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.
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