The Experts below are selected from a list of 264 Experts worldwide ranked by ideXlab platform
Geoffrey E Playford - One of the best experts on this subject based on the ideXlab platform.
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association of ertapenem and Antipseudomonal carbapenem usage and carbapenem resistance in pseudomonas aeruginosa among 12 hospitals in queensland australia
Journal of Antimicrobial Chemotherapy, 2013Co-Authors: David Mcdougall, Anthony Morton, Geoffrey E PlayfordAbstract:Objectives: The objective of this study was to determine the association between ertapenem and Antipseudomonal carbapenem use and carbapenem resistance in Pseudomonas aeruginosa in 12 hospitals in Queensland, Australia. Methods: Data on usage of ertapenem and other Antipseudomonal carbapenems, measured in defined daily doses per 1000 occupied bed-days, were collated using statewide pharmacy dispensing and distribution software from January 2007 until June 2011. The prevalence of unique carbapenem-resistant P. aeruginosa isolates derived from statewide laboratory information systems was collected for the same time period. Mixed-effects models were used to determine any relationship between ertapenem and Antipseudomonal carbapenem usage and carbapenem resistance among P. aeruginosa isolates in the 12 hospitals analysed. Results: No relationship between ertapenem usage and P. aeruginosa carbapenem resistance was observed. The introduction of ertapenem did not replace Antipseudomonal carbapenem prescribing to any significant extent. However, an association between greater usage of Antipseudomonal carbapenems and greater P. aeruginosa carbapenem resistance was demonstrated. Conclusions: It is likely that the only mechanism by which ertapenem can improve P. aeruginosa resistance patterns is by being used as a substitute for, rather than in addition to, Antipseudomonal carbapenems.
David P Nicolau - One of the best experts on this subject based on the ideXlab platform.
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2175. In vitro Potency of Ceftolozane/Tazobactam and Other Antipseudomonal β-Lactams Against P. aeruginosa.
Open Forum Infectious Diseases, 2020Co-Authors: Safa Almarzoky Abuhussain, Christina A Sutherland, David P NicolauAbstract:AbstractBackgroundChallenges due to multidrug resistant Gram-negative bacterial pathogens such as P. aeruginosa (PSA) are increasing globally. Suboptimal antimicrobial therapy of infections caused by PSA is associated with increased morbidity and mortality. As a result, antimicrobial susceptibility (%S) studies are pivotal to identifying trends in antimicrobial resistance that inform decisions regarding choice of antimicrobial therapy. This study assessed the in vitro potency of 7 Antipseudomonal agents including ceftolozane/tazobactam against PSA collected from numerous sites across the United States.MethodsMultiple U.S. hospitals provided nonduplicate respiratory and blood isolates of PSA for potency testing. MICs against PSA were determined using broth microdilution methods according to CLSI for seven antimicrobials with Antipseudomonal activity: aztreonam, cefepime, ceftazidime, ceftolozane/tazobactam, imipenem, meropenem and piperacillin/tazobactam. Susceptibility (%S) was defined per CLSI or FDA breakpoint criteria.ResultsFourteen hospitals geographically spread across the United States provided total of 560 PSA isolates. Of the antibiotics assessed, %S to C/T was the highest at 95% with an MIC50 of 1 µg/mL and MIC90 of 2 µg/mL. In comparison, other %S (MIC50/MIC90) were as follows: ceftazidime 76% (4/64); cefepime 75% (4/32); piperacillin/tazobactam 73% (8/128), meropenem 72% (0.5/16); aztreonam 65% (8/32) and imipenem 65% (2/16).ConclusionFor this geographically diverse PSA population, ceftolozane/tazobactam demonstrated the highest overall susceptibility (95%). Other Antipseudomonal agents inclusive of the carbapenems displayed susceptibilities of 65–76%. In the era of escalating PSA resistance to the β-lactams, the potency of ceftolozane/tazobactam may represent an important clinical option.Disclosures D. P. Nicolau, Merck: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Speaker honorarium.
