Optimal dosing and duration of linezolid for the treatment of multidrug-resistant and rifampicin-resistant tuberculosis: an individual patient data meta-analysis.

We conducted an individual patient data meta-analysisto determine the optimal linezolid dosing strategy.

我们进行了一项针对个体患者数据的荟萃分析，以确定利奈唑胺的最佳剂量策略。

Methods

We searched for randomised controlled trials and prospective cohort studies on short-course all‑oral regimens containing linezolid for treating multidrug-resistant and rifampicin-resistant tuberculosis in PubMed, Embase and Scopus up to 31 August 2023.

我们检索了截至2023年8月31日的关于短程全口服方案治疗耐多药和耐利福平结核病的随机对照试验和前瞻性队列研究，这些方案包含利奈唑胺，并在PubMed、Embase和Scopus中进行搜索。

Patients were grouped according to linezolid dosing patterns.

患者根据利奈唑胺的剂量模式进行分组。

Time to treatment success and adverse events of grade 3 and higher were analysed using the Fine-Gray sub-distribution hazard model.

使用Fine-Gray亚分布风险模型分析了治疗成功时间和3级及以上的不良事件。

Results

Of 12 eligible studies, eight (four randomised controlled trials, four prospective studies) were included.

在12项符合条件的研究中，有八项（四项随机对照试验，四项前瞻性研究）被纳入分析。

Overall, 945 patients were grouped as follows: group 1 (600 mg·day-1 linezolid for 8 weeks), group 2 (600 mg·day-1 for 16 weeks, then 300 mg·day-1 for 8 weeks), group 3 (600 mg·day-1 for 39 weeks) and group 4 (1200 mg·day-1 for 25 weeks).

总体而言，945名患者被分为以下四组：第1组（每日600 mg利奈唑胺治疗8周），第2组（前16周每日600 mg，随后8周每日300 mg），第3组（每日600 mg治疗39周）和第4组（每日1200 mg治疗25周）。

Proportions of patients achieving treatment success were 59.1%, 90.4%, 91.3% and 96.0%, respectively.

治疗成功的患者比例分别为59.1%，90.4%，91.3%和96.0%。

Compared with group 2, group 1 (adjusted sub-distribution hazard ratio(SHR) 0.24, 95% CI 0.08-0.71) and group 3 (adjusted SHR 0.36, 95% CI 0.16-0.81) had lower success rates.

与第2组相比，第1组（调整后的亚分布风险比（SHR）为0.24，95%置信区间为0.08-0.71）和第3组（调整后的SHR为0.36，95%置信区间为0.16-0.81）的成功率较低。

While group 4 showed no significant difference in treatment success versus group 2 (adjusted SHR 0.57, 95% CI 0.23-1.43), it had a higher rate of adverse events of grade 3 and higher (adjusted SHR 2.29, 95% CI 1.37-3.83).

尽管第4组与第2组在治疗成功率上没有显著差异（调整后的SHR为0.57，95%置信区间为0.23-1.43），但其3级及以上的不良事件发生率较高（调整后的SHR为2.29，95%置信区间为1.37-3.83）。

Conclusions

A dosing strategy of 600 mg·day-1 linezolid for 16 weeks then 300 mg·day-1 for 8 weeks could be optimal for treating multidrug-resistant and rifampicin-resistant tuberculosis when considering effectiveness and safety.

在考虑疗效和安全性的情况下，每日600毫克利奈唑胺治疗16周后转为每日300毫克治疗8周的剂量策略，可能是治疗耐多药和耐利福平结核病的最佳选择。