Comparison of BL-S786 with cephalothin, cefamandole and cefoxitin in vitro and in treatment of experimental infections in mice

Abstract

The activity of BL-S786 was compared to that of cephalothin, cefamandole and cefoxitin in vitro and in treatment of experimental infections in mice. In broth dilution tests, the activity of BL-S786 was less than cephalothin or cefamandole against Staphylococcus aureus and less than cefamandole or cefoxitin against Haemophilus influenzae. BL-S786 and cefamandole were the two most active drugs against cephalothin-sensitive Enterobacteriaceae. In tests with cephalothin-resistant Enterobacteriaceae, BL-S786 was generally less active than cefamandole but more active than cefoxitin against all strains except Proteus and Providencia. Regardless of the comparative in vitro activity of the four drugs, BL-S786 was the most effective drug in treatment of mice lethally infected with Enterobacteriaceae. Protection from lethality was associated with clearance of bacteremia by each of the four drugs. In several tests where in vitro activity was not predictive of in vivo efficacy, selection of resistance in vivo was found to have occurred.