Proposed interpretive criteria and quality control parameters for testing susceptibility of Neisseria gonorrhoeae to beta-lactam-clavulanate combinations

Abstract

To support future clinical studies, in vitro susceptibility tests were examined to determine whether Neisseria gonorrhoeae could be tested reliably against two beta-lactam-clavulanate combinations. All isolates that were tested appeared to be susceptible to amoxicillin and ticarcillin in combination with clavulanic acid. In the absence of resistant isolates, only a breakpoint for a susceptible category could be defined for agar dilution tests with amoxicillin-clavulanic acid (MIC of less than or equal to 2.0/1.0 micrograms/ml is tentatively proposed). For disk diffusion tests, a corresponding breakpoint zone diameter of greater than or equal to 28 mm is suggested. The validity of the breakpoints for penicillinase-negative penicillin-resistant strains awaits clinical data. Proposed quality control limits for testing amoxicillin-clavulanic acid by agar dilution and disk diffusion methods are a MIC of 0.25/0.125 to 1.0/0.5 micrograms/ml and zones of 30 to 40 mm in diameter for N. gonorrhoeae ATCC 49226, a MIC of 0.125/0.06 to 0.5/0.25 micrograms/ml for Staphylococcus aureus ATCC 29213, and zones of 30 to 38 mm for S. aureus ATCC 25923. Ticarcillin-clavulanate is currently tested against other species by preparing doubling dilutions of ticarcillin with a constant 2 micrograms of clavulanate per ml. By that method, all gonococci were susceptible to low concentrations. However, the amount of clavulanic acid that is included (2 micrograms/ml) will, by itself, inhibit many strains of N. gonorrhoeae. Consequently, the role of ticarcillin in the combination cannot be determined, and such tests are not recommended.