What are the new WHO guidelines for treating drug‑susceptible tuberculosis in adults and children, multidrug‑resistant/rifampicin‑resistant TB, and rifampicin‑susceptible isoniazid‑resistant TB?

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Last updated: February 27, 2026 • View editorial policy

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New WHO Guidelines for Tuberculosis Treatment

Drug-Susceptible Tuberculosis

Adults with Pulmonary TB

A 4-month regimen of rifapentine, isoniazid, pyrazinamide, and moxifloxacin is now conditionally recommended by WHO for eligible persons aged ≥12 years with pulmonary drug-susceptible TB, shortening treatment from the traditional 6 months. 1

  • The standard 6-month regimen (2 months of isoniazid, rifampin, pyrazinamide, and ethambutol followed by 4 months of isoniazid and rifampin) remains the alternative option when the 4-month regimen cannot be used. 1

Children with Non-Severe TB

  • Children with drug-susceptible, non-severe TB may be treated with a 4-month regimen instead of 6 months, based on SHINE trial data showing non-inferiority. 1, 2
  • The 4-month pediatric regimen uses standard first-line drugs at weight-adjusted doses. 1

Rifampicin-Susceptible, Isoniazid-Resistant TB

For confirmed isoniazid-resistant, rifampicin-susceptible TB, WHO recommends 6 months of rifampin, ethambutol, pyrazinamide, and levofloxacin (or moxifloxacin). 1

  • Injectable agents (streptomycin, amikacin) must NOT be added to this regimen—this is a conditional WHO recommendation based on lack of benefit and added toxicity. 1
  • High-dose isoniazid may be included if the resistance mutation is in inhA (lower-level resistance) rather than katG, though evidence remains limited. 1
  • In cases of fluoroquinolone resistance or contraindication, use rifampin, ethambutol, and pyrazinamide for 6 months (expert opinion, no trial data). 1

Multidrug-Resistant/Rifampicin-Resistant TB (MDR/RR-TB)

Regimen Hierarchy (Most to Least Preferred)

WHO now prioritizes short, all-oral regimens over traditional 18–20-month therapy; the hierarchy is:

  1. BPaLM (6 months): bedaquiline + pretomanid + linezolid + moxifloxacin – first-line choice for eligible MDR/RR-TB. 3, 4, 2
  2. BPaL (6–9 months): bedaquiline + pretomanid + linezolid (without moxifloxacin) – for pre-XDR TB (fluoroquinolone-resistant). 3, 4, 2
  3. 9-month all-oral regimen – when BPaLM/BPaL are unsuitable. 1, 3
  4. Individualized 18–20-month regimen – reserved for extensive resistance, intolerance, or contraindications to shorter regimens. 3

BPaLM Regimen (Preferred for Eligible MDR/RR-TB)

BPaLM is the WHO-recommended first-line treatment for adults ≥14 years with fluoroquinolone-susceptible MDR/RR-TB who have not received >30 days of bedaquiline, pretomanid, or linezolid. 3, 4, 2

Eligibility Criteria

  • Age ≥14 years (pretomanid not studied in younger children). 3, 4
  • Fluoroquinolone-susceptible disease (molecular or phenotypic DST). 3, 4
  • No prior exposure >30 days to bedaquiline, pretomanid, or linezolid. 3, 4
  • Extensive pulmonary disease and cavitation are NO LONGER contraindications—this is a major 2023 WHO update. 3
  • HIV co-infection is eligible; HIV status does not preclude BPaLM. 4

Absolute Contraindications

  • Pregnancy or breastfeeding (pretomanid reproductive toxicity unknown). 1, 3, 4
  • Central nervous system TB, osteoarticular TB, or miliary (disseminated) TB—these sites require longer therapy. 3, 4, 5
  • Confirmed resistance to bedaquiline, pretomanid, or linezolid. 3, 4

Dosing

  • Bedaquiline: 400 mg daily × 2 weeks, then 200 mg three times weekly × 22 weeks. 4
  • Pretomanid: 200 mg daily × 26 weeks. 4
  • Linezolid: 600 mg daily × 26 weeks (may reduce to 300 mg daily if toxicity develops). 3, 4
  • Moxifloxacin: 400 mg daily × 26 weeks. 4

Management of Fluoroquinolone Resistance Detected After Starting BPaLM

  • If fluoroquinolone resistance is discovered after BPaLM initiation, immediately stop moxifloxacin and continue as BPaL (bedaquiline + pretomanid + linezolid) for a total of 9 months. 3, 4

Monitoring Requirements

  • Baseline: ECG, CBC, liver function tests, electrolytes (K⁺, Mg²⁺, Ca²⁺), visual acuity, peripheral neuropathy assessment, HIV status, pregnancy test. 3, 4
  • ECG: Repeat at weeks 2,12, and 24 minimum; discontinue bedaquiline if QTcF >500 ms. 4
  • CBC: Monthly to detect linezolid-induced myelosuppression (anemia, thrombocytopenia). 3, 4
  • Liver function tests: Monthly; stop bedaquiline if ALT/AST >8× ULN or if ALT/AST >3× ULN + bilirubin >2× ULN (Hy's Law). 4
  • Sputum cultures: Monthly throughout the 26-week regimen, even after culture conversion. 4

Common Pitfalls

  • Do NOT extend BPaLM beyond 6 months; if response is inadequate, switch to an 18–20-month individualized regimen rather than prolonging BPaLM. 3
  • Do NOT delay BPaLM waiting for fluoroquinolone DST results; start empirically and adjust to BPaL if resistance is documented. 4
  • Do NOT use BPaLM in children <14 years; use the 9-month all-oral regimen instead. 3

BPaL Regimen (For Pre-XDR TB)

