expression of the dsz operon, activity of the Dsz enzymes, retro-inhibition of the Dsz pathway, availability of reducing power, uptake-secretion of substrate and intermediates, tolerance to organic solvents and metals, and other host-specific limitations. However, to attain a BDS process with industrial applicability, it is necessary to apply all the knowledge and advances achieved at the genetic and metabolic levels to the process engineering level, i.e., kinetic modelling, scale-up of biphasic systems, enhancing mass transfer rates, biocatalyst separation, etc. The production of high-added value products derived from the organosulfur material present in oil can be regarded also as an economically viable process that has barely begun to be explored. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Emergence of Imipenem-Resistant Gram-Negative Bacilli in Intestinal Flora of Intensive Care Patients

    Angebault, Cécile; Barbier, François; Hamelet, Emilie; Defrance, Gilles; Ruppé, Etienne; Bronchard, Régis; Lepeule, Raphaël; Lucet, Jean-Christophe; El Mniai, Assiya; Wolff, Michel; Montravers, Philippe; Plésiat, Patrick; Andremont, Antoine

    2013-01-01

    Intestinal flora contains a reservoir of Gram-negative bacilli (GNB) resistant to cephalosporins, which are potentially pathogenic for intensive care unit (ICU) patients; this has led to increasing use of carbapenems. The emergence of carbapenem resistance is a major concern for ICUs. Therefore, in this study, we aimed to assess the intestinal carriage of imipenem-resistant GNB (IR-GNB) in intensive care patients. For 6 months, 523 consecutive ICU patients were screened for rectal IR-GNB colonization upon admission and weekly thereafter. The phenotypes and genotypes of all isolates were determined, and a case control study was performed to identify risk factors for colonization. The IR-GNB colonization rate increased regularly from 5.6% after 1 week to 58.6% after 6 weeks in the ICU. In all, 56 IR-GNB strains were collected from 50 patients: 36 Pseudomonas aeruginosa strains, 12 Stenotrophomonas maltophilia strains, 6 Enterobacteriaceae strains, and 2 Acinetobacter baumannii strains. In P. aeruginosa, imipenem resistance was due to chromosomally encoded resistance (32 strains) or carbapenemase production (4 strains). In the Enterobacteriaceae strains, resistance was due to AmpC cephalosporinase and/or extended-spectrum β-lactamase production with porin loss. Genomic comparison showed that the strains were highly diverse, with 8 exceptions (4 VIM-2 carbapenemase-producing P. aeruginosa strains, 2 Klebsiella pneumoniae strains, and 2 S. maltophilia strains). The main risk factor for IR-GNB colonization was prior imipenem exposure. The odds ratio for colonization was already as high as 5.9 (95% confidence interval [95% CI], 1.5 to 25.7) after 1 to 3 days of exposure and increased to 7.8 (95% CI, 2.4 to 29.8) thereafter. In conclusion, even brief exposure to imipenem is a major risk factor for IR-GNB carriage. PMID:23318796

  16. The Structural Diversity of Carbohydrate Antigens of Selected Gram-Negative Marine Bacteria

    Elena P. Ivanova

    2011-10-01

    Full Text Available Marine microorganisms have evolved for millions of years to survive in the environments characterized by one or more extreme physical or chemical parameters, e.g., high pressure, low temperature or high salinity. Marine bacteria have the ability to produce a range of biologically active molecules, such as antibiotics, toxins and antitoxins, antitumor and antimicrobial agents, and as a result, they have been a topic of research interest for many years. Among these biologically active molecules, the carbohydrate antigens, lipopolysaccharides (LPSs, O-antigens found in cell walls of Gram-negative marine bacteria, show great potential as candidates in the development of drugs to prevent septic shock due to their low virulence. The structural diversity of LPSs is thought to be a reflection of the ability for these bacteria to adapt to an array of habitats, protecting the cell from being compromised by exposure to harsh environmental stress factors. Over the last few years, the variety of structures of core oligosaccharides and O-specific polysaccharides from LPSs of marine microrganisms has been discovered. In this review, we discuss the most recently encountered structures that have been identified from bacteria belonging to the genera Aeromonas, Alteromonas, Idiomarina, Microbulbifer, Pseudoalteromonas, Plesiomonas and Shewanella of the Gammaproteobacteria phylum; Sulfitobacter and Loktanella of the Alphaproteobactera phylum and to the genera Arenibacter, Cellulophaga, Chryseobacterium, Flavobacterium, Flexibacter of the Cytophaga-Flavobacterium-Bacteroides phylum. Particular attention is paid to the particular chemical features of the LPSs, such as the monosaccharide type, non-sugar substituents and phosphate groups, together with some of the typifying traits of LPSs obtained from marine bacteria. A possible correlation is then made between such features and the environmental adaptations undertaken by marine bacteria.

  17. Quantitative Real-time PCR detection of putrescine-producing Gram-negative bacteria

    Kristýna Maršálková

    2017-01-01

    Full Text Available Biogenic amines are indispensable components of living cells; nevertheless these compounds could be toxic for human health in higher concentrations. Putrescine is supposed to be the major biogenic amine associated with microbial food spoilage. Development of reliable, fast and culture-independent molecular methods to detect bacteria producing biogenic amines deserves the attention, especially of the food industry in purpose to protect health. The objective of this study was to verify the newly designed primer sets for detection of two inducible genes adiA and speF together in Salmonella enterica and Escherichia coli genome by Real-time PCR. These forenamed genes encode enzymes in the metabolic pathway which leads to production of putrescine in Gram-negative bacteria. Moreover, relative expression of these genes was studied in E. coli CCM 3954 strain using Real-time PCR. In this study, sets of new primers for the detection two inducible genes (speF and adiA in Salmonella enterica and E. coli by Real-time PCR were designed and tested. Amplification efficiency of a Real-time PCR was calculated from the slope of the standard curves (adiA, speF, gapA. An efficiency in a range from 95 to 105 % for all tested reactions was achieved. The gene expression (R of adiA and speF genes in E. coli was varied depending on culture conditions. The highest gene expression of adiA and speF was observed at 6, 24 and 36 h (RadiA ~ 3, 5, 9; RspeF ~11, 10, 9; respectively after initiation of growth of this bacteria in nutrient broth medium enchired with amino acids. The results show that these primers could be used for relative quantification analysis of E. coli.

