Anti-anaerobic antibacterials may increase risk of adverse clinical outcomes 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.

Rishi Chanderraj et al. from the University of Michigan Medical School, Ann Arbor, MI; 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. Their finding were published in the Eur Respir J in October 2022. 

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

The investigators found that 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 hospitalization (p=0.011), and domination by Enterobacteriaceae spp. (p=0.045). Enterobacteriaceae were also enriched among respiratory pathogens in anti-anaerobic treated patients. 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).

The investigators concluded that 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. Since the current study was retrospective, prospective studies are warranted to further evaluate this issue.