CARBAPENEM-INDUCED ENDOTOXIN RELEASE IN GRAM-NEGATIVE BACTERIAL SEPSIS RAT MODELS

The carbapenem-induced endotoxin release was evaluated using experimen tal models of Gram-negative bacterial sepsis in Wistar rats. Infection s with Escherichia coli, Serratia marcescens, Klebsiella pneumoniae, P seudomonas aeruginosa, Proteus vulgaris and Proteus mirabilis resulted in an increase of the plasma endotoxin concentration after treatment with ceftazidime and carbapenems including imipenem, panipenem, merope nem and biapenem. Except for P. aeruginosa, the plasma endotoxin conce ntrations after carbapenem treatment were significantly lower than tho se after ceftazidime treatment. It is noteworthy that treatment of P. aeruginosa sepsis with meropenem or biapenem induced significantly mor e endotoxin release than other carbapenems and the endotoxin concentra tions induced by these carbapenems reached those of ceftazidime treatm ent. The plasma endotoxin concentrations appeared to correlate with th e reduction of platelet counts and the elevation of both glutamic oxal oacetic transaminase and glutamic pyruvic transaminase values. (C) 199 8 Federation of European Microbiological Societies. Published by Elsev ier Science B.V. All rights reserved.