目的 探讨伏立康唑静脉滴注＋口服序贯给药治疗肺结核并发肺曲霉菌病的临床效果及安全性，并探讨疗效的影响因素。方法 根据治疗方式不同将2019年1月-2022年3月昆明市第三人民医院收治的162例肺结核并发肺曲霉菌病患者分为对照组和试验组，每组各81例。两组均对咳血、发热等临床症状进行对症药物治疗，同时采用常规抗肺结核药物治疗。对照组常规治疗基础上，采用注射用伏立康唑静脉滴注治疗，每天2次，首次剂量6 mg·kg^-1，之后每次4 mg·kg^-1，连续治疗6周；试验组前2周用药方案与对照组相同，2周后改为伏立康唑分散片口服治疗，每次0.2 g，每天2次，继续服药至6周。比较两组疗效、康复进程及安全性，并采用单因素及Logistic多因素方法分析疗效的影响因素。结果 试验组总有效率75.31%与对照组80.25%比较，差异无统计学意义（P＞0.05）；试验组咳嗽咳痰缓解时间、痰培养真菌转阴时间、肺部啰音消失时间、体温恢复时间与对照组比较，均无统计学意义（P＞0.05）；试验组不良反应总发生率为2.47%，显著低于对照组的11.11%（P＜0.05）。Logistic回归分析表明，肺部空洞、低蛋白血症、粒细胞缺乏是肺结核并发肺曲霉菌病疗效的独立危险因素（P＜0.05）。结论 伏立康唑静脉滴注+口服序贯治疗疗效与其静脉滴注治疗效果相当，且显著降低不良反应发生风险，疗效可靠，安全性高。肺部空洞、低蛋白血症、粒细胞缺乏是肺结核并发肺曲霉菌病疗效的独立危险因素。

Objective To investigate the clinical efficacy and safety of voriconazole intravenous drip plus oral sequential administration in the treatment of pulmonary tuberculosis complicated with pulmonary aspergillosis, and to explore the factors affecting the efficacy. Methods According to different treatment methods, 162 patients with pulmonary tuberculosis complicated with pulmonary aspergillosis admitted to Kunming Third People's Hospital from January 2019 to March 2022 were divided into control group and experimental group, with 81 patients in each group. Patients in both groups were treated with symptomatic drugs for clinical symptoms such as hemoptysis and fever, while conventional anti-tuberculosis drugs were used. On the basis of routine treatment, patients in the control group were treated with intravenous drip of Voriconazole for Injection twice a day, with the first dose of 6 mg·kg^-1, and then 4 mg·kg^-1 each time, for six weeks. The drug regimen of the experimental group was the same as that of the control group in the first two weeks. After two weeks, it was changed to oral Voriconazole Dispersible Tablets, 0.2 g each time, twice a day, and continued to take the drug for six weeks. The curative effect, rehabilitation process and safety of the two groups were compared, and the influencing factors of curative effect were analyzed by single factor and Logistic multifactor methods. Results The total effective rate of the experimental group was 75.31%, compared with 80.25% of the control group, with no significant difference (P> 0.05).There was no significant difference between the experimental group and the control group in the time of cough and sputum remission, the time of sputum culture fungi turning negative, the time of lung rale disappearance, and the time of temperature recovery (P> 0.05). The total incidence of adverse reactions in the experimental group was 2.47%, significantly lower than 11.11% in the control group (P< 0.05). Logistic regression analysis showed that pulmonary cavity, hypoproteinemia and agranulocytosis were independent risk factors for efficacy of pulmonary tuberculosis complicated with pulmonary aspergillosis (P< 0.05). Conclusion The efficacy of voriconazole intravenous drip plus oral sequential therapy is equivalent to that of intravenous drip therapy, and it can significantly reduce the risk of adverse reactions. The efficacy is reliable and safe. Pulmonary cavity, hypoproteinemia and agranulocytosis are independent risk factors for efficacy of pulmonary tuberculosis complicated with pulmonary aspergillosis.

R974

昆明市卫健委卫生科研课题项目（2020-13-01-112）；昆明市科技计划项目（2019-1-S-25318000001154）；云南省孔令义专家工作站项目（2019IC047）