Updated 2025 ATS/CDC/ERS/IDSA Tuberculosis Treatment Recommendations

General Recommendations

• The 2025 ATS/CDC/ERS/IDSA guidelines endorse shorter, all‑oral regimens for tuberculosis, including a 4‑month regimen for children with non‑severe disease and novel 6‑month regimens that contain bedaquiline, pretomanid, and linezolid for drug‑resistant TB. Strong recommendation with moderate certainty of benefit. 1
• Directly observed therapy (DOT) is strongly recommended for adults with newly diagnosed drug‑susceptible pulmonary TB, ideally administered five of seven days per week to ensure adherence. Strong recommendation. 1

Pediatric Regimens

• For children and adolescents aged 3 months to 16 years with non‑severe TB (no cavitation, no suspicion of MDR/RR‑TB), a 4‑month regimen (2 HRZ(E) / 2 HR) is preferred over the traditional 6‑month course, markedly reducing treatment burden. Strong recommendation with moderate certainty of evidence. 1
• The same pediatric recommendation is supported by an additional 2025 ATS/CDC/ERS/IDSA citation emphasizing its evidence grade. Moderate certainty. 2

Rifampin‑Resistant, Fluoroquinolone‑Susceptible TB (Adults ≥ 14 years)

• For adolescents (≥ 14 years) and adults with rifampin‑resistant, fluoroquinolone‑susceptible pulmonary TB, the 6‑month BPaLM regimen (bedaquiline + pretomanid + linezolid + moxifloxacin) is recommended instead of prolonged 15‑month or longer regimens. Strong recommendation. 1

BPaLM Regimen Dosing Details

• All agents should be taken with food and patients should avoid milk, antacids, or other cation‑containing products that impair absorption. DOT is advised five of seven days per week. Strong recommendation. 3

Rifampin‑Resistant TB with Fluoroquinolone Resistance or Intolerance

• When fluoroquinolone resistance or intolerance is present, a 6‑month BPaL regimen (bedaquiline + pretomanid + linezolid, without moxifloxacin) is recommended for patients with ≤ 1 month prior exposure to bedaquiline or linezolid, achieving 90–100 % treatment success. Strong recommendation. 1

Standard 6‑Month Regimen for Drug‑Susceptible Pulmonary Tuberculosis in Adults

Treatment Regimen

Dosing and Adjunctive Measures

Regimens for Rifampin‑Resistant, Fluoroquinolone‑Susceptible TB

Drug‑Specific Dosing within the BPaLM Regimen

Regimen for Rifampin‑Resistant TB with Fluoroquinolone Resistance or Intolerance

BPaLM Regimen for Rifampicin‑Resistant Tuberculosis (ATS/CDC/ERS/IDSA 2025 Guidelines)

Indications

• Adults and adolescents ≥ 14 years with confirmed rifampicin‑resistant pulmonary tuberculosis that is susceptible to fluoroquinolones, and with no prior exposure to bedaquiline or linezolid (or exposure < 1 month), are recommended to receive the all‑oral 6‑month BPaLM regimen (bedaquiline + pretomanid + linezolid + moxifloxacin) 6.

Contraindications

• The BPaLM regimen should not be used when fluoroquinolone resistance is present (use BPaL instead), when resistance to bedaquiline, pretomanid, or linezolid is documented, when the patient has drug‑susceptible tuberculosis, when disease is limited to extrapulmonary sites only, or when there are known contraindications to bedaquiline or linezolid 6.

Dosing Schedule (26 weeks)

All doses are based on the 2025 ATS/CDC/ERS/IDSA guideline recommendation 6.

Administration Requirements

• All four drugs must be taken with food and administered seven days per week 6.
• Co‑administration with milk, antacids, or other cation‑containing products must be avoided because they impair absorption 6.
• Directly observed therapy (DOT) is mandatory for five of seven days per week 6.

Evidence and Efficacy

• The 2025 ATS/CDC/ERS/IDSA guidelines issue a strong recommendation for BPaLM over traditional ≥15‑month regimens, despite very low certainty of evidence 6.
• In the TB‑PRACTECAL trial (modified intention‑to‑treat analysis), unfavorable outcomes occurred in 11 % of BPaLM patients versus 48 % with standard care (risk difference − 37 percentage points) 6.
• The same trial showed a significantly better safety profile, with grade ≥ 3 adverse events in 19 % of BPaLM patients versus 59 % with standard care 6.
• Real‑world implementation studies reported a treatment success rate of 95.3 % for patients receiving BPaLM 6.
• Economic modelling indicated cost savings of US $14,868 per patient over a 20‑year horizon from the provider perspective 6.

Baseline Monitoring (Before Initiation)

• An electrocardiogram (ECG) should be performed to assess QTc interval prior to starting therapy 6.

Ongoing Monitoring During Treatment

• Monthly complete blood counts to detect linezolid‑related myelosuppression 6.
• Monthly visual acuity and color discrimination testing while on linezolid to monitor for optic neuropathy 6.
• Periodic ECG monitoring for QT prolongation (both bedaquiline and moxifloxacin can prolong QTc) 6.
• Liver function tests should be obtained if symptoms of hepatotoxicity develop (e.g., fever, malaise, vomiting, jaundice) 6.

Management of Linezolid‑Related Myelosuppression

• If significant anemia, thrombocytopenia, or neutropenia occurs, reduce the linezolid dose or interrupt therapy until hematologic parameters improve 6.