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Drug-resistant tuberculosis: a persistent global health concern

Nature Reviews Microbiology (2024)Cite this article

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Abstract

Drug-resistant tuberculosis (TB) is estimated to cause 13% of all antimicrobial resistance-attributable deaths worldwide and is driven by both ongoing resistance acquisition and person-to-person transmission. Poor outcomes are exacerbated by late diagnosis and inadequate access to effective treatment. Advances in rapid molecular testing have recently improved the diagnosis of TB and drug resistance. Next-generation sequencing of Mycobacterium tuberculosis has increased our understanding of genetic resistance mechanisms and can now detect mutations associated with resistance phenotypes. All-oral, shorter drug regimens that can achieve high cure rates of drug-resistant TB within 6–9 months are now available and recommended but have yet to be scaled to global clinical use. Promising regimens for the prevention of drug-resistant TB among high-risk contacts are supported by early clinical trial data but final results are pending. A person-centred approach is crucial in managing drug-resistant TB to reduce the risk of poor treatment outcomes, side effects, stigma and mental health burden associated with the diagnosis. In this Review, we describe current surveillance of drug-resistant TB and the causes, risk factors and determinants of drug resistance as well as the stigma and mental health considerations associated with it. We discuss recent advances in diagnostics and drug-susceptibility testing and outline the progress in developing better treatment and preventive therapies.

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Fig. 1: Global epidemiology and cascade of care for MDR/RR-TB.
Fig. 2: Acquisition and transmission of DR-TB.
Fig. 3: Common mechanisms of drug resistance in Mycobacterium tuberculosis.
Fig. 4: Possible regimens for populations living with drug-resistant tuberculosis.

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Author notes

  1. These authors contributed equally: Helen Cox, Marwan Ghanem.

Authors and Affiliations

  1. Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA

    Maha Farhat & Marwan Ghanem

  2. Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA, USA

    Maha Farhat

  3. Institute of Infectious Disease and Molecular Medicine, Wellcome Centre for Infectious Disease Research and Division of Medical Microbiology, University of Cape Town, Cape Town, South Africa

    Helen Cox

  4. Division of Infectious Disease and Tropical Medicine, Heidelberg University Hospital, Heidelberg, Germany

    Claudia M. Denkinger & Mirna S. Abd El Aziz

  5. German Center for Infection Research (DZIF), partner site Heidelberg University Hospital, Heidelberg, Germany

    Claudia M. Denkinger

  6. P.D. Hinduja Hospital and Medical Research Centre, Mumbai, India

    Camilla Rodrigues

  7. Ulaanbaatar, Mongolia

    Handaa Enkh-Amgalan

  8. National TB Control Programme, Manzini, Eswatini

    Debrah Vambe

  9. School of Public and Population Health, University of Texas Medical Branch, Galveston, TX, USA

    Cesar Ugarte-Gil

  10. Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA

    Jennifer Furin

  11. McGill International TB Centre, McGill University, Montreal, Quebec, Canada

    Madhukar Pai

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Contributions

M.P., M.F., H.C., C.M.D., J.F. and M.G. wrote the article and, together with C.R. and M.S.A.E.A. researched data for the article. All authors contributed substantially to the discussion of the content and reviewed and/or edited the manuscript before submission.

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Correspondence to Madhukar Pai.

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Supplementary information

Glossary

Directly observed therapy

Refers to the delivery of anti-tuberculosis drug treatment under direct observation of health workers, community workers or family members with the goal of improving adherence.

Extensively drug-resistant TB

(XDR-TB). Defined as multidrug-resistant or rifampicin-resistant tuberculosis with further resistance to fluoroquinolones and to either bedaquiline or linezolid or both (key second-line drugs).

Inh-resistant and Rif-susceptible TB

(Hr-TB). Defined as resistance to isoniazid and susceptibility to rifampicin.

Multidrug-resistant TB

(MDR-TB). Defined as resistance to rifampicin and isoniazid, the two most important first-line drugs used to treat tuberculosis (TB), regardless of resistance to other TB drugs.

Pre-XDR-TB

Defined as multidrug-resistant or rifampicin-resistant tuberculosis with resistance to fluoroquinolones.

Rif mono-resistant TB

(RMR-TB). Defined as resistance to rifampicin (Rif), with susceptibility to isoniazid.

Rif-resistant TB

(RR-TB). Defined as resistance to rifampicin (Rif), regardless of resistance to other tuberculosis (TB) drugs. Individuals with RR-TB are treated with regimens similar to those for multidrug-resistant TB (MDR-TB) and are therefore grouped with MDR-TB as MDR/RR-TB.

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Farhat, M., Cox, H., Ghanem, M. et al. Drug-resistant tuberculosis: a persistent global health concern. Nat Rev Microbiol (2024). https://doi.org/10.1038/s41579-024-01025-1

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