Copyright © 1991, American Society for Microbiology In Vitro Antibacterial Activity of KP-736, a New Cephem Antibiotic

KP-736, a new cephem antibiotic with a broad antibacterial spectrum and potent antipseudomonal activity, was evaluated for in vitro antibacterial activity in comparison with ceftazidime, cefotaxime, and cefpirome. KP-736 was significantly more active than the test compounds against gram-negative bacteria, including the Pseudomonas group and ceftazidime-, cefotaxime-, or imipenem-resistant strains, but less active against gram-positive bacteria. KP-736 had very high affinities for penicillin-binding protein 3 (PBP 3) of Escherichia coli K-12 and PBP 1A and PBP 3 of Pseudomonas aeruginosa NCTC 10490 and showed potent bactericidal activities against these two strains. It was stable to hydrolysis by penicillinases and cephalosporinases but was slightly hydrolyzed by oxyiminocephalosporinases and type II penicillinase. A number of P-lactam antibiotics with a broad antibacte-rial spectrum of activity have been developed during the past decade. However, the clinical effectiveness of these drugs has been limited owing to the rapid development of resis-tance of Pseudomonas aeruginosa and certain members of the family Enterobacteriaceae, such as Citrobacter and Enterobacter spp., in immunocompromised patients (17-19). Recently, several P-lactam antibiotics containing catechol derivatives in the structure have been reported to possess excellent antibacterial activity against P. aeruginosa (1, 3, 6