耐药肺结核患者氟喹诺酮类药物耐药情况及影响因素

目的 分析耐药肺结核患者对氟喹诺酮类药物的耐药情况及影响因素。方法 采用回顾性研究方法,选取2015年1月至2020年12月于首都医科大学附属北京胸科医院确诊并住院治疗的988例耐药肺结核患者作为研究对象。研究对象均经痰液标本分枝杆菌培养阳性,并经菌种鉴定为结核分枝杆菌,均进行了药物敏感性试验(简称“药敏试验”),证实对异烟肼、利福平、利福喷丁、利福布丁、乙胺丁醇、氯法齐明、阿米卡星、丙硫异烟胺、克拉霉素、卡那霉素、卷曲霉素、链霉素等药物中任意一种或一种以上药物耐药。采用比例法药敏试验对氧氟沙星、左氧氟沙星、莫西沙星等进行耐药检测。分析不同特征研究对象对氟喹诺酮类药物的耐药情况,并采用多因素logistic回归模型分析耐药肺结核患者出现氟喹诺酮类药物耐药的影响因素。结果 988例研究对象中,对氟喹诺酮类药物耐药者有431例,耐药率为43.62%。氟喹诺酮类药物耐药者中年龄<18岁者占0.93%(4/431)、初治患者占17.86%(77/431)、北京地区居住者占14.62%(63/431),均明显高于氟喹诺酮类药物敏感者[分别占3.05%(17/557)、36.98%(206/557)、31.42%(175/557)],差异均有统计学意义(χ²值分别为6.154、43.453、37.508,P值均<0.05);利福平耐药者占94.66%(408/431),明显高于氟喹诺酮类药物敏感者[84.38%(470/557)],差异有统计学意义(χ²=25.968,P<0.01);有氟喹诺酮类药物用药史者占3.81%(15/431),与氟喹诺酮类药物敏感者相比[2.98%(15/557)],差异无统计学意义(χ²=0.465,P=0.495)。多因素logistic回归分析显示,利福平耐药[OR(95%CI)=2.704(1.585~4.615)]、有氟喹诺酮类药物用药史[OR(95%CI)=2.661(1.210~5.854)]是耐药肺结核患者发生氟喹诺酮类药物耐药的危险因素;而初治[OR(95%CI)=0.402(0.283~0.571)]及居住在北京[OR(95%CI)=0.411(0.289~0.585)]是耐药肺结核患者发生氟喹诺酮类药物耐药的保护因素。结论 耐药肺结核患者对氟喹诺酮类药物的耐药率较高;复治、利福平耐药、有氟喹诺酮类药物用药史和非北京地区居住患者发生氟喹诺酮类药物耐药的风险增高。

Resistance to fluoroquinolones and the influencing factors in patients with drug-resistant pulmonary tuberculosis

Objective To analyze the resistance to fluoroquinolones and the influencing factors in patients with drug-resistant pulmonary tuberculosis. Methods Retrospective analysis was conducted on 988 drug-resistant tuberculosis patients diagnosed and hospitalized in Beijing Chest Hospital, Capital Medical University from January 2015 to December 2020. All the subjects were positive in sputum mycobacterium culture and the strains were identified as Mycobacterium tuberculosis. All the patients were tested for drug sensitivity, and resistant to one or more of the following drugs: isoniazid, rifampicin, rifapentine, rifabutin, ethambutol, clofazimine, amikacin, prothiazide, clarithromycin, kanamycin, capreomycin, and streptomycin, etc. Proportional drug sensitivity test was used to detect the resistance of ofloxacin, levofloxacin, and moxifloxacin, etc. The drug resistance of subjects with different characteristics to fluoroquinolones was analyzed, and the influencing factors of fluoroquinolones resistance in patients with drug-resistant pulmonary tuberculosis were analyzed by multivariate logistic regression model. Results Among the 988 subjects, 431 were resistant to fluoroquinolones, and the resistance rate was 43.62%. Of the patients with fluoroquinolones resistant, 0.93% (4/431) were aged <18 years, 17.86% (77/431) were newly treated patients, and 14.62% (63/431) lived in Beijing, all the proportions were significantly higher than those of the patients sensitive to fluoroquinolones (3.05% (17/557), 36.98% (206/557) and 31.42% (175/557), respectively; χ ² were 6.154, 43.453 and 37.508, respectively, all P<0.05); the patients with rifampicin resistance accounted for 94.66% (408/431), significantly higher than that in the patients sensitive to fluoroquinolones (84.38%, 470/557; χ ²=25.968, P<0.01); 3.81% (15/431) had a history of fluoroquinolones, and there was no significant difference compared to those who were sensitive to fluoroquinolones (2.98%, 15/557; χ ²=0.465, P=0.495). Multivariate logistic regression analysis showed that rifampicin resistance (OR(95%CI)=2.704 (1.585-4.615)) and history of fluoroquinolones (OR(95%CI)=2.661 (1.210-5.854)) were the risk factors of fluoroquinolones resistance in patients with drug-resistant pulmonary tuberculosis; while initial treatment (OR (95%CI)=0.402 (0.283-0.571)) and living in Beijing (OR (95%CI)=0.411 (0.289-0.585)) were the protective factors. Conclusion Drug-resistant pulmonary tuberculosis patients had a higher rate of resistance to fluoroquinolone drugs. The risk of fluoroquinolone drug resistance increased in patients with retreatment, rifampicin resistance, fluoroquinolone history, and non-Beijing residents.