Abstract
C54-29 Piperacillin-Tazobactam Depletes Gut Bacterial Metabolites and Suppresses Cytokine Production in Experimental Sepsis
American journal of respiratory and critical care medicine, Vol.212(Supplement_1), aamag1626246
05/01/2026
DOI: 10.1093/ajrccm/aamag162.6246
Abstract
Introduction/Rationale Anti-anerobic antibiotics are widely used in sepsis and have recently been associated with increased mortality and secondary infections; The mechanisms behind this harm are unknown. Piperacillin-tazobactam, depletes gut anaerobes, yet its effects on immunomodulatory bacterial metabolites, such as short-chain fatty acids (SCFAs), and systemic immunity in sepsis are unknown. We used a murine model to test whether piperacillin-tazobactam alters gut bacterial metabolites and cytokine responses during sepsis. Methods Female C57BL/6 mice were pretreated for three days with piperacillin-tazobactam, cefepime (anaerobe-sparing comparator), or vehicle. Sepsis was modeled using systemic endotoxin (5 mg/kg i.p.). Mice were euthanized 24 hours post-injection. Intestinal SCFAs were quantified by LC-MS, and serum CXCL-1, a key neutrophil chemoattractant, was quantified via bead-based immunoassay Results Antibiotic pretreatment had significant, divergent effects on SCFAs. Piperacillin-tazobactam significantly reduced SCFA levels by 100-fold compared to control and cefepime (p < 0.0001) , whereas cefepime increased SCFA levels compared to both groups (p < 0.001). Following endotoxin challenge, piperacillin-tazobactam-treated mice had reduced plasma CXCL-1 levels compared to untreated mice (p < 0.001). Cefepime-treated mice exhibited similar CXCL-1 levels to untreated mice (p > 0.05). Conclusion Piperacillin-tazobactam depleted intestinal metabolites and blunted pro-inflammatory cytokine responses during experimental sepsis, unlike cefepime. These findings suggest anti-anaerobic antibiotics may impair early immune activation during sepsis, through microbiome disruption. In future studies, we test whether SCFA repletion rescues immune responses in piperacillin-tazobactam treated mice, to determine whether metabolite depletion drives immune suppression. This abstract is funded by: None
Details
- Title: Subtitle
- C54-29 Piperacillin-Tazobactam Depletes Gut Bacterial Metabolites and Suppresses Cytokine Production in Experimental Sepsis
- Creators
- L A Maynard - University of MichiganM D Adame - University of MichiganR P Dickson - University of MichiganK S Bongers - University of IowaN Falkowski - University of MichiganR McDonald - University of Michigan
- Resource Type
- Abstract
- Publication Details
- American journal of respiratory and critical care medicine, Vol.212(Supplement_1), aamag1626246
- DOI
- 10.1093/ajrccm/aamag162.6246
- ISSN
- 1535-4970
- eISSN
- 1535-4970
- Publisher
- Oxford University Press
- Language
- English
- Date published
- 05/01/2026
- Academic Unit
- Internal Medicine
- Record Identifier
- 9985164609502771
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