Experimental infections for the evaluation of beta-lactamase resistance.
The antibacterial activity and pharmacokinetics of the beta-lactamase-stable cephalosporin cefuroxime and the gram-negative beta-lactamase-susceptible cephalosporin cefazolin were compared in two contrasting infection models in which Proteus morganii 82, which produces chromosomally mediated beta-lactamase, was the pathogen. In the rat paw model, characterized by high numbers of localized bacteria, cefazolin was destroyed at the site of infection and consequently did not produce a therapeutic response. In the mouse intraperitoneal model cefazolin was also inactive, despite peritoneal concentrations being unaffected by high counts of the beta-lactamase-producing P. morganii in the body cavity. In contrast the pharmacokinetics of cefuroxime was unaffected by the presence of the beta-lactamase-producing P. morganii, and good therapeutic responses were seen in both models.
D000818:Animals; D002437:Cefazolin / Q000378:metabolism / Q000494:pharmacology; D002444:Cefuroxime / Q000378:metabolism / Q000494:pharmacology; D002511:Cephalosporins / Q000378:metabolism / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D007700:Kinetics; D008297:Male; D051379:Mice; D011512:Proteus Infections / Q000188:drug therapy* / Q000201:enzymology; D051381:Rats; D014018:Tissue Distribution; D001618:beta-Lactamases / Q000378:metabolism*
D002511:Cephalosporins; D001618:beta-Lactamases; D002437:Cefazolin; D002444:Cefuroxime