Updated Recommendations for Drug-Susceptible and Drug-Resistant Tuberculosis
June 1, 2025
By Stan Deresinski, MD, FACP, FIDSA
Synopsis: The authors provide an update of recommendations for the treatment of tuberculosis, including cases with drug resistance. The recommendations include the use of newer drugs that have undergone clinical trials and shorter durations of therapy.
Source: Saukkonen JJ, Duarte R, Munsiff SS, et al; on behalf of the American Thoracic Society, U.S. Centers for Disease Control and Prevention, European Respiratory Society, and Infectious Diseases Society of America. Updates on the treatment of drug-susceptible and drug-resistant tuberculosis: An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline. Am J Respir Crit Care Med. 2025;211:15-33.
A 25-member panel representing multiple societies reviewed the 2022 World Health Organization (WHO) guideline on the treatment of tuberculosis and updated the recommendations in light of clinical trial data published since that time. The recommendations were considered for use in settings with effective relevant laboratory support. Although the update also addresses treatment of children, only treatment of adolescents and adults will be reviewed here.
The conditionally recommended regimen for patients with rifampin- and isoniazid-susceptible tuberculosis is a four-drug regimen consisting of isoniazid, rifapentine, pyrazinamide, and moxifloxacin for four months. This is recommended in place of the standard six-month regimen (2HRZE/4HR).
In patients with tuberculosis caused by rifampin- and fluoroquinolone-resistant organisms or who are intolerant to fluoroquinolones, the guideline update strongly recommends administration of bedaquiline, pretomanid, and linezolid (BPaL) for six months. This replaces regimens lasting ≥ 15 months. If the pathogen is rifampin-resistant but fluoroquinolone-susceptible, a six-month regimen of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) is strongly recommended, rather than the previous ≥ 15-month regimen.
Commentary
The recommended regimens are effective and allow significantly shorter durations of therapy. However, they do present issues with potential toxicity. Thus, these regimens require laboratory and clinical monitoring in addition to the standard element. Among these is performing an electrocardiogram (ECG) for QTcF measurement at baseline, two, 12, and 24 weeks while receiving bedaquiline, and monthly if also receiving other QTcF-prolonging drugs, such as moxifloxacin. Visual acuity and color discrimination should be performed at baseline and monthly during receipt of linezolid. Patients receiving linezolid also should be monitored for development of peripheral neuropathy. If symptoms suggestive of toxicity occur, therapeutic drug monitoring of linezolid after two weeks of therapy should be performed and should be repeated if signs of toxicity occur. A trough serum concentration < 2 mcg/mL is recommended to minimize adverse reactions.
The treatment of both drug-susceptible and drug-resistant tuberculosis has been progressively advancing. This guideline update, based on newer clinical trial data, makes rational recommendations for therapy that integrate the use of newer agents and, importantly, significantly shortens the duration of therapy. It also recommends that therapy be directly observed and be part of an integrated case management program.
Stan Deresinski, MD, FACP, FIDSA, is Clinical Professor of Medicine, Stanford University.
The authors provide an update of recommendations for the treatment of tuberculosis, including cases with drug resistance. The recommendations include the use of newer drugs that have undergone clinical trials and shorter durations of therapy.
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