Beta-lactamase stability and inhibitory activity of meropenem combined with a potent antibacterial activity

The affinity of meropenem for various known types of β-lactamases and its stability to them were tested in comparison with other β-lactams, including imipenem. Meropenem exhibited a marked stability to all β-lactamases tested and was only hydrolyzed 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), Ia 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 Pseudomonas aeruginosa, but its induction potential was higher than that of ceftazidime. Meropenem induced, β-lactamases at concentrations above the MIC.