联合用药减少铜绿假单胞菌 耐药突变体的体外研究

目的在体外探讨环丙沙星(CIP)、阿米卡星(AMK)、头孢他啶(CAZ)两两联合是否有利于减少铜绿假单胞菌耐药突变体的产生。方法分别应用琼脂平板稀释法和棋盘格法测定单独以及联合之后的最低抑菌浓度（MIC），采用琼脂平板稀释法测定单独及联合时对铜绿假单胞菌的防耐药突变浓度（MPC），并计算选择指数（SI）即MPC/MIC，根据SI下降的程度来判断防耐药突变能力。结果CIP、AMK、CAZ单药对铜绿假单胞菌的SI分别为16、16、＞32。两两联合后各自单药的SI分别为:CIP+AMK (CIP 8，AMK 4); CIP+CAZ (CIP 4，CAZ 8)；AMK+CAZ(AMK 8，CAZ 4)。结论以上3种药物任意两两联合均可以降低单独用药时对铜绿假单胞菌的SI，有利于防止铜绿假单胞菌耐药突变体的产生。

Antibiotics in reducing resistant mutants of Pseudomonas  aeruginosa in vitro

To study whether the combinations of two drugs of ciprofloxacin amikacin(CIP), ciprofloxacin ceftazidime(AMK) and ceftazidime amikacin(CAZ) will decrease drug resistant mutants of Pseudomonas aeruginosa in vitro. MethodsMinimum inhibitory concentration (MIC) of CIP,AMK, and CAZ alone was determined by an agar plates dilution method and MIC of the combinations of  them was determined by a checkerboard method. Mutant prevention concentration (MPC) of each single and of combinations were determined by the agar plates dilution method, and then the value of SI(MPC/MIC) was obtained.  Capacity in preventing the appearance of drug resistant mutants was determined based on degree that SI dropped. ResultsSI of CIP, AMk, and CAZ was 16, 16, and ＞32, and of ciprofloxacin amikacin(CIP 8; AMK 4); ciprofloxacin ceftazidime(CIP 4; CAZ 8); ceftazidime amikacin(AMK 8; CAZ 4). ConclusionCompared with each one alone, two drug combinations can decrease MPC and SI to pseudomonas aeruginosa and restrain the drug resistant mutants.