Mono versus dual antibiotic therapy of Staphylococcus aureus endocarditis - a nationwide cohort study

Abstract Introduction Choice of antibiotic treatment for infective endocarditis is based on observational data and studies on treatment strategies and practice patterns are sparse. Staphylococcus aureus endocarditis is particularly aggressive with high risk of adverse outcomes and dual antibiotic treatment has been suggested to better prognosis relative to mono therapy. Purpose To examine the prevalence of mono antibiotic therapy and dual antibiotic therapy in patients with Staphylococcus aureus endocarditis in the initial acute phase of endocarditis treatment. Methods All patients with first-time left-sided Staphylococcus aureus endocarditis between 2016-2021 were included from the complete NatIonal Danish endocarditis stUdieS (NIDUS) registry. Antibiotic treatment within the first 10 days after diagnosis was described and categorized into a mono therapy group, if patients received one type of antibiotics and in a dual therapy group, if they received at least 2 types of antibiotics. We compared groups by baseline characteristics, adverse events during hospital admission, surgery and in-hospital mortality. Results We included 868 Staphylococcus aureus endocarditis cases out of 2888 patients in the NIDUS registry. Staphylococcus aureus endocarditis cases were managed with dual therapy in 558 cases (64.3%), and 310 cases (35.7%) mono therapy. Patients had similar age distributions (median 73.6 vs. 74.0 years, p=0.4) and sex proportions (60.0% vs. 57.4% male, p=0.5). There was no significant difference in the prevalence of chronic renal disease, diabetes, prior heart failure or congenital heart disease (all p0.08). However, prosthetic valve endocarditis was more common in the dual therapy group (23.8% vs. 2.6%, p 0.001) and patients were more likely to undergo surgery in the dual therapy group in general (22.9% vs. 14.7%, p0.01). Sepsis was more prevalent in the dual therapy group (41.0% vs. 28.1%, p 0.01) while acute kidney failure during hospitalization was similar between groups (26.7% vs. 21.6%, p=0.1), patients in dual therapy were more likely to require dialysis (11.6% vs 6.1%, p 0.01) than their mono therapy counterparts. No difference was found in prevalence of relapse within 6 months after hospitalization (2.2% vs. 2.9%, p=0.7) or in the recurrence of endocarditis (4.7% vs. 5.2%, p=0.8) between dual and mono therapy. In-hospital mortality did not differ significantly between the groups (26.3% vs. 25.8%, p=0.9). Conclusion Dual antibiotic therapy was the most common approach for treating Staphylococcus aureus endocarditis in the initial phase of treatment and these patients were more likely to have prosthetic valve endocarditis and to undergo surgery. Despite differences in the two groups, endocarditis relapse, recurrence and in-hospital mortality were similar. Future studies – and preferably randomized – are needed to clarify the optimal antibiotic strategy in IE.Comparison of treatment and outcomes