Caitlyn Stulpin , 2025-04-16 18:43:00
April 16, 2025
3 min read
Key takeaways:
- The CDC, IDSA and other agencies created updated guidance for treating drug-susceptible and drug-resistant TB.
- The guidance is for both adolescents and adults.
Following the success of recent clinical trials, several major infectious disease agencies updated treatment guidance for drug-susceptible and drug-resistant tuberculosis for adolescents and adults.
The guidance, which was created by the American Thoracic Society, CDC, European Respiratory Society and Infectious Diseases Society of America, include updated recommendations for the use of a novel 4-month regimen for people with pulmonary TB and a shortened 4-month regimen for children with nonsevere TB, among other things.
We spoke with Pennan M. Barry, MD, MPH, chief of surveillance and epidemiology in the California Department of Public Health’s Tuberculosis Control Branch, about what prompted this new guidance and what clinicians should know.
Healio: What prompted the guideline update?
Barry: The guideline update was prompted by successful international clinical treatment trials for both drug-susceptible and drug-resistant TB. These trials were the product of global collaborations on drug development and clinical research. Their results represent a significant leap forward for patients because regimens with shorter durations were shown to have equivalent efficacy to longer regimens that were recommended in previous versions of the guidelines. The guideline panel felt that access to these regimens in the United States and other low TB burden settings was important.
Healio: What are the new recommendations?
Barry: The guideline recommendations cover three main areas:
- Isoniazid- and rifampin-susceptible pulmonary TB in people aged 12 years and older: A 4-month regimen composed of 2 months of isoniazid, rifapentine, pyrazinamide and moxifloxacin followed by 2 months of isoniazid, rifapentine and moxifloxacin is as efficacious and safe as the previously recommended standard 6-month regimen of 2 months of isoniazid, rifampin, pyrazinamide and ethambutol followed by 4 months of isoniazid and rifampin.
Both regimens are recommended and either can be used. - Nonsevere TB known or presumed to be susceptible to isoniazid and rifampin in children aged 3 months to 16 years: A 4-month regimen composed of 2 months of isoniazid, rifampin, pyrazinamide and ethambutol followed by 2 months of isoniazid and rifampin rather than the standard 6-month drug-susceptible TB regimen.
- Rifampin-resistant TB in people aged 14 years and older: A 6-month regimen of bedaquiline, pretomanid and linezolid (BPaL) with addition of moxifloxacin (BPaLM) for patients with fluoroquinolone-susceptible TB rather than the previously recommended regimens lasting more than 15 months. This recommendation also applies to people with intolerance to rifampin. Exclusions to this recommendation include prior exposure to drugs in the regimen as well as patient populations and forms of TB that were not studied in the clinical trials including patients that are pregnant and severe forms of extrapulmonary TB such as TB meningitis.
Healio: What data led to these changes?
Barry: The guideline recommendations were based on a structured review of clinical trial data compiled and reanalyzed by WHO for its 2022 TB treatment guideline. The panel critically appraised and evaluated the WHO analyses and guidelines and focused on adapting the evidence and recommendations to low TB burden, high-resource settings such as the United States.
The underlying data used by WHO came primarily from four clinical trials. These were:
- study 31/A5349 trial investigating a 4-month regimen for pulmonary TB;
- the SHINE trial that studied a 4-month regimen for treatment of nonsevere TB in children; and
- two trials of 6-month bedaquiline-based regimens for rifampin-resistant TB: ZeNIX and TB-PRACTECAL.
Details of these trials and their findings are included in the guideline and supplemental materials.
Healio: What is the clinical takeaway of the new guidance?
Barry: In select patients and populations, the newly recommended treatment regimens can substantially shorten duration of treatment and the accompanying disruption to patient lives. It is important for clinicians to be familiar with the criteria for eligibility and subgroup considerations for these shorter regimens. For example, TB in children will need to be determined to be nonsevere according to criteria in the guideline which assesses clinical, microbiologic and imaging characteristics.
Clinicians may need to change other aspects of management when implementing these regimens. Clinicians aiming to use the 4-month treatment for drug-susceptible pulmonary disease in adolescents or adults will need to ensure a supply of rifapentine throughout treatment and pursue drug susceptibility testing for fluoroquinolones.
Patients with drug-resistant TB treated with the shorter BPaLM or BPaL regimens will need to undergo routine QT interval monitoring with ECGs, and drug susceptibility testing for the drugs in the regimen should be pursued.
Reference:
For more information:
Pennan M. Barry, MD, MPH, can be reached at media@cdph.ca.gov.
Sources/Disclosures
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Healio Interviews
Disclosures:
Barry reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.