The clinical significance of endotoxin released by antibiotics: What is the evidence?

Basic investigations indicate variation among antibiotics in their propensity to release endotoxin from bacterial cells. Evidence for the clinical significance of this phenomenon includes: anecdotal reports; studies evaluating changes in endotoxin levels in response to antibiotics in a variety of infectious diseases; two studies which have prospectively evaluated changes in endotoxin levels in response to different antibiotics and correlated the changes with the patients' clinical course; and one study which evaluated differences in mortality in injured patients based on the endotoxin-releasing potential of antibiotics they received. These studies suggest: (i) different types of antibiotics do induce differing levels of endotoxin release during treatment of bacterial infections in humans; (ii) such antibiotic-associated endotoxin release probably does have a biologic consequence; and (iii) this biologic consequence is possibly of clinical relevance. However, the data are not sufficient to advocate changes in current antibiotic prescribing or dosing decisions. Rather, a variety of in vitro and in vivo experiments as well as clinical studies are advocated.