Antibiotic-induced endotoxin release in patients with gram-negative urosepsis: a double-blind study comparing imipenem and ceftazidime.
The clinical significance of differences between antibiotics in endotoxin-liberating potential is unknown. Thirty patients with gram-negative urosepsis were randomized between imipenem and ceftazidime, which have, respectively, a low and a high endotoxin-liberating potential in vitro. In patients treated with ceftazidime, a slower defervescence was noticed. After 4 h of treatment, the blood endotoxin level decreased in all 3 endotoxemic patients receiving imipenem, whereas it increased in 2 of the 4 endotoxemic patients receiving ceftazidime, and in ceftazidime-treated patients, the endotoxin level in urine decreased less than in imipenem-treated subjects. Serum and urine cytokine levels increased 10%-40% after 4 h of ceftazidime treatment compared with no increase in the imipenem-treated patients (P > .05). Endotoxin release during antibiotic killing in vitro, assessed for all microorganisms, was 10-fold higher with ceftazidime (P < .001). These results indicate that differences between antibiotics in endotoxin release may affect the inflammatory response during treatment.
Prins
J M
JM
Department of Internal Medicine, Academic Medical Center, Amsterdam, Netherlands.
van Agtmael
M A
MA
Kuijper
E J
EJ
van Deventer
S J
SJ
Speelman
P
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016470:Bacteremia / Q000188:drug therapy* / Q000503:physiopathology; D002442:Ceftazidime / Q000627:therapeutic use*; D004311:Double-Blind Method; D004731:Endotoxins / Q000096:biosynthesis / Q000097:blood*; D016972:Enterobacter cloacae / Q000302:isolation & purification; D004926:Escherichia coli / Q000302:isolation & purification; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D015378:Imipenem / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000097:blood / Q000652:urine; D016209:Interleukin-8 / Q000652:urine; D007711:Klebsiella pneumoniae / Q000302:isolation & purification; D008875:Middle Aged; D011446:Prospective Studies; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014552:Urinary Tract Infections / Q000188:drug therapy* / Q000503:physiopathology
D004731:Endotoxins; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D015378:Imipenem; D002442:Ceftazidime