WHO Guidelines for Antitubercular Therapy
The World Health Organization recommends a standard 6-month regimen consisting of 2 months of isoniazid, rifampicin, pyrazinamide, and ethambutol (2HRZE) followed by 4 months of isoniazid and rifampicin (4HR) for drug-susceptible tuberculosis, with daily dosing strongly preferred. 1
Drug-Susceptible TB Treatment
First-Line Regimen
- Initial intensive phase (2 months): Isoniazid (H) + Rifampicin (R) + Pyrazinamide (Z) + Ethambutol (E)
- Continuation phase (4 months): Isoniazid (H) + Rifampicin (R)
- Fixed-dose combinations (FDCs) may provide more convenient administration 1
Dosing
- Isoniazid: 5 mg/kg (up to 300 mg) daily 2
- Rifampicin: 10 mg/kg (up to 600 mg) daily 3
- Pyrazinamide: 15-30 mg/kg daily
- Ethambutol: 15 mg/kg daily
Special Situations
- TB Meningitis: Adjuvant corticosteroid therapy (dexamethasone or prednisone) during first 6-8 weeks 1
- TB Pericarditis: Corticosteroids to prevent constrictive pericarditis
- Renal TB: Corticosteroids to prevent ureteric stenosis
- Spinal TB with cord compression: Corticosteroids recommended
Drug-Resistant TB Treatment
Isoniazid-Resistant TB
- Rifampicin, ethambutol, pyrazinamide, and a later-generation fluoroquinolone for 6 months 1
- Pyrazinamide may be shortened to 2 months in non-cavitary disease or if toxicity develops
Multidrug-Resistant TB (MDR-TB)
WHO recommends an individualized longer regimen including:
Group A drugs (include all when possible):
- Levofloxacin or Moxifloxacin
- Bedaquiline
- Linezolid
Group B drugs (add one or both):
- Clofazimine
- Cycloserine or Terizidone
Group C drugs (add when regimen cannot be composed with Group A and B alone):
- Ethambutol
- Delamanid
- Pyrazinamide
- Imipenem-cilastatin or Meropenem (with amoxicillin-clavulanate)
- Ethionamide or Prothionamide
- p-aminosalicylic acid
Total duration: 18-20 months (can be modified based on individual response) 1
Drugs NOT Recommended
- Kanamycin and capreomycin should not be included in MDR-TB regimens 1
- Amoxicillin-clavulanate should not be included except when administering a carbapenem 1
- Macrolides (azithromycin, clarithromycin) should not be included 1
Patient-Centered Approach
WHO emphasizes a patient-centered approach to TB treatment that includes:
- Direct observation of medication ingestion (DOT) or video-observed treatment (VOT)
- Identification and training of treatment supporters
- Health education and counselling
- Material support for patients
- Regular monitoring for treatment adherence and adverse effects 1
Monitoring During Treatment
- Regular clinical evaluations to assess treatment response and adverse effects
- Sputum cultures to monitor bacteriological response
- Liver function tests for patients with pre-existing liver disease or symptoms of hepatotoxicity 4
- Drug susceptibility testing (DST) to guide treatment decisions, especially for MDR-TB
Important Considerations
- Drug susceptibility testing should be performed on initial isolates from all newly diagnosed TB patients 1
- Treatment must be modified if resistance is detected
- Pyridoxine (vitamin B6) should be given with isoniazid to patients at risk of neuropathy
- Ethambutol can be discontinued once susceptibility to isoniazid and rifampicin is confirmed
Treatment of TB in Special Populations
- Pregnant women: Avoid streptomycin (ototoxic to fetus); standard regimen without injectable agents is recommended
- HIV co-infection: Standard regimens apply, but careful monitoring for drug interactions with antiretrovirals is essential
- Pre-existing liver disease: Careful monitoring of liver function; consider regimens with fewer hepatotoxic drugs 4
The WHO guidelines emphasize the importance of adherence to the complete treatment regimen to prevent the development of drug resistance, which is a major global concern in TB management.