GeneXpert MTB/RIF检测利福平耐药结核分枝杆菌的表型药物敏感性试验耐药情况

Analysis of phenotypic drug sensitivity test of rifampicin-resistant Mycobacterium tuberculosis by GeneXpert MTB/RIF

目的分析经GeneXpert MTB/RIF(简称"Xpert")诊断的利福平耐药结核分枝杆菌分离株的表型药物敏感性试验(简称"表型药敏试验")耐药情况及耐药类型。方法采用回顾性研究的方法,搜集2015年1月至2020年12月深圳市第三人民医院经Xpert确诊的346例利福平耐药肺结核患者(初、复治患者分别为142例和204例),分析其结核分枝杆菌临床分离株对10种抗结核药品(利福平、异烟肼、链霉素、利福布汀、乙胺丁醇、左氧氟沙星、对氨基水杨酸、阿米卡星、丙硫异烟胺、卷曲霉素)的表型药敏试验耐药情况及耐药类型。结果 346株利福平耐药结核分枝杆菌分离株对10种抗结核药品的表型药敏耐药率由高至低依次为利福平(95.95%,332/346)、异烟肼(84.68%,293/346)、链霉素(58.38%,202/346)、利福布汀(57.23%,198/346)、乙胺丁醇(50.29%,174/346)、左氧氟沙星(34.39%,119/346)、对氨基水杨酸(11.85%,41/346)、阿米卡星(10.69%,37/346)、丙硫异烟胺(5.78%,20/346)、卷曲霉素(5.20%,18/346)。其中,复治患者分离株对异烟肼、左氧氟沙星、乙胺丁醇、阿米卡星的耐药率[分别为88.24%(180/204)、40.69%(83/204)、55.39%(113/204)、13.73%(28/204)]均明显高于初治患者分离株[分别为79.58%(113/142)、25.35%(36/142)、42.96%(61/142)、6.34%(9/142)],差异均有统计学意义(χ^(2)=4.838,P=0.028;χ^(2)=8.725,P<0.01;χ^(2)=6.372,P=0.012;χ^(2)=4.784,P=0.029)。耐药类型分析显示,菌株的耐多药率为84.68%(293/346),含左氧氟沙星耐药和二线注射剂耐药的准广泛耐药率分别为26.30%(91/346)和5.20%(18/346),广泛耐药率为6.65%(23/346);其中,复治患者分离株的耐多药率[88.24%(180/204)]、准广泛耐药率[37.75%(77/204)]均明显高于初治患者分离株[分别为79.58%(113/142)和22.54%(32/142)],而复治利福平单耐药率[11.76%(24/204)]明显低于初治患者分离株[20.42%(29/142)],差异均有统计学意义(χ^(2)=4.147,P=0.042;χ^(2)=8.976,P<0.01;χ^(2)=4.838,P=0.028)。结论经Xpert诊断的利福平耐药结核分枝杆菌对异烟肼、左氧氟沙星的耐药率也较高,尤其是复治患者,应尽早对Xpert诊断的利福平耐药肺结核患者进行异烟肼及氟喹诺酮类药物的快速耐药检测,以指导临床用药。

Objective To analyze the drug resistance and types of phenotypic drug sensitivity test(phenotypic drug sensitivity test)of rifampicin-resistant Mycobacterium tuberculosis(MTB)isolates diagnosed by GeneXpert MTB/RIF(Xpert). Methods A retrospective study was conducted in which 346 rifampicin-resistant pulmonary tuberculosis(RR-PTB)patients(142 new cases and 204 re-treated cases)from the Third People’s Hospital of Shenzhen between January 2015 and December 2020.The drug resistance and types of phenotypic drug sensitivity test of clinical isolates of MTB strains to 10 anti-tuberculosis drugs(rifampicin,isoniazid,streptomycin,rifabutin,ethambutol,levofloxacin,p-aminosalicylic acid,amikacin,protionamide,capreomycin)were analyzed.Results The resistance rates of the 346 strains to 10 anti-tuberculosis drugs from high to low were rifampicin(95.95%,332/346),isoniazid(84.68%,293/346),streptomycin(58.38%,202/346),rifabutin(57.23%,198/346),ethambutol(50.29%,174/346),levofloxacin(34.39%,119/346),p-aminosalicylic acid(11.85%,41/346),amikacin(10.69%,37/346),protionamide(5.78%,41/346)and capreomycin(5.20%,18/346).In the re-treated cases,the resistant rates to isoniazid,levofloxacin,ethambutol and amikacin were significantly higher than those in the new cases(88.24%(180/204)vs.79.58%(113/142),χ^(2)=4.838,P=0.028;40.69%(83/204)vs.25.35%(36/142),χ^(2)=8.725,P<0.01;55.39%(113/204)vs.42.96%(61/142),χ^(2)=6.372,P=0.012;13.73%(28/204)vs.6.34%(9/142),χ^(2)=4.784,P=0.029,respectively).Analysis of drug resistance types showed that the multi-drug resistant(MDR)rate was 84.68%(293/346),the pre-extensive drug resistance rates(pre-XDR)of levofloxacin resistance and second-line injection resistance were 26.30%(91/346)and5.20%(18/346),and the extensive drug resistance(XDR)rate was 6.65%(23/346).The MDR and pre-XDR rate in re-treated cases were significantly higher than those in the new cases(88.24%(180/204)vs.79.58%(113/142),χ^(2)=4.147,P=0.042;37.75%(77/204)vs.22.54%(32/142),χ^(2)=8.976,P<0.01),while the single resistance rate of rifampicin in the re-treated was significantly lower than that in the new cases(11.76%(24/204)vs.20.42%(29/142),χ^(2)=4.838,P =0.028). Conclusion The rifampicin-resistant tuberculosis strains showed a higher rate of resistance to isoniazid and levofloxacin,especially in re-treated cases.It was necessary to detect resistance to isoniazid and fluoroquinolones as early as possible in rifampicin-resistant pulmonary tuberculosis patients,to optimize the treatment regimen.