Anaemia, hypoalbuminemia, and risk of cycloserine-associated neuropsychiatric toxicity in a shortened oral regimen for multidrug/rifampicin-resistant TB.

BACKGROUND: All-oral shortened regimens for multidrug/rifampicin-resistant TB (MDR/RR-TB) commonly include cycloserine, which is associated with neuropsychiatric toxicity. Predictors of cycloserine-related adverse events remain poorly defined. We assessed whether baseline anaemia or hypoalbuminemia predict neuropsychiatric toxicity. METHODS: We conducted a prospective cohort study of three 9-month standardised MDR/RR-TB regimens in Kazakhstan. Regimens shared a core of a fluoroquinolone, bedaquiline, and linezolid; one regimen included cycloserine. Neuropsychiatric adverse events of special interest (AESIs) included peripheral neuropathy, seizures, and psychosis. We conducted logistic regression to calculate associations between baseline anaemia and hypoalbuminemia and neuropsychiatric or central nervous system (CNS)-specific AESIs. RESULTS: In 556 cycloserine-treated individuals, 29 (5.2%) developed neuropsychiatric AESIs. Adjusted odds ratios comparing anaemia vs. no anaemia were 2.40 (95% confidence interval [CI]: 1.01-5.72) for neuropsychiatric AESIs and 2.71 (95% CI: 0.74-9.91) for CNS-specific AESIs. Adjusted odds ratios for grade ≥2 hypoalbuminemia were 3.59 (95% CI: 0.88-14.60) and 7.40 (95% CI: 1.58-34.66), respectively. In 146 individuals without cycloserine, neuropsychiatric AESI occurred in 0/49 with anaemia versus 5/97 without anaemia (0% vs 5.2%; P = 0.168), and in 1/3 with grade ≥2 hypoalbuminemia versus 3/90 without (33.3% vs 3.3%; Fisher's exact P = 0.125). CONCLUSIONS: Baseline anaemia and hypoalbuminemia were associated with increased neuropsychiatric toxicity risk during treatment with a cycloserine-containing regimen. Whether these associations are specific to cycloserine merits further study.