Comparative effectiveness of nafcillin or cefazolin versus vancomycin in methicillin-susceptible Staphylococcus aureus bacteremia

BMC Infectious Diseases, Oct 2011

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.

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Comparative effectiveness of nafcillin or cefazolin versus vancomycin in methicillin-susceptible Staphylococcus aureus bacteremia

BMC Infectious Diseases Comparative effectiveness of nafcillin or cefazolin versus vancomycin in methicillin-susceptible Staphylococcus aureus bacteremia Marin L Schweizer 0 1 2 Jon P Furuno 0 Anthony D Harris 0 J Kristie Johnson 6 Michelle D Shardell 0 Jessina C McGregor 5 Kerri A Thom 0 Sara E Cosgrove 4 George Sakoulas 3 7 Eli N Perencevich 0 1 2 0 Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine , Baltimore, MD , USA 1 Iowa City VA Health Care System , Iowa City, IA , USA 2 Department of Internal Medicine, University of Iowa Carver College of Medicine , Iowa City, IA , USA 3 Department of Pediatrics, University of San Diego School of Medicine , La Jolla, CA 4 Division of Infectious Diseases, Johns Hopkins University School of Medicine , Baltimore, MD , USA 5 Department of Pharmacy Practice, College of Pharmacy, Oregon Health & Science University , Portland, OR , USA 6 Department of Pathology, University of Maryland School of Medicine , Baltimore, MD , USA 7 Department of Medicine, Sharp Memorial Hospital , San Diego, CA 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. - Background Through the American Recovery and Reinvestment Act of 2009, Congress requested that the Institute of Medicine (IOM) recommend national priorities for research questions to be addressed by Comparative Effectiveness Research. The first quartile of the IOMs list included a call to compare the effectiveness of strategies for reducing healthcare-associated infections [1]. One such strategy to reduce antibiotic resistant healthcare-associated infections would be to optimize antibiotic therapy. The high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) has led clinicians to select antibiotics that have coverage against MRSA, usually vancomycin, for empiric therapy for suspected staphylococcal infections [2,3] Patients treated initially with empiric vancomycin are frequently continued on vancomycin for dosing convenience even after culture results identify methicillin-susceptible S. aureus (MSSA), particularly in patients with renal insufficiency [4]. However, high vancomycin selective pressure may lead to decreased susceptibility to vancomycin in both MSSA and MRSA [5]. Vancomycin has been associated with poor outcomes such as nephrotoxicity, persistent bacteremia and treatment failure among MSSA patients [3,5-9]. Higher mortality in patients with MRSA bacteremia compared to patients with MSSA bacteremia has been attributable to differences in host viability, differences in microbial pathogenicity, and differences in antimicrobial potency, particularl (...truncated)


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Marin L Schweizer, Jon P Furuno, Anthony D Harris, J Kristie Johnson, Michelle D Shardell, Jessina C McGregor, Kerri A Thom, Sara E Cosgrove, George Sakoulas, Eli N Perencevich. Comparative effectiveness of nafcillin or cefazolin versus vancomycin in methicillin-susceptible Staphylococcus aureus bacteremia, BMC Infectious Diseases, 2011, pp. 279, 11, DOI: 10.1186/1471-2334-11-279