RELEVANCE OF IN VITRO ANTIBACTERIAL ACTIVITIES OF CEFOTIAM AND CEFAZOLIN TO THEIR THERAPEUTIC EFFECTS ON EXPERIMENTAL PNEUMONIA CAUSED BY KLEBSIELLA PNEUMONIAE DT-S IN MICE

Abstract

The MICs of cefotiam and cefazolin against K. pneunzoniae DT-S were Unaffected by the inoculum size and were 0.1 and 1.56μg/ml, respectively. Bactericidal and bacteriolytic activities of the cephalosporins were more potent in bacterial concentrations of 10⁷ colonyforming units (CFU)/ml than in concentrations of 10⁸ CFU/ml. Both activities of cefotiam were more markedly influenced by bacterial concentrations than those of cefazolin. Therapeutic activity of cefotiam was about 9-15 times as potent as that of cefazolin in experimental pneumonia caused by K. pneumoniae DT-S in mice, and this finding was in accordance with the ratio of in vitro antibacterial activities of the two cephalosporins as judged by the MICs or the bactericidal and bacteriolytic activities in bacterial suspension of 10⁷ CFU/ml. The range of concentrations of cefotiam which induced cell filamentation in vitro, was wider than that of cefazolin. This difference, however, was not reflected on the therapeutic activities of the two cephalosporins in the model infection. In the pneumonic lungs, definite therapeutic doses of both cephalosporins (80 mg of cefotiam per kg and 640 mg of cefazolin per kg) produced mainly bacteriolysis of the challenge organisms.