Radiographic and Microbiologic Predictors of Treatment Outcomes in Patients Treated with a Shortened All-Oral Regimen for Multidrug- or Rifampicin-Resistant Tuberculosis (MDR/RR-TB) in Lesotho

Background Shortened, all-oral regimens endorsed by the WHO have improved tolerability and outcomes for MDR/RR-TB, treatment but predictors of poor outcomes under these regimens remain incompletely characterized. We evaluated baseline microbiologic and radiographic predictors of unfavorable outcomes among patients receiving a 9-month all-oral regimen in Lesotho. Methods We conducted a prospective study of adults with bacteriologically-confirmed, fluoroquinolone-susceptible pulmonary MDR/RR-TB treated with a 9-month regimen of levofloxacin, bedaquiline, delamanid, linezolid, and clofazimine. Baseline radiographic features (cavitation, fibrosis, bilateral involvement) and sputum smear grade were assessed. Associations with time to culture conversion, end-of-treatment outcomes, and final post-treatment outcomes were evaluated using Cox and logistic regression. Results Among 238 participants (median age 41 [IQR 31–56], 29% female, 62% living with HIV), 90.8% and 88.7% achieved favorable end-of-treatment and final post-treatment outcomes, respectively. Fibrosis, cavitation, bilateral disease, and high smear grade were associated with delayed culture conversion and lower odds of treatment success. Bilateral disease was more strongly associated with unfavorable outcomes in those without HIV, whereas fibrosis and high smear grade showed stronger associations among those with HIV. Phenotypes of cavitation plus high smear grade (OR 0.36, 95% CI 0.13–0.99), and severe fibrocavitary disease (multi-lobar fibrosis and any cavities, or cavities ≥5 cm and any fibrosis) (OR 0.20, 95% CI 0.06–0.65) were associated with reduced odds of favorable final outcomes. Conclusion Baseline radiographic and microbiologic features, particularly in combination, identify patients at higher risk of unfavorable outcomes with shortened all-oral MDR/RR-TB regimens and may inform risk-adapted strategies in high-burden settings.