氧氟沙星和左氧氟沙星抗结核分枝杆菌临床耐药界限的研究

目的通过测定氧氟沙星(OFLX)及左氧氟沙星(LVFX)对101株临床分离的结核分枝杆菌的最低抑菌浓度(MIC)、分析MIC与既往氟喹诺酮类药物(Fos)的用药史及经过含有FQs方案治疗的疗效相关性,以期确定OFLX及LVFX的临床耐药界限.方法 1999年1月～2000年9月间在我院住院的结核病患者101例,留取痰或脓液行结核分枝杆菌培养、药敏试验及MIC,并系统观察47例肺结核患者接受含喹诺酮类药物治疗方案的痰菌阴转率和X线吸收好转率.各组间率的比较用X2检验. 结果(1)96%的菌株OFLX的MIC(MICF)比LVFX的MIC(MICV)高2倍.(2)既往未用过FQs治疗的临床分离株中,MICF<8.0μg/ml与MICV<4.0μg/ml者分别占91%及92%;既往曾接受FQs治疗的临床分离株中,MICF≥8.0μg/ml与MICV≥4.0μg/ml分别占54%及57%.(3)如以MICF≥8.0μg/ml、MICV≥4.0μg/ml为临床耐药界限,MICF<8.0μg/ml与MICF≥8.0μg/ml比较,3、6、12个月患者痰菌阴转率分别为54%、75%、82%及16%、32%、42%,两组比较差异均有非常显著性(P<0.01),两组12个月X线吸收好转率分别为89%、47%,差异有非常显著性(P<0.01);MICV<4.0μg/ml与MICV≥4μg/ml比较,3、6、12个月患者痰菌阴转率分别为53%、73%、83%及 12%、29%、35%,两组比较差异有非常显著性(P<0.01),12个月X线好转率分别为90%、41%,两组比较差异有非常显著性(P<0.01).结论 (1)曾接受FQs治疗的结核病患者的分离株MICF及MICV显著高于未接受FQs者.随着用药时间延长,MIC随之升高.(2)根据MICF及MICV与临床疗效分析结果,提示采用MICF≥8.0μg/ml、MICV≥μg/ml为临床耐药界限为宜.(3)既往曾接受FQs治疗的结核病患者,应行FQs的药敏试验,并坚持合理、联合用药的原则、防止耐药株产生.

A preliminary study on the definition of resistant breakpoints of ofloxacin and levofloxacin for Mycobacterium tuberculosis

OBJECTIVE: To test the MIC of ofloxacin and levofloxacin (MIC(F) and MIC(V)) in 101 strains of Mycobacterium tuberculosis (M. tb) isolated from patients with active tuberculosis and to analyze the relation between MIC and past history of fluoroquinolones (FQs) administration. And according to the analysis of the therapeutic effect of the regimen including FQs, we want to define the resistant breakpoints of OFLX and LVFX clinically. METHOD: All isolates from sputa or pus obtained from in-patients in our hospital from Jan 1999 to Sept 2000 were tested for MIC and susceptibility. 47 patients with pulmonary tuberculosis received regimens including FQs were observed consecutively. Chi-square test was applied for the statistical analysis. RESULT: (1) The MIC(V) of 96% clinical isolates tested were 2 times lower than MIC(F). (2) The MIC(F) < 8 microg/ml and MIC(V) < 4 microg/ml were found among 91% and 92% patients without previous FQs administration, while only the MIC(F) > or = 8 microg/ml and MIC(V) > or = 4 microg/ml were found among 54% and 57% for the patients with FQs administration history. (3) If MIC(F) > or = 8 microg/ml and MIC(V) > or = 4 microg/ml were defined as the clinical resistant breakpoints, in susceptible group, the sputum negative conversion rates were 54%, 75% and 82% respectively after receiving the regimens including FQs in 3, 6, and 12 months, while 16%, 32%, and 42% respectively in resistant group, (P < 0.01). Also, there were significant differences between these two groups for chest X-ray improvements after 12 months' treatment, (P < 0.01). There were significant differences for sputum conversion rates and chest X-ray improvement between MIC(V) < 4 microg/ml and MIC(V) > or = 4 microg/ml groups (P < 0.01). CONCLUSIONS: According to the evaluation for the therapeutic effects of regimens including FQs, it is suggested that MIC(F) > or = 8 microg/ml and MIC(V) > or = 4 microg/ml be defined as resistant breakpoints clinically. The emergence of resistance to FQs in patients with tuberculosis can influence the therapeutic effects.