The Experts below are selected from a list of 222 Experts worldwide ranked by ideXlab platform
Kristi A. Traugott - One of the best experts on this subject based on the ideXlab platform.
-
β lactam therapy for methicillin susceptible staphylococcus aureus bacteremia a comparative review of cefazolin versus Antistaphylococcal Penicillins
Pharmacotherapy, 2017Co-Authors: Kelly Echevarria, Kristi A. TraugottAbstract:Methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia is associated with high morbidity and mortality. Traditionally, Antistaphylococcal Penicillins (ASPs) have been considered the agents of choice for the treatment of MSSA bacteremia. Vancomycin has been demonstrated to have poorer outcomes in several studies and is only recommended for patients with severe penicillin allergies. Although cefazolin is considered as an alternative to the ASPs for patients with nonsevere penicillin allergies, cefazolin offers several pharmacologic advantages over ASPs, such as more convenient dosing regimens, and antimicrobial stewardship programs are increasingly using cefazolin as the preferential agent for MSSA infections as part of cost-saving initiatives. Concerns about susceptibility to hydrolysis by type A β-lactamases, particularly at high inocula seen in deep-seated infections such as endocarditis; selective pressures from unnecessary gram-negative coverage; and lack of comparative clinical data have precluded recommending cefazolin as a first-line therapy for MSSA bacteremia. Recent clinical studies, however, have suggested similar clinical efficacy but better tolerability, with lower rates of discontinuation due to adverse drug reactions, of cefazolin compared with ASPs. Other variables, such as adequate source control (e.g., intravascular catheter removal, debridement, or drainage) and enhanced pharmacodynamics through aggressive cefazolin dosing, may mitigate the role of cefazolin inoculum effect and factor into determining improved clinical outcomes. In this review, we highlight the utility of cefazolin versus ASPs in the treatment of MSSA bacteremia with a focus on clinical efficacy and safety.
-
β‐Lactam Therapy for Methicillin‐Susceptible Staphylococcus aureus Bacteremia: A Comparative Review of Cefazolin versus Antistaphylococcal Penicillins
Pharmacotherapy, 2017Co-Authors: Kelly Echevarria, Kristi A. TraugottAbstract:Methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia is associated with high morbidity and mortality. Traditionally, Antistaphylococcal Penicillins (ASPs) have been considered the agents of choice for the treatment of MSSA bacteremia. Vancomycin has been demonstrated to have poorer outcomes in several studies and is only recommended for patients with severe penicillin allergies. Although cefazolin is considered as an alternative to the ASPs for patients with nonsevere penicillin allergies, cefazolin offers several pharmacologic advantages over ASPs, such as more convenient dosing regimens, and antimicrobial stewardship programs are increasingly using cefazolin as the preferential agent for MSSA infections as part of cost-saving initiatives. Concerns about susceptibility to hydrolysis by type A β-lactamases, particularly at high inocula seen in deep-seated infections such as endocarditis; selective pressures from unnecessary gram-negative coverage; and lack of comparative clinical data have precluded recommending cefazolin as a first-line therapy for MSSA bacteremia. Recent clinical studies, however, have suggested similar clinical efficacy but better tolerability, with lower rates of discontinuation due to adverse drug reactions, of cefazolin compared with ASPs. Other variables, such as adequate source control (e.g., intravascular catheter removal, debridement, or drainage) and enhanced pharmacodynamics through aggressive cefazolin dosing, may mitigate the role of cefazolin inoculum effect and factor into determining improved clinical outcomes. In this review, we highlight the utility of cefazolin versus ASPs in the treatment of MSSA bacteremia with a focus on clinical efficacy and safety.
Kelly Echevarria - One of the best experts on this subject based on the ideXlab platform.
