Impact of Antibiotic Duration on Gut Microbiome Composition and Antimicrobial Resistance: A Substudy of the BALANCE Randomized Controlled Trial
Abstract
Abstract Background Maintaining a diverse gut microbiome and minimizing antimicrobial resistance gene (ARG) carriage through reduced antibiotic utilization may decrease antimicrobial resistance. We compared gut microbiome disruption and ARG carriage following 7 or 14 days of antibiotics for treatment of bacteremia in a substudy of the BALANCE randomized controlled trial. Methods The BALANCE randomized controlled trial enrolled 3631 participants with bacteremia, who were randomized 1:1 to receive 7 or 14 days of antibiotics. Rectal swabs were collected from 131 participants and analyzed with metagenomic sequencing to characterize the gut microbiome and ARGs. The primary outcome was change in gut microbiome diversity at day 7 vs 14. Results Forty-one participants (n = 28 in the 14-day group, n = 13 in the 7-day group) had samples available for the primary analysis, with an imbalance in piperacillin-tazobactam exposure between groups. Change in gut microbiome diversity at day 7 vs 14 was comparable between the 14-day group (median, 0.07; IQR, −0.46 to +0.51) and 7-day group (median, 0.19; IQR, −0.77 to +0.22; P = .49). Change in ARG abundance at day 7 vs 14 did not differ by treatment duration, nor did the abundance of individual ARGs. We did not observe any change in gut microbiome diversity or ARG carriage at enrollment vs day 7. Conclusions In this subset of patients from the BALANCE randomized controlled trial, we did not detect greater gut microbiome disruption or ARG…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 3,631 participants or records.
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