Antibiotic Treatment Duration for Uncomplicated Monomicrobial Enterococcal Bloodstream Infection: A Multicenter...

Enterococcal bloodstream infection (BSI) is common with 30-day mortality rates approaching 25-30%, yet evidence guiding optimal antibiotic treatment duration, particularly for patients with uncomplicated infection, is limited.

We conducted a retrospective cohort study using a target trial emulation framework across eight hospitals in Israel (2013-2023) of adults hospitalized with uncomplicated monomicrobial enterococcal BSI. Treatment strategies were defined as short (7±2 days) vs long (14±2 days) antibiotic therapy. A cloning-censoring-weighting framework with inverse probability of censoring weights was applied to account for immortal time bias and potential confounders. The primary outcome was 30-day all-cause mortality; secondary outcomes included 90-day all-cause mortality, recurrence, length of stay, readmission and Clostridioides difficile infection. Analyses were performed using pooled logistic regression and negative binomial regression models, with prespecified subgroup and sensitivity analyses.

Of 3,450 patients with enterococcal bacteremia screened, 870 were eligible, and 485 received treatment durations consistent with the study treatment strategies (short n=283, long n=202). Mean age was 74 years (±15.0); 87/485 (18%) had pre-existing cardiac hardware, 164/485 (34%) a urinary source and 180/485 (37%) had nosocomial BSI. Adjusted analyses demonstrated no difference in 30-day mortality between short and long therapy (21.6% vs 21.3%; adjusted risk ratio 1.01, 95% confidence intervals [CI] 0.84 to 1.22). There was no evidence of differences across the secondary outcomes. Results were consistent across subgroup and sensitivity analyses.

Short-course antibiotic treatment was associated with comparable clinical outcomes to long-course treatment in uncomplicated monomicrobial enterococcal BSI, supporting the use of short treatment durations in appropriately selected patients.