What is the recommended treatment regimen for tuberculosis (TB) in children?

Treatment of Tuberculosis in Children

Children with pulmonary tuberculosis should receive a 6-month regimen consisting of rifampin, isoniazid, and pyrazinamide for the first 2 months, followed by rifampin and isoniazid for 4 additional months, with ethambutol added to the initial phase until drug susceptibility results confirm low resistance risk. 1, 2

Standard Treatment Regimen for Pulmonary/Intrathoracic TB

Initial Phase (2 months)

• Rifampin: 10-20 mg/kg/day (maximum 600 mg) 3, 4
• Isoniazid: 10-15 mg/kg/day (maximum 300 mg) 3, 4
• Pyrazinamide: 15-30 mg/kg/day (maximum 2 g) 4
• Ethambutol: 15-25 mg/kg/day - include until susceptibility confirmed, unless isoniazid resistance is <4% in the community and no prior treatment or drug-resistant exposure 1, 2

Continuation Phase (4 months)

• Rifampin: 10-20 mg/kg/day 3
• Isoniazid: 10-15 mg/kg/day 3

Important caveat: Ethambutol can be safely used in children ≥5 years at 15 mg/kg/day without excessive concern for visual toxicity, though monitoring remains important. For younger children where visual acuity cannot be assessed, streptomycin may be substituted if a fourth drug is needed. 5, 1

Dosing Administration Principles

• Round dosages up to facilitate administration of appropriate syrup volumes or tablet strengths 1
• Recalculate doses as the child gains weight during treatment 1
• Pyridoxine supplementation is recommended for breastfed infants, malnourished children, and HIV-infected children, but not routinely required otherwise 5

Directly Observed Therapy (DOT)

All children should receive DOT to ensure adherence. 3, 6 Intermittent dosing (twice or three times weekly) is acceptable but must be given by DOT:

• Twice weekly: Isoniazid 20-40 mg/kg (max 900 mg), Rifampin 10-20 mg/kg (max 600 mg), Pyrazinamide 50-70 mg/kg 4, 7
• This approach requires as few as 58 doses over 6 months and has comparable efficacy to daily therapy 7

TB Meningitis and CNS Disease

Extend treatment to 12 months total for any CNS involvement: 5, 1

• Initial 2 months: Rifampin, isoniazid, pyrazinamide, plus fourth drug (streptomycin or ethambutol) 5
• Continuation 10 months: Rifampin and isoniazid 5
• Add corticosteroids for moderate to severe disease (stages II and III) - typically prednisolone 60 mg/day initially, tapering over several weeks 5, 1

Critical pitfall: Ethambutol should be used cautiously in unconscious patients (stage III meningitis) as visual acuity cannot be monitored; consider streptomycin instead. 5

Disseminated/Miliary TB

• 6-month standard regimen is adequate unless CNS involvement is present 5
• Lumbar puncture is mandatory in miliary TB due to high risk of meningeal spread; if positive, treat as meningitis for 12 months 5

Extrapulmonary TB (Non-CNS)

• Peripheral lymph nodes, bone/joint, genitourinary: Use standard 6-month regimen 5
• Exception: Some experts recommend 12 months for bone/joint TB in young children 5, 8

Important note: Lymph nodes may enlarge, form abscesses, or new nodes may appear during or after treatment without indicating treatment failure or relapse. 5

Drug-Resistant TB

Isoniazid-Resistant TB

• Rifampin, pyrazinamide, ethambutol for 6-12 months 1
• Add fluoroquinolone for extensive disease 1
• Alternative: Rifampin alone for 6 months in contacts with latent infection 5

Rifampin-Resistant TB

• Isoniazid, pyrazinamide, ethambutol, fluoroquinolone for 12-15 months 1
• Add injectable agent (amikacin, kanamycin, capreomycin) for first few months in extensive disease 1

Multidrug-Resistant TB (MDR-TB)

• Treatment duration: 18-24 months typically 1
• Regimen must be based on susceptibility testing with at least 4-5 likely effective drugs 5, 1

Special Monitoring Considerations

Hepatotoxicity Monitoring

• Routine liver enzyme monitoring is not necessary in otherwise healthy children 5
• Monitor closely if pre-existing liver disease, HIV infection, or malnutrition present 5
• If hepatitis develops, investigate non-drug causes and discontinue hepatotoxic agents 5

Ototoxicity (Injectable Agents)

• Baseline and monthly audiometry (pure tone audiometry or otoacoustic emissions) when using aminoglycosides 5
• Stop injectable immediately if any hearing loss detected 5

Visual Monitoring (Ethambutol)

• Monthly visual acuity and color vision testing using Ishihara charts in children who can cooperate 5
• Stop ethambutol if any deterioration in visual fields or color vision 5

HIV Co-Infection

• Same basic regimen as HIV-negative children 5, 2
• Avoid once-weekly isoniazid-rifapentine in continuation phase 5
• Extend treatment to minimum 12 months for pulmonary TB in HIV-positive children 8
• Monitor for drug interactions between rifamycins and antiretroviral agents 5
• Routine pyridoxine supplementation recommended 5

Common Pitfalls to Avoid

1. Inadequate treatment duration: Do not stop at 6 months for CNS disease - requires 12 months 5, 1
2. Omitting fourth drug inappropriately: Include ethambutol in initial phase unless resistance risk is definitively low 1, 2
3. Poor adherence without DOT: Children rarely complete treatment without directly observed therapy 7, 6
4. Misinterpreting radiographic response: Chest x-ray abnormalities resolve slowly; 63% of children still have abnormalities at treatment completion despite cure 7
5. Stopping treatment for lymph node enlargement: New or enlarging nodes during treatment do not indicate failure 5