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The in vitro antibacterial activities of cefoperazone (CPZ) against clinical isolates including various beta-lactamase-producing strains were studied and compared with those of cefotiam (CTM). CPZ had a broad spectrum against Gram-negative and Gram-positive bacteria. Especially, CPZ showed apparently more potent antibacterial activities than CTM against Enterobacter cloacae, Serratia marcescens, and Pseudomonas aeruginosa. However, CPZ was less active than CTM against Staphylococcus aureus and Proteus mirabilis. The stability and affinity of CPZ for various types of beta-lactamase were also studied. CPZ was more resistant to hydrolysis by typical cephalosporinase (CSase) and cefuroximase (CXase) than CTM, but was less stable to penicillinase (PCase). CPZ often showed higher affinity to beta-lactamases than CTM. The study for the inducer-activity revealed that CPZ hardly induced CSase production in E. cloacae and Proteus vulgaris while CTM highly induced in both strains. CPZ was more active against CSase-producers than CTM, especially against strains which inducibly produced the enzyme. It was speculated that this activity was responsible for the superior stability to CSase and low inducer-activity for CSase production.
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