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in vitro potency of Antipseudomonal β lactams against blood and respiratory isolates of p aeruginosa collected from us hospitals
Journal of Thoracic Disease, 2019Co-Authors: Safa Almarzoky Abuhussain, Christina A Sutherland, David P NicolauAbstract:Background: Challenges due to multidrug resistant (MDR) Gram-negative bacterial pathogens such as P. aeruginosa (PSA) are increasing globally. Suboptimal antimicrobial therapy of infections caused by PSA is associated with increased morbidity and mortality. As a result, antimicrobial susceptibility (%S) studies are pivotal to identifying trends in antimicrobial resistance that inform decisions regarding choice of antimicrobial therapy. This study assessed the in vitro potency of 7 Antipseudomonal agents including ceftolozane/tazobactam (C/T) against PSA collected from numerous sites across the US. Methods: Multiple US hospitals provided non-duplicate respiratory and blood isolates of PSA for potency testing. MICs against PSA were determined using broth microdilution methods according to CLSI for 7 antimicrobials with Antipseudomonal activity: aztreonam (ATM), cefepime (FEP), ceftazidime (CAZ), C/T, imipenem (IPM), meropenem (MEM) and piperacillin/tazobactam (TZP). %S was defined per CLSI or FDA breakpoint criteria. Results: Thirty-five hospitals geographically spread across the US provided a total of 1,209 PSA isolates. Of the antibiotics assessed, %S to C/T was the highest at 95% with an MIC 50 of 0.5 mg/L and MIC 90 of 2 mg/L. In comparison, other %S (MIC 50 /MIC 90 ) was as follows: ATM 66% (8/32); FEP 76% (4/32); CAZ 78% (4/64); IPM 68% (2/16); MEM 74% (0.5/16); and TZP 73% (8/128). Conclusions: For this geographically diverse PSA population, C/T demonstrated the highest overall susceptibility (95%). Other Antipseudomonal agents inclusive of the carbapenems displayed susceptibilities of 66–78%. In the era of escalating PSA resistance to the β-lactams, the potency of C/T may represent an important clinical option.
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2175 in vitro potency of ceftolozane tazobactam and other Antipseudomonal β lactams against p aeruginosa
Open Forum Infectious Diseases, 2018Co-Authors: Safa Almarzoky Abuhussain, Christina A Sutherland, David P NicolauAbstract:AbstractBackgroundChallenges due to multidrug resistant Gram-negative bacterial pathogens such as P. aeruginosa (PSA) are increasing globally. Suboptimal antimicrobial therapy of infections caused by PSA is associated with increased morbidity and mortality. As a result, antimicrobial susceptibility (%S) studies are pivotal to identifying trends in antimicrobial resistance that inform decisions regarding choice of antimicrobial therapy. This study assessed the in vitro potency of 7 Antipseudomonal agents including ceftolozane/tazobactam against PSA collected from numerous sites across the United States.MethodsMultiple U.S. hospitals provided nonduplicate respiratory and blood isolates of PSA for potency testing. MICs against PSA were determined using broth microdilution methods according to CLSI for seven antimicrobials with Antipseudomonal activity: aztreonam, cefepime, ceftazidime, ceftolozane/tazobactam, imipenem, meropenem and piperacillin/tazobactam. Susceptibility (%S) was defined per CLSI or FDA breakpoint criteria.ResultsFourteen hospitals geographically spread across the United States provided total of 560 PSA isolates. Of the antibiotics assessed, %S to C/T was the highest at 95% with an MIC50 of 1 µg/mL and MIC90 of 2 µg/mL. In comparison, other %S (MIC50/MIC90) were as follows: ceftazidime 76% (4/64); cefepime 75% (4/32); piperacillin/tazobactam 73% (8/128), meropenem 72% (0.5/16); aztreonam 65% (8/32) and imipenem 65% (2/16).ConclusionFor this geographically diverse PSA population, ceftolozane/tazobactam demonstrated the highest overall susceptibility (95%). Other Antipseudomonal agents inclusive of the carbapenems displayed susceptibilities of 65–76%. In the era of escalating PSA resistance to the β-lactams, the potency of ceftolozane/tazobactam may represent an important clinical option.Disclosures D. P. Nicolau, Merck: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Speaker honorarium.
