COMPARATIVE IN-VITRO ACTIVITY OF BIAPENEM AGAINST ENTEROBACTERIA WITH BETA-LACTAMASE-MEDIATED ANTIBIOTIC-RESISTANCE

The effects of enterobacterial β-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 β-lactamase expression, β-Lactamase-derepressed organisms in these series were as susceptible as β-lactamase-inducible strains to biapenem; β-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 βlactamases. Piperacillin and the cephalo-sporins, 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 β-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 β-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 carbapcnemase. 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 β-lactamases of enterobacteria. © 1994 The British Society for Antimicrobial Chemotherapy.