EFFECT OF HYPERPRODUCTION OF TEM-1 BETA-LACTAMASE ON IN-VITRO SUSCEPTIBILITY OF ESCHERICHIA-COLI TO BETA-LACTAM ANTIBIOTICS

The susceptibility of 173 TEM-1-producing isolates of Escherichia coli was assessed by determination of MICs by the agar dilution method. MICs of amoxicillin, mezlocillin, cephaloridine, and, to a smaller extent, amoxicillin-clavulanic acid (but not cephalexin, cefuroxime, cefotaxime, ceftazidime, or imipenem) were higher for isolates that produced large amounts of beta-lactamase than for isolates that produced smaller amounts. The effect of fixed concentrations of clavulanic acid on resistance-to amoxicillin was assessed for 34 selected TEM-l-producing isolates. Low concentrations of the inhibitor (0.5 to 1 mu g/ml) reduced the amoxicillin MICs substantially for almost all the isolates, although the reductions were not sufficient to render any of the isolates amoxicillin susceptible.]Higher concentrations of clavulanic acid had progressively greater effects on amoxicillin MICs, but even at 8 mu g/ml some of the isolates with high beta-lactamase activities remained resistant or only moderately susceptible to amoxicillin. All the isolates were inhibited by clavulanic acid (in the absence of amoxicillin) at concentrations of 16 to 32 mu g/ml. TEM-1 beta-lactamase activity was inhibited in vitro by clavulanic acid, but not totally, with approximately 2% of the initial activity remaining at 2 mu g/ml and 0.4% remaining at 8 mu g/ml. These findings suggest that the amount of beta-lactamase activity is a major determinant of the degree of resistance to several beta-lactam antibiotics and can make the difference between susceptibility and resistance to some compounds, notably the combination of amoxicillin with clavulanic acid.