Treatment Outcomes with Cefazolin versus Oxacillin for Deep-Seated Methicillin-Susceptible Staphylococcus aureus Bloodstream Infections

Abstract

Despite the rise and impact of methicillin-resistant Staphylococcus aureus, methicillin-susceptible S. aureus (MSSA) continues to contribute to the overall burden of S. aureus infections, representing Ն50% of clinical S. aureus strains (1-3) with known appreciable mortality outcomes (4, 5). Prevailing evidence supports the use of semisynthetic penicillins, such as oxacillin or nafcillin, or the first-generation cephalosporin cefazolin in preference to vancomycin as optimal therapy for MSSA bloodstream infections (BSI) (6-11). Moreover, an early switch from vancomycin to either nafcillin or cefazolin with definitive MSSA identification was associated with a 69% risk reduction in 30-day in-hospital mortality in a recent retrospective cohort study (11).Cefazolin offers a convenient dosing scheme with a favorable adverse event profile, allowing many institutions to consider its use in the management of MSSA infections (12). However, deepseated infections with a high burden of S. aureus have been shown to overproduce certain types of ␤-lactamases, rendering cefazolin inactive and thus resulting in possible treatment failure (13-15). Furthermore, current practice guidelines, such as those for infective endocarditis, suggest reserving the use of cefazolin for patients with nonanaphylactoid-type penicillin allergies (7). As a result, clinician preference for either nafcillin or oxacillin for more severe or deep-seated MSSA infection has evolved in practice, while the use of cefazolin in this setting remains controversial (12,16,17). The purpose of this study was to evaluate and compare treatment outcomes using cefazolin or oxacillin for MSSA BSI, including deep-seated sources of infection.(Portions of this paper were presented as a poster at the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy, 5 to 9 September 2014, Washington, DC.) MATERIALS AND METHODS Study design.From January 2010 to April 2013, a retrospective cohort study was conducted at Rush University Medical Center (RUMC) and Northwestern Memorial Hospital (NMH), two tertiary care academic medical centers in Chicago, IL. The study methods were reviewed and approved by the institutional review boards at RUMC, NMH, and Midwestern University. Adult patients who received in-hospital definitive treatment with cefazolin or oxacillin within 48 h of finalized blood cultures with MSSA were eligible for inclusion in the study. Patients were included only once, and only the first (index) in-hospital admission during the study period was evaluated. The index blood culture was the first blood culture growing MSSA during the index admission. Patients were excluded if they (i) were Ͻ18 years of age, (ii) received antibiotics other than cefazolin or oxacillin for definitive treatment of an MSSA BSI, (iii) received Ն5 days of an empirical antibiotic agent active against MSSA prior to definitive treatment with cefazolin or oxacillin, (iv) had a docu-

Does the Beta-Lactam Matter? Nafcillin versus Cefazolin for Methicillin-Susceptible <b><i>Staphylococcus aureus</i></b> Bloodstream Infections

“…Efficacy data from recent retrospective studies comparing antistaphylococcal penicillins to cefazolin for treatment of MSSA BSI are conflicting. Similar to the results of our study, several other retrospective studies have suggested that cefazolin and antistaphylococcal penicillin agents may have similar efficacy in the treatment of MSSA BSI [6-9]. Others have even suggested a treatment benefit with cefazolin over antistaphylococcal penicillins [17, 24].…”

“…Patients were classified into a nafcillin arm or a cefazolin arm based on the initial choice of directed therapy. Similar to a previous study, transition between study agents was not considered a treatment failure, and patient outcomes were assessed according to their initial treatment regimen [6]. Baseline patient characteristics and treatment parameters were compared between treatment groups using the Student t test and Kruskal-Wallis test for continuous variables, and the Fisher’s exact test for categorical variables.…”

“…AKI was defined as an increase in SCr ≥0.5 mg/dL or a 50% increase from baseline during the hospital stay [6, 17, 18]. AIN was defined as AKI plus one or more of the following symptoms: leukocyturia, hematuria, proteinuria, eosinophiluria, eosinophilia, or fever.…”

“…A growing body of literature evaluating the efficacy of cefazolin compared with antistaphylococcal penicillins has been published in recent years [6-10]. Efficacy data from contemporary retrospective studies comparing antistaphylococcal penicillins to cefazolin for treatment of MSSA BSI are somewhat conflicting and often analyze varied endpoints.…”

Association between Type A blaZ Gene Polymorphism and Cefazolin Inoculum Effect in Methicillin-Susceptible Staphylococcus aureus

“…Recent retrospective studies have suggested that cefazolin had outcomes comparable to those of antistaphylococcal penicillins such as nafcillin and oxacillin (1,(17)(18)(19), even for serious infections. However, there are concerns about cefazolin therapeutic failures and relapses in the treatment of MSSA strains that demonstrate the CIE (2,3,20,21).…”