Abstract:

Objective To analyze the adverse events in multidrug-resistant pulmonary tuberculosis patients treated with cycloserine-containing chemotherapy regimen.Methods A total of 623 multidrug-resistant pulmonary tuberculosis patients who were eligible for inclusion in the Global Fund’s fifth round of multidrug-resistance control program during January 2013 to June 2016 from 11 hospitals in China were selected. All patients used a standardized treatment regimen: 6PZA-Am(Cm)-Lfx(Mfx)-Pto-Cs/18PZA-Lfx(Mfx)-Pto-Cs; alternatives: PAS instead of Pto, Cm instead of Am, Mfx replacement Lfx (PZA: pyrazinamide, Am: amikacin, Cm: capreomycin, Lfx: levofloxacin, Mfx: moxifloxacin, Pto: prothionamide, Cs: cycloserine, PAS: p-aminosalicylide sodium). The adverse events during treatment were collected, their clinical characteristics, severity, occurring time, duration, treatment method and prognosis were analyzed, and the correlation between the drugs and adverse events were determined.Results Of the 623 multidrug-resistant pulmonary tuberculosis patients treated with cycloserine-containing regimen, 316 (50.7%) patients had at least one adverse event, and 36 (5.8%) patients discontinued the treatment or changed the treatment regimen due to adverse reactions. The most common adverse reactions were hyperuricemia (22.8%, 142/623) and abnormal liver function (18.8%, 117/623). Twenty-seven (4.3%, 27/623) patients developed central nervous system or psychiatric symptoms that were likely to be associated with cycloserine, and the median (interquartile range) time of occurrence was 3 (2, 6) months. After drug discontinuance or psychological counseling, the symptoms disappeared.Conclusion In multidrug-resistant pulmonary tuberculosis patients who received cycloserine-containing regimen, the occurrence of nervous system or psychiatric symptoms was mainly related to cycloserine. Patients need to be closely monitored for these symptoms during treatment that includes cycloserine.

Key words: Cycloserine, Tuberculosis, multidrug-resistant, Drug toxicity, Drug evaluation