Anti-Anaerobic Antibiotics, Gut Microbiota, and Sepsis-associated Acute Kidney Injury
Recommended Citation
Winner KM, Chanderraj R, Nuppnau M, He Y, Petouhoff AM, Falkowski NR, Woods RJ, Schaub JA, Heung M, Ranjan P, Luth JE, Bongers KS, Sjoding MW, and Dickson RP. Anti-Anaerobic Antibiotics, Gut Microbiota, and Sepsis-associated Acute Kidney Injury. Am J Respir Crit Care Med 2025.
Document Type
Article
Publication Date
7-30-2025
Publication Title
American journal of respiratory and critical care medicine
Abstract
RATIONALE: Acute kidney injury (AKI) is a common complication of sepsis. Anti-anaerobic antibiotics, which deplete gut commensal bacteria, are common in the initial management of sepsis. Recent studies have reported an association between anti-anaerobic antibiotics and mortality, but the mechanisms underlying this relationship remain unknown.
OBJECTIVE: To determine whether anti-anaerobic antibiotics and gut microbiome disruption increase patient susceptibility to sepsis-associated AKI.
METHODS: We identified a cohort of patients with sepsis and performed four complementary analyses: 1) comparing AKI incidence among patients who did and did not receive early anti-anaerobic antibiotics, 2-3) two instrumental variable analyses using the 2015-16 piperacillin-tazobactam shortage to determine the effect of anti-anaerobic antibiotics on the onset and resolution of AKI, and 4) a matched case-control study comparing gut microbiota in septic patients who did and did not develop AKI. We then modeled sepsis in genetically-identical but microbially-heterogenous mice and compared creatinine elevation with gut microbiota.
MEASUREMENTS AND MAIN RESULTS: In a retrospective cohort study (N=12,776), early exposure to anti-anaerobic antibiotics was independently associated with a 61% increased risk of sepsis-associated AKI (95% CI-37%-92%). In instrumental variable analyses of AKI onset (N=3,036) and resolution (N=2,177), treatment with anti-anaerobic antibiotics (piperacillin-tazobactam) was associated with an increased hazard of AKI onset (HR-1.65, 95% CI-1.18-2.30) and decreased AKI resolution (HR-0.74, 95% CI-0.61-0.88). In a matched case-control study of gut microbiota in 372 patients with sepsis, increased gut bacterial density and enrichment with Enterobacteriaceae and Lachnospiraceae spp. predicted subsequent AKI onset. In a murine model of sepsis (N=53), creatinine elevation was strongly associated with vendor and gut community composition (P< 0.001 for all), with relative abundance of Lachnospiraceae spp. explaining 18% of variation in serum creatinine.
CONCLUSIONS: Anti-anaerobic antibiotics are associated with increased risk of AKI in sepsis, potentially via modulation of the gut microbiome.
PubMed ID
40737346
ePublication
ePub ahead of print
