Differential antibiotic-induced endotoxin release in severe melioidosis.
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.
Simpson
A J
AJ
Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Opal
S M
SM
Angus
B J
BJ
Prins
J M
JM
Palardy
J E
JE
Parejo
N A
NA
Chaowagul
W
W
White
N J
NJ
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002442:Ceftazidime / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood; D004731:Endotoxins / Q000378:metabolism*; D005260:Female; D006801:Humans; D015378:Imipenem / Q000627:therapeutic use*; D008297:Male; D008554:Melioidosis / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D008875:Middle Aged; D011446:Prospective Studies
D000900:Anti-Bacterial Agents; D016207:Cytokines; D004731:Endotoxins; D015378:Imipenem; D002442:Ceftazidime