目的 探討伏立康唑靜脈滴注＋口服序貫給藥治療肺結(jié)核并發(fā)肺曲霉菌病的臨床效果及安全性，并探討療效的影響因素。方法 根據(jù)治療方式不同將2019年1月-2022年3月昆明市第三人民醫(yī)院收治的162例肺結(jié)核并發(fā)肺曲霉菌病患者分為對照組和試驗組，每組各81例。兩組均對咳血、發(fā)熱等臨床癥狀進行對癥藥物治療，同時采用常規(guī)抗肺結(jié)核藥物治療。對照組常規(guī)治療基礎(chǔ)上，采用注射用伏立康唑靜脈滴注治療，每天2次，首次劑量6 mg·kg^-1，之后每次4 mg·kg^-1，連續(xù)治療6周；試驗組前2周用藥方案與對照組相同，2周后改為伏立康唑分散片口服治療，每次0.2 g，每天2次，繼續(xù)服藥至6周。比較兩組療效、康復(fù)進程及安全性，并采用單因素及Logistic多因素方法分析療效的影響因素。結(jié)果 試驗組總有效率75.31%與對照組80.25%比較，差異無統(tǒng)計學(xué)意義（P＞0.05）；試驗組咳嗽咳痰緩解時間、痰培養(yǎng)真菌轉(zhuǎn)陰時間、肺部啰音消失時間、體溫恢復(fù)時間與對照組比較，均無統(tǒng)計學(xué)意義（P＞0.05）；試驗組不良反應(yīng)總發(fā)生率為2.47%，顯著低于對照組的11.11%（P＜0.05）。Logistic回歸分析表明，肺部空洞、低蛋白血癥、粒細胞缺乏是肺結(jié)核并發(fā)肺曲霉菌病療效的獨立危險因素（P＜0.05）。結(jié)論 伏立康唑靜脈滴注+口服序貫治療療效與其靜脈滴注治療效果相當，且顯著降低不良反應(yīng)發(fā)生風(fēng)險，療效可靠，安全性高。肺部空洞、低蛋白血癥、粒細胞缺乏是肺結(jié)核并發(fā)肺曲霉菌病療效的獨立危險因素。

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

昆明市衛(wèi)健委衛(wèi)生科研課題項目（2020-13-01-112）；昆明市科技計劃項目（2019-1-S-25318000001154）；云南省孔令義專家工作站項目（2019IC047）