Association of anti-anaerobic antibiotics with mortality and the gut microbiome: a sub-study of the BALANCE randomized clinical trial
Abstract
BACKGROUND
Patients with suspected bloodstream infection often receive broad-spectrum antibiotics with anaerobic activity in the absence of clinical indication for anaerobic coverage. Anti-anaerobic antibiotics have been linked to adverse clinical outcomes in other populations, potentially by depleting intestinal anaerobes.
METHODS
We conducted a planned sub-study of the multisite BALANCE randomized controlled trial of antibiotic duration for bloodstream infection to assess the impact of anti-anaerobic antibiotics (receipt from three days pre-index culture to seven days post-index) on mortality and gut microbiome composition with metagenomic sequencing in patients without clinical indication for anaerobic coverage who survived to seven days post-index culture. The primary exposure was receipt of anti-anaerobic antibiotics from three days prior to the index culture to seven days post-index culture.
RESULTS
Among the 2851 eligible patients included in our primary analysis, 2106 (74%) received anti-anaerobic antibiotics and 745 (26%) did not. After balancing measured potential confounders through inverse probability of treatment weighting, anti-anaerobic antibiotics were associated with higher 90-day mortality (OR = 1.41, 95% CI 1.03 to 1.92, p = 0.03) and depletion of gut anaerobe relative abundance (fixed effect estimate = -16.59, 95% CI -30.67 to -2.52, p = 0.02). Increased duration of anti-anaerobic antibiotics was associated with greater mortality risk and additional gut…
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: 2,851 participants or records.
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