Antibiotic-induced release of endotoxin: a reappraisal

A three- to 20-fold increase in the total concentration of endotoxin occurs as a consequence of antibiotic action on gram-negative bacteria both in vitro and in vivo. There is considerable overlap between the effect of beta-lactam antibiotics and non-beta-lactam antibiotics. Moreover, there is an unexplained delay between the lethal activity of antibiotics and the release of endotoxin. Hence, the mechanism whereby antibiotic action leads to the release of endotoxin is unclear, and mechanisms other than bacterial lysis warrant consideration. The evidence that the release of endotoxin has clinical importance is conflicting, and the issue is unresolved. However, nonlytic release may have implications for the therapeutic efficacy of antiendotoxin immunotherapy. Although frequently cited in the context of the antibiotic-induced release of endotoxin, a number of important differences pertain to conditions, such as the Jarisch-Herxheimer reaction and the tumor lysis syndrome, for which there is clear evidence of an initial deterioration with effective therapy.