Early treatment with anti-anaerobic antibiotics tied to increased mortality in critically ill patients

Critically ill patients routinely receive antibiotics with activity against anaerobic gut bacteria. Yet in other disease states and animal models, gut anaerobes are protective against pneumonia, organ failure, and mortality. They, therefore, designed a translational series of analyses and experiments to determine the effects of anti-anaerobic antibiotics on the risk of adverse clinical outcomes among critically ill patients.

They conducted a retrospective single-center cohort study of 3032 critically ill patients, comparing patients who did and did not receive early anti-anaerobic antibiotics. They compared ICU outcomes (ventilator-associated pneumonia [VAP]-free survival, infection-free survival, overall survival) in all patients, and changes in gut microbiota in a 116-patient subcohort. In murine models, we studied the effects of anaerobe depletion in infectious (K. pneumoniae and S. aureus pneumonia) and noninfectious (hyperoxia) injury models.

Results:

• Early administration of anti-anaerobic antibiotics was associated with decreased VAP-free survival, infection-free survival, and overall survival
• Patients who received anti-anaerobic antibiotics had decreased initial gut bacterial density (p=0.00038), increased microbiome expansion during hospitalisation (p=0.011), and domination by Enterobacteriaceae spp. (p=0.045).
• Enterobacteriaceae were also enriched among respiratory pathogens in anti-anaerobic treated patients (p<2.2×10−16).
• In murine models, treatment with anti-anaerobic antibiotics increased susceptibility to Enterobacteriaceae pneumonia (p<0.05) and increased the lethality of hyperoxia (p=0.0002).

In critically ill patients, early treatment with anti-anaerobic antibiotics is associated with increased mortality. Mechanisms may include enrichment of the gut with respiratory pathogens, but increased mortality is incompletely explained by infections alone. Given consistent clinical and experimental evidence of harm, the widespread use of anti-anaerobic antibiotics should be reconsidered.

Reference:

Rishi Chanderraj, et al. In critically ill patients, anti-anaerobic antibiotics increase risk of adverse clinical outcomes. European Respiratory Journal 2022; DOI: 10.1183/13993003.00910-2022

Keywords:

Rishi Chanderraj, Jennifer M. Baker, Stephen G. Kay, Christopher A. Brown, Kevin J. Hinkle, Daniel J. Fergle, Roderick A. McDonald, Nicole R. Falkowski, Joseph D. Metcalf, Keith S. Kaye, Robert J. Woods, Hallie C. Prescott, Michael W. Sjoding, Robert P. Dickson, critically, ill patients, anti-anaerobic antibiotic, increase, risk, adverse, clinical, outcomes,