Influence of spontaneous and inducible beta-lactamase production on the antimicrobial activity of recently developed beta-lactam compounds.
The activity of 9 recently developed beta-lactam compounds was evaluated in 185 ampicillin-resistant isolates of Enterobacteriaceae. Moreover, in all strains, spontaneous and inducible beta-lactamase production was quantified and correlated with the minimal inhibitory concentration (MIC) of each compound. In most species, no correlation could be observed between spontaneously produced beta-lactamase and the MICs, with the only exceptions of Serratia spp. and Morganella morganii isolates for methoxyimino cephalosporins and azthreonam. On the other hand, the increase of MICs of third-generation cephalosporins and azthreonam correlated well with the total amount of enzyme produced. With respect to temocillin and the penem compound Sch 29 482, there was a significant correlation of enzyme production and MICs only among the Citrobacter spp. isolates. It can be assumed that the effectiveness of the new agents is not only due to the low rate of hydrolysis, but also to the rapid binding to the lethal target.
D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D002511:Cephalosporins / Q000378:metabolism / Q000494:pharmacology*; D004755:Enterobacteriaceae / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004790:Enzyme Induction; D008826:Microbial Sensitivity Tests; D010403:Penicillin Resistance; D010406:Penicillins / Q000378:metabolism / Q000494:pharmacology*; D001618:beta-Lactamases / Q000096:biosynthesis*
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D010406:Penicillins; C031367:temocillin; D001618:beta-Lactamases