Cycloserine for treatment of multidrug-resistant tuberculosis: a retrospective cohort study in China

Yang Li,1,* Fei Wang,2,* Limin Wu,3 Min Zhu,4 Guiqing He,5 Xinchang Chen,1 Feng Sun,1 Qihui Liu,1 Xiaomeng Wang,2 Wenhong Zhang1 1Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200032, China; 2Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang 310051, China; 3Hangzhou Center for Disease Control and Prevention, Hangzhou, Zhejiang 310021, China; 4Tuberculosis Treatment Center, Hangzhou Red Cross Hospital, Hangzhou 310003, China; 5Department of Infectious Diseases, Wenzhou Center Hospital, Wenzhou 325000, China *These authors contributed equally to this work Purpose: Cycloserine has been used in multidrug-resistant tuberculosis (MDR-TB) treatment since the 1950s. We evaluated the efficacy and safety of cycloserine and sought to clarify the role of cycloserine for treatment of simple MDR-TB, pre-extensively drug-resistant tuberculosis (pre-XDR-TB), and extensively drug-resistant tuberculosis (XDR-TB).Materials and methods: A retrospective observational study was performed in Zhejiang Province, China. We enrolled 144 cycloserine-treated and 181 cycloserine-nontreated patients consecutively and determined the treatment outcome as the primary outcome. The proportion of patients with sputum culture conversion and the frequency of adverse drug reactions were also assessed.Results: One-hundred (69.4%) out of 144 patients in the cycloserine group successfully completed treatment. The HR of any unfavorable treatment outcome after the introduction of cycloserine was 0.58 (95% CI: 0.38–0.86, P=0.008). Subgroup analysis showed that cycloserine could benefit simple MDR-TB cases reducing the risk of unfavorable treatment outcomes (HR: 0.43, 95% CI: 0.24–0.76, P=0.004), but not pre-XDR-TB (HR: 0.65, 95% CI: 0.30–1.38, P=0.263) or XDR-TB (HR: 0.73, 95% CI: 0.22–2.37, P=0.589). The culture conversion rate at the intensive phase was similar whether cycloserine was administered or not (P=0.703). Of the 144 patients treated with cycloserine, a total of 16 (11.1%) patients experienced side effects attributed to cycloserine.Conclusion: Cycloserine is an attractive agent for the treatment of MDR-TB, and its safety profile warrants its use in most MDR-TB cases. Cycloserine significantly improved the chance of a favorable outcome for patients with simple MDR-TB but not pre-XDR-TB and XDR-TB. Thus, more aggressive regimens might be required for pre-XDR-TB or XDR-TB patients. Keywords: cycloserine, multidrug-resistant tuberculosis, efficacy, safety, extensively drug-resistant tuberculosis, treatment outcome