Global Spread of Resistance Threatens New Tuberculosis Treatments

Even the newest tuberculosis treatments are already under threat. A recent study shows that strains resistant to the latest drug combinations are not only appearing but also spreading across continents, raising fears that ‘totally drug resistant TB’ could soon become a reality.

Background

Multidrug resistant tuberculosis (MDR TB) remains a growing global threat. The World Health Organization (WHO) has endorsed new regimens using bedaquiline, pretomanid, and linezolid (BPaL/M) but resistance to these drugs is already emerging.

The Problem

While resistance often reduces bacterial “fitness,” meaning it spreads less easily, researchers found BPaL/M resistant TB strains are being transmitted between people, not just developing in individuals.

Study Overview

• Location: Georgia (high MDR TB prevalence)

• Samples: 6,926 TB samples over 13 years

• Findings: 60 highly drug resistant strains

  • Resistant to first line drugs, fluoroquinolones, and at least one BPaL/M drug

  • 28% of these were in transmission clusters → indicative of spread

Global Findings

• Data: 81,576 TB genomes from 26 countries

• Findings: 454 highly drug resistant strains in 27 countries

  • 28% linked to ongoing transmission

  • 9 strains resistant to all BPaL/M drugs → possible “totally drug resistant TB”

Why It Matters

• Resistance to new TB drugs is already global despite recent rollout

• Person to person spread is a key driver

• Without stronger diagnostics, infection control, and surveillance, treatment options will quickly erode

Key Takeaways

New drugs have bought us time against MDR-TB — but that time is running out. Global action is needed now to preserve them.

References

• Farhat M, Cox H, Ghanem M, et al. Drug-resistant tuberculosis: a persistent global health concern. Nat Rev Microbiol 2024;22:617-635.

• Gagneux S, Long CD, Small PM, Van T, Schoolnik GK, Bohannan BJM. The competitive cost of antibiotic resistance in Mycobacterium tuberculosis. Science 2006;312:1944-1946.

• Global tuberculosis report 2023. Geneva: World Health Organization, 2023 (https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2023).

• Gygli SM, Loiseau C, Jugheli L, et al. Prisons as ecological drivers of fitness-compensated multidrug-resistant Mycobacterium tuberculosis. Nat Med 2021;27:1171-1177.

• WHO consolidated guidelines on tuberculosis: Module 4: treatment — drug-resistant tuberculosis treatment, 2022 update. Geneva: World Health Organization, 2022 (https://www.who.int/publications/i/item/9789240063129).