411: CEFAZOLIN VERSUS NAFCILLIN IN THE TREATMENT OF MSSA ENDOCARDITIS

Abstract

Introduction: Methicillin-sensitive Staphylococcus aureus (MSSA) is associated with considerable mortality, particularly in infections such as infective endocarditis (IE). Current guidelines endorse nafcillin (NAF) as first-line therapy for MSSA IE, while cefazolin (CFZ) is an alternative for patients with penicillin allergy. Reluctance in using CFZ stems from the inoculum effect, a phenomenon of reduced CFZ susceptibility in the presence of high organism burden. CFZ is more conveniently dosed with a favorable safety profile, positioning it as an appealing option for the prolonged treatment duration required for IE. New evidence suggests similar rates of clinical failure between CFZ and NAF in MSSA bacteremia, but data in IE, where organism inoculum is higher, is limited. This study compares the effectiveness and safety of CFZ and NAF in patients with MSSA IE. Methods: This multicenter retrospective cohort study included patients with definite or possible MSSA IE from 2015-2021. Subjects were treated with CFZ or NAF within 48 hours of MSSA identification. The primary outcome examined 30-day all-cause mortality, persistent bacteremia, and changes in agent due to treatment failure. Secondary outcomes are treatment failure, and adverse events. Results: Among 140 patients, 111 received CFZ and 29 were treated with NAF. While groups had comparable durations of antibiotic therapy, CFZ patients experienced significantly shorter hospital stays at a median of 15 days compared to 24 days in the NAF group. There was no significant difference between 90-day mortality, readmission, or reinfection between treatment groups, although NAF showed a significantly increased incidence of persistent bacteremia. Beyond this, treatment NAF led to more LFT elevations, acute kidney injury and a higher rate of antimicrobial switches. Conclusions: CFZ demonstrated comparable effectiveness to NAF in the treatment of MSSA IE. Significantly fewer patients in the CFZ group had persistent bacteremia, while patients receiving NAF required more changes in therapy. This may be reflective of the significantly higher rate of acute kidney injury and LFT abnormalities. These results emphasize that CFZ continues to be better tolerated by patients, while the prospect of treatment failure from the inoculum effect was not evident in this study.