ABSTRACT
OBJECTIVE:To study the effects of combined use of cefoperazone/sulbactam(CFS),meropenem(MRP)with le-vofloxacin (LVX) on mutant prevention concentration for Acinetobacter baumannii so as to provide a experimental foundation for preventing bacterial drug resistance. METHODS:In the test,there were groups of single use of CFS,MRP and LVX,and groups of combined use of CFS+LVX and MRP+LVX. Double dilution agar method was used to respectively detect minimal inhibitory con-centration (MIC) for standard Acinetobacter baumannii strains ATCC 19606 and 36 clinically isolated strains in all groups,and then the index of fraction inhibitory concentration(FIC)was calculated. Agar dilution method on plates was employed to detect mu-tant prevention concentration (MPC) for Acinetobacter baumannii in all groups,and then corresponding selection index (SI) was calculated. RESULTS:After combined use of CFS or MRP with LVX,synergistic effect accounted for 55%(20/36)and 50%(18/36). For standard strain ATCC 19606,after combined use of CFS+LVX and MRP+LVX,MPC reduced from 32.0 and 4.0 mg/L to 1.8 and 0.8 mg/L;For 36 clinically isolated strains,after combined use of CFS+LVX and MRP+LVX,MPC reduced from 8.0-32.0 and 1.0-2.0 mg/L to 0.25-1.0 and 0.25-0.5 mg/L. SI were all obviously reduced after combination. CONCLUSIONS:The combina-tion of CFS or MRP with LVX can reduce MPC for Acinetobacter baumannii more significantly than the single use,and narrow mu-tant selection window.
ABSTRACT
Aim To study the change of mutant pre- vention concentration (MPC) in carbapenem-resistant Acinetobacter baumannii (CRAB) treated with moxi- floxacin ( MFX ) and/ or cefoperazone/ sulbactam (CFS) in vitro, and provide a theoretical support for preventing the bacterial resistance. Methods To cal- culate the fractional inhibitory concentration (FIC) in- dex, the minimum inhibitory concentration (MIC) of 20 clinical isolates of CRAB treated with MFX and/ or CFS was determined by checkerboard microdilution as- say. In addition, to calculate the selection index (SI), the MPC of 20 clinical isolates of CRAB treated with MFX and/ or CFS was determined by agar plate di- lution assay. Results Our study showed that there was synergistic/ addictive action, rather than antago- nism action against clinical isolates of CRAB when treated with MFX + CFS. The SI of the 20 isolates trea- ted with MFX or CFS alone was 4 ~128 and 8 ~64 re- spectively, but reduced to 1 ~8 and 4 ~16 when trea- ted with MFX + CFS, which decreased by 2 ~16 and 2 ~4 times respectively compared with the single treat- ment. Conclusion These results suggest that the combination treatment of MFX + CFS against clinical isolates of CRAB might lower the MPC of the isolates treated with MFX/ CFS alone, narrow the mutant selec- tion window, and prevent the generation of drug - re- sistant mutants.
ABSTRACT
Objective To study the correlation between mutant selection window (MSW) and selective enrichment of Staphylococcus aureus resistant mutants in vivo. Methods Tuberculosis patients colonized with S. aureus in anterior nares were selected as experimental group. The susceptibility of S. aureus to rifampicin was determined at the beginning of and 2,4 and 5 weeks after the anti-tuberculosis therapy with rifampicin-containing regimens. S. aureus isolates developing acquired resistance were examined by molecular strain typing. Diabetes patients colonized with S. aureus served as an untreated control. Results The S. aureus isolated from 5 patients acquired rifampicin resistance in 58 tuberculosis patients. It was determined by pulsed-field gel electrophoresis and protein A repeat sequence the strains of S. aureus were different, but the isolates obtained from the same patient before and after acquisition of resistance were the same strains. No resistance was acquired in 39 untreated control patients, which differed statistically from treated patients. Conclusion The selective enrichment of rifampicin-resistant S. aureus mutants occurred when rifampicin concentration was in the mutant selection window.