Activity of mecillinam against Escherichia coli resistant to third-generation cephalosporins

To assess the activity of mecillinam against two groups of Escherichia coli: (i) a selection of international isolates with mechanisms of resistance caused by the presence of defined beta-lactamases; and (ii) isolates resistant to third-generation cephalosporins referred from across Wales. Antibiotic susceptibility testing with mecillinam, meropenem, amoxicillin, co-amoxiclav, cefotaxime, piperacillin/tazobactam, ciprofloxacin, nitrofurantoin, trimethoprim and gentamicin was performed using the BSAC agar dilution method against 30 international strains of E. coli with known beta-lactamase presence. Antibiotic susceptibility testing with mecillinam using the same method was performed against 325 regional isolates of E. coli resistant to third-generation cephalosporins. The susceptibility results showed that the only antibiotics to which the 30 international isolates were consistently susceptible were mecillinam (100%) and meropenem (100%), irrespective of the presence of beta-lactamases. Of the local isolates, 93.5% (304/325) were susceptible to mecillinam, having MICs < 8 mg/L. Our results show that mecillinam has excellent in vitro activity against a range of E. coli exhibiting beta-lactamase activity, some with the production of multiple beta-lactamases. It is time to further evaluate the clinical utility of mecillinam in the treatment of infections caused by such organisms.