The efficacy and safety of high-dose isoniazid-containing therapy for multidrug-resistant tuberculosis: a systematic review and meta-analysis

Ming Zhou; Ai-Mei Liu; Xiao-Bing Yang; Cui-Ping Guan; Yan-An Zhang; Mao-Shui Wang; Ya-Li Chen

doi:10.3389/fphar.2023.1331371

The efficacy and safety of high-dose isoniazid-containing therapy for multidrug-resistant tuberculosis: a systematic review and meta-analysis

Front Pharmacol. 2024 Jan 8:14:1331371. doi: 10.3389/fphar.2023.1331371. eCollection 2023.

Authors

Ming Zhou^#¹, Ai-Mei Liu^#², Xiao-Bing Yang¹, Cui-Ping Guan^{3

4}, Yan-An Zhang^{4

5}, Mao-Shui Wang^{3

4}, Ya-Li Chen^{3

4}

Affiliations

¹ Department of Laboratory Medicine, Chest Hospital of Guangxi Zhuang Autonomous Region, Liuzhou, Guangxi, China.
² Department of Infectious Diseases, Chest Hospital of Guangxi Zhuang Autonomous Region, Liuzhou, Guangxi, China.
³ Department of Lab Medicine, Shandong Public Health Clinical Center, Shandong University, Jinan, Shandong, China.
⁴ Shandong Key Laboratory of Infectious Respiratory Disease, Jinan, Shandong, China.
⁵ Department of Cardiovascular Surgery, Shandong Public Health Clinical Center, Shandong University, Jinan, Shandong, China.

^# Contributed equally.

Abstract

Objectives: Accumulating evidence are available on the efficacy of high-dose isoniazid (INH) for multidrug-resistant tuberculosis (MDR-TB) treatment. We aimed to perform a systematic review and meta-analysis to compare clinical efficacy and safety outcomes of high-dose INH- containing therapy against other regimes. Methods: We searched the following databases PubMed, Embase, Scopus, Web of Science, CINAHL, the Cochrane Library, and ClinicalTrials.gov. We considered and included any studies comparing treatment success, treatment unsuccess, or adverse events in patients with MDR-TB treated with high-dose INH (>300 mg/day or >5 mg/kg/day). Results: Of a total of 3,749 citations screened, 19 studies were included, accounting for 5,103 subjects, the risk of bias was low in all studies. The pooled treatment success, death, and adverse events of high-dose INH-containing therapy was 76.5% (95% CI: 70.9%-81.8%; I²: 92.03%), 7.1% (95% CI: 5.3%-9.1%; I²: 73.75%), and 61.1% (95% CI: 43.0%-77.8%; I²: 98.23%), respectively. The high-dose INH administration is associated with significantly higher treatment success (RR: 1.13, 95% CI: 1.04-1.22; p < 0.01) and a lower risk of death (RR: 0.45, 95% CI: 0.32-0.63; p < 0.01). However, in terms of other outcomes (such as adverse events, and culture conversion rate), no difference was observed between high-dose INH and other treatment options (all p > 0.05). In addition, no publication bias was observed. Conclusion: In MDR-TB patients, high-dose INH administration is associated with a favorable outcome and acceptable adverse-event profile. Systematic review registration: identifier CRD42023438080.

Keywords: MDR-TB; death; high dose; isoniazid; treatment success.

Publication types

Systematic Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The study was supported by the Science and Technology of Guangxi Zhuang Autonomous Region (No. AA22096027) and Taishan Scholar Project of Shandong Province (No. tsqn202211358). This study is marked as the third one of Shandong Tuberculosis Elimination Project (STEP-3).