Differential antibiotic-induced endotoxin release in severe melioidosis

Severe melioidosis is a life-threatening, systemic bacterial infection caus ed by Burkholderia pseudomallei. A prospective, randomized treatment trial was conducted in northeast Thailand to compare ceftazidime (a penicillin-bi nding protein [PBP]-3-specific agent that causes release of large amounts o f endotoxin in vitro) and imipenem (a PBP-2-specific agent that kills B. ps eudomallei more rapidly but releases low amounts of endotoxin) in severe me lioidosis over a 6-h time course after the first dose of antibiotic. Despit e similar clinical, microbiological, endotoxin, and cytokine measures at st udy 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%]). Different ial antibiotic-induced endotoxin release is demonstrable in severe melioido sis, These differences in endotoxin release did not appear to have a signif icant impact on survival in this group of patients.