What are the 2024 WHO pulmonary tuberculosis guidelines for treating drug‑susceptible adults, non‑severe disease in children, preventive therapy for contacts of rifampicin‑resistant or multidrug‑resistant TB, and for confirmed MDR/pre‑XDR/XDR TB?

Current Pulmonary Tuberculosis Treatment Guidelines

Drug-Susceptible Pulmonary TB in Adults

For adults with drug-susceptible pulmonary TB, use a 4-month regimen consisting of rifapentine, isoniazid, pyrazinamide, and moxifloxacin given daily, which has now replaced the traditional 6-month regimen as the preferred first-line treatment. 1

Standard 6-Month Regimen (Alternative)

• Intensive phase (2 months): Isoniazid, rifampin, pyrazinamide, and ethambutol given daily for 56 doses 2
• Continuation phase (4 months): Isoniazid and rifampin given daily for 126 doses 2
• Ethambutol can be discontinued once susceptibility to isoniazid and rifampin is confirmed 2

Treatment Duration Extensions

• Extend to 9 months total (7-month continuation phase) if cavitary disease is present on initial chest radiograph OR if sputum cultures remain positive after 2 months of treatment 2

Critical Monitoring Requirements

• Obtain sputum cultures monthly until two consecutive negative results are documented 2
• Sputum conversion must occur within 3 months of treatment initiation 2
• If sputum remains smear-positive at 3 months, immediately evaluate for non-adherence, treatment failure, or drug resistance 2
• Perform drug susceptibility testing on all initial isolates before starting therapy 2

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Non-Severe Drug-Susceptible TB in Children

Children with non-severe drug-susceptible TB should receive a shortened 4-month regimen rather than the traditional 6-month course. 1

Important Caveats

• This recommendation is based on a single trial with methodological limitations that affect its generalizability 3
• The definition of "non-severe" TB in the trial was based on smear negativity, but current WHO recommendations omit smear microscopy altogether, creating practical implementation challenges 3
• For children with extensive disease (miliary TB, bone/joint TB, or tuberculous meningitis), a minimum of 12 months of therapy is required 4

Adjunctive Therapy for Children

• Pyridoxine should be given if children are HIV-infected, malnourished, breastfed, or receiving terizidone, cycloserine, or high-dose isoniazid 5
• Steroids improve outcomes in tuberculous meningitis and are also indicated for airway obstruction and pericardial TB 5
• Multivitamin supplements are recommended for all children being treated for drug-resistant TB 5

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

For adults with MDR/RR-TB who are fluoroquinolone-susceptible, the BPaLM regimen (bedaquiline, pretomanid, linezolid 600 mg daily, and moxifloxacin) for 6 months is the preferred first-line treatment. 6

BPaLM Eligibility Criteria

• Adults with MDR/RR-TB who are fluoroquinolone-susceptible 6
• No prior exposure exceeding 30 days to bedaquiline, pretomanid, or linezolid 6
• Not pregnant, breastfeeding, or under 14 years of age 6
• HIV-positive patients are eligible; HIV status does not preclude BPaLM use 6

BPaLM Treatment Duration and Adjustments

• Total duration: 26 weeks (6 months), to be completed within 7 months to account for missed doses 6
• If fluoroquinolone resistance is detected after starting BPaLM: Switch immediately to BPaL (without moxifloxacin) and extend total treatment to 9 months 6
• If linezolid toxicity develops: Dose reduction to 300 mg daily is acceptable to mitigate toxicity while maintaining efficacy 6

Pre-XDR and XDR TB

• Pre-XDR TB (fluoroquinolone-resistant but not XDR) should receive BPaL without moxifloxacin from the start, not BPaLM 6
• XDR-TB (defined as MDR-TB with additional resistance to fluoroquinolones plus bedaquiline and/or linezolid) requires individualized treatment for a minimum of 24 months in children 5
• The 2021 definition of XDR-TB has been updated from the previous definition that included second-line injectable drugs 7