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clinical pharmacodynamics of Antipseudomonal cephalosporins in patients with ventilator associated pneumonia
Antimicrobial Agents and Chemotherapy, 2014Co-Authors: Shawn H Macvane, Joseph L Kuti, David P NicolauAbstract:Advanced-generation cephalosporins are frequently used for empirical coverage of ventilator-associated pneumonia (VAP) due to their activity against a broad spectrum of Gram-positive and Gram-negative aerobic bacteria, including Pseudomonas aeruginosa and Enterobacteriaceae. Providing optimal antibiotic exposure is essential to achieving successful response in patients with VAP. We evaluated exposures of two Antipseudomonal cephalosporins, ceftazidime and cefepime, in patients with VAP due to Gram-negative bacilli to identify the pharmacodynamic parameter predictive of microbiological success. Population pharmacokinetic models were used to estimate individual free drug exposures. Pharmacodynamic indices were determined for each patient using the baseline Gram-negative bacilli with the highest drug MIC. Classification and regression tree analysis was utilized to partition exposure breakpoints, and multivariate logistic regression was conducted to identify predictors of microbiological success. A total of 73 patients (18 receiving ceftazidime therapy and 55 receiving cefepime therapy) were included. MICs ranged widely from 0.047 to 96 μg/ml. The microbiological success rate was 58.9%. Predictive breakpoints were identified for all pharmacodynamic parameters, including a serum fT > MIC greater than 53% (P = 0.02). When controlling for APACHE II (odds ratio [OR], 1.01; 95% confidence interval, 0.93 to 1.09; P = 0.85) and combination therapy (OR, 0.74; 95% confidence interval, 0.25 to 2.19; P = 0.59), achieving a greater than 53% fT > MIC remained a significant predictor of success (OR, 10.3; 95% confidence interval, 1.1 to 92.3; P = 0.04). In patients with VAP due to Gram-negative bacilli, serum exposure of greater than 53% fT > MIC was found to be a significant predictor of favorable microbiological response for Antipseudomonal cephalosporins. These data are useful when determining dosing regimens for cephalosporin agents under development for pneumonia.
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absence of association between use of ertapenem and change in Antipseudomonal carbapenem susceptibility rates in 25 hospitals
Infection Control and Hospital Epidemiology, 2010Co-Authors: Kathryn J Eagye, David P NicolauAbstract:OBJECTIVE. Ertapenem exposure has been reported to select for cross-resistance to other carbapenems in Pseudomonas aeruginosa in vitro. Single-center investigations report conflicting results. We evaluated ertapenem use and Antipseudomonal carbapenem susceptibility for 6 years spanning the time of ertapenem adoption at each of 25 US hospitals. DESIGN. Retrospective primary and secondary data analysis. METHODS. Use density ratios for imipenem and meropenem (collectively, "other carbapenems") and ertapenem were derived from data in a commercial database on the total number of grams used in the 3 years before and the 3 years after adoption of ertapenem at each hospital. A general linear model using repeated measures analysis of variance was used to explore associations between the 6-year change in Antipseudomonal carbapenem susceptibility rates (determined from hospital antibiograms) and ertapenem use in each year, while controlling for other carbapenem use. RESULTS. Ertapenem use increased once adopted. With regard to the postadoption period, the median use density ratio for year 4 was 4.1 (interquartile range [IQR], 1.7-5.2), for year 5 was 6.0 (IQR, 2.7-8.5), and for year 6 was 6.5 (IQR, 4.0-11.6). The median use density ratio for other carbapenem use for year 1 was 8.7 (IQR, 5.7-13.5), and by year 6 it had increased to 19.3 (IQR, 9.6-26.2). Change in mean Antipseudomonal carbapenem susceptibility across time (85% in year 1 to 82% in year 6) was not significant (P = .22). Change in 6-year Antipseudomonal carbapenem susceptibility was not associated with ertapenem use in any year while controlling for other carbapenem use (P > .20 for all years of ertapenem use). CONCLUSION. Although significant change in P. aeruginosa susceptibility to Antipseudomonal carbapenems was not detected during this multicenter study, which to our knowledge is the most extensive assessment to date of this important drug use-susceptibility relationship, continued evaluation of the relationship is prudent.