  18. Sequential hand hygiene promotion contributes to a reduced nosocomial bloodstream infection rate among very low-birth weight infants: an interrupted time series over a 10-year period.

    Helder, Onno K; Brug, Johannes; van Goudoever, Johannes B; Looman, Caspar W N; Reiss, Irwin K M; Kornelisse, René F

    2014-07-01

    Sustained high compliance with hand hygiene (HH) is needed to reduce nosocomial bloodstream infections (NBSIs). However, over time, a wash out effect often occurs. We studied the long-term effect of sequential HH-promoting interventions. An observational study with an interrupted time series analysis of the occurrence of NBSI was performed in very low-birth weight (VLBW) infants. Interventions consisted of an education program, gain-framed screen saver messages, and an infection prevention week with an introduction on consistent glove use. A total of 1,964 VLBW infants admitted between January 1, 2002, and December 31, 2011, were studied. The proportion of infants with ≥1 NBSI decreased from 47.6%-21.2% (P Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

  19. Expression levels of matrix metalloproteinase-9 and gram-negative bacteria in symptomatic and asymptomatic periapical lesions.

    Ahmed, Geraldine M; El-Baz, Alaa A; Hashem, Ahmed Abdel Rahman; Shalaan, Abeer K

    2013-04-01

    The aim of this study was to test the hypothesis that the expression of matrix metalloproteinase (MMP)-9 is significantly elevated in patients with symptomatic apical periodontitis and to correlate this with the detected amount of gram-negative bacteria. Twenty-six patients with periapical lesions involving at least 2 teeth were included in this study. The patients were divided into 2 groups: the symptomatic (SYM) group included 13 patients expressing pain with periapical lesions, and the asymptomatic (ASYM) group included 13 patients expressing no pain. Root canal treatment was performed followed by endodontic surgery and periapical lesion collection. Periapical lesions were serially cut into 4-μ sections. Some sections were processed for histologic examination using hematoxylin-eosin stain. Other sections were processed for immunohistochemical examination. For MMP-9, the area fraction of the positive cells was measured, and the percentage of the MMP-9-immunopositive area to the total area of the microscopic field was calculated. For gram-negative stain cells, the number of cells showing the pink-red color was counted per microscopic field. The Student's t test was used to compare the SYM and ASYM groups. The Pearson correlation coefficient was used to determine a significant correlation between the number of cells and the MMP-9 level. The significance level was set at P ≤ .05. The SYM group showed a statistically significantly higher mean number of gram-negative cells (P = .001) and MMP-9 area percent (P < .001) than the ASYM group. There was a statistically significant positive (r = .927) correlation between the number of gram-negative cells and the MMP-9 area percent (P< .001). There is good evidence to suspect a significant role of gram-negative bacteria and MMP-9 in symptomatic periapical lesions. Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  20. The Role of Monitoring Gentamicin Levels in Patients with Gram-Negative Peritoneal Dialysis-Associated Peritonitis

    Tang, Wen; Cho, Yeoungjee; Hawley, Carmel M.; Badve, Sunil V.; Johnson, David W.

    2014-01-01

    ♦ Background: There is limited available evidence regarding the role of monitoring serum gentamicin concentrations in peritoneal dialysis (PD) patients receiving this antimicrobial agent in gram-negative PD-associated peritonitis. ♦ Methods: Using data collected in all patients receiving PD at a single center who experienced a gram-negative peritonitis episode between 1 January 2005 and 31 December 2011, we investigated the relationship between measured serum gentamicin levels on day 2 following initial empiric antibiotic therapy and subsequent clinical outcomes of confirmed gram-negative peritonitis. ♦ Results: Serum gentamicin levels were performed on day 2 in 51 (77%) of 66 first gram-negative peritonitis episodes. Average serum gentamicin levels on day 2 were 1.83 ± 0.84 mg/L with levels exceeding 2 mg/L in 22 (43%) cases. The overall cure rate was 64%. No cases of ototoxicity were observed. Day-2 gentamicin levels were not significantly different between patients who did and did not have a complication or cure. Using multivariable logistic regression analysis, failure to cure peritonitis was not associated with either day-2 gentamicin level (adjusted odds ratio (OR) 0.96, 95% confidence interval (CI) 0.25 - 3.73) or continuation of gentamicin therapy beyond day 2 (OR 0.28, 0.02 - 3.56). The only exception was polymicrobial peritonitis, where day-2 gentamicin levels were significantly higher in episodes that were cured (2.06 ± 0.41 vs 1.29 ± 0.71, p = 0.01). In 17 (26%) patients receiving extended gentamicin therapy, day-5 gentamicin levels were not significantly related to peritonitis cure. ♦ Conclusion: Day-2 gentamicin levels did not predict gentamicin-related harm or efficacy during short-course gentamicin therapy for gram-negative PD-related peritonitis, except in cases of polymicrobial peritonitis, where higher levels were associated with cure. PMID:24385334