氟喹诺酮类药物对肺炎克雷伯杆菌体外防耐药突变浓度的研究

In vitro study of mutant prevention concentration of fluoroquinolones for Klebsiella pneunoniae

目的:测定氟喹诺酮类药物(FQNs)对肺炎克雷伯杆菌的防耐药突变浓度(MPC),比较其防耐药突变能力,了解细菌对FQNs的耐药性。方法:肉汤法富集1010CFU.ml-1的菌液接种于不同浓度环丙沙星及加替沙星琼脂平皿上,采用琼脂二倍稀释法测定环丙沙星、加替沙星对临床分离肺炎克雷伯杆菌、ATCC700603及耐药突变体的最低抑菌浓度(MIC)、防耐药突变浓度(MPC)。结果:环丙沙星、加替沙星对肺炎克雷伯杆菌ATCC700603的MPC分别为8与1.6mg/mL,细菌耐药选择指数(MPC/MIC)分别为16与4mg/mL。2种氟喹诺酮类药物的第一步耐药突变体对筛选药物的MIC较ATCC700603提高4～24倍,第二步突变体又较第一步突变体高2～6倍。结论:加替沙星限制肺炎克雷伯杆菌耐药突变株选择的能力强于环丙沙星,肺炎克雷伯杆菌对FQNs耐药是累积性的。

Objective:To measure MPC of fluoroquinolones for Klebsiella pneunoniae(KP) and compare the capacity of fluoroquinolones to prevent the resistant mutant strain and fluoroquinolones resistant was observed.Methods:The KP strain ATCC700603 was enriched in broth,and the bacterial concentrations were adjusted to 1010 colony forming units per milliliter.The minimal inhibitory concentration(MIC) and MPC of gatifloxacin,ciprofloxacin for KP were determined by agar plates dilution method.Results:The MPC of gatifloxacin and ciprofloxacin for KP strain ATCC700603 were 1.6,4 mg/L,and the MPC/MIC were 4 and 16 mg/Lrespectively.The MICs of 2 fluoroquinolones for the first-step isogenic mutants were 4-24 folds greater than those of ATCC700603.The MICs of 2 fluoroquinolones for the second-step mutants were 2-6 folds greater than those of the first.Conclusions:The capacity of gatifloxacin for restricting the selection of KP resistant mutants is stronger than that of ciprofloxacin.The KP resistance of fluoroquinolones is developed step by step.