Treatment of Drug-Susceptible and Drug-Resistant Tuberculosis (ATS 2025 Guidelines)
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Anum Ijaz M.B.B.S., M.D.[2]
Overview:
The updated ATS/CDC/ERS/IDSA tuberculosis treatment guidelines incorporate recent clinical trial data on drug-susceptible and drug-resistant TB in adults and children. The recommendations were developed by a joint multidisciplinary panel in collaboration with American Thoracic Society methodologists, using the GRADE methodology to ensure evidence-based and transparent decision-making.
Recommendations for Drug-Susceptible TB
1. Treatment of Isoniazid-Susceptible, Rifampin-Susceptible TB in Adults
| In people aged 12 years or older with DS pulmonary tuberculosis, we conditionally recommend the use of a 4-month regimen of isoniazid, rifapentine,moxifloxacin, and pyrazinamide. (Conditional Recommendation*; Moderate Certainty of Evidence) |
* We conditionally recommend” is analogous to the phrase “we suggest” in the 2016 and 2019 joint panel TB guidelines.[1]
| 4-Month Rifapentine–Moxifloxacin Regimen |
|---|
40–55 kg → 1000 mg 55–75 kg → 1500 mg 75 kg → 2000 mg
|
| Pyridoxine (vitamin B6), 25–50 mg/d, should be given with isoniazid to all patients. |
Monitoring & Safety:
Clinical: Monthly review for cough resolution, weight gain, and radiographic improvement.
LFTs: Baseline, repeat if hepatotoxic symptoms appear.
Cardiac: ECG only if cardiac disease, age >50, or QT-prolonging medications.
Drug Resistance: Obtain molecular/phenotypic fluoroquinolone DST before initiation.
Adverse Events: Watch for moxifloxacin-related neuropathy, tendinitis, QT prolongation, dysglycemia.
Adherence: DOT ≥5/7 days weekly preferred.
Pregnancy: Not validated; avoid unless no alternative.
2. Treatment of Nonsevere, Presumed Isoniazid-Susceptible, Rifampin-Susceptible TB in Children
| In children and adolescents between 3 months and 16 years of age with nonsevere TB (without suspicion or evidence of MDR/RR-TB), we recommend the use of a 4-month treatment regimen of 2HRZ(E)/2HR rather than the 6-month DS-TB regimen of 2HRZ(E)/4HR ( Strong Recommendation*; Moderate Certainty of Evidence) |
*Strong recommendations will apply to most patients for whom these recommendations are made, but they may not apply to all patients in all conditions; no recommendation can take into account all of the unique features of individual patients and clinical circumstances.[1]
| 4-month standard regimen (2HRZE/2HR) |
|---|
|
| §Pyridoxine (vitamin B6), 25–50 mg/d, should be given with isoniazid to all patients.
*To avoid potential ocular toxicity, some clinicians exclude ethambutol for children who are HIV-uninfected, have no prior TB treatment history, live in an area of low prevalence of DR-TB, and have no exposure to an individual from an area of high prevalence of DR-TB. Prevalence and risk factors can be difficult to ascertain; therefore, the American Academy of Pediatrics and most experts include ethambutol as part of the intensive phase regimen for children with TB. |
Identifying children eligible for 4-month regimens:
Figure developed by the Joint Panel on the basis of data in the SHINE trial and Study 31/A5349 to address eligibility of some children for either the RPT/MOX regimen or the 4-month standard drug regimen.[1]
Monitoring & Special Considerations:
Clinical: Monthly assessment of weight and clinical symptoms.
LFTs: As indicated for HIV, malnutrition, or hepatotoxic symptoms.
Recurrence Surveillance: 3, 6, and 12 months post-treatment.
HIV Co-infection: Acceptable with close follow-up; extend to 6 months if slow response.
Severe Malnutrition or Age <3 months: Use 6-month regimen.
Peripheral Lymph Node TB: Eligible for 4-month regimen; expect slow regression.
Recommendations for Drug-Resistant TB
1. Rifampin-Resistant, Fluoroquinolone-Resistant TB
| In adolescents aged 14 years and older and adults with rifampin-resistant pulmonary TB who have resistance or patient intolerance to fluoroquinolones and either have had no previous exposure to bedaquiline and linezolid or have been exposed for less than 1 month, we recommend the use of the 6-month treatment regimen, composed of bedaquiline, pretomanid, and linezolid (BPaL), rather than more than 15-month regimens. (Strong Recommendation*; Very Low Certainty of Evidence). |
* Strong recommendations will apply to most patients for whom these recommendations are made, but they may not apply to all patients in all conditions; no recommendation can take into account all of the unique features of individual patients and clinical circumstances. [1]
| BPaL Regimen |
|---|
|
| Medications should be administered 7 d/wk with food, with DOT 5 of 7 days per week. |
Monitoring & Evaluation:
Baseline: ECG, CBC, LFTs, renal profile, and vision check.
Follow-up: Clinical, radiologic, and laboratory review monthly or as needed.
Hematologic: CBC weekly ×1 month, then monthly (linezolid myelosuppression).
ECG: At baseline, 2, 12, and 24 weeks (QTc from bedaquiline).
Neuropathy: Screen for paresthesias and visual disturbances (linezolid toxicity).
Post-treatment: Monitor relapse for 12–24 months.
Contraindications: >1 month prior exposure to bedaquiline/linezolid, pregnancy, hepatic failure.
Special Populations:
HIV: Use safely regardless of CD4; avoid efavirenz (lowers bedaquiline).
Children <14 / Pregnant: Use longer regimens until data available.
Extrapulmonary TB: Only nonsevere EPTB eligible
2. Rifampin-Resistant, Fluoroquinolone-Susceptible TB
| In adolescents aged 14 years and older and adults with rifampin-resistant, fluoroquinolone-susceptible pulmonary TB, we recommend the use of a 6-month treatment regimen, composed of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM), rather than the 15-month or longer regimens in patients with MDR/RR-TB. (Strong Recommendation; Very Low Certainty of Evidence) |
*Strong recommendations will apply to most patients for whom these recommendations are made, but they may not apply to all patients in all conditions; no recommendation can take into account all of the unique features of individual patients and clinical circumstances.[1]
| BPaLM Regimen |
|---|
|
| Medications should be administered 7 d/wk with food, avoiding milk, antacids, or other cationic items with DOT 5 of 7 days per week |
Monitoring & Evaluation:
Baseline: CBC, LFTs, ECG, vision check.
ECG: Baseline and monthly due to QT risk (bedaquiline + moxifloxacin).
Hematologic: CBC monthly; check for linezolid-induced anemia and thrombocytopenia.
Hepatic: ALT/AST and bilirubin monthly.
Bacteriologic: Sputum weekly → every 2 weeks → monthly until conversion.
DST: Repeat if delayed conversion; use sequencing for resistance mutation detection.
Post-treatment: Relapse surveillance 12–24 months.
Monitoring for Patients on BPaL and BPaLM Regimen:[1]
