The stability of meropenem in the presence of renal dehydropeptidase I (DHP-I) varied extremely with the animal source of the enzyme. Meropenem, compared with imipenem, was rather easily hydrolyzed by DHP-Is from mice, rabbits, and monkeys, while it showed a higher resistance to guinea pig and beagle dog DHP-Is. In addition, meropenem was four times more resistant than imipenem to human DHP-I. The 1 beta-methyl substituent on carbapenems, i.e., meropenem and 1 beta-methyl imipenem, made them considerably more resistant to mouse and swine DHP-Is than the 1-unsubstituted derivatives are.

The affinity of meropenem for various known types of β-lacta-mases and its stability to them were tested in comparison with other β-lactams, including imipenem. Meropenem exhibited a marked stability to all p-lactamases tested and was only hydro-lyzed by Xanthomonas maltophilia β-lactamase, as were other β-lactams. This was responsible for the potent antibacterial activities of meropenem against β-lactamase-producing strains. Meropenem and imipenem had almost the same, relatively high affinity for β-lactamases; however, they had a lower affinity than clavulanic acid for penicillin β-lactamases and cefoxitin for cephalosporin β-lactamases. Meropenem also had higher β-lactamase inhibitory activity than imipenem. Meropenem inhibited type III (TEM-1), la Citrobacter freundii and Ic Proteus vulgaris β-latamases in a progressive manner. Meropenem was thought to be a potent inhibitor of various β-lactamase because of its ability to form stable enzyme-meropenem acyl-complexes. Meropenem generally exhibited a lower induction potential than imipenem against five clinical isolates of C. freundii, Enterobacter cloacae and Pseudomonasaeruginosa, but its induction potential was higher than that of ceftazidime. Meropenem induced β-lactamases at concentrations above the MIC.