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Adverse Events Associated With the Treatment of Multidrug-Resistant Tuberculosis: A Systematic Review and Meta-analysis

Wu, Shanshan MM; Zhang, Yuelun; Sun, Feng MD, PhD; Chen, Mingting MD; Zhou, Lin MD; Wang, Ni MPH; Zhan, Siyan MD, PhD

doi: 10.1097/01.mjt.0000433951.09030.5a
Therapeutic Reviews

Multidrug-resistant tuberculosis (MDR-TB) is a growing public health problem. Due to long duration of therapy and concurrent use of multiple second-line drugs, adverse drug events (ADEs) are regarded as the most important clinical consideration in patients undergoing anti-MDR-TB treatment. To evaluate the frequency and type of treatment-related ADEs owing to MDR-TB therapy. The Cochrane Library, MEDLINE, and EMBASE were searched from inception through October 1, 2012, with additional manual search of International Journal of Tuberculosis and Lung Disease. Studies with available ADEs were selected if MDR-TB patients were treated with regimen including second-line drugs. Pooled estimations of incidence for each specific type of ADEs were calculated with 95% confidence intervals using random-effects model. Of the 5346 patients included, 2602 (57.3%) experienced at least 1 kind of ADE. The 3 most common side effects were gastrointestinal disorders (32.1%), ototoxicity (14.6%), and psychiatric disorders (13.2%). Subgroup analyses based on each characteristic (study population, previous tuberculosis treated, human immunodeficiency virus prevalence, and length of treatment) did not show any significant difference between groups. Additionally, among 1519 patients who developed ADEs with available data of impact on MDR-TB therapy, 70.4% required change of MDR-TB treatment. Adverse events were common among MDR-TB cases, occurring in more than half of the cases, with over two-thirds requiring change of anti-MDR-TB treatment. MDR-TB patients should be monitored closely and managed aggressively for side effects during therapy, especially for ototoxicity and psychiatric disorders.

1Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China; and

2Department of Patients Care, National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.

Address for correspondence: Professor, Department of Epidemiology and Biostatistics, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, China. E-mail: siyan-zhan@bjmu.edu.cn

Supported by China Program for the Global Fund to Fight TB (NO: TB12-001).

The authors have no conflicts of interest to declare.

S. Y. Zhan designed the study and revised the manuscript. F. Sun, M. T. Chen, L. Zhou, and N. Wang edited the manuscript. S. S. Wu and Y. L. Zhang extracted the data. S. S. Wu and F. Sun verified the data. S. S. Wu researched the data and wrote the manuscript. All authors have given final approval of the version to be published.

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