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Anti-Anaerobic Antibiotics, Gut Microbiota, and Sepsis-associated Acute Kidney Injury
Journal article   Peer reviewed

Anti-Anaerobic Antibiotics, Gut Microbiota, and Sepsis-associated Acute Kidney Injury

Katherine M Winner, Rishi Chanderraj, Mark Nuppnau, Ying He, Annastasia M Petouhoff, Nicole R Falkowski, Robert J Woods, Jennifer A Schaub, Michael Heung, Piyush Ranjan, …
American journal of respiratory and critical care medicine, Vol.212(2)
02/2026
DOI: 10.1164/rccm.202411-2281OC
PMID: 40737346

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Abstract

Rationale Acute kidney injury (AKI) is a common complication of sepsis. Antianaerobic antibiotics, which deplete gut commensal bacteria, are common in the initial management of sepsis. Recent studies have reported an association between antianaerobic antibiotics and mortality, but the mechanisms underlying this relationship remain unknown. Objectives To determine whether antianaerobic 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 antianaerobic antibiotics, 2 and 3) two instrumental variable analyses using the 2015–2016 piperacillin-tazobactam shortage to determine the effect of antianaerobic 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 heterogeneous mice and compared creatinine elevation with gut microbiota. Measurements and Main Results In a retrospective cohort study (N = 12,776), early exposure to antianaerobic antibiotics was independently associated with a 61% increased risk of sepsis-associated AKI (95% confidence interval [CI], 37–92%). In instrumental variable analyses of AKI onset (n = 3,036) and resolution (n = 2,177), treatment with antianaerobic antibiotics (piperacillin-tazobactam) was associated with an increased hazard of AKI onset (hazard ratio, 1.65; 95% CI, 1.18–2.30) and decreased AKI resolution (hazard ratio, 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 Antianaerobic antibiotics are associated with increased risk of AKI in sepsis, potentially via modulation of the gut microbiome.
 Antibiotics acute kidney injury microbiome sepsis

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