IN-VITRO ACTIVITIES OF BETA-LACTAM-BETA-LACTAMASE INHIBITOR COMBINATIONS AGAINST STENOTROPHOMONAS-MALTOPHILIA - CORRELATION BETWEEN METHODSFOR TESTING INHIBITORY ACTIVITY, TIME-KILL CURVES, AND BACTERICIDAL ACTIVITY

The activities of ampicillin, ampicillin-sulbactam, amoxicillin, amoxi cillin-clavulanic acid, ticarcillin, ticarcillin-clavulanic acid, pipe racillin, piperacillin-tazobactam, aztreonam, and aztreonam-clavulanic against Stenotrophomonas maltophilia strains for which the MICs of pe nicillins and commercially available beta-lactam-beta-lactamase inhibi tor combinations were higher than the breakpoints usually recommended for Pseudomonas aeruginosa in commercially available broth microdiluti on methods were tested by the agar diffusion, agar dilution, and broth microdilution methods. Time-kill curve studies were performed when di screpancies between these methods were observed. The MICs obtained by the commercially available broth microdilution method, the agar diluti on method, and the broth microdilution method were almost identical. T wenty-five percent of the strains tested showed inhibition diameters o f greater than or equal to 15 mm for ticarcillin-clavulanic acid, and 43.7% of the strains tested showed inhibition diameters of greater tha n or equal to 18 mm for piperacillin-tazobactam by the agar diffusion method. The time-kill curves for these strains confirmed the results o btained by dilution methods. Aztreonam-clavulanic acid (2:1) at concen trations of less than or equal to 16 mu g/ml inhibited all of these st rains (MIG range, 1 to 16 mu g/ml). The time-kill curves confirmed thi s activity. The addition of piperacillin to this combination did not m odify the MICs. The combination aztreonam-clavulanic acid-ticarcillin was two-to fourfold more active than aztreonam-clavulanic acid alone. We studied the inhibitory and bactericidal activities of the two most active combinations (aztreonam-clavulanic acid and aztreonam-clavulani c acid-ticarcillin) against the standard inoculum and 10 and 50 times the standard inoculum. Inoculum modifications did not modify the MICs. Both combinations showed good bactericidal activity against the stand ard inoculum. With 10 times the standard inoculum, minimum bactericida l concentration (MBC) results were heterogeneous (for 55% of the strai ns, MBCs were between the MIC and 4-fold the MIG, and for 45% of the s trains MBCs were between 8- and >32-fold the MIG). With 50 times the s tandard inoculum, MBCs were at least 32-fold the MICs for all the stra ins tested.