中文摘要：

目的通过测定4种氟喹诺酮类药物（FQ）对粪肠球菌ATCC29212及其同源耐药突变体、粪肠球菌临床分离株的最低抑菌浓度（MIC）、防耐药突变浓度（MPC）和突变选择窗（MSW），比较其抗菌活性及防耐药突变的能力。方法采用4种FQs（环丙沙星、左氧氟沙星、莫西沙星和加替沙星）筛选粪肠球菌ATCC29212同源的第一步耐药突变体，用加替沙星筛选第二步耐药突变体；采用琼脂二倍稀释法测定粪肠球菌ATCC29212及其同源耐药突变体、粪肠球菌临床分离株的MIC、暂定MPC（MPCpr）和MPC，并计算MIC90、MPCpr90、选择指数SI（MPCpr90/MIC90及MPC／MIC）。结果加替沙星、莫西沙星、左氧氟沙星和环丙沙星对粪肠球菌ATCC29212的MPC分别为1．2、1．2、5．6和6．4μg／mL，选择指数分别为3．4、6、8和8；对30株环丙沙星敏感的粪肠球菌临床分离株的MPCpr90分别为2、1、4和4μg／mL，选择指数分别为4、4、8和8；而加替沙星和莫西沙星对15株环丙沙星中介耐药株的MPCpr90分别为32和16μg／mL，选择指数均达到了32。4种FQs药物对ATCC29212第一步耐药突变体的MIC及MPC值均较其源菌株升高；加替沙星和莫西沙星对第二步耐药突变体的MPC己高达32μg／mL；加替沙星、莫西沙星和左氧氟沙星对第一步耐药突变体的MSW较源菌株增宽。结论对于粪肠球菌临床分离株、ATCC29212及其同源的耐药突变体，加替沙星和莫西沙星的抗菌活性均高于左氧氟沙星和环丙沙星，且加替沙星和莫西沙星限制粪肠球菌耐药突变体被选择出来的能力强于左氧氟沙星和环丙沙星，结合药动学参数，加替沙星和莫西沙星能限制下一步耐药突变株的产生，而环丙沙星和左氧氟沙星则很容易筛选出下一步耐药突变株。但对于第二步耐药突变株，加替沙星和莫西沙星则很容易筛选出对这两种药物也耐药的菌株。因此，临床上为延长加替

英文摘要：

Objective To study the antibacterial activities and the abilities of restricting selection of resistant mutants of fluoroquinolones （FQs） by testing minimal inhibitory concentration （MIC）, mutant prevention concentration （MPC） and mutant selection window（MSW） of fluoroquinolones of Enterococcusfaecalis ATCC29212 and its isogenic mutants strain and clinical isolates in vitro. Methods The first-step resistant mutants of Enterococcus faecalis ATCC29212 was selected by ciprofloxacin, levofloxacin, moxifloxacin and gatifloxacin, the second-step resistant mutants was selected by gatifloxacin. MICs and MPCs of 4 fluoroquinolones for Enterococcus faecalis ATCC29212 and its isogenic resistant mutants and clinical isolates were determined by agar plates dilution method,and the ratio of MPCpr90/MIC90 and MPC/MIC were defined as selection index（SI）. Results The MPCs of gatifloxacin, moxifloxacin, levofloxacin and ciprofloxacin for Enterococcusfaecalis ATCC29212 were 1.2, 1.2, 5.6 and 6.4μg/mL and the selection index（SI） was 3.4, 6, 8and 8; and the MPCpr90 for the 30 ciprofloxacin-susceptible clinical isolates were2, 1, 4 and 4μg/mL, the SI were 4, 4, 8 and 8; however, the MPCpr90 of gatifloxacin and moxifloxacin for 15 ciprofloxacin-intermediate clinical isolates were 32 and 16μg/mL, selection index both reached to 32; The MICs and MPCs of 4 FQs for the first-step isogenic mutants were higher than those for strain ATCC29212. MPCs of gatifloxacin and moxifloxacin for second-step resistant mutants were 32μg/mL. The MSWs of gatifloxacin, moxifloxacin and levofloxacin for the first-step mutants were wider than those for its isogenic strain ATCC29212. Conclusion For Enterococcus faecalis ATCC29212 and its isogenic mutants and clinical isolates, the antibacterial activities and the abilities of restricting the selection of next-step resistant mutants of gatifloxacin and moxifloxacin were both stronger than those of levofloxacin and ciproxacin. Combined with published pharmacokinetic parameters, gatiflox