Individualized Therapy Guided by Drug Susceptibility Testing for Multidrug-Resistant Tuberculosis.

Background: Drug-resistant tuberculosis remains a major health challenge, with treatment success for multidrug- or rifampicin-resistant (MDR/RR) disease substantially lower than for drug-susceptible tuberculosis. Access to accurate and timely drug susceptibility testing (DST) is essential for designing effective treatment regimens. Methods: We conducted a retrospective cohort study of adults with pulmonary tuberculosis treated at the Research Center Borstel in Germany between March 2019 and November 2021. Patients with culture-confirmed tuberculosis and either fully drug-susceptible disease or phenotypically confirmed MDR/RR tuberculosis were included. Comprehensive phenotypic DST (pDST) and molecular DST (mDST) by whole-genome sequencing (WGS) were performed. Treatment outcomes were assessed using the WHO 2021 definitions as the primary endpoint, with TBnet outcome definitions evaluated secondarily. Firth's penalized logistic regression identified predictors of cure. Results: Sixty-six patients were included: 43 with drug-susceptible tuberculosis and 23 with MDR/RR tuberculosis. Concordance between pDST and WGS-based mDST was high. In drug-susceptible disease, 13 (30%) were cured and 28 (65%) completed treatment, resulting in a WHO-defined success rate of 95%; 33 (77%) met TBnet cure criteria. Among MDR/RR patients, four (17%) were cured and 16 (70%) completed treatment, yielding a WHO-defined success rate of 87%; 19 (83%) were cured per TBnet criteria. No significant predictors of cure were identified. Conclusions: In this high-resource setting with access to comprehensive pDST and mDST, patients with MDR/RR tuberculosis achieved outcomes comparable to those with drug-susceptible disease. High concordance between phenotypic and molecular DST supports the reliability of mDST for guiding individualized treatment.