Differential Antibiotic-Induced Endotoxin Release in Severe Melioidosis.
Simpson, A. J. H. 1,3; Opal, S. M. 4; Angus, B. J. 1,3; Prins, J. M. 5; Palardy, J. E. 4; Parejo, N. A. 4; Chaowagul, W. 2; White, N. J. 1,3
[Article] Journal of Infectious Diseases. 181(3):1014-1019, March 2000.

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: Severe melioidosis is a life-threatening, systemic bacterial infection caused by Burkholderia pseudomallei. A prospective, randomized treatment trial was conducted in northeast Thailand to compare ceftazidime (a penicillin-binding protein [PBP]-3-specific agent that causes release of large amounts of endotoxin in vitro) and imipenem (a PBP-2-specific agent that kills B. pseudomallei more rapidly but releases low amounts of endotoxin) in severe melioidosis over a 6-h time course after the first dose of antibiotic. Despite similar clinical, microbiological, endotoxin, and cytokine measures at study entry, ceftazidime-treated patients (n = 34) had significantly greater systemic endotoxin (P < .001) than patients treated with imipenem (n = 34) after the first dose of antibiotic. No overall difference in mortality was observed (35% in both groups [95% confidence interval, 20%-50%]). Differential antibiotic-induced endotoxin release is demonstrable in severe melioidosis. These differences in endotoxin release did not appear to have a significant impact on survival in this group of patients.

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