104株大肠埃希菌对3种氟喹诺酮类药物突变抑制浓度的比较研究

Comparison of Mutant Prevention Concentrations of 3 Fluoroquinolones in 104 Escherichia coli Isolates

目的探讨3种氟喹诺酮类药物对不同人群及不同来源大肠埃希菌(ECO)的防突变浓度(MPC)与最低抑菌浓度(MIC)、药物在血中的峰浓度(Cmax)间的关系,为临床合理用药提供依据。方法采用标准琼脂稀释法,测定大肠埃希菌对3种氟喹诺酮类药物的MIC值;琼脂稀释法测定MPC,但接种细菌浓度>1010CFU/ml,计算MPC90。结果从正常人肠道分离出的菌株中,8.2%对莫西沙星中度敏感,从患者标本中分离的ECO对莫西沙星有23.3%中度敏感、2.3%耐药,而104株菌均对环丙沙星和左氧氟沙星敏感,即大肠埃希菌对莫西沙星的敏感性低于对环丙沙星和左氧氟沙星;不同人群的大肠埃希菌对3种氟喹诺酮药物的MIC分布差异无统计学意义;无论从患者中还是从正常人肠道分离的大肠埃希菌对环丙沙星、左氧氟沙星和莫西沙星的MIC值与MPC90差异无统计学意义(P>0.05);当按口服剂量使用环丙沙星、莫西沙星时,正常人肠道及临床患者无菌部位的大肠埃希菌分别有44.2%和29.5%、18.7%和10.7%的菌株将被选择出耐药突变菌;而当静脉滴注环丙沙星、莫西沙星时,正常人肠道及临床患者无菌部位的大肠埃希菌分别有9.3%和8.2%、6.2%和8.9%的菌株发生耐药突变。结论不同人群、不同部位的大肠埃希菌MIC和防突变浓度之间存在不一致性,不能由MIC推测MPC;正常人肠道和患者血液及腹水和胆汁中分离的大肠埃希菌的MPC、MPC90之间差异无统计学意义。

OBJECTIVE To determine the mutant prevention concentrations （MPC） of three fluoroquinolones in 104 Escherichia coli isolates from two kinds of populations, to reveal the relationship between the MPC and MIC, and Cmax, and to provide a guide for choosing fluoroquinolones to significantly reduce the development of resistance. METHODS Measurements of MIC and MPC were carried out using agar dilution method. As for MIC, approximately 10^5 CFU were applied to each of a series of agar plates containing various antibiotic concentrations, but for MPC, the CFU was on the order of 10^. 0 The values of MIC90 and MIC90 were calculated. RESULTS Among all 104 ciprofloxacin-susceptible E. coli isolates, 61 isolates were from the health population, and another 43 isolates from the patients. For the health population, 8. 2% of the isolates tested were intermediate to moxifloxacin, and for the patients, 23.3 % of the E. coli isolates were intermediate to and 2.3 % were resistant to moxifloxacin. The distributions of MIC values of 3 fluoroquinolones （ciprofloxacin, levofloxacin, and moxifloxaein） in all tested isolates from two group populations showed no discrepancy （P〉0. 05）. The values of MIC and MPC90 of 3 fluoroquinolones also showed no significant discrepancy （P〉0.05）. Our results showed that, for recommended oral doses of ciprofloxacin and moxifloxacin, 44.2% of E. coli isolates from the intestine of the health population, and 29.5%, 18.7% and 10.7% of isolates from the three sterile sites of the patients, would be selected as resistant mutants. When ciprofloxacin and moxifloxacin were taken by injection route, the ratio of the selection of resistant mutants would be 9. 3% for E. coli isolates from the intestine of the health population and 8.2%, 6.2% and 8.9% for the three sterile sites of the patients, respectively. The maximum attainable concentration of levofloxacin in serum showed little distinction between the oral and the other routes. CONCLUSIONS The values of MIC and MPC of three fluoroquinolones in E. coli isolates from different populations and sites show no association. The values of MPC couldn＇t be predicted by the MIC. The values of MPC and MPC90 of three drugs show no significant discrepancy for tested isolates, these E. coli strains are isolated from the intestine of heath persons, and from the blood, ascites, bile of patients.