Despina Perrea - One of the best experts on this subject based on the ideXlab platform.
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acute kidney injury following the concurrent administration of Antipseudomonal beta lactams and vancomycin a network meta analysis
Clinical Microbiology and Infection, 2020Co-Authors: Ioannis Bellos, Vasilios Karageorgiou, Vasilios Pergialiotis, Despina PerreaAbstract:Abstract Background and objectives Acute kidney injury represents a major complication of vancomycin treatment, especially when it is co-administered with other nephrotoxins. This meta-analysis aims to comparatively assess the nephrotoxicity of Antipseudomonal beta-lactams when combined with vancomycin. Data Sources Medline, Scopus, CENTRAL and Clinicaltrials.gov databases were systematically searched from inception through 20 August 2019. Study eligibility criteria Studies evaluating acute kidney injury risk following the concurrent use of Antipseudomonal beta-lactams and vancomycin were selected. Participants Adult and pediatric patients treated in hospital or intensive care unit. Intervention Administration of vancomycin combined with any Antipseudomonal beta-lactam. Methods Acute kidney injury incidence was defined as the primary outcome. Secondary outcomes included severity, onset, duration, need of renal replacement therapy, length of hospitalization and mortality. Quality of evidence was assessed using the ROBINS-I tool and the Confidence In Network Meta-Analysis approach. Results Forty-seven cohort studies were included, with a total of 56,984 patients. In the adult population, the combination of piperacillin-tazobactam and vancomycin resulted in significantly higher nephrotoxicity rates compared to vancomycin monotherapy (Odds ratio-OR: 2.05, 95% confidence intervals-CI [1.17-3.46]) and its concurrent use with meropenem (OR: 1.84, 95% CI [1.02-3.10]) or cefepime (OR: 1.80, 95% CI [1.13-2.77]). In pediatric patients, acute kidney injury was significantly higher with vancomycin plus piperacillin-tazobactam than vancomycin alone (OR: 4.18, 95% CI [1.01-17.29]) or vancomycin plus cefepime OR: 3.71, 95% CI [1.08-11.24]). No significant differences were estimated for the secondary outcomes. Credibility of outcomes was judged as moderate, mainly due to imprecision and inter-study heterogeneity. Conclusions The combination of vancomycin and piperacillin-tazobactam is associated with higher acute kidney injury rates compared to its parallel use with meropenem or cefepime. Current evidence is exclusively observational and is limited by inter-study heterogeneity. Randomized controlled trials are needed to verify these results and define preventive strategies to minimize nephrotoxicity risk.
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Acute kidney injury following the concurrent administration of Antipseudomonal beta-lactams and vancomycin: a network meta-analysis.
