Antibiotic Treatment Duration for Uncomplicated Monomicrobial Enterococcal Bloodstream Infection: A Multicenter Target Trial Emulation
Abstract
Background: 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.
Methods: We conducted a retrospective cohort study using a target trial emulation framework across 8 hospitals in Israel (2013–2023) of adults hospitalized with uncomplicated monomicrobial enterococcal BSI. Treatment strategies were defined as short (7 ± 2 days) versus 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.
Results: Of 3450 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% CI 0.84 to 1.22). There was no evidence of differences across the secondary outcomes. Results were consistent across subgroup and sensitivity analyses.
Conclusions: 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.
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BibTeX
@article{mudrikzohar2026antibiotic,
title = {{Antibiotic Treatment Duration for Uncomplicated Monomicrobial Enterococcal Bloodstream Infection: A Multicenter Target Trial Emulation}},
author = {Hadar Mudrik-Zohar and Sean W X Ong and Steven Y C Tong and Tzipi Hornik-Lurie and Ayalla Sabbah and Orly Weinstein and Michal Chowers},
journal = {Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America},
year = {2026},
month = jul,
doi = {10.1093/cid/ciag387},
url = {https://doi.org/10.1093/cid/ciag387},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Antibiotic Treatment Duration for Uncomplicated Monomicrobial Enterococcal Bloodstream Infection: A Multicenter Target Trial Emulation
AU - Hadar Mudrik-Zohar
AU - Sean W X Ong
AU - Steven Y C Tong
AU - Tzipi Hornik-Lurie
AU - Ayalla Sabbah
AU - Orly Weinstein
AU - Michal Chowers
PY - 2026
DA - 2026/07/03
JO - Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
DO - 10.1093/cid/ciag387
UR - https://doi.org/10.1093/cid/ciag387
AB - Background: 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. Methods: We conducted a retrospective cohort study using a target trial emulation framework across 8 hospitals in Israel (2013–2023) of adults hospitalized with uncomplicated monomicrobial enterococcal BSI. Treatment strategies were defined as short (7 ± 2 days) versus 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. Results: Of 3450 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% CI 0.84 to 1.22). There was no evidence of differences across the secondary outcomes. Results were consistent across subgroup and sensitivity analyses. Conclusions: 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.
SN - 1058-4838
SN - 1537-6591
ER -