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Shorter duration, fully oral treatment regimens for tuberculosis (TB) are now recommended for most adults and children.

Updated joint guidelines from the American Thoracic Society, the CDC, European Respiratory Society, and Infectious Diseases Society of America called for a novel 4-month regimen for drug-susceptible cases of pulmonary TB and a shortened 4-month regimen for children with nonsevere TB.

For drug-resistant TB, the document released online in the now recommends regimens containing bedaquiline (Sirturo), pretomanid, and linezolid (Zyvox) with or without moxifloxacin.

"There has been a quest and concerted effort to develop shorter treatments for TB, after decades of little drug development," Jussi Saukkonen, MD, of the Boston Veterans' Administration Health Care System and a lead author of the guidelines, said in a statement. "With recent studies we have been able to shorten the regimen durations for both drug-susceptible and drug-resistant TB for most patients, down to 4 and 6 months, respectively."

However, not all patients are eligible for these shorter regimens; for ineligible patients, recommendations in the 2016 and still stand.

"While these new regimens have allowed significant treatment shortening, it is important to recognize that drug-resistance in TB isolates could emerge with incomplete adherence to these regimens," cautioned Saukkonen in the statement. "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."

The targeted update to the guidelines suggested that people aged 12 years or older with drug-susceptible pulmonary TB should consider a 4-month regimen of isoniazid, rifapentine, moxifloxacin, and pyrazinamide. This was a conditional recommendation with moderate certainty of evidence, calling for shared decision making in line with patients' values and preferences.

Nonsevere TB in children age 3 months to 16 years were strongly recommended to be treated with a 4-month regimen comprised of 2 months of isoniazid, rifampin, pyrazinamide, and ethambutol (2HRZE) followed by 2 months of isoniazid and rifampin (2HR) rather than the 6-month, drug-susceptible TB regimen of 2HRZ(E) followed by 4 months of isoniazid and rifampin (4HR). Eligible cases are those without suspicion or evidence of multidrug-resistant (MDR) or rifampin-resistant TB that affect the peripheral lymph nodes or intrathoracic lymph nodes without airway obstruction, are uncomplicated TB pleural effusion, or paucibacillary and noncavitary disease confined to one lobe of the lungs or without a miliary pattern. Other pediatric cases that don't meet those criteria should receive the standard 6-month 2HRZE/4HR regimen or recommended treatment regimens for severe forms of extrapulmonary TB. Some children may be eligible for the 4-month rifapentine-moxifloxacin regimen, the guideline writers noted.

For patients 14 years and older who have rifampin-resistant pulmonary TB with resistance or patient intolerance to fluoroquinolones and little to no prior exposure to bedaquiline and linezolid, the guideline strongly recommended 6 months of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM), rather than regimens that last over 15 months. In such patients with MDR but fluoroquinolone-susceptible disease, the recommendation was still strongly in favor of a 6-month BPaLM regimen, rather than the longer regimens. Both recommendations, though, were based on "very low certainty of evidence."

The panel of 25 international specialists in pulmonary medicine, infectious diseases, pediatrics, epidemiology, and public health who reached a consensus for the document found no additional clinical trial evidence published since the on pertinent questions for TB treatment and thus was largely an adaptation of those recommendations to the U.S. guidelines.

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