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 2020Co-Authors: Ioannis Bellos, Vasilios Karageorgiou, Vasilios Pergialiotis, Despina PerreaAbstract:Acute kidney injury represents a major complication of vancomycin treatment, especially when it is co-administered with other nephrotoxins. This meta-analysis aims to comparatively assess the nephrotoxicity of Antipseudomonal beta-lactams when combined with vancomycin. Medline, Scopus, CENTRAL and Clinicaltrials.gov databases were systematically searched from inception through 20 August 2019. Studies evaluating acute kidney injury risk following the concurrent use of Antipseudomonal beta-lactams and vancomycin were selected. Adult and pediatric patients treated in hospital or intensive care unit. Administration of vancomycin combined with any Antipseudomonal beta-lactam. Acute kidney injury incidence was defined as the primary outcome. Secondary outcomes included severity, onset, duration, need of renal replacement therapy, length of hospitalization and mortality. Quality of evidence was assessed using the ROBINS-I tool and the Confidence In Network Meta-Analysis approach. Forty-seven cohort studies were included, with a total of 56,984 patients. In the adult population, the combination of piperacillin-tazobactam and vancomycin resulted in significantly higher nephrotoxicity rates compared to vancomycin monotherapy (Odds ratio-OR: 2.05, 95% confidence intervals-CI [1.17-3.46]) and its concurrent use with meropenem (OR: 1.84, 95% CI [1.02-3.10]) or cefepime (OR: 1.80, 95% CI [1.13-2.77]). In pediatric patients, acute kidney injury was significantly higher with vancomycin plus piperacillin-tazobactam than vancomycin alone (OR: 4.18, 95% CI [1.01-17.29]) or vancomycin plus cefepime OR: 3.71, 95% CI [1.08-11.24]). No significant differences were estimated for the secondary outcomes. Credibility of outcomes was judged as moderate, mainly due to imprecision and inter-study heterogeneity. The combination of vancomycin and piperacillin-tazobactam is associated with higher acute kidney injury rates compared to its parallel use with meropenem or cefepime. Current evidence is exclusively observational and is limited by inter-study heterogeneity. Randomized controlled trials are needed to verify these results and define preventive strategies to minimize nephrotoxicity risk. Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Robert G Canady - One of the best experts on this subject based on the ideXlab platform.
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nitrogen redox balance in the cystic fibrosis airway effects of Antipseudomonal therapy
American Journal of Respiratory and Critical Care Medicine, 2002Co-Authors: Benjamin Gaston, Felix Ratjen, John W Vaughan, Neil R Malhotra, Robert G CanadyAbstract:Denitrifying bacteria metabolize nitrogen oxides through assimilatory and dissimilatory pathways. These redox reactions may affect lung physiology. We hypothesized that airway colonization with denitrifying bacteria could alter nitrogen balance in the cystic fibrosis (CF) airway. We measured airway nitrogen redox species before and after antimicrobial therapy for Pseudomonas aeruginosa in patients with CF. We also studied ammonium (NH4 +) and nitric oxide (NO) metabolism in clinical strains of P. aeruginosa in vitro and in CF sputum ex vivo. Ammonium concentrations in both sputum and tracheal aspirates decreased with therapy. Nitric oxide reductase (NOR) was present in clinical strains of P. aeruginosa, which both produced NH4 + and consumed NO. Further, NO consumption by CF sputum was inhibited by tobramycin ex vivo. We conclude that treatment of pseudomonal lung infections is associated with decreased NH4 + concentrations in the CF airways. In epithelial cells, NH4 + inhibits chloride transport, and nit...
Jordi Rello - One of the best experts on this subject based on the ideXlab platform.
