Cycloserine For Treatment Of Multidrug-Resistant Tuberculosis: A Retrospective Cohort Study In China

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.