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System for Efficacy and Cytotoxicity Screening of Inhibitors Targeting Intracellular Mycobacterium tuberculosis
Published on: April 5, 2017
Individualized Therapy Guided by Drug Susceptibility Testing for Multidrug-Resistant Tuberculosis
Thomas Theo Brehm1,2,3, Dagmar Schaub1, Viola Dreyer2,4
1Clinical Infectious Diseases, Research Center Borstel, Leibniz Lung Center, Borstel, Germany.
Drug-resistant tuberculosis treatment outcomes were comparable to drug-susceptible disease when using comprehensive drug susceptibility testing (DST). High concordance between phenotypic DST and molecular DST (mDST) supports mDST for guiding personalized tuberculosis treatment.
Area of Science:
- Infectious Diseases
- Genomics
- Public Health
Background:
- Drug-resistant tuberculosis (DR-TB) poses a significant global health threat, with lower treatment success rates compared to drug-susceptible TB.
- Accurate and timely drug susceptibility testing (DST) is critical for effective DR-TB management.
- Multidrug- or rifampicin-resistant (MDR/RR) TB requires specialized treatment strategies informed by DST.
Purpose of the Study:
- To compare treatment outcomes between drug-susceptible and MDR/RR tuberculosis in a high-resource setting.
- To evaluate the concordance between phenotypic DST (pDST) and molecular DST (mDST) using whole-genome sequencing (WGS).
- To identify predictors of cure in patients with pulmonary tuberculosis.
Main Methods:
- Retrospective cohort study of adults with pulmonary tuberculosis treated between March 2019 and November 2021.
- Inclusion of patients with culture-confirmed tuberculosis, categorized as drug-susceptible or MDR/RR.
- Performance of comprehensive pDST and WGS-based mDST, with treatment outcomes assessed using WHO 2021 and TBnet criteria.
Main Results:
- Sixty-six patients were included: 43 with drug-susceptible TB and 23 with MDR/RR TB.
- High concordance was observed between pDST and WGS-based mDST.
- WHO-defined treatment success rates were 95% for drug-susceptible TB and 87% for MDR/RR TB; no significant predictors of cure were identified.
Conclusions:
- Patients with MDR/RR TB achieved comparable outcomes to those with drug-susceptible TB in a high-resource setting with comprehensive DST.
- High concordance between pDST and mDST validates the reliability of molecular methods for guiding personalized TB treatment.
- Molecular DST offers a promising approach for optimizing treatment regimens in drug-resistant tuberculosis.
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