Effectiveness and safety of daptomycin versus vancomycin in methicillin-resistant Staphylococci left-side infective endocarditis. Results from a nationwide prospective multicenter cohort.

Abstract

Objective: The aim of the study was to compare the effectiveness and safety of daptomycin versus vancomycin treatment for left-sided infective endocarditis (IE) caused by methicillin-resistant staphylococci (MRS). We specifically aimed to explore the effectiveness of different daptomycin-based regimens.

Methods: Prospective, multicenter cohort including consecutive patients with definite left-sided MRS-IE from January 2008 to December 2023. Patients were in two groups whether they received daptomycin or vancomycin as main antibiotic. Those patients in whom neither antibiotic could be considered the main antibiotic were excluded. The primary endpoint was in-hospital mortality. Multivariable logistic regression was used for adjusted in-hospital mortality and Cox regression for 1-year mortality RESULTS: A total of 617 patients were included: 421 (68.2%) received daptomycin-based and 196 (31.8%) received vancomycin-based regimens. In the adjusted analysis, daptomycin showed with similar in-hospital mortality compared to vancomycin (adjusted odds ratio [aOR] 0.79 [95% CI 0.48-1.28]). Daptomycin was associated with a significantly lower rate of adverse drug reactions (14.5% [61/421] vs 26.0% [51/196], p=0.001), mainly driven by less acute kidney injury (8.7% [36/421] vs 16.8% [32/196], p=0.003). In subgroup analyses, high-dose daptomycin (HDD, ≥8 mg/kg) in combination was associated with lower in-hospital mortality than other daptomycin regimens (aOR 0.55, 95% CI 0.31-0.98) without more adverse reactions (14.5% [34/234] vs 14.4% [27/187], p=1.000). Compared to vancomycin, HDD-based combination strategy was not associated with statistically significant difference in in-hospital mortality (aOR 0.66, 95%CI 0.38-1.09) but was associated with lower one-year mortality (adjusted hazard ratio 0.55; 95% CI 0.31-0.98). and lower rate of adverse reactions (14.5% [34/234] vs 26.0% [51/19], p=0.003).

Conclusions: In this large, real-world cohort, daptomycin demonstrated comparable effectiveness to vancomycin. However, it was associated with lower adverse reactions. High-daptomycin dose-based combinations with a second agent could be associated with improved outcomes. This strategy could be considered as a therapeutic option for MRS-IE.