An Overview of Disease and Health Research Vol. 12

Drug-resistant tuberculosis remains a major global public health challenge. Multidrug-resistant TB (MDR-TB), caused by Mycobacterium tuberculosis resistant to rifampicin and isoniazid, poses a significant threat to Tuberculosis (TB) control. Improving treatment outcomes for drug-resistant tuberculosis remains a critical global priority for tuberculosis control programs. India reports the highest number of MDR-TB cases worldwide; however, no longitudinal studies have evaluated factors influencing treatment outcomes in public sector settings. This study evaluated factors associated with unsuccessful treatment outcomes among patients with MDR-TB receiving outpatient care under the National Tuberculosis Elimination Programme in Puducherry, India, from January 2020 to December 2023. Suspected TB patients were initially screened at NAAT sites using Xpert MTB/RIF or TrueNat assays, and confirmed rifampicin-resistant cases were referred to PMDT centres. Samples were further analysed for drug susceptibility testing. Genetic mutations associated with rifampicin resistance (RR) were identified using the GenoType MTBDRplus version 2 assay. Patients received standardised MDR-TB treatment regimens as per national guidelines, and treatment outcomes were classified into favourable (cure, completion) and unfavourable (death, failure, loss to follow-up). Multivariate regression methods were used to estimate odds ratios with 95% confidence intervals to identify determinants of unsuccessful treatment outcomes. From 2020 to 2023, 192 MDR/RR-TB patients were enrolled, including 61 (31.8%) RR-TB and 131 (68.2%) MDR-TB cases; most were new cases (150), and 148 (77.1%) received shorter regimens with a higher treatment success rate (63.2%) compared to longer regimens (56.8%). Clinical data indicated an overall treatment success rate of 60.42%. Patients undergoing retreatment were more likely to experience unsuccessful outcomes. Co-infection with HIV and the use of alcohol or tobacco further increased the odds of treatment failure. Patients exhibiting heteroresistant patterns had 2.72 times the odds of an unsuccessful outcome compared with those with inferred or true-resistant patterns. Additionally, patients residing in rural areas experienced poorer treatment outcomes and higher rates of loss to follow-up than those in urban areas. Longer treatment regimens were associated with greater loss to follow-up than shorter regimens. True resistance due to rpoB gene mutations accounted for 65.9% (29 out of 44) of total deaths, with mutations at codon S450L contributing to 47.7% of these fatalities, a novel finding. The study demonstrated a strong association between heteroresistance in the rpoB gene and poor treatment outcomes. These results underscore the need for detailed molecular-level investigations to optimise drug selection for MDR/RR tuberculosis. Further research is warranted to clarify the impact of heteroresistance on individual patient outcomes.