The action of beta-lactamases on desacetyl-cefotaxime and cefotaxime.
Desacetyl-cefotaxime is the main cefotaxime metabolite. Its antibacterial activity is less than that of the parent molecule, but the combination of cefotaxime and desacetyl-cefotaxime is often synergistic. We analysed the hydrolysis of desacetyl-cefotaxime, in comparison with cefotaxime, by 10 beta-lactamases, mostly cephalosporinases, isolated from various Gram-negative species. From partially purified beta-lactamase preparations of high specific activity, we determined the maximum rates of hydrolysis (Vm) and the Michaelis constants (Ki and Km when possible). It appeared for 7 beta-lactamases the rate of desacetyl-cefotaxime hydrolysis was 2.1 times greater than that of cefotaxime, in terms of geometrical mean value, but with 3 enzymes no hydrolysis was shown for one compound. For 8 enzymes, the Ki, and sometimes Km, of desacetyl cefotaxime are 39 times higher than those of cefotaxime (geometric mean value), which corresponds to a lower affinity.
D002439:Cefotaxime / Q000031:analogs & derivatives* / Q000378:metabolism*; D004338:Drug Combinations; D004357:Drug Synergism; D006868:Hydrolysis; D007700:Kinetics; D001618:beta-Lactamases / Q000494:pharmacology*
D004338:Drug Combinations; C029281:desacetylcefotaxime; D001618:beta-Lactamases; D002439:Cefotaxime