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Michael J Rybak - One of the best experts on this subject based on the ideXlab platform.
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impact of high inoculum staphylococcus aureus on the activities of Nafcillin vancomycin linezolid and daptomycin alone and in combination with gentamicin in an in vitro pharmacodynamic model
Antimicrobial Agents and Chemotherapy, 2004Co-Authors: Kerry L Laplante, Michael J RybakAbstract:We evaluated the impact of high (9.5 log10 CFU/g) and moderate (5.5 log10 CFU/g) inocula of methicillin-susceptible and -resistant Staphylococcus aureus (MSSA and MRSA, respectively) on the activities of Nafcillin, linezolid, vancomycin, and daptomycin, alone and in combination with gentamicin in an in vitro pharmacodynamic model with simulated endocardial vegetations over 72 h. Human therapeutic dosing regimens for Nafcillin, daptomycin, vancomycin, linezolid, and gentamicin were simulated. At a moderate inoculum, Nafcillin (MSSA only), vancomycin, and daptomycin demonstrated equivalent and significant (P < 0.01) bactericidal (99.9% kill) activities (decreases of 3.34 +/- 1.1, 3.28 +/- 0.4, and 3.34 +/- 0.8 log10 CFU/g, respectively). Bactericidal activity was demonstrated at 4 h for Nafcillin and daptomycin and at 32 h for vancomycin. Linezolid demonstrated bacteriostatic activity over the course of the study period. At a high inoculum, daptomycin exhibited bactericidal activity against both MSSA and MRSA by 24 h (decrease of 5.51 to 6.31 +/- 0.10 log10 CFU/g). Nafcillin (versus MSSA), vancomycin, and linezolid (MSSA and MRSA) did not achieve bactericidal activity throughout the 72-h experiment. The addition of gentamicin increased the rate of 99.9% kill to 8 h for daptomycin (P < 0.01) and 48 h for Nafcillin (MSSA only) (P = 0.01). The addition of gentamicin did not improve the activity of vancomycin or linezolid for either isolate for the 72-h period. Overall, high-inoculum Staphylococcus aureus had a significant impact on the activities of Nafcillin and vancomycin. In contrast, daptomycin was affected minimally and linezolid was not affected by inoculum.
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impact of high inoculum staphylococcus aureus on the activities of Nafcillin vancomycin linezolid and daptomycin alone and in combination with gentamicin in an in vitro pharmacodynamic model
Antimicrobial Agents and Chemotherapy, 2004Co-Authors: Kerry L Laplante, Michael J RybakAbstract:We evaluated the impact of high (9.5 log 10 CFU/g) and moderate (5.5 log 10 CFU/g) inocula of methicillin-susceptible and -resistant S taphylococcus aureus (MSSA and MRSA, respectively) on the activities of Nafcillin, linezolid, vancomycin, and daptomycin, alone and in combination with gentamicin in an in vitro pharmacodynamic model with simulated endocardial vegetations over 72 h. Human therapeutic dosing regimens for Nafcillin, daptomycin, vancomycin, linezolid, and gentamicin were simulated. At a moderate inoculum, Nafcillin (MSSA only), vancomycin, and daptomycin demonstrated equivalent and significant ( P 10 CFU/g, respectively). Bactericidal activity was demonstrated at 4 h for Nafcillin and daptomycin and at 32 h for vancomycin. Linezolid demonstrated bacteriostatic activity over the course of the study period. At a high inoculum, daptomycin exhibited bactericidal activity against both MSSA and MRSA by 24 h (decrease of 5.51 to 6.31 ± 0.10 log 10 CFU/g). Nafcillin (versus MSSA), vancomycin, and linezolid (MSSA and MRSA) did not achieve bactericidal activity throughout the 72-h experiment. The addition of gentamicin increased the rate of 99.9% kill to 8 h for daptomycin ( P P = 0.01). The addition of gentamicin did not improve the activity of vancomycin or linezolid for either isolate for the 72-h period. Overall, high-inoculum Staphylococcus aureus had a significant impact on the activities of Nafcillin and vancomycin. In contrast, daptomycin was affected minimally and linezolid was not affected by inoculum.
Marin L. Schweizer - One of the best experts on this subject based on the ideXlab platform.
