Comparative in-vitro activity of biapenem against enterobacteria with beta-lactamase-mediated antibiotic resistance.
The effects of enterobacterial beta-lactamases were studied for biapenem (L627), a new carbapenem. Susceptibility tests were performed for isogenic mutant series of Citrobacter freundii, Enterobacter cloacae, Morganella morganii, Serratia marcescens and Proteus vulgaris which varied only in chromosomal beta-lactamase expression. beta-Lactamase-derepressed organisms in these series were as susceptible as beta-lactamase-inducible strains to biapenem; beta-lactamase-basal mutants were up to eight-fold more susceptible. Similar patterns of relative activity against the different expression types were noted for imipenem and biapenem. These data were related to direct induction and hydrolysis assays: biapenem, like imipenem, was a strong inducer of several Class I enzymes and of the P. vulgaris cefuroximase and, like the other carbapenems, was only very slowly hydrolysed by these enzymes. Moreover, like meropenem, biapenem reversibly deactivated these beta-lactamases. Piperacillin and the cephalosporins, tested as comparators, were more labile than carbapenems to the Class I enzymes, were weak inducers below their MICs and lacked deactivator function. In consequence their MICs were higher for derepressed organisms than for those with inducible or basal beta-lactamase expression. Unlike the carbapenems, they selected derepressed mutants from inducible populations. Biapenem, like imipenem and meropenem, retained full activity against most transconjugants of Escherichia coli K-12 that produced plasmid-mediated beta-lactamases, including extended-spectrum TEM mutants. Only production of OXA-10 (previously PSE-2) enzyme gave a slight reduction in susceptibility to the new carbapenem. Biapenem resistance (MIC 16 mg/L) did, however, occur in S. marcescens S6, which produced a chromosomal carbapenemase. This enzyme hydrolysed biapenem. Overall, our findings indicate that biapenem shares the favourable properties of imipenem and meropenem in its interactions with the most important beta-lactamases of enterobacteria.
Department of Medical Microbiology, London Hospital Medical College, UK.
H Y
HY
Chen
D M
DM
Livermore
D004352:Drug Resistance, Microbial; D004755:Enterobacteriaceae / Q000187:drug effects* / Q000201:enzymology; D004790:Enzyme Induction; D006868:Hydrolysis; D008826:Microbial Sensitivity Tests; D013845:Thienamycins / Q000378:metabolism / Q000494:pharmacology*; D001618:beta-Lactamases / Q000378:metabolism*
D013845:Thienamycins; D001618:beta-Lactamases; C065257:biapenem