World Tuberculosis Day 2025, observed on March 24, underscores the urgent need to end tuberculosis — the world’s deadliest infectious disease. In 2023, tuberculosis (TB) affected 10.8 million people, resulting in 1.25 million deaths. The disease continues to have severe health, social, and economic impacts worldwide. In recognition of World TB Day and its call to action, this article outlines key guideline changes on the treatment of drug-susceptible and drug-resistant TB from 2016 to 2024.

TB is caused by the bacterium Mycobacterium tuberculosis, primarily affecting the lungs but is capable of spreading to other organs. TB treatment aims to: (1) reduce bacterial load to lessen severity, prevent death, and stop transmission, (2) eliminate persistent bacteria to prevent relapse, and (3) avoid drug resistance.

Traditional TB treatment consists of two phases: 

  • intensive phase (first 2 months) using four first-line antibiotics (isoniazid, rifampin, pyrazinamide, and ethambutol), and 
  • continuation phase (next 4 months) using isoniazid and rifampin.

Multidrug-Resistant Tuberculosis (MDR-TB), which is resistant to at least isoniazid and rifampin, was traditionally treated with prolonged regimens that included injectable medications.

This article compares the 2024, 2019, and 2016 tuberculosis treatment guidelines from the American Thoracic Society (ATS), Centers for Disease Control and Prevention (CDC), European Respiratory Society (ERS), and Infectious Diseases Society of America (IDSA), highlighting changes in treatment duration, drug selection, and delivery methods.

Guidelines Referenced:

  • Treatment of Drug-Resistant Tuberculosis 
    • American Thoracic Society (ATS), Centers for Disease Control and Prevention (CDC), European Respiratory Society (ERS), and Infectious Diseases Society of America (IDSA)
    • Published: November 15, 2019

Key Shifts From 2016 to 2024

Delivery Method

  • The 2016 guidelines included both oral and injectable antibiotics as first-line treatments for drug-susceptible TB.
  • The 2019 guidelines placed emphasis on oral regimens for MDR-TB, while reducing the reliance on injectable drugs.
  • The 2024 guidelines recommended all oral delivery for both drug-susceptible and drug-resistant cases of TB.

Treatment Duration

  • Drug-Susceptible TB (2016): 6 month treatment (2 month intensive phase, 4 month continuation phase)
  • Drug Susceptible TB (2024): 4 month treatment (2 month intensive phase, 2 month continuation phase)
  • Drug Resistant TB (2019): 15-21 month treatment for MDR-TB
  • Drug Resistant TB (2024): 6 month treatment for MDR-TB

Choice of Antibiotics

  • Drug-Susceptible TB:
    • 2024 guidelines substitute moxifloxacin for ethambutol in adults/adolescents.
  • MDR-TB:
    • 2024 recommendations focus on rifampin and fluoroquinolone resistance, simplifying regimens compared to 2019.
      • For MDR-TB, the 2019 guideline suggested at least 5 preferred drugs (a later generation fluoroquinolone like moxifloxacin or levofloxacin, bedaquiline, linezolid, clofazimine and cycloserine) for the intensive phase of treatment, and 4 of these preferred drugs during the continuation phase.
      • The 2024 guideline focused on rifampin and fluoroquinolone resistance, recommending 3 of the same drugs recommended in 2019 for MDR-TB: bedaquiline, pretomanid and linezolid (BPaL). 
    • For those rifampin-resistant but fluoroquinolone-susceptible, the 2024 guideline recommended the addition of the later-generation fluoroquinolone moxifloxacin (BPaLM).
Guideline TitleRoute of AdministrationTreatment DurationKey Drug Changes
Treatment of Drug-Susceptible TB (2016)Oral and injectable options6 monthsStandard regimen (isoniazid, rifampin, pyrazinamide, ethambutol)
Treatment of Drug-Resistant TB (2019)Emphasis on oral regimens for MDR-TB15–21 months (MDR-TB)Addition of bedaquiline, linezolid, clofazimine, and cycloserine; fluoroquinolone substitution for isoniazid-resistant TB
Updates on Drug-Susceptible & Drug-Resistant TB (2024)All-oral regimens4 months (drug-susceptible TB), 6 months (drug-resistant TB)Moxifloxacin replaces ethambutol in some cases; new BPaL and BPaLM regimens for MDR-TB

Summary

  • The approaches to treating drug-susceptible and drug-resistant TB have evolved over time. The most salient change from 2016 to 2024 is the updated recommendation to move toward shorter treatment regimens for both drug-susceptible and drug-resistant TB. 
  • There has been a more gradual shift over time favoring the use of oral delivery of antibiotics over IV or IM delivery for both drug-susceptible and drug-resistant TB. 
  • The choice of first-line antibiotics for empiric treatment of drug-susceptible TB is fairly consistent between the 2016 and 2024 guidelines for adults and children, but differs for drug-susceptible adults and adolescents by replacing ethambutol with the later-generation fluoroquinolone moxifloxacin. 
  • While the antibiotic choices for drug-resistant tuberculosis between 2019 and 2024 guidelines are not completely aligned, they overlap. In addition, both include recommendations for using later-generation fluoroquinolones.

As TB treatment guidelines have evolved toward shorter, all-oral regimens, we’ve seen a reduction in treatment burden while maintaining efficacy. The transition from injectable to oral therapies reflects advances in clinical research and patient-centered care. Future updates will likely continue this trend, focusing on further optimizing treatment duration and efficacy.

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