Cephalosporinase interactions and antimicrobial activity of BMY-28142, ceftazidime and cefotaxime.
Cephalosporinases of Enterobacter cloacae and Citrobacter freundii were responsible for resistance to newer cephalosporins such as cefotaxime and ceftazidime but not BMY-28142. Interaction of these cephalosporins including hydrolysis, binding, inhibition, and inactivation with cephalosporinases from E. cloacae GN7471 and C. freundii GN7391 were studied. BMY-28142 was much more stable against the both enzymes than cephalothin, but more hydrolyzable than cefotaxime and ceftazidime at higher concentration such as 100 microM. Because of low affinity for the enzymes, i.e. large Km and Ki, the calculated hydrolysis rate of BMY-28142 at 0.1 microM was smaller than those of cefotaxime and ceftazidime, that explained the difference in activity against cephalosporinase-producing strains between BMY-28142 and cefotaxime or ceftazidime. The effects of cephalosporinase production on susceptibility of Escherichia coli omp mutants were examined using a plasmid having cephalosporinase gene of C. freundii GN346. Decrease in susceptibility of E. coli by cephalosporinase production was larger in the strain lacking outer membrane proteins (Omp) F and C, and smaller in the strain producing OmpF constitutively.
Hiraoka
M
M
Episome Institute, Gunma, Japan.
Masuyoshi
S
S
Mitsuhashi
S
S
Tomatsu
K
K
Inoue
M
M
D000077723:Cefepime; D002439:Cefotaxime / Q000378:metabolism* / Q000494:pharmacology; D002442:Ceftazidime / Q000378:metabolism* / Q000494:pharmacology; D002510:Cephalosporinase / Q000494:pharmacology*; D002511:Cephalosporins / Q000378:metabolism* / Q000494:pharmacology; D002954:Citrobacter / Q000201:enzymology; D004754:Enterobacter / Q000201:enzymology; D006868:Hydrolysis; D007700:Kinetics; D001618:beta-Lactamases / Q000494:pharmacology*
D002511:Cephalosporins; D000077723:Cefepime; D002442:Ceftazidime; D002510:Cephalosporinase; D001618:beta-Lactamases; D002439:Cefotaxime