-
β lactam therapy for methicillin susceptible staphylococcus aureus bacteremia a comparative review of cefazolin versus Antistaphylococcal Penicillins
Pharmacotherapy, 2017Co-Authors: Kelly Echevarria, Kristi A. TraugottAbstract:Methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia is associated with high morbidity and mortality. Traditionally, Antistaphylococcal Penicillins (ASPs) have been considered the agents of choice for the treatment of MSSA bacteremia. Vancomycin has been demonstrated to have poorer outcomes in several studies and is only recommended for patients with severe penicillin allergies. Although cefazolin is considered as an alternative to the ASPs for patients with nonsevere penicillin allergies, cefazolin offers several pharmacologic advantages over ASPs, such as more convenient dosing regimens, and antimicrobial stewardship programs are increasingly using cefazolin as the preferential agent for MSSA infections as part of cost-saving initiatives. Concerns about susceptibility to hydrolysis by type A β-lactamases, particularly at high inocula seen in deep-seated infections such as endocarditis; selective pressures from unnecessary gram-negative coverage; and lack of comparative clinical data have precluded recommending cefazolin as a first-line therapy for MSSA bacteremia. Recent clinical studies, however, have suggested similar clinical efficacy but better tolerability, with lower rates of discontinuation due to adverse drug reactions, of cefazolin compared with ASPs. Other variables, such as adequate source control (e.g., intravascular catheter removal, debridement, or drainage) and enhanced pharmacodynamics through aggressive cefazolin dosing, may mitigate the role of cefazolin inoculum effect and factor into determining improved clinical outcomes. In this review, we highlight the utility of cefazolin versus ASPs in the treatment of MSSA bacteremia with a focus on clinical efficacy and safety.
-
β‐Lactam Therapy for Methicillin‐Susceptible Staphylococcus aureus Bacteremia: A Comparative Review of Cefazolin versus Antistaphylococcal Penicillins
Pharmacotherapy, 2017Co-Authors: Kelly Echevarria, Kristi A. TraugottAbstract:Methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia is associated with high morbidity and mortality. Traditionally, Antistaphylococcal Penicillins (ASPs) have been considered the agents of choice for the treatment of MSSA bacteremia. Vancomycin has been demonstrated to have poorer outcomes in several studies and is only recommended for patients with severe penicillin allergies. Although cefazolin is considered as an alternative to the ASPs for patients with nonsevere penicillin allergies, cefazolin offers several pharmacologic advantages over ASPs, such as more convenient dosing regimens, and antimicrobial stewardship programs are increasingly using cefazolin as the preferential agent for MSSA infections as part of cost-saving initiatives. Concerns about susceptibility to hydrolysis by type A β-lactamases, particularly at high inocula seen in deep-seated infections such as endocarditis; selective pressures from unnecessary gram-negative coverage; and lack of comparative clinical data have precluded recommending cefazolin as a first-line therapy for MSSA bacteremia. Recent clinical studies, however, have suggested similar clinical efficacy but better tolerability, with lower rates of discontinuation due to adverse drug reactions, of cefazolin compared with ASPs. Other variables, such as adequate source control (e.g., intravascular catheter removal, debridement, or drainage) and enhanced pharmacodynamics through aggressive cefazolin dosing, may mitigate the role of cefazolin inoculum effect and factor into determining improved clinical outcomes. In this review, we highlight the utility of cefazolin versus ASPs in the treatment of MSSA bacteremia with a focus on clinical efficacy and safety.
