Comparative potency of mecillinam and other beta-lactam antibiotics against Escherichia coli strains producing different beta-lactamases

The activity of mecillinam, a beta-lactam antibiotic with high affinity for gram-negative penicillin-binding protein 2 (PBP2), was assessed against ampicillin-resistant Escherichia coli strains producing beta-lactamases representing the three molecular classes, A (TEM-1 and -3, SHV-3 and IRT-5), C (AmpC) and D (OXA-3). The antimicrobial activity of mecillinam and other beta-lactam antibiotics was evaluated by determining their MICs on Mueller-Hinton agar. The time course of hydrolysis in crude extracts prepared from the various beta-lactamase-producing strains was also measured and was used to determine the relative rate of hydrolysis and the apparent affinity for ampicillin, cephalothin and mecillinam. When compared with the other beta-lactam antibiotics, mecillinam demonstrated significantly greater antibacterial potency and higher stability to beta-lactamase hydrolysis in TEM-, IRT- and AmpC-producing isolates. These findings confirm that the antimicrobial potency of mecillinam compares favourably with those of the other penicillins included in the present study, suggesting that mecillinam use in the treatment of infections caused by gram-negative bacteria should be re-evaluated.