Characteristics, Treatment Strategies, and Long-term Health Outcomes of People With Bedaquiline-resistant Tuberculosis in Karakalpakstan, Uzbekistan—A Retrospective Cohort Study

Abstract

Abstract Background Bedaquiline resistance is increasing globally, threatening effectiveness of short regimens for rifampicin/multidrug-resistant (RR/MDR)-tuberculosis. Limited data exist describing the treatment and long-term outcomes of people with bedaquiline-resistant tuberculosis. s1 Methods We did a retrospective cohort study of patients with bedaquiline-resistant tuberculosis in Karakalpakstan, Uzbekistan, from January 2017 until June 2025. Clinical and laboratory records were reviewed to describe treatment regimens, drug sensitivity profiles, and sputum results. We measured time to sustained sputum culture conversion (SCC), mortality, and the proportion of patients who had tuberculosis-free survival (alive, and had completed treatment or were in care, and had SCC) 18 months after bedaquiline resistance was detected. s2 Results Among 50 patients with bedaquiline-resistant tuberculosis who received treatment, the median age was 41 years (IQR: 27–52), 64% (32/50) were male, 69% (34/49) had fluoroquinolone resistance, and 32% (16/50) had not previously received bedaquiline. The median treatment duration was 18.8 months (IQR: 9.0–22.4), with bedaquiline prescribed for 84% for a median 5.6 months (IQR: 2.2–12.9), imipenem for 66% for a median 8.1 months (IQR: 4.5–11.3), and amikacin for 50% for a median 7.9 months (IQR: 4.4–11.1). The median time to SCC was 5.9 months (IQR: 2.1–15.9) and the probabilities of survival to 18 months and 5 years were 79.7% (95% CI: 69.2–91.8) and 63.4% (95% CI: 48.8–82.4). Of 48 patients who had an assessable 18-month outcome, 60.4% (29/48) had tuberculosis-free survival. s3 Conclusions Management of bedaquiline-resistant tuberculosis in Uzbekistan required prolonged antituberculosis therapy, often with injectables, resulting in delayed culture conversion and poor long-term health outcomes. s4 In this retrospective cohort study in Uzbekistan, people with bedaquiline-resistant tuberculosis needed a median of five drugs for over 18 months, often including the toxic injectables of the pre-bedaquiline era - yet only 60% were alive and free of tuberculosis at 18 months, and less than two-thirds were alive after five years. These findings add to the growing body of evidence that bedaquiline resistance threatens to undermine efforts to end the global tuberculosis epidemic; highlight the importance of rapid, sensitive drug-susceptibility testing for bedaquiline; and demonstrate the urgent need for new treatments for people with bedaquiline-resistant tuberculosis. teaser