Impact of carbapenem administration on systemic endotoxemia in patients with severe sepsis and Gram-negative bacteremia.
In order to investigate the effect of carbapenems on systemic endotoxemia, 20 patients with severe sepsis due to ventilator-associated pneumonia and Gram-negative bacteremia were enrolled; 10 (group A) were administered 1 g t.i.d. of imipenem/cilastatin and 10 (group B) 2 g t.i.d. of meropenem. Blood was sampled at 0 time and after 1, 2, 4, 6, 12, 24, 36, 48, 60, 72, 84 and 96 hours for detection of endotoxins (LPS), interleukin-6 (IL-6), C-reactive protein (CRP) and drug levels. LPS were determined by the QCL-1000 LAL assay, IL-6 by an enzymeimmunoassay, CRP by nephelometry and carbapenem levels by a microbiological assay. We did not find that carbapenems had any effect on the kinetics of LPS and CRP; IL-6 of group A was lower than group B at 72 and 84 hours. No correlation was observed between drug levels of any carbapenem and LPS, IL-6 or CRP. It is concluded that in septic patients with Gram-negative bacteremia administration of either imipenem or meropenem did not affect systemic endotoxemia. The above data support the safe administration of both carbapenems in patients with severe sepsis.
Giamarellos-Bourboulis
E J
EJ
4th Department of Internal Medicine, University of Athens, Medical School, Greece. giamarel@ath.forthnet.gr
Mega
A
A
Pavleas
I
I
Archontoulis
N
N
Rigas
K
K
Vernikos
P
P
Giamarellou
H
H
Thomopoulos
G
G
D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D016470:Bacteremia / Q000188:drug therapy*; D002097:C-Reactive Protein / Q000032:analysis; D015780:Carbapenems / Q000008:administration & dosage*; D015377:Cilastatin / Q000008:administration & dosage; D000077728:Cilastatin, Imipenem Drug Combination; D004338:Drug Combinations; D019446:Endotoxemia / Q000188:drug therapy*; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy*; D006801:Humans; D015378:Imipenem / Q000008:administration & dosage; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000097:blood; D008297:Male; D008875:Middle Aged; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy; D018805:Sepsis / Q000188:drug therapy*
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D004338:Drug Combinations; C508600:IL6 protein, human; D015850:Interleukin-6; D008070:Lipopolysaccharides; D015377:Cilastatin; D015378:Imipenem; D002097:C-Reactive Protein; D000077728:Cilastatin, Imipenem Drug Combination