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versus vancomycin in methicillin-susceptible Staphylococcus aureus bacteremia
2013Co-Authors: Marin L. Schweizer, Michelle D. Shardell, Jon P Furuno, Jessina C. Mcgregor, George Sakoulas, Sara E Cosgrove, Kerri A. Thom, Anthony D Harris, Kristie J Johnson, Eli N PerencevichAbstract:Comparative effectiveness of Nafcillin or cefazoli
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comparative effectiveness of Nafcillin or cefazolin versus vancomycin in methicillin susceptible staphylococcus aureus bacteremia
BMC Infectious Diseases, 2011Co-Authors: Michelle D. Shardell, Jon P Furuno, Jessina C. Mcgregor, Sara E Cosgrove, Marin L. Schweizer, Kerri A. Thom, Anthony D Harris, Kristie J Johnson, George SakoulasAbstract:The high prevalence of methicillin-resistant S. aureus (MRSA) has led clinicians to select antibiotics that have coverage against MRSA, usually vancomycin, for empiric therapy for suspected staphylococcal infections. Clinicians often continue vancomycin started empirically even when methicillin-susceptible S. aureus (MSSA) strains are identified by culture. However, vancomycin has been associated with poor outcomes such as nephrotoxicity, persistent bacteremia and treatment failure. The objective of this study was to compare the effectiveness of vancomycin versus the beta-lactam antibiotics Nafcillin and cefazolin among patients with MSSA bacteremia. The outcome of interest for this study was 30-day in-hospital mortality. This retrospective cohort study included all adult in-patients admitted to a tertiary-care facility between January 1, 2003 and June 30, 2007 who had a positive blood culture for MSSA and received Nafcillin, cefazolin or vancomycin. Cox proportional hazard models were used to assess independent mortality hazards comparing Nafcillin or cefazolin versus vancomycin. Similar methods were used to estimate the survival benefits of switching from vancomycin to Nafcillin or cefazolin versus leaving patients on vancomycin. Each model included statistical adjustment using propensity scores which contained variables associated with an increased propensity to receive vancomycin. 267 patients were included; 14% (38/267) received Nafcillin or cefazolin, 51% (135/267) received both vancomycin and either Nafcillin or cefazolin, and 35% (94/267) received vancomycin. Thirty (11%) died within 30 days. Those receiving Nafcillin or cefazolin had 79% lower mortality hazards compared with those who received vancomycin alone (adjusted hazard ratio (HR): 0.21; 95% confidence interval (CI): 0.09, 0.47). Among the 122 patients who initially received vancomycin empirically, those who were switched to Nafcillin or cefazolin (66/122) had 69% lower mortality hazards (adjusted HR: 0.31; 95% CI: 0.10, 0.95) compared to those who remained on vancomycin. Receipt of Nafcillin or cefazolin was protective against mortality compared to vancomycin even when therapy was altered after culture results identified MSSA. Convenience of vancomycin dosing may not outweigh the potential benefits of Nafcillin or cefazolin in the treatment of MSSA bacteremia.
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comparative effectiveness of Nafcillin or cefazolin versus vancomycin in methicillin susceptible staphylococcus aureus bacteremia
BMC Infectious Diseases, 2011Co-Authors: Michelle D. Shardell, Jon P Furuno, Jessina C. Mcgregor, Sara E Cosgrove, Marin L. Schweizer, Kerri A. Thom, Anthony D Harris, Kristie J Johnson, George SakoulasAbstract:Background The high prevalence of methicillin-resistant S. aureus (MRSA) has led clinicians to select antibiotics that have coverage against MRSA, usually vancomycin, for empiric therapy for suspected staphylococcal infections. Clinicians often continue vancomycin started empirically even when methicillin-susceptible S. aureus (MSSA) strains are identified by culture. However, vancomycin has been associated with poor outcomes such as nephrotoxicity, persistent bacteremia and treatment failure. The objective of this study was to compare the effectiveness of vancomycin versus the beta-lactam antibiotics Nafcillin and cefazolin among patients with MSSA bacteremia. The outcome of interest for this study was 30-day in-hospital mortality.
