When to Use Second-Line TB Drugs
Second-line TB drugs should be used for patients with drug-resistant tuberculosis, particularly those with rifampicin-resistant TB (RR-TB) or multidrug-resistant TB (MDR-TB), and in cases of serious adverse events to first-line drugs. 1
Primary Indications for Second-Line TB Drugs
- Confirmed MDR-TB or RR-TB: Second-line drugs are required when resistance to both isoniazid and rifampicin (MDR-TB) or rifampicin alone (RR-TB) is confirmed through molecular or phenotypic drug susceptibility testing (DST) 1
- Extensively drug-resistant TB (XDR-TB): Treatment with new medicines including bedaquiline and delamanid along with repurposed medicines like linezolid and clofazimine is required for patients with XDR-TB 1
- Resistance to fluoroquinolones or second-line injectables: Patients with resistance to these drugs require specialized regimens with new and repurposed drugs 1
- Serious adverse events to first-line drugs: When patients cannot tolerate first-line medications, second-line drugs may be necessary as alternatives 1
Drug Selection for MDR/RR-TB Regimens
Longer Regimens (18-20 months)
For individualized longer regimens, drugs should be selected according to the following hierarchy 1, 2:
Group A (include all when possible):
- Levofloxacin or Moxifloxacin
- Bedaquiline
- Linezolid 2
Group B (add one or both):
- Clofazimine
- Cycloserine 2
Group C (add to complete regimen when drugs from Groups A and B cannot be used):
Shorter MDR-TB Regimen (9-11 months)
A shorter MDR-TB regimen may be used when 1, 3:
- Patient has not been previously treated with second-line drugs for more than 1 month
- Resistance to fluoroquinolones and second-line injectable agents has been excluded
- No intolerance to any medicine in the shorter regimen
- No pregnancy
- No extrapulmonary disease
- All medicines in the regimen are available 1
Contraindications to Shorter Regimens
Do not use the shorter MDR-TB regimen when 1, 3:
- Confirmed resistance to any medicine in the shorter regimen
- Previous exposure to second-line medicines for >1 month
- Intolerance to medicines in the regimen
- Pregnancy
- Extrapulmonary TB
- Unavailability of any medicine in the regimen 1
Important Principles for Second-Line TB Treatment
- Never add a single effective drug to a failing regimen as this promotes development of further drug resistance 1, 2
- Regimens should include at least five effective TB medicines during the intensive phase for longer regimens 1
- Treatment decisions should be made by a team of experts rather than individual physicians to minimize mistakes and share expertise 1
- Regular monitoring of treatment response through monthly sputum smear and culture is essential 1, 2
- Adverse events should be managed according to international recommendations to prevent discontinuation of effective drugs 1, 4
Special Considerations
- HIV co-infection: Antiretroviral therapy should be started as early as possible (within the first 8 weeks) following initiation of anti-TB treatment 1, 5
- Surgical intervention: Elective partial lung resection may be considered in selected cases with pulmonary TB, especially those with large cavities confined to one lobe 1
- Drug susceptibility testing: Second-line DST should be performed to confirm the drug resistance pattern and guide the correct choice of treatment 1, 6
Common Pitfalls to Avoid
- Inadequate regimen design: Using too few effective drugs increases risk of treatment failure and further resistance 1, 7
- Poor monitoring: Failure to monitor for adverse effects can lead to poor adherence and treatment failure 4, 1
- Delayed DST: Not performing rapid DST for second-line drugs can lead to ineffective treatment and resistance amplification 6, 5
- Standardized regimens without DST: Using standardized regimens without knowledge of resistance patterns can worsen outcomes 8, 7
Second-line TB drugs require careful selection based on resistance patterns, patient history, and monitoring for adverse effects to ensure optimal outcomes and prevent further drug resistance.