-
comparison of cefazolin versus oxacillin for treatment of complicated bacteremia caused by methicillin susceptible staphylococcus aureus
Antimicrobial Agents and Chemotherapy, 2014Co-Authors: Kelly Echevarria, Darrel W Hughes, Jose Cadena, Jason Bowling, James S LewisAbstract:Contrary to prior case reports that described occasional clinical failures with cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infections, recent studies have demonstrated no difference in outcomes between cefazolin and Antistaphylococcal Penicillins for the treatment of MSSA bacteremia. While promising, these studies described low frequencies of high-inoculum infections, such as endocarditis. This retrospective study compares clinical outcomes of cefazolin versus oxacillin for complicated MSSA bacteremia at two tertiary care hospitals between January 2008 and June 2012. Fifty-nine patients treated with cefazolin and 34 patients treated with oxacillin were included. Osteoarticular (41%) and endovascular (20%) sources were the predominant sites of infection. The rates of clinical cure at the end of therapy were similar between cefazolin and oxacillin (95% versus 88%; P=0.25), but overall failure at 90 days was higher in the oxacillin arm (47% versus 24%; P=0.04). Failures were more likely to have received surgical interventions (63% versus 40%; P=0.05) and to have an osteoarticular source (57% versus 33%; P=0.04). Failures also had a longer duration of bacteremia (7 versus 3 days; P=0.0002), which was the only predictor of failure. Antibiotic selection was not predictive of failure. Rates of adverse drug events were higher in the oxacillin arm (30% versus 3%; P=0.0006), and oxacillin was more frequently discontinued due to adverse drug events (21% versus 3%; P=0.01). Cefazolin appears similar to oxacillin for the treatment of complicated MSSA bacteremia but with significantly improved safety. The higher rates of failure with oxacillin may have been confounded by other patient factors and warrant further investigation.
Chadwick K. Mellen - One of the best experts on this subject based on the ideXlab platform.
-
meta analysis of trials comparing cefazolin to Antistaphylococcal Penicillins in the treatment of methicillin sensitive staphylococcus aureus bacteraemia
British Journal of Clinical Pharmacology, 2018Co-Authors: Joseph P. Rindone, Chadwick K. MellenAbstract:AIMS The objective of this study was to determine the effectiveness and safety of cefazolin vs. Antistaphylococcal penicillin (ASP) in the treatment of methicillin-sensitive Staphylococcus aureus (MSSA) bacteraemia. METHODS The databases of PubMed, Embase and Cochrane Central were used to identify comparative trials of cefazolin vs. ASP in MSSA bacteraemia. Meta-analysis of included trials was performed to assess any differences regarding mortality, clinical cure, recurrence and withdrawal from adverse effects between groups. Data were analysed using fixed effect model. Studies were weighted using Mantel-Haenszel methodology. Heterogeneity was calculated using the I2 statistic. RESULTS Nine retrospective and one prospective trials were identified involving 4728 patients, 2954 with ASP and 1774 with cefazolin. Meta-analysis showed a lower mortality rate with cefazolin vs. ASP using fixed effect model [risk ratio (RR) 0.78, 95% confidence interval (CI) 0.69-0.88, P < 0.0001] with borderline high heterogeneity (I2 = 51%). Clinical cure was noted more often with cefazolin (RR 1.09, 95% CI 1.02-1.17, P = 0.02), although no difference was noted with relapse (RR 1.29, 95% CI 0.96-1.74 P = 0.09). Analysis also showed more withdrawals from adverse events with ASP vs. cefazolin (RR 0.27, 95% CI 0.16-0.47, P < 0.00001). A minority of patients enrolled in these trials were admitted to the intensive care unit or had endocarditis (11.4% with ASP and 9% with cefazolin). CONCLUSION Our meta-analysis of retrospective data demonstrate that cefazolin is more effective and safer ASP in patients with MSSA bacteraemia from various causes. Low quality of trials, borderline high heterogeneity, and possible publication bias may limit the validity of our findings. Randomized trials are needed to confirm these findings.
-
Meta-analysis of trials comparing cefazolin to Antistaphylococcal Penicillins in the treatment of methicillin-sensitive Staphylococcus aureus bacteraemia.