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Comparative effectiveness of Nafcillin or cefazolin versus vancomycin in methicillin-susceptible Staphylococcus aureus bacteremia
BMC Infectious Diseases, 2011Co-Authors: Marin L. Schweizer, Michelle D. Shardell, Jon P Furuno, Jessina C. Mcgregor, J. Kristie Johnson, Sara E Cosgrove, Kerri A. Thom, Anthony D Harris, George SakoulasAbstract:BACKGROUND The high prevalence of methicillin-resistant S. aureus (MRSA) has led clinicians to select antibiotics that have coverage against MRSA, usually vancomycin, for empiric therapy for suspected staphylococcal infections. Clinicians often continue vancomycin started empirically even when methicillin-susceptible S. aureus (MSSA) strains are identified by culture. However, vancomycin has been associated with poor outcomes such as nephrotoxicity, persistent bacteremia and treatment failure. The objective of this study was to compare the effectiveness of vancomycin versus the beta-lactam antibiotics Nafcillin and cefazolin among patients with MSSA bacteremia. The outcome of interest for this study was 30-day in-hospital mortality. METHODS This retrospective cohort study included all adult in-patients admitted to a tertiary-care facility between January 1, 2003 and June 30, 2007 who had a positive blood culture for MSSA and received Nafcillin, cefazolin or vancomycin. Cox proportional hazard models were used to assess independent mortality hazards comparing Nafcillin or cefazolin versus vancomycin. Similar methods were used to estimate the survival benefits of switching from vancomycin to Nafcillin or cefazolin versus leaving patients on vancomycin. Each model included statistical adjustment using propensity scores which contained variables associated with an increased propensity to receive vancomycin. RESULTS 267 patients were included; 14% (38/267) received Nafcillin or cefazolin, 51% (135/267) received both vancomycin and either Nafcillin or cefazolin, and 35% (94/267) received vancomycin. Thirty (11%) died within 30 days. Those receiving Nafcillin or cefazolin had 79% lower mortality hazards compared with those who received vancomycin alone (adjusted hazard ratio (HR): 0.21; 95% confidence interval (CI): 0.09, 0.47). Among the 122 patients who initially received vancomycin empirically, those who were switched to Nafcillin or cefazolin (66/122) had 69% lower mortality hazards (adjusted HR: 0.31; 95% CI: 0.10, 0.95) compared to those who remained on vancomycin. CONCLUSIONS Receipt of Nafcillin or cefazolin was protective against mortality compared to vancomycin even when therapy was altered after culture results identified MSSA. Convenience of vancomycin dosing may not outweigh the potential benefits of Nafcillin or cefazolin in the treatment of MSSA bacteremia.
George Sakoulas - One of the best experts on this subject based on the ideXlab platform.
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versus vancomycin in methicillin-susceptible Staphylococcus aureus bacteremia
2013Co-Authors: Marin L. Schweizer, Michelle D. Shardell, Jon P Furuno, Jessina C. Mcgregor, George Sakoulas, Sara E Cosgrove, Kerri A. Thom, Anthony D Harris, Kristie J Johnson, Eli N PerencevichAbstract:Comparative effectiveness of Nafcillin or cefazoli
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comparative effectiveness of Nafcillin or cefazolin versus vancomycin in methicillin susceptible staphylococcus aureus bacteremia
BMC Infectious Diseases, 2011Co-Authors: Michelle D. Shardell, Jon P Furuno, Jessina C. Mcgregor, Sara E Cosgrove, Marin L. Schweizer, Kerri A. Thom, Anthony D Harris, Kristie J Johnson, George SakoulasAbstract:The high prevalence of methicillin-resistant S. aureus (MRSA) has led clinicians to select antibiotics that have coverage against MRSA, usually vancomycin, for empiric therapy for suspected staphylococcal infections. Clinicians often continue vancomycin started empirically even when methicillin-susceptible S. aureus (MSSA) strains are identified by culture. However, vancomycin has been associated with poor outcomes such as nephrotoxicity, persistent bacteremia and treatment failure. The objective of this study was to compare the effectiveness of vancomycin versus the beta-lactam antibiotics Nafcillin and cefazolin among patients with MSSA bacteremia. The outcome of interest for this study was 30-day in-hospital mortality. This retrospective cohort study included all adult in-patients admitted to a tertiary-care facility between January 1, 2003 and June 30, 2007 who had a positive blood culture for MSSA and received Nafcillin, cefazolin or vancomycin. Cox proportional hazard models were used to assess independent mortality hazards comparing Nafcillin or cefazolin versus vancomycin. Similar methods were used to estimate the survival benefits of switching from vancomycin to Nafcillin or cefazolin versus leaving patients on vancomycin. Each model included statistical adjustment using propensity scores which contained variables associated with an increased propensity to receive vancomycin. 267 patients were included; 14% (38/267) received Nafcillin or cefazolin, 51% (135/267) received both vancomycin and either Nafcillin or cefazolin, and 35% (94/267) received vancomycin. Thirty (11%) died within 30 days. Those receiving Nafcillin or cefazolin had 79% lower mortality hazards compared with those who received vancomycin alone (adjusted hazard ratio (HR): 0.21; 95% confidence interval (CI): 0.09, 0.47). Among the 122 patients who initially received vancomycin empirically, those who were switched to Nafcillin or cefazolin (66/122) had 69% lower mortality hazards (adjusted HR: 0.31; 95% CI: 0.10, 0.95) compared to those who remained on vancomycin. Receipt of Nafcillin or cefazolin was protective against mortality compared to vancomycin even when therapy was altered after culture results identified MSSA. Convenience of vancomycin dosing may not outweigh the potential benefits of Nafcillin or cefazolin in the treatment of MSSA bacteremia.
