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Efficacy and safety of cycloserine-containing regimens in the treatment of multidrug-resistant tuberculosis: a nationwide retrospective cohort study in China

Authors Wang J, Pang Y, Jing W, Chen W, Guo R, Han X, Wu L, Yang G, Yang K, Chen C, Jiang L, Cai C, Dou Z, Diao L, Pan H, Wang J, Du F, Xu T, Wang L, Li R, Chu N

Received 13 November 2018

Accepted for publication 1 February 2019

Published 3 April 2019 Volume 2019:12 Pages 763—770


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 2

Editor who approved publication: Dr Joachim Wink

Jing Wang,1* Yu Pang,2* Wei Jing,1* Wei Chen,1* Ru Guo,1* Xiqin Han,1 Limin Wu,3 Guangxu Yang,4 Kunyun Yang,5 Cong Chen,6 Lin Jiang,7 Chunkui Cai,8 Zhi Dou,9 Lijuan Diao,10 Hongqiu Pan,11 Jianyun Wang,12 Feifei Du,13 Tao Xu,14 Lixia Wang,15 Renzhong Li,16 Naihui Chu1

1Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing 101149, P.R. China; 2National Clinical Laboratory on Tuberculosis, Beijing Chest Hospital affiliated to Capital Medical University, Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing 101149, P.R. China; 3Tuberculosis Prevention Institute, Hangzhou Center for Disease Control and Prevention, Zhejiang 310021, P.R. China; 4Tuberculosis Prevention Institute, Changchun Infectious Disease Hospital, Jilin 130123, P.R. China; 5Department of Tuberculosis Resistance, Hunan Chest Hospital, Hunan 410013, P.R. China; 6Multidrug Resistant Tuberculosis Project Office, Wuhan Pulmonary Hospital, Hubei 430030, P.R. China; 7Department of Internal Medicine, The Fifth People’s Hospital of Ganzhou, Jiangxi 341000, P.R. China; 8Department of Drug-Resistant Tuberculosis, Dalian Tuberculosis Hospital, Liaoning, 116033, P.R. China; 9Department of Tuberculosis, Qiqihar Tuberculosis Prevention and Control Institute, Heilongjiang 161006, P.R. China; 10Department of Tuberculosis, Nanyang Tuberculosis Control Institute, Henan 473000, P.R. China; 11Department of Tuberculosis, The Third People’s Hospital of Zhenjiang, Jiangsu 212000, P.R. China; 12Department of Infection, Lanzhou Pulmonary Hospital, Gansu 730046, P.R. China; 13Department of Respiratory, The Fourth People’s Hospital of Ningxia Hui Autonomous Region, Ningxia 750021, P.R. China; 14Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing 100005, P.R. China; 15National Center for Tuberculosis Control and Prevention, Chinese Center For Disease Control and Prevention, Beijing 102206, P.R. China; 16Department of Tuberculosis Resistance Prevention and Control, Chinese Center for Disease Control and Prevention, Beijing 102206, P.R. China

*These authors contributed equally to this work

Background: Our aim was to assess whether the use of cycloserine (CS) would bring additional benefit for multidrug-resistant tuberculosis (MDR-TB) patients, and to estimate the incidence and associated risk factors of adverse drug reactions (ADRs) from CS.
Patients and methods: In this study, we retrospectively reviewed the clinical outcomes and ADRs of MDR-TB patients treated with CS containing regimens between January 2012 and June 2015 in China.
Results: A total of 623 MDR-TB cases enrolled in this study received regimens containing CS. Of these cases, in 411 of the patients 374 (66.0%) were “cured” and 37 (5.9%) “complete treatment” by the end of the study. The elderly, patients with prolonged previous exposure to and history of anti-TB drugs, and pre-existing co-morbidity were more likely to be associated with adverse outcomes of MDR-TB patients (P<0.05). Hyperuricemia (22.8%, 142/623) was the most frequently observed ADR among these cases, while the most noted ADRs associated with the administration of CS was psychiatric symptoms, accounting for 4.3% (27/623) of study population. Nineteen (70.4%) out of 27 cases with psychiatric symptoms occurred before the 6-month timepoint, and were notably, the highest proportion of serious adverse, 29.6% (8/27) of which were noted after discontinuation of CS.
Conclusion: Our study demonstrates that a CS-containing regimen achieved a highly successful outcome in the treatment of MDR-TB and promising tolerance in Chinese population. The potential emergence of serious psychiatric symptoms highlights that patients need to be closely monitored for these conditions during treatment that includes CS.

Keywords: multidrug-resistant tuberculosis, cycloserine, treatment, China, adverse events

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