Alternative Longer MDR-TB Regimen (18-20 months)

When BPaLM is not suitable, use:

• Backbone drugs: Levofloxacin (750-1000 mg daily) or moxifloxacin (400 mg daily), bedaquiline, and linezolid 8
• Group B drugs: Add at least one from clofazimine (100 mg daily) or cycloserine/terizidone (10-15 mg/kg daily, maximum 1000 mg) 8
• Total duration: 18-20 months from start, or 15-17 months after culture conversion, whichever is longer 8
• Bedaquiline is typically given for 24 weeks but may be extended with careful monitoring 8

Critical Monitoring for MDR-TB Treatment

• Cardiac: Baseline and repeat ECG at 2,12, and 24 weeks minimum; discontinue bedaquiline if QTcF >500 ms 6, 8
• Hematologic: Monthly complete blood counts to detect linezolid-induced myelosuppression 8
• Hepatic: Monthly AST, ALT, bilirubin, and alkaline phosphatase 6
• Neurologic: Regular assessment for peripheral neuropathy and optic neuropathy 8
• Therapeutic drug monitoring for linezolid, when available, significantly improves safety outcomes 6

Conditional Eligibility Requiring Caution

• Patients with hemoglobin <7 g/dL or platelets <75,000/mm³ can receive BPaLM, but other regimens are preferred due to linezolid's myelosuppressive effects 6
• Patients with pre-existing Grade III-IV peripheral neuropathy can receive BPaLM, but other regimens are preferred due to linezolid's neurotoxicity 6
• Patients with low BMI (<17) are eligible but require close monitoring 6

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Preventive Therapy for Contacts of Rifampicin-Resistant or MDR-TB

The provided evidence does not contain specific 2024 WHO guidelines for preventive therapy in contacts of rifampicin-resistant or MDR-TB cases. The available guidelines focus primarily on treatment of active disease rather than preventive therapy for exposed contacts.

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Mono-Resistant TB

Isoniazid Mono-Resistant TB

• Treat for 6-12 months with rifampin, pyrazinamide, and ethambutol 5
• For extensive disease or tuberculous meningitis, add a fluoroquinolone and one other drug 5

Rifampin Mono-Resistant TB

• Treat with isoniazid, pyrazinamide, ethambutol, and a fluoroquinolone for 12-15 months 5
• For extensive disease, add an injectable agent for the first few months and extend treatment to 18 months 5
• Important caveat: If genotypic tests are used for drug susceptibility testing, most programs treat rifampin mono-resistant TB with an MDR-TB regimen because these tests do not identify all mutations conferring isoniazid resistance 5

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Common Pitfalls to Avoid

• Do not delay BPaLM waiting for fluoroquinolone susceptibility results; start empirically and switch to BPaL if resistance is documented 6
• Do not use BPaLM for patients with CNS TB, osteoarticular TB, or disseminated (miliary) TB; switch to an 18-20 month individualized regimen 6
• Do not treat recurrent TB with the same regimen that failed previously—this guarantees further resistance 2
• Do not rely on clinical improvement alone—bacteriologic confirmation of cure is essential 2
• Prior brief exposure (<30 days) to component drugs is not a contraindication to BPaLM; only exposure >30 days requires ruling out resistance 6
• Avoid kanamycin and capreomycin in MDR/RR-TB regimens; injectable agents should only be used when the isolate is documented susceptible and five effective oral drugs cannot be assembled 8

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Recent Advances and Context

The tuberculosis treatment landscape has undergone dramatic changes in recent years, with multiple international guidelines updated to reflect new clinical trial data 5. The introduction of all-oral, shorter treatment regimens represents a major advance in improving treatment completion rates and reducing morbidity 5, 1. However, some recommendations—particularly the 4-month regimen for children with non-severe TB—are based on limited evidence and require cautious implementation with attention to resource implications 3.