Effect of beta-lactamase and salt on mecillinam susceptibility of enterobacterial strains

Out of 15 selected enterobacterial strains resistant to ampicillin, 12 were able to transfer resistance to mecillinam to Escherichia coli K-12. This resistance to mecillinam was found to be coupled to the presence of beta-lactamase. One strain contained a beta-lactamase characterized as a class IV beta-lactamase, whereas the other 14 strains possessed a class III (TEM-like) beta-lactamase. The specific activity of the class IV beta-lactamase against mecillinam was 55%, and those of the class III beta-lactamase sensitivity of mecillinam, the minimal inhibitory concentrations were lower than might be expected. However, after enzymatic hydrolysis of mecillinam, no antibacterial activity was found. At increasing salt or buffer concentrations the minimal inhibitory concentrations of mecillinam increase to a varying extent for all strains, independently of beta-lactamase production. This study indicates that the increase in minimal inhibitory concentration is dependent on the salt concentration. The study also shows that this increase is not due to salt-mediated hydrolysis or to stimulation either of beta-lactamase activity or of beta-lactamase production. To explain the difference between ampicillin and mecillnam resistance in the beta-lactamase-positive strains, a hypothetical model is presented and discussed.