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determinants of empirical Antipseudomonal antibiotic prescription for adults with pneumonia in the emergency department
BMC Pulmonary Medicine, 2020Co-Authors: Nuria Angrill, Miguel Gallego, Juli Font, Jordi Valles, Anisi Moron, Eduard Monso, Jordi RelloAbstract:BACKGROUND: Antipseudomonal antibiotics should be restricted to patients at risk of Pseudomonas aeruginosa infection. However, the indications in different guidelines on community-acquired pneumonia (CAP) are discordant. Our objectives were to assess the prevalence of Antipseudomonal antibiotic prescriptions and to identify determinants of empirical antibiotic choices in the emergency department. METHODS: Observational, retrospective, one-year cohort study in hospitalized adults with pneumonia. Antibiotic choices and clinical and demographic data were recorded on a standardized form. Antibiotics with Antipseudomonal activity were classified into two groups: a) beta-lactam Antipseudomonals (beta-APS), including carbapenems, piperacillin / tazobactam or cefepime (in monotherapy or combination) and b) monotherapy with Antipseudomonal quinolones. RESULTS: Data were recorded from 549 adults with pneumonia, with Pseudomonas aeruginosa being isolated in only nine (1.6%). Most (85%) prescriptions were compliant with SEPAR guidelines and 207 (37%) patients received antibiotics with Antipseudomonal activity (14% beta-APS and 23% levofloxacin). The use of beta-APS was independently associated with ICU admission (OR 8.16 95% CI 3.69-18.06) and prior hospitalization (OR 6.76 95% CI 3.02-15.15), while levofloxacin was associated with negative pneumococcal urine antigen tests (OR 3.41 95% CI 1.70-6.85) but negatively associated with ICU admission (OR 0.26 95% CI 0.08-0.86). None of these factors were associated with P aeruginosa episodes. In univariate analysis, prior P aeruginosa infection/colonization (2/9 vs 6/372, p = 0.013), severe COPD (3/9 vs 26/372, p = 0.024), multilobar involvement (7/9 vs 119/372, p = 0.007) and prior antibiotic (6/9 vs 109/372, p = 0.025) were significantly associated with P aeruginosa episodes. CONCLUSIONS: Antipseudomonal prescriptions were common, in spite of the very low incidence of Pseudomonas aeruginosa. The rationale for prescription was influenced by both severity-of-illness and pneumococcal urine antigen test (levofloxacin) and prior hospitalization and ICU admission (beta-APS). However, these factors were not associated with P aeruginosa episodes. Only prior P aeruginosa infection/colonization and severe COPD seem to be reliable indicators in clinical practice.
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Determinants of empirical Antipseudomonal antibiotic prescription for adults with pneumonia in the emergency department.
BMC pulmonary medicine, 2020Co-Authors: Nuria Angrill, Miguel Gallego, Juli Font, Jordi Valles, Anisi Moron, Eduard Monso, Jordi RelloAbstract:Antipseudomonal antibiotics should be restricted to patients at risk of Pseudomonas aeruginosa infection. However, the indications in different guidelines on community-acquired pneumonia (CAP) are discordant. Our objectives were to assess the prevalence of Antipseudomonal antibiotic prescriptions and to identify determinants of empirical antibiotic choices in the emergency department. Observational, retrospective, one-year cohort study in hospitalized adults with pneumonia. Antibiotic choices and clinical and demographic data were recorded on a standardized form. Antibiotics with Antipseudomonal activity were classified into two groups: a) β-lactam Antipseudomonals (β-APS), including carbapenems, piperacillin / tazobactam or cefepime (in monotherapy or combination) and b) monotherapy with Antipseudomonal quinolones. Data were recorded from 549 adults with pneumonia, with Pseudomonas aeruginosa being isolated in only nine (1.6%). Most (85%) prescriptions were compliant with SEPAR guidelines and 207 (37%) patients received antibiotics with Antipseudomonal activity (14% β-APS and 23% levofloxacin). The use of β-APS was independently associated with ICU admission (OR 8.16 95% CI 3.69-18.06) and prior hospitalization (OR 6.76 95% CI 3.02-15.15), while levofloxacin was associated with negative pneumococcal urine antigen tests (OR 3.41 95% CI 1.70-6.85) but negatively associated with ICU admission (OR 0.26 95% CI 0.08-0.86). None of these factors were associated with P aeruginosa episodes. In univariate analysis, prior P aeruginosa infection/colonization (2/9 vs 6/372, p = 0.013), severe COPD (3/9 vs 26/372, p = 0.024), multilobar involvement (7/9 vs 119/372, p = 0.007) and prior antibiotic (6/9 vs 109/372, p = 0.025) were significantly associated with P aeruginosa episodes. Antipseudomonal prescriptions were common, in spite of the very low incidence of Pseudomonas aeruginosa. The rationale for prescription was influenced by both severity-of-illness and pneumococcal urine antigen test (levofloxacin) and prior hospitalization and ICU admission (β-APS). However, these factors were not associated with P aeruginosa episodes. Only prior P aeruginosa infection/colonization and severe COPD seem to be reliable indicators in clinical practice.
