Xpert MTB/RIF检测利福平耐药结核分枝杆菌的表型药敏结果分析

Analysis of phenotypic drug sensitivity of rifampicin-resistant Mycobacterium tuberculosis detected by Xpert MTB/RIF

目的:分析Xpert MTB/RIF(Xpert)检测利福平耐药肺结核患者的表型药敏结果,为耐药结核病的治疗方案制定提供依据。方法:选取2015年1月至2020年12月期间在温州市中心医院感染科就诊,且痰液或肺泡灌洗液Xpert检测显示利福平耐药的结核患者,回顾分析患者结核分枝杆菌表型药敏结果。结果:570例Xpert检测利福平耐药患者获得一线抗结核药物药敏试验结果,总耐药顺位为利福平(90.18%)>异烟肼(88.60%)>链霉素(56.32%)>乙胺丁醇(29.47%);复治患者异烟肼、利福平、乙胺丁醇的耐药率(分别为94.50%、94.50%、35.78%)均高于初治患者(分别为84.94%、87.50%、25.57%),差异有统计学意义(均P<0.05);24株菌株对一线抗结核药物均敏感,耐1种、2种、3种及4种药物分别有46株、156株、226株、118株;耐多药结核菌株476株,初治278株,复治198株,复治患者耐多药结核病比例更高(90.83%vs.78.98%,χ^(2)=13.723,P<0.001)。302例Xpert检测利福平耐药患者获得二线抗结核药物药敏试验结果,总耐药顺位为氧氟沙星(35.76%)=阿米卡星(35.76%)>卡那霉素(13.25%)=卷曲霉素(13.25%);初治患者氧氟沙星耐药率低于复治患者(26.46%vs.51.33%,χ^(2)=19.044,P<0.05);128株菌株对二线抗结核药物全敏感,耐1种、2种、3种及4种药物分别有111株、23株、21株、19株;泛耐药结核菌株50株,初治、复治各25株,复治患者泛耐药结核病比例更高(22.12%vs.13.23%,χ^(2)=4.051,P=0.044)。结论:异烟肼、氧氟沙星及阿米卡星耐药在Xpert利福平耐药肺结核患者中常见;复治患者耐药情况比初治患者更为严峻,应尽早获得一二线抗结核药物药敏结果,以指导临床用药。

Objective:To analyze the results of the phenotypic drug sensitivity test of rifampicin-resistant tuberculosis patients diagnosed by Xpert MTB/RIF(Xpert) assay to provide a scientific basis for the treatment of drug-resistant tuberculosis.Methods:Tuberculosis patients who were treated in the Infection Department of Wenzhou Central Hospital between January 2015 and December 2020 and showed rifampicin resistance in sputum or alveolar lavage fluid Xpert test were selected,and the results of phenotypic drug sensitivity of Mycobacterium tuberculosis were retrospectively analyzed.Results:The result of the first-line anti-tuberculosis drug susceptibility test was obtained from 570 rifampicin-resistant pulmonary tuberculosis diagnosed by Xpert,and the order of the drug resistance rate was rifampicin(90.18%) > isoniazid(88.60%) > streptomycin(56.32%)> ethambutol(29.47%);the resistance rates to isoniazid,rifampicin,and ethambutol in re-treated patients(94.50%,94.50%,and 35.78%,respectively) were significantly higher than those in the new patients(84.94%,87.50%,and 25.57%,respectively).There were 24 strains sensitive to first-line anti-tuberculosis drugs,and 46,156,226 and 118 strains resistant to 1,2,3,and 4 drugs,respectively.There were 476 patients(278 new patients and 198 re-treated patients) diagnosed with multidrug-resistant tuberculosis(MDR-TB),with the proportion of MDR-TB significantly higher in re-treated patients that in the new patients(90.83% vs.78.98%,χ^(2)=13.723,P<0.001).The results of second-line antituberculosis drug sensitivity test obtained from 302 patients showed the order of resistance rate was ofloxacin(35.76%) = amikacin(35.76%) > kanamycin > kanamycin(13.25%) =capreomycin(13.25%),with the resistance rate to ofloxacin in new patients significantly lower than in re-treated patients(26.46% vs.51.33%,χ^(2)=19.044,P<0.05);128 strains were fully susceptible to second-line antituberculosis drugs,and 111,23,21 and 19 strains were resistant to 1,2,3 and 4 drugs,respectively.There were 50 patients(25new patients and 25 re-treated patients) diagnosed with extensively drug-resistant tuberculosis(XDR-TB),with a higher proportion of re-treated patients with XDR-TB(22.12% vs.13.23%,χ^(2)=4.051,P=0.044).Conclusion:Resistance to isoniazid,ofloxacin,and amikacin is common in rifampicin-resistant patients diagnosed by Xpert.Re-treated patients have more severe drug-resistance than new patients.The drug sensitivity results for first-and second-line anti-tuberculosis drugs should be obtained as early as possible to guide clinical use.