Effectiveness of Meropenem and Cefmetazole Combination Treatment Against KPC-2-Producing .

Optimal treatment regimens are yet to be established for carbapenemase-producing (CPE). We assessed the efficacy of meropenem (MEM) and cefmetazole (CMZ) combination treatment against -positive , in comparison with that of double-carbapenem therapy using ertapenem (ERT). We performed checkerboard assay for 10 -positive clinical isolates and BAA-1705 (possessing ), with synergistic effect being defined by a fractional inhibitory concentration index of ≤0.5. Subsequently, we conducted time-kill assays using BAA-1705 with an initial inoculum of 10-10 colony forming unit (CFU)/mL. Bactericidal effect was defined as the reduction of initial bacterial count by ≥10 CFU/mL in 24 hr. Finally, we applied scanning electron microscopy to observe morphological changes induced by the combination of MEM and CMZ. Checkerboard assays revealed a synergistic effect in 7 out of 11 -positive when the MEM and CMZ combination was used, and no effect when the MEM and ERT combination was used. The minimum inhibitory concentration of MEM decreased 4-8-fold when combined with CMZ. Time-kill assays with an initial inoculum of 5 × 10 CFU/mL revealed regrowth under the combination of MEM and ERT (0.25 × minimum inhibitory concentration [MIC] each), whereas the combination of 0.25 × MIC each of MEM and CMZ exhibited bactericidal effect. Scanning electron microscopy results demonstrated that the combination of 0.5 × MIC MEM and 0.5 × MIC CMZ facilitated bacterial cell lysis compared with each antibiotic alone. The combination therapy using MEM and CMZ potentially has bactericidal effect against KPC-producing .