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目的:前瞻性观察含贝达喹啉方案治疗耐多药和利福平耐药肺结核（MDR/RR-PTB）患者体内贝达喹啉血药浓度情况，并探索疗效和不良反应与血药浓度的相关性。方法:选择2019年9月至2021年8月在重庆市公共卫生医疗救治中心住院，并使用含贝达喹啉方案治疗的37例MDR/RR-PTB患者，其中男23例，女14例，年龄15~60岁。采用超高效液相色谱质谱联用技术测定贝达喹啉血药浓度。观察患者体内贝达喹啉血药浓度情况，并对患者近期疗效、不良反应的发生情况与血药浓度的相关性进行分析。贝达喹啉血药浓度最佳截断值采用受试者工作特征曲线进行分析，并应用SPSS 26.0软件对数据进行统计分析， P<0.05为差异有统计学意义。 结果:37例患者服药后2 h（C 2 h）、6 h（C 6 h）、下次服药前（C 24 h）的贝达喹啉血药浓度分别为0.01~6.52、0.88~7.60、0.11~4.14 mg/L。C 6 h显著高于C 2 h和C 24 h，差异均有统计学意义（ P<0.05）。37例患者中，30例痰结核菌培养转阴成功、1例转阴失败，3例因QTcF≥500 ms停药、3例失访，痰结核菌培养首次转阴时间2~12（6.00±2.79）周，12周痰结核菌培养转阴率为94.60%。C 24 h与痰结核菌培养首次转阴时间、C 6 h与病灶改善和其他不良反应（除QT间期）情况呈正相关（ P<0.05）。C 24 h与影像学改善和不良反应、C 6 h与QT间期情况不相关（ P>0.05），但高C 24 h组病灶改善（显著吸收+吸收）和空洞改善（闭合+缩小）、不良反应的比例均多于低C 24 h组；高C 6 h组整体QTcF值高于低C 6 h组、发生QT间期延长的患者亦多于低C 6 h组。 结论:应用贝达喹啉治疗西南地区MDR/RR-PTB患者的总体治疗效果和安全性较好，当贝达喹啉C 24 h>0.78 mg/L时，患者首次转阴时间可能更短；贝达喹啉C 6 h>2.85 mg/L时，可能更有利于病灶吸收、但同时不良反应发生率可能更高。并且随着血药浓度增加，患者可能存在治疗效果更好、不良反应更多的趋势。

Objective:To observe the serum concentration of bedaquiline in multidrug-resistant and rifampicin-resistant pulmonary tuberculosis(PTB) patients, and to explore the correlation between efficacy, safety and serum concentration.Methods:A total of 37 MDR/RR-PTB patients hospitalized in Chongqing Public Health Medical Center from September 2019 to August 2021 were selected and treated with bedaquiline, including 23 males and 14 females, aged 15-60 years. The serum concentration of bedaquiline was determined by ultra performance liquid chromatography-mass spectrometry. The serum concentration and the correlation between efficacy, safety and serum concentration of bedaquiline were evaluated. The optimal cut-off value of bedaquiline concentration was analyzed by receiver operating characteristic curve. SPSS 26.0 statistical software was used for data analysis, and P<0.05 was considered statistically significant. Results:The serum concentration of bedaquiline in 2 hours (C 2 h), 6 hours (C 6 h) and next time of taking medicine (C 24 h) were 0.01-6.52,0.88-7.60,0.11-4.14 mg/L, respectively. Among the 37 patients, sputum culture turned negative in 30, but one case was still tested positive for Mycobacterium tuberculosis, while the drug was stopped in 3 cases due to QTcF≥500 ms, and another 3 cases were lost to follow-up. The sputum culture negative conversion time was 2-12 (6.00±2.79) weeks, and the sputum culture negative conversion rate in 12 weeks was 94.60%. Correlation analysis showed that C 24 h of bedaquiline was positively correlated with the sputum culture negative conversion time, and C 6 h of bedaquiline was positively correlated with improvement of lesions and adverse reactions (all P<0.05). Although there was no statistically significant difference, the constituent ratio of lesions and cavities in lung and adverse reaction in high C 24 h group were more than that those in low C 24 h group, and the QTcF and the constituent ratio of QT interval prolonged were higher in the high C 6 h group. Conclusions:The overall efficacy and safety of bedaquiline in the treatment of MDR/RR-PTB were satisfactory. The sputum culture negative conversion time might be shorter when C 24 h was more than 0.78 mg/L. Meanwhile, C 6 h above 2.85 mg/L was beneficial to improvement of lesions, but the rate of adverse reactions might be higher. There was a trend of correlation between serum concentration and short-term efficacy and safety.