4种氟喹诺酮类药物对金黄色葡萄球菌的防耐药变异浓度

Mutant prevention concentrations of fluoroquinolones for staphylococcus aureus

目的 建立防耐药变异浓度 (MPC)体外测定方法 ,并测定氟喹诺酮类 (FQ)药物对金黄色葡萄球菌的MPC。方法 肉汤法富集 10 10 CFU/ml金黄色葡萄球菌ATCC2 5 92 3和 2 0株对环丙沙星敏感的金黄色葡萄球菌临床分离菌 ,采用平板稀释法测定莫西沙星、加替沙星、帕珠沙星和环丙沙星对金黄色葡萄球菌的最低抑菌浓度 (MIC)、MIC99、初测MPC(MPCpr)及MPC。结果 莫西沙星、加替沙星、帕珠沙星和环丙沙星对金黄色葡萄球菌ATCC2 5 92 3的MPC分别为 0 18、0 3、0 75l和 1 8μg/ml,选择指数 (MPC/MIC99)分别为 9 0、7 5、8 0和 10 6。而以上药物对 2 0株临床分离菌的MPCpr90 值分别为 1、1、4和 8μg/ml,MPCpr90 /MIC90 分别为 8、8、16和 16。结论 莫西沙星和加替沙星限制金黄色葡萄球菌耐药突变株选择的能力优于帕珠沙星和环丙沙星。结合药代动力学参数 ,莫西沙星和加替沙星对环丙沙星敏感的金黄色葡萄球菌临床分离菌能有效限制耐药突变株的选择 。

Objective To establish a method to measure mutant prevention concentration(MPC) in vitro, and to measure MPC of fluoroquinolones for staphylococcus aureus.Methods The staphylococcus aureus strain ATCC25923 and 20 ciprofloxacin-susceptible clinical isolates were enriched in broth,and the bacterial concentrations were adjusted to 10 10 colony forming units per milliliter. The minimal inhibitory concentration(MIC) , MIC for 99% of input cells (MIC 99 ), provisional MPC(MPCpr) and MPC of moxifloxacin, gatifloxacin, pasufloxacin and ciprofloxacin for staphylococcus aureus were determined by agar plates dilution method.Results The MPC of moxifloxacin,gatifloxacin, pasufloxacin and ciprofloxacin for staphylococcus aureus strain ATCC25923 were 0.18, 0.3, 0.75 and 1.8 μg/ml, and the MPC/MIC 99 were 9.0, 7.5, 8.0 and 10.6 respectively. The MPC for 90% of the isolates(MPCpr 90 ) of moxifloxacin, gatifloxacin, pasufloxacin and ciprofloxacin for 20 staphylococcus aureus clinical isolates were 1, 1, 4 and 8 μg/ml ,and the MPCpr 90 /MIC 90 were 8, 8, 16 and 16 respectively.Conclusion The capacity of moxifloxacin and gatifloxacin for restricting the selection of staphylococcus aureus resistant mutants were stronger than that of pasufloxacin and ciprofloxacin. Combined with pharmacokinetic parameters, moxifloxacin and gatifloxacin may restrict the selective enrichment of resistant mutants among ciprofloxacin-susceptible staphylococcus aureus clinical isolates,and ciprofloxacin is expected to selectively enrich mutants easily.