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comparative effectiveness of Nafcillin or cefazolin versus vancomycin in methicillin susceptible staphylococcus aureus bacteremia
BMC Infectious Diseases, 2011Co-Authors: Michelle D. Shardell, Jon P Furuno, Jessina C. Mcgregor, Sara E Cosgrove, Marin L. Schweizer, Kerri A. Thom, Anthony D Harris, Kristie J Johnson, George SakoulasAbstract:Background The high prevalence of methicillin-resistant S. aureus (MRSA) has led clinicians to select antibiotics that have coverage against MRSA, usually vancomycin, for empiric therapy for suspected staphylococcal infections. Clinicians often continue vancomycin started empirically even when methicillin-susceptible S. aureus (MSSA) strains are identified by culture. However, vancomycin has been associated with poor outcomes such as nephrotoxicity, persistent bacteremia and treatment failure. The objective of this study was to compare the effectiveness of vancomycin versus the beta-lactam antibiotics Nafcillin and cefazolin among patients with MSSA bacteremia. The outcome of interest for this study was 30-day in-hospital mortality.
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Comparative effectiveness of Nafcillin or cefazolin versus vancomycin in methicillin-susceptible Staphylococcus aureus bacteremia
BMC Infectious Diseases, 2011Co-Authors: Marin L. Schweizer, Michelle D. Shardell, Jon P Furuno, Jessina C. Mcgregor, J. Kristie Johnson, Sara E Cosgrove, Kerri A. Thom, Anthony D Harris, George SakoulasAbstract:BACKGROUND The high prevalence of methicillin-resistant S. aureus (MRSA) has led clinicians to select antibiotics that have coverage against MRSA, usually vancomycin, for empiric therapy for suspected staphylococcal infections. Clinicians often continue vancomycin started empirically even when methicillin-susceptible S. aureus (MSSA) strains are identified by culture. However, vancomycin has been associated with poor outcomes such as nephrotoxicity, persistent bacteremia and treatment failure. The objective of this study was to compare the effectiveness of vancomycin versus the beta-lactam antibiotics Nafcillin and cefazolin among patients with MSSA bacteremia. The outcome of interest for this study was 30-day in-hospital mortality. METHODS This retrospective cohort study included all adult in-patients admitted to a tertiary-care facility between January 1, 2003 and June 30, 2007 who had a positive blood culture for MSSA and received Nafcillin, cefazolin or vancomycin. Cox proportional hazard models were used to assess independent mortality hazards comparing Nafcillin or cefazolin versus vancomycin. Similar methods were used to estimate the survival benefits of switching from vancomycin to Nafcillin or cefazolin versus leaving patients on vancomycin. Each model included statistical adjustment using propensity scores which contained variables associated with an increased propensity to receive vancomycin. RESULTS 267 patients were included; 14% (38/267) received Nafcillin or cefazolin, 51% (135/267) received both vancomycin and either Nafcillin or cefazolin, and 35% (94/267) received vancomycin. Thirty (11%) died within 30 days. Those receiving Nafcillin or cefazolin had 79% lower mortality hazards compared with those who received vancomycin alone (adjusted hazard ratio (HR): 0.21; 95% confidence interval (CI): 0.09, 0.47). Among the 122 patients who initially received vancomycin empirically, those who were switched to Nafcillin or cefazolin (66/122) had 69% lower mortality hazards (adjusted HR: 0.31; 95% CI: 0.10, 0.95) compared to those who remained on vancomycin. CONCLUSIONS Receipt of Nafcillin or cefazolin was protective against mortality compared to vancomycin even when therapy was altered after culture results identified MSSA. Convenience of vancomycin dosing may not outweigh the potential benefits of Nafcillin or cefazolin in the treatment of MSSA bacteremia.
