Second-Line Antitubercular Therapy Regimens
The standard second-line antitubercular therapy for multidrug-resistant tuberculosis (MDR-TB) should include at least five effective TB medicines during the intensive phase, with drugs selected from WHO-designated groups based on confirmed drug susceptibility patterns. 1
Drug Selection Algorithm for MDR-TB Treatment
Standard Longer Regimen (20-24 months)
The individualized regimen should follow this structure:
- Duration: 20-24 months total with 8-month intensive phase 1
- Drug selection: At least 5 effective drugs including:
- Pyrazinamide
- One drug from Group A (fluoroquinolones)
- One drug from Group B (injectable agents)
- At least two drugs from Group C (other core second-line agents) 1
Current WHO Drug Classification (2022)
| Priority | Drug Groups |
|---|---|
| Group A | • Levofloxacin OR Moxifloxacin • Bedaquiline • Linezolid |
| Group B | • Clofazimine • Cycloserine OR Terizidone |
| Group C | • Ethambutol • Delamanid • Pyrazinamide • Imipenem-cilastatin OR Meropenem with amoxicillin/clavulanate • Amikacin OR Streptomycin • Ethionamide OR Prothionamide • p-aminosalicylic acid |
Shorter MDR-TB Regimen Options
Shorter All-Oral Bedaquiline Regimen (9-11 months)
For eligible patients with confirmed MDR/RR-TB who have not been previously treated with second-line drugs for >1 month and in whom fluoroquinolone resistance has been excluded:
Intensive phase (4-6 months):
- Bedaquiline (6 months)
- Levofloxacin/Moxifloxacin
- Clofazimine
- Pyrazinamide
- Ethambutol
- High-dose Isoniazid
- Ethionamide
Continuation phase (5 months):
- Levofloxacin/Moxifloxacin
- Clofazimine
- Pyrazinamide
- Ethambutol
Traditional Shorter Regimen (WHO)
4–6 Km-Mfx-Pto-Cfz-Z-H(high-dose)-E/5 Mfx-Cfz-Z-E 1
Important Considerations
Eligibility Criteria for Shorter Regimens
Shorter regimens should NOT be used if any of the following apply:
- Confirmed resistance to any medicine in the regimen
- Previous exposure to second-line medicines for >1 month
- Intolerance to any medicine in the regimen
- Pregnancy
- Extrapulmonary TB
- Unavailability of any medicine in the regimen 1
Drug Resistance Management
- Never add only one effective drug to a failing regimen to prevent selection of resistant mutants 1
- For patients with XDR-TB or resistance to fluoroquinolones/injectables, treatment with bedaquiline, delamanid, linezolid, and clofazimine along with other drugs to which the strain is likely sensitive is required 1
Monitoring and Management
- Drug susceptibility testing (DST) should be performed before initiating second-line therapy 1
- Adverse events should be managed according to international recommendations 1
- Treatment decisions should be made by a team of experts (TB Consilium) rather than individual physicians 1
Common Second-Line Drug Adverse Effects
- Fluoroquinolones: QT prolongation, tendinopathy, CNS effects
- Bedaquiline: QT prolongation, hepatotoxicity
- Linezolid: Myelosuppression, peripheral neuropathy, optic neuritis
- Cycloserine: Neuropsychiatric effects, seizures (pyridoxine 100-200 mg/day may help prevent these) 1
- Ethionamide: Gastrointestinal toxicity, hepatotoxicity 2
- Injectable agents: Nephrotoxicity, ototoxicity
- Clofazimine: Skin discoloration, QT prolongation
Special Situations
Surgery in MDR-TB
Surgery may be considered in selected cases with pulmonary TB, especially those with large cavities confined to one lobe 1
Extensively Drug-Resistant TB (XDR-TB)
For XDR-TB, treatment should include new medicines (bedaquiline, delamanid) along with repurposed medicines (linezolid, clofazimine) and any second-line medicines to which the strain is likely sensitive 1
Remember that the management of drug-resistant TB requires expertise and should ideally be done in consultation with specialists experienced in treating these complex cases. Regular monitoring for adverse effects and ensuring patient adherence are crucial for successful outcomes and preventing further drug resistance.