β‐Lactam Therapy for Methicillin‐Susceptible Staphylococcus aureus Bacteremia: A Comparative Review of Cefazolin versus Antistaphylococcal Penicillins

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.