The Safety and Economic Impact of Cefazolin versus Nafcillin for the Treatment of Methicillin-Susceptible Staphylococcus aureus Bloodstream Infections

INTRODUCTION: Anti-staphylococcal penicillins are generally accepted as first-line therapy for methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia, but their use may be limited by interstitial nephritis and acute kidney injury. Alternatives include first-generation cephalosporins including cefazolin. METHODS: We conducted a retrospective cohort study to compare adverse effects and clinical outcomes among patients with MSSA bacteremia treated with cefazolin or nafcillin. The primary endpoint was acute kidney injury (AKI), defined as a 0.3 mg/dL or 50% increase from baseline. RESULTS: Incidence of AKI was 27/82 (33%) versus 9/68 (13%) (p = 0.007) in the nafcillin and cefazolin arms, respectively. After adjusting for endocarditis and intensive care unit admission in multivariate logistic regression, nafcillin was an independent predictor of AKI [adj odds ratio (OR) = 2.74; 95% (CI) 1.1–6.6]. Patients who experienced AKI were more likely to have a prolonged intensive care unit stay. CONCLUSION: Risk of nephrotoxicity is increased with nafcillin compared with cefazolin. Cefazolin should considered as a safer alternative to nafcillin for select patients with MSSA bacteremia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40121-017-0148-z) contains supplementary material, which is available to authorized users.