Evaluation of the in-vivo efficacy of Sch 34343

Abstract

Sch 34343 showed a linear dose response (with respect to AUCs) in mice following both intravenous and subcutaneous administration. It was 100% bioavailable following subcutaneous administration. Peak serum levels, AUCs, beta-phase half-life and recovery of Sch 34343 from the urine of mice indicated that it was similar to cephalothin and cefamandole. In experimental mouse infections, against Gram-negative strains, Sch 34343 was more active than cephalothin, equal to or more active than cefamandole and cefoxitin, but less active than latamoxef (moxalactam) and cefotaxime following single or multiple dose therapy. It was the most active compound against Staphylococcus. Sch 34343 was equally active against strains sensitive to beta-lactams and strains producing beta-lactamases. In an anaerobic abscess model in mice, Sch 34343 was more active than cefoxitin and clindamycin against Bacteroides fragilis. In Escherichia coli meningitis in rabbits, it cured rabbits with a single intravenous dose of 50 mg/kg.