Effect of some antimicrobials on endotoxin release in gram-negative sepsis

ABSTRACT

This study was conducted on seven groups of rats Group 1 included a normal control group, group 2 included E. coli infected untreated rats, group 3 included infected, cefotaxime-treated [90 mg/kg] rats, group 4 included infected, gentamicin-treated [7.2 mg/kg], group 5 included infected, clindamycin-treated [27 mg/kg], group 6 included infected, cefotaxime- and clindamycin-treated rats and group 7 included infected, gentamicin- and clindamycin-treated rats. In all groups, mean arterial blood pressure, heart rate, temperature and lethality percentage were measured and blood samples were collected at 0, 3, 6, 12 and 24 hours from the antimicrobial injection. While, blood cell [WBCs] count, tumor necrosis factor-alpha [TNF-alpha], interleukin-6 [IL-6] and erythropoietin plasma levels were measured. It was concluded that antimicrobials resulting in lower amounts of free endotoxin may be more efficacious in treating Gram-negative sepsis. Also, in order to reduce the mortality during treatment of sepsis by Gram-negative E. Coli, a focus should be done on both reduction of endotoxin production and killing of bacteria. Regimen with the combination of bactericidal antimicrobial and a protein synthesis inhibitor, which offers the advantage of potent antimicrobial activity with an inhibition of endotoxin synthesis, may be an alternative to therapy by antimicrobial producing large amounts of endotoxin during its bactericidal action