4种氟喹诺酮类药物对嗜麦芽寡养单胞菌防耐药变异浓度的测定

Mutant prevention concentration of fluoroquinolones for Stenotrophomonas maltophilia

目的为了解4种氟喹诺酮类药物对嗜麦芽寡养单胞菌的防耐药变异能力,以指导临床合理用药。方法采用标准琼脂二倍稀释法测定莫西沙星、左氧氟沙星、洛美沙星、环丙沙星对嗜麦芽寡养单胞菌的最低抑菌浓度;将总量为1.2×1010CFU的细菌接种于含不同浓度药物的琼脂平皿上,无菌落生长的最低药物浓度即为该药的防耐药变异浓度(MPC)。结果莫西沙星和左氧氟沙星对嗜麦芽寡养单胞菌的敏感率为100%,洛美沙星敏感率为64.5%,环丙沙星敏感率为9.7%。莫西沙星和左氧氟沙星MPC90为64mg/L,洛美沙星和环丙沙星MPC90为256m g L/。4种药物的M PC90/MIC90均为64。结论莫西沙星和左氧氟沙星对嗜麦芽寡养单胞菌具有高度的抗菌活性,但结合药代动力学参数,4种药物血药浓度均位于MIC和MPC之间,提示单药治疗易导致耐药突变菌株的富集生长,应联合用药以限制细菌耐药的发生。

Objective To determine the mutant prevention concentration （MPC） in vitro of fluoroquinolones fagainetor the clinical Stenotrophomonas maltophilia, and guide the clinical rationable use of the agents. Methods The minimal inhibitory concentrations （MIC） of moxifloxacin, levofloxacin, lomefloxacin and ciprofloxacin against Stenotrophomonas maltophilia were determined by agar twofold dilution method. MPC were determined by agar twofold dilution with bacterial population inocubated 1.2 × 10^10 CFU, and were defined as the lowest drug concentrations that prevented recovery of colonies. Results The MIC90 of moxifloxacin, levofloxacin, lomefloxacin and ciprofloxacin were ling/L, ling/L, 4mg/L and 4mg/L, respectively. Moxifloxacin and levofloxacin showed the highest antimicrobial activity, their sensitive rates were 100%. The sensitive rates of lomefloxacin and ciprofloxacin were 64. 5% and 9.7%, respectively. The MPC for 90% of the isolates （MPC90） of moxifloxacin and levofloxacin were 64mg/L and that were 256mg/L for lomefloxacin and ciprofloxacin. The MPC90/MIC90 of the four agents were the same value, which were 64. Conclusion Moxifloxacin and levofloxacin demonstrated highest activity against Stenotrophomonas mahophilia. However, combined with pharmacokinetic parameters, the serum concentrations of the four agents were all between MIC and MPC, which suggested the agents could not restrict the selective enrichment of resistant mutants while being used alone. Due to the tendency of resistant mutants selection, moxifloxacin and levofloxacin should be administered in combination with other agents.