In vitro and in vivo studies with BL-S786, cefoxitin, and cefamandole

The in vitro antimicrobial activities of BL-S786, cefoxitin, and cefamandole against 90 isolates of Enterobacteriaceae, including Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae and E. aerogenes, were studied by using an agar dilution procedure. Comparison of geometric mean minimal inhibitory concentrations showed that BL-S786 was half as active as cefamandole against Enterobacter species, 2 to 4 times more active than cefamandole against all other species, and 4 to 25 times more active than cefoxitin against all species. In vivo experiments employed acute protection tests in infected mice, using five isolates each of the five genera. Drugs were administered intramuscularly in two doses 3 h apart at dosages of 2.5, 5, 10, 20, and 40 mg per mouse. In most instances, BL-S786 was the most efficacious drug, being some 1.3 to 9.1 times more active than cefoxitin in all experiments and 1.5 to 8.7 times more active than cefamandole in most experiments. BL-S786 and cefamandole were comparable in activity in experiments with E. aerogenes, whereas BL-S786 was superior in experiments with E. cloacae.