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.