Association of anti-anaerobic antibiotics with mortality and the gut microbiome: a sub-study of the BALANCE randomized clinical trial
In brief
Anti-anaerobic antibiotics raise 90-day mortality by about 40% in bloodstream infection
In a sub-study of 2,851 patients with bloodstream infection who lacked a clear need for anaerobic coverage, those given anti-anaerobic drugs had a 41% higher odds of dying within 90 days and showed a marked loss of gut anaerobic bacteria. Longer exposure worsened both outcomes, suggesting that limiting unnecessary anti-anaerobic therapy may improve survival, but prospective trials are needed.
- Journal
- Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Q1)
- Published
- 4 August 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Eric Armstrong, Ruxandra Pinto, Maria Kulikova, Noelle R Yee, Asgar Rishu, John Muscedere, et al.
- PMID
- 42549478
- DOI
- 10.1093/cid/ciag460
Why clinicians should know about it
- Picked for Microbiology (medical) (top studies of the week, 9 August 2026): Anti‑anaerobic antibiotics increase mortality and deplete gut anaerobes
- Picked for Infectious Diseases (paper of the day, 5 August 2026).
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 anaerobe depletion. CONCLUSIONS: Anti-anaerobic antibiotics are associated with increased mortality and gut microbiome disruption in patients with bloodstream infection. Minimizing exposure to anti-anaerobic antibiotics for bloodstream infection should be further explored in clinical trials as a potential treatment strategy to improve patient outcomes.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.