pH effects on the inhibition of extended-spectrum and classical TEM beta-lactamases by penicillanic acid sulphones.

MICs of piperacillin with tazobactam or sulbactam (4 mg/L) were higher at pH 6.5 than at pH 8.0 for Escherichia coli transconjugants with TEM-1 or TEM-2 enzymes, but not for those with TEM-3 or TEM-10 enzymes. Investigation showed: (i) all four enzymes were less sensitive to sulphones at pH 6.5 than at pH 8.0; (ii) pH effects on MICs arose also for the TEM-3 and TEM-10 producers at lower sulphone concentrations; (iii) the TEM-3 and TEM-10 producers formed less enzyme than those with TEM-1 and TEM-2 and (iv) pH effects on the MICs for TEM-1 producers depended on enzyme quantity. We conclude that all four TEM enzymes have pH-dependent susceptibility to sulphones, but whether this affects MICs depends on the inhibitor:enzyme ratio achieved in the bacteria.