BPaL (bedaquiline + pretomanid + linezolid, without moxifloxacin) is recommended for MDR-TB with fluoroquinolone resistance (pre-XDR). 3, 4, 2

  • Duration: 6 months, extendable to 9 months if sputum cultures remain positive between months 4–6. 3
  • Eligibility and monitoring are identical to BPaLM except fluoroquinolone resistance is expected. 3, 4

9-Month All-Oral Regimen (When BPaLM/BPaL Not Feasible)

The 9-month regimen is indicated when BPaLM/BPaL cannot be used due to contraindications, drug intolerance, or unavailability, provided the patient is fluoroquinolone-susceptible and has no prior >1 month exposure to second-line drugs. 1, 3

Typical Composition

  • Intensive phase (4–6 months): bedaquiline + linezolid (or ethionamide) + fluoroquinolone (levofloxacin or moxifloxacin) + clofazimine + pyrazinamide + ethambutol + high-dose isoniazid (if applicable). 3
  • Continuation phase (≈5 months): fluoroquinolone + clofazimine + pyrazinamide + ethambutol. 3

Exclusions

  • Severe extrapulmonary TB (CNS, miliary, osteoarticular disease) is ineligible; these patients require 18–20-month therapy. 3, 5
  • Pregnancy (ethionamide is teratogenic); substitute with linezolid-based variation. 3

Key Requirements

  • Mandatory fluoroquinolone DST; susceptibility to all regimen drugs should be confirmed. 3
  • Do NOT modify the standardized 9-month regimen; adding or removing drugs increases failure and resistance amplification risk. 3

Individualized 18–20-Month Regimen (Last Resort)

An individualized longer regimen is used when BPaLM, BPaL, and the 9-month regimen are all unsuitable due to extensive resistance, intolerance, drug-drug interactions, or contraindicated disease sites. 3

Drug Selection (WHO Grouping)

  • Group A (core backbone—use all three if possible):

    • Levofloxacin or moxifloxacin (strong recommendation). 1, 3
    • Bedaquiline (strong recommendation for adults ≥18 years; conditional for ages 6–17). 1, 3
    • Linezolid (strong recommendation). 1, 3

  • Group B (add at least one):

    • Clofazimine (conditional recommendation). 1, 3
    • Cycloserine or terizidone (conditional recommendation). 1, 3

  • Group C (add as needed to reach ≥4 effective drugs):

    • Ethambutol (conditional recommendation). 1, 3
    • Delamanid (conditional recommendation for ages ≥3 years). 1, 3
    • Pyrazinamide (conditional recommendation; MDR-TB is defined as resistance to isoniazid + rifampin only, so pyrazinamide often remains active). 1, 3
    • Carbapenems (imipenem-cilastatin or meropenem) + amoxicillin-clavulanate (conditional recommendation). 1, 3
    • Amikacin (only if no oral alternatives; requires monthly audiometry). 1, 3
    • Kanamycin and capreomycin are strongly discouraged due to poor outcomes and high toxicity. 1, 3

Core Requirements

  • ≥4 effective drugs in the intensive phase (5–7 months after culture conversion) and ≥3 in the continuation phase. 3
  • Total duration: 18–20 months (15–21 months after culture conversion). 3
  • Do NOT add a single drug to a failing regimen; this creates functional monotherapy and amplifies resistance—add at least two susceptible drugs. 3

Injectable Agents

  • Amikacin or streptomycin may be included only when an adequate number of effective oral drugs cannot be assembled and susceptibility is confirmed. 3
  • WHO no longer recommends routine use of injectable agents; they are reserved as last-resort options. 1, 3

Key Diagnostic and Monitoring Principles

Drug Susceptibility Testing

  • CBNAAT (GeneXpert) is the WHO-recommended first-line test for all suspected TB; it simultaneously detects M. tuberculosis and rifampicin resistance. 3
  • Comprehensive DST for fluoroquinolones and all second-line drugs is required to inform MDR/RR-TB regimen selection. 3
  • Fluoroquinolone DST is pivotal for deciding between BPaLM, BPaL, the 9-month regimen, or longer individualized therapy. 3
  • Standard CBNAAT does not detect isoniazid resistance; line-probe assay or culture-based DST is needed. 3

Baseline Evaluation Before MDR/RR-TB Therapy

  • Obtain CBC, liver function tests, renal function tests, ECG, weight, HIV status, pregnancy status, and detailed prior TB drug exposure history. 3
  • Additional assessments: electrolytes (K⁺, Mg²⁺, Ca²⁺) for QTc-prolongation risk, visual acuity, and audiometry if injectable agents might be used. 3

Active Drug-Safety Monitoring

  • Active drug-safety monitoring (aDSM) is mandatory for all DR-TB patients to detect and manage toxicity early. 3

Common Pitfalls Across All Regimens

  • Do NOT use fewer than four effective drugs in the intensive phase of long regimens; this predisposes to treatment failure. 3
  • Do NOT discontinue therapy early even after culture conversion; complete the full prescribed duration (6,9, or 18–20 months). 3
  • Do NOT give BPaLM to children <14 years (pretomanid not studied); opt for the 9-month regimen instead. 3
  • Do NOT use ethionamide in pregnancy; substitute with a linezolid-based variation of the 9-month regimen. 3
  • Do NOT modify standardized regimens (BPaLM, BPaL, 9-month); adding or removing drugs increases failure and resistance amplification risk. 3

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

3
Guideline

WHO Guidelines for Diagnosis and Treatment of Drug‑Resistant Tuberculosis (2021‑2023)

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

4
Guideline

BPaLM Eligibility and Usage Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

5
Guideline

Treatment for Intestinal Tuberculosis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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