British journal of clinical pharmacology, 2018Co-Authors: Joseph P. Rindone, Chadwick K. MellenAbstract:AIMS The objective of this study was to determine the effectiveness and safety of cefazolin vs. Antistaphylococcal penicillin (ASP) in the treatment of methicillin-sensitive Staphylococcus aureus (MSSA) bacteraemia. METHODS The databases of PubMed, Embase and Cochrane Central were used to identify comparative trials of cefazolin vs. ASP in MSSA bacteraemia. Meta-analysis of included trials was performed to assess any differences regarding mortality, clinical cure, recurrence and withdrawal from adverse effects between groups. Data were analysed using fixed effect model. Studies were weighted using Mantel-Haenszel methodology. Heterogeneity was calculated using the I2 statistic. RESULTS Nine retrospective and one prospective trials were identified involving 4728 patients, 2954 with ASP and 1774 with cefazolin. Meta-analysis showed a lower mortality rate with cefazolin vs. ASP using fixed effect model [risk ratio (RR) 0.78, 95% confidence interval (CI) 0.69-0.88, P
Henry F. Chambers - One of the best experts on this subject based on the ideXlab platform.
-
Cefazolin versus Nafcillin for Methicillin-Sensitive Staphylococcus aureus Bloodstream Infection in a California Tertiary Medical Center.
Antimicrobial agents and chemotherapy, 2016Co-Authors: Simon Pollett, Sanjiv M. Baxi, George W. Rutherford, Sarah B Doernberg, Peter Bacchetti, Henry F. ChambersAbstract:Recent observational studies have suggested possible reductions in mortality in patients receiving cefazolin versus Antistaphylococcal Penicillins. We examined 90-day mortality in patients receiving cefazolin compared to nafcillin for methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infection (BSI). We identified persons with MSSA BSI admitted to San Francisco General Hospital from January 2008 to July 2013 through a hospital-wide infection surveillance system and confirmed 90-day mortality using U.S. national vital registries. We included persons receiving cefazolin or nafcillin as the predominant intravenous antimicrobial agent; all participants received inpatient Infectious Diseases service consultation. We estimated the association between receipt of cefazolin and 90-day risk of death by multivariate logistic regression, including a propensity score for receiving cefazolin as the second predictor. Of 230 MSSA BSI cases, 30 received nafcillin and 70 received cefazolin as the predominant antimicrobial; 10 died within 90 days, 5 from each group. Unadjusted analysis showed substantial but not statistically significant reduced odds of death in those receiving cefazolin (odds ratio, 0.38; 95% confidence interval [CI], 0.10 to 1.44). Multivariate analysis with propensity scores found a similar adjusted odds ratio (0.40; 95% CI, 0.09 to 1.74; P = 0.22). We found a large reduction in 90-day mortality in those receiving cefazolin compared to nafcillin for MSSA BSI, but this finding was not statistically significant. The magnitude of effect seen in this and other studies justifies further study.
-
initial low dose gentamicin for staphylococcus aureus bacteremia and endocarditis is nephrotoxic
Clinical Infectious Diseases, 2009Co-Authors: Sara E Cosgrove, Henry F. Chambers, Gloria Vigliani, Marilyn Campion, Vance G Fowler, Elias Abrutyn, Ralph G Corey, Donald P Levine, Mark E Rupp, Adolf W KarchmerAbstract:Background. The safety of adding initial low-dose gentamicin to Antistaphylococcal Penicillins or vancomycin for treatment of suspected Staphylococcus aureus native valve endocarditis is unknown. This study evaluated the association between this practice and nephrotoxicity. Methods. We performed a prospective cohort study of safety data from a randomized, controlled trial of therapy for S. aureus bacteremia and native valve infective endocarditis involving 236 patients from 44 hospitals in 4 countries. Patients either received standard therapy (Antistaphylococcal penicillin or vancomycin) plus initial low-dose gentamicin (n = 116) or received daptomycin monotherapy (n = 120). We measured renal adverse events and clinically significant decreased creatinine clearance in patients (1) in the original randomized study arms and (2) who received any initial low-dose gentamicin either, as a study medication or ≤2 days before enrollment. Results. Renal adverse events occurred in 8 (7%) of 120 daptomycin recipients, 10 (19%) of 53 vancomycin recipients, and 11 (17%) of 63 Antistaphylococcal penicillin recipients. Decreased creatinine clearance occurred in 9 (8%) of 113 of evaluable daptomycin recipients, 10 (22%) of 46 vancomycin recipients, and 16 (25%) of 63 Antistaphylococcal penicillin recipients. An additional 21 patients received initial low-dose gentamicin ≤2 days before study enrollment. A total of 22% of patients who received initial low-dose gentamicin versus 8% of patients who did not receive initial low-dose gentamicin experienced decreased creatinine clearance (P =.005). Independent predictors of a clinically significant decrease in creatinine clearance were age ≥65 years and receipt of any initial low-dose gentamicin. Conclusions. Initial low-dose gentamicin as part of therapy for S. aureus bacteremia and native valve infective endocarditis is nephrotoxic and should not be used routinely, given the minimal existing data supporting its benefit.
