Comparative outcomes of cefazolin versus anti-staphylococcal penicillins in methicillin-susceptible Staphylococcus aureus infective endocarditis: a post-hoc analysis of a prospective multicentre French cohort study

OBJECTIVES Current guidelines recommend cefazolin as an alternative to anti-staphylococcal penicillins (ASPs) in methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis despite the lack of comparative study. The objective of this study was to evaluate the comparative outcomes of cefazolin versus ASPs in MSSA infective endocarditis. METHODS This was a retrospective analysis of an observational multicenter cohort study using prospectively collected data from patients with MSSA endocarditis confirmed by endocarditis team and treated either by cefazolin or ASPs between July 2013 and December 2018. Patients were excluded if they received both treatments. The primary outcome was 90-day all-cause mortality. RESULTS Of 210 patients included, 53 (25.2%) patients received cefazolin and 157 (74.8%) received ASPs. The overall 90-day mortality rate was 27.6% (58/210 patients), 24.5% (13/53) in the cefazolin group versus 28.7% (45/157) in the ASPs group (p=.561). Premature antimicrobial discontinuation due to adverse events were less frequent with cefazolin than with ASPs (0/53 versus 13/157 patients, p=.042). In multivariate analysis, there was no difference in 90-day mortality between cefazolin and ASPs (aOR 1.2; 95% CI 0.49-2.91, p=.681), while age (aOR 1.06; 95% CI 1.03-1.09, p<.001), Charlson index (aOR 1.18; 95% CI 1.02-1.36 p=.023), cerebral embolism (aOR 2.83; 95% CI 1.33 - 6.14, p=.007) and intensive care unit admission (aOR 4.16; 95% CI 1.89-9.59, p=.001) were factors significantly associated with higher mortality. CONCLUSIONS Cefazolin seems to be a possible alternative to ASPs in MSSA endocarditis. More studies are needed to confirm these results and determine which treatment should be recommended as first-line therapy.