Evaluation of combination therapy duration for endocarditis secondary to Enterobacterales

Combination antimicrobial treatment for endocarditis secondary to Enterobacterales may be associated with clinical benefits, but this benefit comes with an increased risk of adverse drug reactions (ADRs). We hypothesized that short-course combination therapy would optimize clinical benefits while minimizing ADRs. This was a retrospective, multicenter study of adult patients with definitive endocarditis secondary to Enterobacterales. Short-course combination treatment was defined as receipt of combination therapy for ≤14 days. Seventy-three patients met the inclusion criteria. Serratia marcescens was the most common pathogen and was recovered in 62% (45/73) of patients. Patients who received short-course combination treatment were more likely to be admitted prior to 2016 (44% [12/27] vs 17% [8/46], P = 0.012) and to receive an aminoglycoside in combination regimens (63% [17/27] vs 28% [13/46], P = 0.013). Patients who received short-course combination treatment had a shorter post-infection length of stay (18 [13-25] days vs 29 [20-42], P = 0.021), but no significant difference in the rate of discontinuation of antimicrobial therapy due to an ADR (26% [7/27] vs 24% [11/46], P = 0.847). In the multivariate logistic regression model, short-course combination treatment was not associated with a higher risk of 90-day mortality (OR = 2.89; 95% CI: 0.63-13.35; P = 0.175). This is the first study to compare short- and long-duration combination therapy in patients with Enterobacterales endocarditis. Overall, shorter courses of combination therapy were commonly prescribed, which supports future studies that are designed to identify the optimal duration of combination therapy for patients with Enterobacterales endocarditis.