Biochemical comparison of imipenem, meropenem and biapenem: permeability, binding to penicillin-binding proteins, and stability to hydrolysis by β-lactamases

Biological activities of biapenem, imipenem, and meropenem were compared with respect to permeability into Gram-negative bacteria, binding to penicillin-binding proteins (PBPs), and hydrolysis by β-lactamases. Permeability for the threecar-bapenems was similar when measured in Serratia marcescens S6 producing a carbapenem-hydrolyzing β-lactamase. Penetration of the carbapenems was comparable with cephaloridine and faster than piperacillin or the extendedspectrum cephalosporin cefotaxime. All the carbapenems bound most strongly to PBP 2 of Escherichia coli and Pseudomonas aeruginosa, and to PBP 1 of Staphylococcw aureus. In addition, biapenem showed strong affinity with PBP la of E. coli and PBP lb of P. aeruginosa. Selected serine β-lactamases, including the extended spectrum plas-mid-mediated β-lactamases, hydrolyzed these carbapenems at rates <0.1% that of cephaloridine. Metallo-β-lactamases hydrolysed the carbapenems at measurable rates, with enzymes from Bacteroides fragilis and Xanthomonas maltophilia hydrolyzing biapenem at lower Vmax values than meropenem or imipenem. In conclusion, all the carbapenems exhibited good rates of penetration, bound strongly to PBPs in both Gram-negative and Gram-positive bacteria, and were stable to most Group 1 and Group 2 serine β-lactamases, but were hydrolyzed by metallo-β-lactamases.