Treating tuberculosis in adults and children: Updated guideline Q&A
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A major challenge in tuberculosis treatment has been the long duration of therapy needed to effectively treat the disease. A new clinical practice guideline from the American Thoracic Society, the Centers for Disease Control and Prevention, the European Respiratory Society and IDSA includes recommendations for all-oral, shorter treatment regimens in eligible children and adults. Sonal S. Munsiff, MD, FIDSA — IDSA co-chair for the guideline panel — answered questions from Science Speaks about the guideline.
Who is this new guideline primarily intended for? Who will find it most useful?
These guidelines are designed for clinicians managing people with TB, including pulmonologists and infectious diseases physicians, as well as clinicians in TB control programs, migrant health clinics, pediatricians and anyone else who helps manage persons with TB.
What are the most notable updates or changes compared to previous guidelines on TB treatment?
People with both drug-susceptible and drug-resistant TB and their clinicians would prefer shorter treatment duration, oral regimens and less adverse drug effects from TB treatment. There has been a quest and concerted effort to develop shorter treatments for TB after decades of little drug development. With recent studies, we can now achieve many of these goals.
These regimens have been studied in recent clinical trials and, since then, have been endorsed by the World Health Organization for use in appropriate persons with TB and also have been recommended by the Centers for Disease Control and Prevention.
Now, this multi-society guideline targeting clinicians in North America and Europe brings all these different regimens together into one document and offers guidance on use of shorter regimens for children, adolescents and adults for drug-susceptible and drug-resistant TB.
This guidelines update tells us that for many forms of pulmonary TB in children and adults, we now have shorter treatment regimens of 4-6 months. For drug susceptible TB, we now have effective regimens that reduce treatment duration by one-third. For dug-resistant TB, we now have 6-month, all-oral regimens that reduce treatment duration by about two-thirds compared to the old standard-of-care regimen. These new regimens appear more effective and safer than prior standard-of-care regimens for drug-resistant TB, and these regimens can also be used for people with intolerance to rifampin, which is a key drug for short-course TB chemotherapy.
The shorter duration of equally or, in some cases, more effective treatment may improve completion of treatment; reduce the period of illness, reduce adverse events; and possibly hasten other aspects of recovery. Oral regimens, particularly if there is a reduction in the number of pills, are easier to administer and to take. These regimens are still intended to be administered with directly observed therapy, and a shorter treatment duration reduces the duration of directly observed therapy, which is personnel-intensive.
How does this update address considerations for different subgroups of patients, such as people with HIV?
All these regimens are recommended for people with and without HIV infection. Some dug-drug interactions may need to be addressed for those on antiretroviral therapy, and these interactions may preclude use of some regimens or warrant adjustment of the drugs.
What else should clinicians know about the new guideline?
Directly observed treatment and the use of drug-susceptibility testing for TB isolates remain standard of care. Most individuals with drug-susceptible TB are eligible for 4-month regimens, but exceptions remain. Similarly, most individuals with drug-resistant TB or those with rifampin intolerance are eligible for 6-month regimens, but similar exceptions remain. Those who are not eligible for these shorter regimens should be treated according to the 2016 and 2019 recommendations, and clinicians should reference those recommendations as needed for treatment decisions.
While these new regimens have allowed for significantly shorter treatment, it is important to recognize that drug resistance in TB isolates could emerge with incomplete adherence to these regimens. Directly observed treatment, close monitoring for safety and effectiveness of regimens, and drug-susceptibility testing are essential to the effective treatment of TB and for the overall success of TB programs.
What are some of the key research areas that would help inform future guidelines on this topic?
There are many research needs for the new regimens, and so we created a table (Table 9) about future research needs in the updated guidelines. These regimens are based on single or small studies, which may not reflect TB populations in the United States and Europe. TB clinical trial participants were younger than TB patients in the United States and Europe. Adverse events may be more common in older individuals and may differ between trial and TB programmatic settings. These studies also excluded children with severe TB or drug-resistant TB, pregnant individuals and patients with severe forms of extra-pulmonary TB. We urgently need studies of treatment with these regimens involving individuals excluded from previous trials so that these vulnerable populations can benefit from these regimens.
Implementation of these regimens will involve collaboration with national TB programs, health care institutions and other stakeholders to integrate these new protocols into existing TB care frameworks. We need to understand if programs have access to rapid diagnostic tests for rifampin and fluoroquinolones. Monitoring and evaluation are also crucial to ensure that the guidelines are being followed correctly and to assess their impact on TB control. This will help identify any challenges or barriers to implementation and allow for adjustments to improve the effectiveness of TB care.
We also need studies on implementation challenges, access to rapid diagnostics for susceptibility to the new drugs, emergence of resistance to the new drugs and other issues which will inform future guidelines.
To learn more, see the full guideline, “Updates on the Treatment of Drug-Susceptible and Drug-Resistant Tuberculosis: An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline.”
