Influence of In-Vivo Endotoxin Liberation on Anti-Anaerobic Antimicrobial Efficacy

AbstractThe ability of cefoxitin, clindamycin, imipenem, meropenem, metronidazole and piperacillin-tazobactam to cause Gram-negative anaerobic bacteria to release endotoxin and the influence of such liberated endotoxin on antibiotic efficacy were investigated in In-Vivo experiments in animal models. Experimental infections in various animal models (mice, hamster and infant rats) with cultures of wild and reference strains of Bacteroides fragilis group and Fusobacterium spp. were carried out by injecting these animals with different inocula (106, 107 and 108 cfu/ml) of the bacterial suspension. Appropriate doses of the test antibiotics were then injected and the plasma lipopolysaccharide (endotoxin) release measured by the Limulus Amoebocyte Lysate (LAL) Assay. Evidence of worsening of the outcome of the infections post-therapy was assessed, including histopathological changes in the internal organs. Infection with generalized septicemia was established with F. nuclea-tum in the mice and hamster models whi...