-
Methicillin-resistant Staphylococcus aureus. Mechanisms of resistance and implications for treatment.
Postgraduate medicine, 2001Co-Authors: Henry F. ChambersAbstract:The frequency of methicillin-resistant Staphylococcus aureus (MRSA) continues to increase steadily, with nosocomial isolates approaching 50% of the total tested. Primarily isolated in hospitals, strains of MRSA have now spread into the community, complicating the management of this sometimes-fatal pathogen. Methicillin resistance in S aureus is mediated by the mecA gene, which encodes for a novel penicillin-binding protein (PBP), PBP-2a. In MRSA, exposure to methicillin inactivates the 4 high-binding-affinity PBPs normally present. PBP-2a, which displays a low affinity for methicillin, takes over the functions of these PBPs, permitting the cell to grow. Regulation of the methicillin-resistant phenotype and production of PBP-2a are influenced by the action of other genes. Two genes located upstream from mecA--mecR1 and mecI--control expression of PBP-2a. Antibiotics with high affinity for PBP-2a have displayed efficacy against MRSA in vivo, but none of these agents has made it beyond the investigational stage. Vancomycin remains the drug of choice for treatment of infections caused by MRSA, although it is intrinsically less active than the Antistaphylococcal Penicillins. Combinations of vancomycin with ss-lactam antibiotics may be synergistic in vivo against MRSA strains, including those with intermediate susceptibility to vancomycin. Given the increasing prevalence of MRSA in hospitals and in community settings, alternative approaches are needed for treatment of infections caused by MRSA.
-
Borderline susceptibility to Antistaphylococcal Penicillins is not conferred exclusively by the hyperproduction of beta-lactamase.
Antimicrobial agents and chemotherapy, 1991Co-Authors: N L Barg, Henry F. Chambers, Douglas S. KernodleAbstract:Staphylococcus aureus strains bearing the 17.2-kb beta-lactamase plasmid pBW15 and belonging to phage group 94/96 exhibit borderline susceptibility to the Antistaphylococcal Penicillins. Borderline susceptibility within phage group 94/96 is thought to be mediated by the hyperproduction of type A staphylococcal beta-lactamase. Evaluation of 84 non-94/96 phage type S. aureus strains that also produced the type A enzyme identified 7 additional hyperproducing strains. However, none of these isolates contained pBW15, and only one met the criteria for borderline susceptibility. To determine the role of pBW15 and the 94/96 phage type in the expression of borderline susceptibility, pBW15 was transformed in two plasmid-free, penicillin-susceptible strains, one of which belonged to phage group 94/96. Penicillin MICs for both transformants and quantitative beta-lactamase activity were comparable to those for the parent pBW15-containing strain. A fourfold difference in the oxacillin MICs for the 94/96 and non-94/96 phage type transformants (1.0 and 0.25 microgram/ml, respectively) was identified, and only the 94/96 phage type transformant met the criteria for borderline susceptibility. Chromosomal DNA from borderline-susceptible phage group 94/96 strains did not hybridize with a probe for mecA, and the beta-lactam binding affinity of PBPs 1, 2, 3, and 4 from a penicillin-susceptible 94/96 phage type strain and a non-94/96 phage type strain were comparable. Although hyperproduction of the type A beta-lactamase appears to be necessary for the expression of borderline susceptibility within certain phage group 94/96 strains, beta-lactamase production of a comparable magnitude by a group of S. aureus strains belonging to other phage types does not confer borderline susceptibility. These data suggest that borderline susceptibility is not solely due to the hyperproduction of beta-lactamase.
