Tuberculosis
Sonya Collins
A joint panel, including representatives from the American Thoracic Society, CDC, the European Respiratory Society, and the Infectious Diseases Society of America, released updated clinical practice guidelines for treatment-susceptible and -resistant TB in children and adults. The new recommendations were published in the American Journal of Respiratory and Critical Care Medicine in January 2025.
“The guidelines tackle four new regimens for treating tuberculosis in different populations,” said Sonal Munsiff, MD, an infectious disease specialist at the University of Rochester Medical Center and a coauthor of the new guidelines. “We have shorter regimens for adults with drug-susceptible TB, shorter regimens for children with nonsevere TB, and two regimens for drug-resistant TB that are all oral.”
Drug-resistant TB
For the treatment of rifampin- and fluoroquinolone-resistant TB in adults and adolescents over 14 years old, or rifampin-resistant TB in patients who cannot tolerate fluoroquinolone, the new guidelines call for a 6-month regimen of bedaquiline, pretomanid, and linezolid in lieu of the previously used regimens of 15 to 24 months.
In adults and adolescents over 14 years old with rifampin-resistant/fluoroquinolone-susceptible TB, the recommendation is for a 6-month regimen of bedaquiline, pretomanid, linezolid, and moxifloxacin rather than the previously used regimens of 15 months or more.
The previously used 15- to 24-month regimens, besides being up to 4 times longer than the newly recommended protocol, included injectable medications that added to both the treatment burden and adverse effects for patients.
“This is revolutionary,” Munsiff said. “This now gives official sanction to these regimens and hopefully will make it easier for people to get access to the drugs.”
The guideline includes a recommended schedule for monitoring patients on these drugs. “The drugs are new, and the side effects vary for each one.”
Nonsevere TB in children
Based on recent clinical trial data, the guideline reduces treatment time for children and adolescents with non-
severe TB by 2 months, from 6 months to 4 months.
The guideline defines nonsevere as peripheral lymph node TB; intrathoracic lymph node TB without airway obstruction; uncomplicated TB pleural effusion; or paucibacillary and noncavitary disease confined to one lobe of the lungs or without a miliary pattern. Patients with severe TB should receive the standard 6-month regimen.
The change, which was based on robust clinical trial results, will have benefits both for patients and their parents or caregivers as well as public health officials, Munsiff said.
“That’s 2 less months you have to push meds down children’s throats and two less months that programs will need to follow the children,” said Munsiff.
Drug-susceptible TB
Treatment of drug-susceptible TB in adults and adolescents over 14 years old will also be shortened by 2 months, according to the new guidelines. This population will receive a 4-month rifapentine-moxifloxacin regimen versus a 6-month regimen.
“This was based on a large clinical trial, a noninferiority study, which found that the new regimen, 4 months of rifapentine and moxifloxacin with isoniazid pyrazinamide, was as effective as our standard 6-month isoniazid, rifampin, pyrazinamide, and ethambutol-based regimen,” said Munsiff.
Potential challenges ahead
While the new regimens will reduce treatment burden and improve adverse effect profiles, they may come with challenges as well. Rifapentine is often in short supply; the new regimens have a higher pill burden than before; and the clinical trial data are based on younger and healthier than average patients with TB, which likely attenuated adverse effects.
“Physicians will rely on pharmacists to help keep track of side effects and drug–drug interactions,” Munsiff said. Pharmacists will also play a key role in helping patients and prescribers access these drugs.
Nevertheless, the new regimens address a significant need in TB treatment. “We’ve been needing shorter and better-tolerated regimens for a long time,” Munsiff said. ■