New recommendations emphasize shorter, all-oral regimens for both drug-susceptible and drug-resistant TB.
Different TB tests
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New clinical practice guidelines for tuberculosis (TB) treatment, based on recent clinical trial data, have been issued by the American Thoracic Society (ATS), US CDC, European Respiratory Society (ERS), and the Infectious Diseases Society of America (IDSA). These updates apply to both drug-susceptible and drug-resistant TB in settings with access to diagnostic tools such as mycobacterial cultures, drug susceptibility tests, and radiographic studies. The guidelines recommend all-oral, shorter treatment regimens for eligible patients.1
“The new shorter regimens are probably acceptable to clinicians and people with TB. The all-oral, shorter-duration regimen with a reduced pill burden offered by BPaL/BPaLM is likely to confer substantial benefits, although these advantages were not directly quantified in clinical trials,” investigators said.1
A Joint Panel, using the GRADE and GRADE-ADOLOPMENT methodologies, reviewed evidence and made recommendations. Updates for drug-susceptible TB include a 4-month regimen for adults with pulmonary TB and a 4-month regimen for children with nonsevere TB. For drug-resistant TB, new regimens include bedaquiline, pretomanid, and linezolid, with or without moxifloxacin.1
“The Joint Panel judged the 6-month BPaL/BPaLM regimens to be safer and easier for patient tolerance and adherence relative to prior longer SoC regimens,” investigators said. The strong recommendation in favor of the 6-month regimens is warranted.”1
A 4-month regimen of isoniazid, rifapentine, moxifloxacin, and pyrazinamide (2 months of all four, followed by 2 months of isoniazid, rifapentine, and moxifloxacin) is conditionally recommended over the standard 6-month regimen for adults with drug-susceptible pulmonary TB, based on moderate evidence.
A 4-month regimen (2 months of isoniazid, rifampin, pyrazinamide, and ethambutol, followed by 2 months of isoniazid and rifampin) is strongly recommended for children (3 months to 16 years) with nonsevere, drug-susceptible pulmonary TB, supported by moderate evidence.
For adolescents (14+) and adults with rifampin-resistant, fluoroquinolone-resistant TB, a 6-month BPaL regimen (bedaquiline, pretomanid, and linezolid) is recommended over longer regimens (>15 months), with very low certainty of evidence.
For adolescents (14+) and adults with rifampin-resistant, fluoroquinolone-susceptible TB, a 6-month BPaLM regimen (bedaquiline, pretomanid, linezolid, and moxifloxacin) is recommended over longer regimens, with very low certainty of evidence.
4-month regimen is now recommended for both adults with drug-susceptible TB and children with nonsevere TB, replacing the standard 6-month regimen.
The 6-month BPaL/BPaLM regimens are recommended for patients with rifampin-resistant TB, offering improved safety and tolerance compared to longer, traditional treatments.
The guidelines are informed by the latest clinical trial data and focus on reducing pill burden, minimizing adverse events, and improving patient adherence.
The main limitations of this guideline update are methodological, due to the use of ADOLOPMENT, and the level of evidence certainty. Raw data from WHO were not reviewed; instead, the update focused on WHO's updated recommendations for the PICO questions, with some regimens excluded. PICO questions 3 and 4 compared 15-month or longer regimens, while WHO data included 9-month regimens. Despite low certainty for some outcomes, the shorter all-oral regimens showed positive treatment effects with fewer adverse events.1
The WHO Global Tuberculosis Report 2024 shows progress in slowing the rise of global TB cases and reducing deaths, but the disease burden remains high, particularly in South-East Asia and Africa. In 2023, 10.8 million people fell ill with TB and 1.25 million died. Treatment success rates have remained high and preventive treatment coverage has improved, but global targets for reducing TB incidence and mortality are off-track. Key challenges include funding shortfalls, drug-resistant TB, and the need for new vaccines. Accelerating progress toward TB elimination requires translating commitments from the 2023 UN high-level meeting on TB into action, while addressing social determinants and investing in TB research.2
The updated TB treatment guidelines align with these findings by recommending shorter, all-oral regimens, which can improve adherence and reduce the burden, particularly in regions still affected by disruptions. Although broader efforts addressing social factors and health system strengthening are critical to meeting global TB elimination goals.
In conclusion, the updated TB treatment guidelines emphasize shorter, all-oral regimens for both drug-susceptible and drug-resistant TB, with adjusted recommendations based on new evidence and patient characteristics. These guidelines aim to improve treatment adherence, reduce patient burden, and enhance safety, though some evidence remains of low certainty.
