Second-Line Anti-Tubercular Drugs
Key Points
- Used in drug-resistant TB and treatment failures
- Require longer treatment duration
- Higher risk of adverse effects
- Need close monitoring
- Individualized regimens based on susceptibility
General Principles
- Never add single drug to failing regimen
- Consider cross-resistance patterns
- Always include pyrazinamide
- Use at least 4-5 effective drugs
WHO Classification of Second-Line Drugs
Group A: Fluoroquinolones
- Levofloxacin:
- Dosing: 15-20 mg/kg/day
- Maximum: 750-1000 mg/day
- Better safety profile
- Moxifloxacin:
- Dosing: 10-15 mg/kg/day
- Maximum: 400 mg/day
- Higher bactericidal activity
Group B: Injectable Agents
- Amikacin:
- Dosing: 15-20 mg/kg/day
- Maximum: 1000 mg/day
- Preferred aminoglycoside
- Streptomycin:
- Dosing: 20-40 mg/kg/day
- Maximum: 1000 mg/day
- Limited by resistance
Group C: Core Second-Line Agents
- Ethionamide/Prothionamide:
- Dosing: 15-20 mg/kg/day
- Maximum: 750-1000 mg/day
- Give divided doses
- Cycloserine:
- Dosing: 15-20 mg/kg/day
- Maximum: 750-1000 mg/day
- Monitor neuropsychiatric effects
- Linezolid:
- Dosing: 10 mg/kg/day
- Maximum: 600 mg/day
- Monitor blood counts
- Clofazimine:
- Dosing: 2-5 mg/kg/day
- Maximum: 100 mg/day
- Skin pigmentation common
New Drugs
- Bedaquiline:
- Dosing based on weight bands
- 6-month duration
- Monitor QT interval
- Delamanid:
- Pediatric dosing available
- Good safety profile
- 6-month regimen
MDR-TB Treatment Regimens
1. Shorter MDR-TB Regimen
- Duration: 9-12 months
- Intensive Phase (4-6 months):
- Kanamycin
- Moxifloxacin
- Prothionamide
- Clofazimine
- Pyrazinamide
- High-dose Isoniazid
- Ethambutol
- Continuation Phase (5 months):
- Moxifloxacin
- Clofazimine
- Pyrazinamide
- Ethambutol
2. Longer MDR-TB Regimen
- Duration: 18-24 months
- Design Principles:
- Include at least 5 effective drugs
- Use all Group A drugs possible
- Add Group B drugs if needed
- Complete with Group C drugs
3. Special Situations
- HIV Co-infection:
- Drug interactions with ARVs
- Increased monitoring needed
- Consider timing of ART
- Extensive Drug Resistance:
- Individualized regimens
- New drug combinations
- Extended duration
Monitoring and Adverse Effects
1. Baseline Investigations
- Complete blood count
- Liver and renal function
- Thyroid function tests
- ECG (if on QT-prolonging drugs)
- Audiometry
- Visual assessment
2. Drug-Specific Monitoring
- Aminoglycosides:
- Monthly audiometry
- Renal function
- Vestibular symptoms
- Fluoroquinolones:
- Joint symptoms
- QT interval
- Tendon problems
- Linezolid:
- Weekly CBC initially
- Peripheral neuropathy
- Optic neuritis
- Bedaquiline:
- Monthly ECG
- Liver function
- Symptoms of arrhythmia
3. Common Adverse Effects
- Gastrointestinal:
- Nausea/vomiting
- Hepatotoxicity
- Diarrhea
- Neurological:
- Peripheral neuropathy
- Psychiatric symptoms
- Seizures
- Endocrine:
- Hypothyroidism
- Diabetes
Disclaimer
The notes provided on Pediatime are generated from online resources and AI sources and have been carefully checked for accuracy. However, these notes are not intended to replace standard textbooks. They are designed to serve as a quick review and revision tool for medical students and professionals, and to aid in theory exam preparation. For comprehensive learning, please refer to recommended textbooks and guidelines.
