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

Abstract

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.

Efficacy of Ceftaroline against Methicillin-Susceptible Staphylococcus aureus Exhibiting the Cefazolin High-Inoculum Effect in a Rat Model of Endocarditis

“…using a PubMed database search (January 1996 to June 2016) stated that most of the reports of clinical failure with cefazolin are case reports or case series and that the clinical relevance of the cefazolin InE is not entirely clear, especially as susceptibility testing in clinical microbiology laboratories uses a standardized inoculum (8). This review states that, in addition, limited by small sample size and possible selection bias, the only comparative study to date examining the clinical impact of the cefazolin InE (i.e., the study referred to above from Asia [South Korea] [7]) did not show any significant differences in outcomes when comparing isolates with and without cefazolin InE.…”

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

“…Others have even suggested a treatment benefit with cefazolin over antistaphylococcal penicillins [17, 24]. Several comprehensive reviews of these data have been published elsewhere [12, 25, 26]. Limitations of previous studies include small patient populations, retrospective study design, and lack of adverse effect analyses.…”

Systematic Review and Meta-analysis of the Safety of Antistaphylococcal Penicillins Compared to Cefazolin

“…The findings from this systematic review suggest that treatment with cefazolin in adults is associated with a clinically important favorable safety profile compared to antistaphylococcal penicillins because of lower risks of nephrotoxicity, acute interstitial nephritis, hepatotoxicity, hypersensitivity reactions, and discontinuation due to ADRs. In other studies, cefazolin has demonstrated at least equivalent efficacy compared to antistaphylococcal penicillins (26) and improved cost-effectiveness (14). Therefore, cefazolin should be considered a first-line treatment option for MSSA bacteremia.…”

“…Moreover, a recent large multicenter retrospective cohort study by Mc-Danel et al (29) showed a significantly lower mortality risk with cefazolin than with nafcillin or oxacillin. If this difference in mortality is true, it is possibly due to antibioticrelated ADRs and the associated antibiotic discontinuation rates in light of findings from more-recent studies that suggest equivalent efficacies of cefazolin and antistaphylococcal penicillins (26).…”