Kerry L Laplante - One of the best experts on this subject based on the ideXlab platform.
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comparative effectiveness of exclusive exposure to Nafcillin or oxacillin cefazolin piperacillin tazobactam and fluoroquinolones among a national cohort of veterans with methicillin susceptible staphylococcus aureus bloodstream infection
Open Forum Infectious Diseases, 2019Co-Authors: Maya Beganovic, Kerry L Laplante, Jaclyn Cusumano, Vrishali Lopes, Aisling R CaffreyAbstract:Objective Beta-lactam antibiotics are recommended as first-line for treatment of methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia. The objective of this study was to compare effectiveness of anti-MSSA therapies among bacteremia patients exclusively exposed to 1 antimicrobial. Method This was a national retrospective cohort study of patients hospitalized in Veterans Affairs medical centers with MSSA bacteremia from January 1, 2002, to October 1, 2015. Patients were included if they were treated exclusively with Nafcillin, oxacillin, cefazolin, piperacillin/tazobactam, or fluoroquinolones (moxifloxacin and levofloxacin). We assessed 30-day mortality, time to discharge, inpatient mortality, 30-day readmission, and 30-day S. aureus reinfection. Hazard ratios (HRs) and 95% confidence intervals (CI) were calculated using propensity-score (PS) matched Cox proportional hazards regression model. Results When comparing Nafcillin/oxacillin (n = 105) with cefazolin (n = 107), 30-day mortality was similar between groups (PS matched n = 44; HR, 0.67; 95% CI, 0.11-4.00), as were rates of the other outcomes assessed. As clinical outcomes did not vary between Nafcillin/oxacillin and cefazolin, they were combined for comparison with piperacillin/tazobactam (n = 113) and fluoroquinolones (n = 103). Mortality in the 30 days after culture was significantly lower in the Nafcillin/oxacillin/cefazolin group compared with piperacillin/tazobactam (PS matched n = 48; HR, 0.10; 95% CI, 0.01-0.78), and similar when compared with fluoroquinolones (PS matched n = 32; HR, 1.33; 95% CI, 0.30-5.96). Conclusions In hospitalized patients with MSSA bacteremia, no difference in mortality was observed between Nafcillin/oxacillin and cefazolin or fluoroquinolones. However, higher mortality was observed with piperacillin/tazobactam as compared with Nafcillin/oxacillin/cefazolin, suggesting it may not be as effective as a monotherapy in MSSA bacteremia.
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impact of high inoculum staphylococcus aureus on the activities of Nafcillin vancomycin linezolid and daptomycin alone and in combination with gentamicin in an in vitro pharmacodynamic model
Antimicrobial Agents and Chemotherapy, 2004Co-Authors: Kerry L Laplante, Michael J RybakAbstract:We evaluated the impact of high (9.5 log10 CFU/g) and moderate (5.5 log10 CFU/g) inocula of methicillin-susceptible and -resistant Staphylococcus aureus (MSSA and MRSA, respectively) on the activities of Nafcillin, linezolid, vancomycin, and daptomycin, alone and in combination with gentamicin in an in vitro pharmacodynamic model with simulated endocardial vegetations over 72 h. Human therapeutic dosing regimens for Nafcillin, daptomycin, vancomycin, linezolid, and gentamicin were simulated. At a moderate inoculum, Nafcillin (MSSA only), vancomycin, and daptomycin demonstrated equivalent and significant (P < 0.01) bactericidal (99.9% kill) activities (decreases of 3.34 +/- 1.1, 3.28 +/- 0.4, and 3.34 +/- 0.8 log10 CFU/g, respectively). Bactericidal activity was demonstrated at 4 h for Nafcillin and daptomycin and at 32 h for vancomycin. Linezolid demonstrated bacteriostatic activity over the course of the study period. At a high inoculum, daptomycin exhibited bactericidal activity against both MSSA and MRSA by 24 h (decrease of 5.51 to 6.31 +/- 0.10 log10 CFU/g). Nafcillin (versus MSSA), vancomycin, and linezolid (MSSA and MRSA) did not achieve bactericidal activity throughout the 72-h experiment. The addition of gentamicin increased the rate of 99.9% kill to 8 h for daptomycin (P < 0.01) and 48 h for Nafcillin (MSSA only) (P = 0.01). The addition of gentamicin did not improve the activity of vancomycin or linezolid for either isolate for the 72-h period. Overall, high-inoculum Staphylococcus aureus had a significant impact on the activities of Nafcillin and vancomycin. In contrast, daptomycin was affected minimally and linezolid was not affected by inoculum.
