Antibiotic-induced release of endotoxin. A therapeutic paradox

Drug Saf. 1995 Mar;12(3):183-95. doi: 10.2165/00002018-199512030-00004.


There is clear experimental evidence that antibiotics increase the bioavailability of endotoxin from Gram-negative bacteria. In this review, data for 2 variables, level of endotoxin and level of bacteria, at the time point closest to 2 hours post-antibiotic exposure were abstracted as a change from baseline readings from each available study, to enable presentation in a graphical overview. This overview indicates that the phenomenon is not limited to beta-lactam agents nor is it apparent only for the more rapidly bactericidal agents. However, evidence that this phenomenon is of clinical importance is scant. With the Jarisch-Herxheimer reaction (JHR), there is clear evidence for an acute deterioration with the initiation of antibiotic therapy and yet uncertainty as to the nature of the bacterial mediator(s) of this reaction. There is no evidence to support the commonly stated concern that therapy with antibiotics with a more rapid bactericidal action may result in the sudden lysis of bacteria with the release of cell wall components and cause a deterioration that might be avoidable through the use of antibiotics with a slower time course of action.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Bacterial Agents / adverse effects*
  • Anti-Bacterial Agents / therapeutic use*
  • Endotoxins / metabolism*
  • Gram-Negative Bacteria / metabolism*
  • Humans
  • Sepsis / drug therapy
  • Sepsis / microbiology


  • Anti-Bacterial Agents
  • Endotoxins