Clinical implications of antibiotic-induced endotoxin release in septic shock

Antibiotic-induced release of bacterial cell wall components can have immediate adverse effects for the patient. This article reviews the data on endotoxin release after initiation of antibiotic therapy and its role in the pathogenesis of sepsis and septic shock. Antibiotics differ in their potential to liberate endotoxins from bacterial cell walls. When used for treatment of systemic Gram-negative infection, some classes of beta-lactam antibiotics lead to markedly increased levels of free endotoxins while treatment with carbapenems and aminoglycosides produces relatively low amounts of endotoxins. Antibiotics that induce the formation of long, aberrant bacterial cells before effectively killing the microorganisms show the highest degree of endotoxin liberation. There is increasing evidence from animal models and clinical studies of sepsis that the antibiotic-mediated release of biologically active cell wall components derived from Gram-positive, Gram-negative or fungal organisms is associated with a rapid clinical deterioration.