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

Abstract

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 Bacteroides fragilis and Xanthomonas maltophilia hydrolyzing biapenem at lower V_max 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.