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impact of high inoculum staphylococcus aureus on the activities of Nafcillin vancomycin linezolid and daptomycin alone and in combination with gentamicin in an in vitro pharmacodynamic model
Antimicrobial Agents and Chemotherapy, 2004Co-Authors: Kerry L Laplante, Michael J RybakAbstract:We evaluated the impact of high (9.5 log 10 CFU/g) and moderate (5.5 log 10 CFU/g) inocula of methicillin-susceptible and -resistant S taphylococcus aureus (MSSA and MRSA, respectively) on the activities of Nafcillin, linezolid, vancomycin, and daptomycin, alone and in combination with gentamicin in an in vitro pharmacodynamic model with simulated endocardial vegetations over 72 h. Human therapeutic dosing regimens for Nafcillin, daptomycin, vancomycin, linezolid, and gentamicin were simulated. At a moderate inoculum, Nafcillin (MSSA only), vancomycin, and daptomycin demonstrated equivalent and significant ( P 10 CFU/g, respectively). Bactericidal activity was demonstrated at 4 h for Nafcillin and daptomycin and at 32 h for vancomycin. Linezolid demonstrated bacteriostatic activity over the course of the study period. At a high inoculum, daptomycin exhibited bactericidal activity against both MSSA and MRSA by 24 h (decrease of 5.51 to 6.31 ± 0.10 log 10 CFU/g). Nafcillin (versus MSSA), vancomycin, and linezolid (MSSA and MRSA) did not achieve bactericidal activity throughout the 72-h experiment. The addition of gentamicin increased the rate of 99.9% kill to 8 h for daptomycin ( P P = 0.01). The addition of gentamicin did not improve the activity of vancomycin or linezolid for either isolate for the 72-h period. Overall, high-inoculum Staphylococcus aureus had a significant impact on the activities of Nafcillin and vancomycin. In contrast, daptomycin was affected minimally and linezolid was not affected by inoculum.
Henry F. Chambers - One of the best experts on this subject based on the ideXlab platform.
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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.
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subinhibitory fluoroquinolone exposure selects for reduced beta lactam susceptibility in methicillin resistant staphylococcus aureus and alterations in the sos mediated response
Research in Microbiology, 2009Co-Authors: Pierre Tattevin, Li Basuino, Henry F. ChambersAbstract:Growth of fluoroquinolone (FQ)-susceptible methicillin-resistant Staphylococcus aureus (MRSA) in the presence of sub-MIC FQ has been shown to enhance methicillin resistance in traditional nosocomial MRSA isolates. We aimed to confirm this phenomenon in nine community-associated MRSA (CA-MRSA) clinical isolates, and to identify candidate genes that might account for this unusual phenotype. Overnight growth of CA-MRSA strains in tryptic soy broth containing a subinhibitory concentration of either ciprofloxacin or levofloxacin resulted in a concentration-related increase in the number of colonies that grew on Nafcillin agar, such that about one CFU in four exhibited significantly higher resistance to Nafcillin, with only a modest increase in FQ MIC. No mutations were found in the quinolone-resistance determining region of gyrA and grlA. DNA microarray studies of a representative levofloxacin-exposed clone found that gene expression was increased for 53 open reading frames (ORFs), including norR and mecA, and decreased for 10. The majority of these ORFs encode regulatory and stress response proteins. In conclusion, sublethal exposure to FQ alters the SOS response in CA-MRSA and selects in a non-lethal manner for stable mutants with enhanced expression of methicillin resistance.
