Efficacy and safety of antistaphylococcal penicillin or cephazolin-based combinations versus monotherapy for methicillin-susceptible Staphylococcus aureus infective endocarditis: A propensity score analysis of nationwide prospective cohort

Objectives: We aimed to evaluate the usefulness of antistaphylococcal penicillin (ASP) or cephazolin-based combinations versus monotherapy in patients with native-valve infective endocarditis (IE) caused by methicillin-susceptible Staphylococcus aureus (MSSA). Methods: Post-hoc analysis of a multicentre prospective cohort. We include patients from 2008 to 2022 with definite native-valve, left-side IE due to MSSA treated primarily with ASP/cephazolin. Patients were categorized according to whether they initially received monotherapy or combination therapy for more than 72 h. A propensity score-matched cohort was planned. Results: Out of 420 included cases, 94 (22.4%) received monotherapy and 326 (77.6%) combination. Median combination duration was 14 days (interquartile range 10-20). Sixty-eight combination cases were matched with 68 monotherapy controls. Baseline characteristics were well balanced. There were no differences in in-hospital or one-year mortality between groups (OR 0.85, 95%CI 0.33-2.18 and HR 0.68, 95%CI 0.35-1.31, respectively). Endocarditis relapses and persistent bacteraemia rates were similar (0% vs 1.5%, p = 1.000; and 19.1% vs 13.2%, p = 0.352, respectively). Drug- related adverse events were more frequent in the combination group (15.0% vs 1.1%, p < 0.001). Conclusions: Antibiotic combinations for patients with native valve left-sided MSSA endocarditis did not improve patient's outcomes. Drug-related adverse events were more frequent in combination patients. (c) 2024 The Author(s). Published by Elsevier Ltd on behalf of The British Infection Association. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).