Joseph P. Rindone - One of the best experts on this subject based on the ideXlab platform.
-
meta analysis of trials comparing cefazolin to Antistaphylococcal Penicillins in the treatment of methicillin sensitive staphylococcus aureus bacteraemia
British Journal of Clinical Pharmacology, 2018Co-Authors: Joseph P. Rindone, Chadwick K. MellenAbstract:AIMS The objective of this study was to determine the effectiveness and safety of cefazolin vs. Antistaphylococcal penicillin (ASP) in the treatment of methicillin-sensitive Staphylococcus aureus (MSSA) bacteraemia. METHODS The databases of PubMed, Embase and Cochrane Central were used to identify comparative trials of cefazolin vs. ASP in MSSA bacteraemia. Meta-analysis of included trials was performed to assess any differences regarding mortality, clinical cure, recurrence and withdrawal from adverse effects between groups. Data were analysed using fixed effect model. Studies were weighted using Mantel-Haenszel methodology. Heterogeneity was calculated using the I2 statistic. RESULTS Nine retrospective and one prospective trials were identified involving 4728 patients, 2954 with ASP and 1774 with cefazolin. Meta-analysis showed a lower mortality rate with cefazolin vs. ASP using fixed effect model [risk ratio (RR) 0.78, 95% confidence interval (CI) 0.69-0.88, P < 0.0001] with borderline high heterogeneity (I2 = 51%). Clinical cure was noted more often with cefazolin (RR 1.09, 95% CI 1.02-1.17, P = 0.02), although no difference was noted with relapse (RR 1.29, 95% CI 0.96-1.74 P = 0.09). Analysis also showed more withdrawals from adverse events with ASP vs. cefazolin (RR 0.27, 95% CI 0.16-0.47, P < 0.00001). A minority of patients enrolled in these trials were admitted to the intensive care unit or had endocarditis (11.4% with ASP and 9% with cefazolin). CONCLUSION Our meta-analysis of retrospective data demonstrate that cefazolin is more effective and safer ASP in patients with MSSA bacteraemia from various causes. Low quality of trials, borderline high heterogeneity, and possible publication bias may limit the validity of our findings. Randomized trials are needed to confirm these findings.
-
Meta-analysis of trials comparing cefazolin to Antistaphylococcal Penicillins in the treatment of methicillin-sensitive Staphylococcus aureus bacteraemia.
British journal of clinical pharmacology, 2018Co-Authors: Joseph P. Rindone, Chadwick K. MellenAbstract:AIMS The objective of this study was to determine the effectiveness and safety of cefazolin vs. Antistaphylococcal penicillin (ASP) in the treatment of methicillin-sensitive Staphylococcus aureus (MSSA) bacteraemia. METHODS The databases of PubMed, Embase and Cochrane Central were used to identify comparative trials of cefazolin vs. ASP in MSSA bacteraemia. Meta-analysis of included trials was performed to assess any differences regarding mortality, clinical cure, recurrence and withdrawal from adverse effects between groups. Data were analysed using fixed effect model. Studies were weighted using Mantel-Haenszel methodology. Heterogeneity was calculated using the I2 statistic. RESULTS Nine retrospective and one prospective trials were identified involving 4728 patients, 2954 with ASP and 1774 with cefazolin. Meta-analysis showed a lower mortality rate with cefazolin vs. ASP using fixed effect model [risk ratio (RR) 0.78, 95% confidence interval (CI) 0.69-0.88, P