Antibacterial activity of cefotaxime.

Cefotaxime (CTAX), a new cephalosporin derivative, has a broad antibacterial spectrum and is stable to β-lactamases produced by various species of bacteria. However, CTAX is hydrolysed by β-lactamases produced by Proteus vulgaris, Pseudomonas cepacia and Bacteroides fragilis, called cefuroxime-hydrolysing enzyme (Group III). Slightly low activity toward Pseudomonas aeruginosa is probably due to the low penetrability of the drug into the cells. The mechanism of action of CTAX was studied with respect to its binding affinities to penicillin-binding proteins (PBPs) and morphological changes of bacteria treated by CTAX in vitro. Cefotaxime showed especially high affinity for Escherichia coli PBP-1A, -1Bs, -3 and -4 and low affinities for PBP-2, -4, -5 and -6. Similar results were obtained with Ps. aeruginosa, in which this compound showed high affinities for PBP-3, -1A, -1B and 2. These results are compatible with morphological observations that at concentrations near its minimal inhibitory concentration or more, this antibiotic induced the formation of filamentous cells of E. coli and Ps. aeruginosa. At higher concentrations or after prolonged incubation, it induced lysis of the cells. [ABSTRACT FROM PUBLISHER]