Table 7.
Summary of first-line TB drugs and dosage recommendations in children
| First-line drugs | Mode and mechanism of action | Main toxicitiesa | Daily dose mg/kg (range) [maximum dose]b |
|---|---|---|---|
| Isoniazid (INH) |
Bactericidal—inhibits cell wall synthesis; most potent early bactericidal activity offering the best protection to companion drugs Contributes mainly by rapidly killing actively metabolizing extracellular bacilli; contributes to sterilization if given for a prolonged period |
Hepatitis; peripheral neuropathy | 10 (7–15) [300 mg] |
| Rifampicin (RMP) |
Bactericidal and sterilizing—inhibits RNA synthesis; contributes by killing extracellular and slower growing intracellular bacilli; important contribution to sterilization | Hepatitis; orange discoloration of secretions; drug–drug interactions | 15 (10–20) [600 mg] |
| Pyrazinamide (PZA) |
Sterilizing—disrupts energy metabolism; contributes by specifically killing bacilli that persist within the acidic centers of caseating granulomas | Hepatitis; arthralgia | 35 (30–40) [2000 mg] |
| Ethambutol (EMB) |
Bacteriostatic—inhibits cell wall synthesis; contributes mainly by offering some additional protection against drug-resistant mutants | Visual disturbance (acuity, color vision) |
20 (15–25) [1200 mg] |
| Suggested treatment regimens | ||
|---|---|---|
| Disease category | Treatment regimen | Rationale |
| Uncomplicated intrathoracic disease | INH, RMP, PZA (2-mo intensive phase) INH, RMP (4-mo continuation phase) |
Organism load low; drug penetration good |
| Extensive lung infiltrates and/or cavities | Add EMB during 2-mo intensive phase | Organism load high; drug penetration good |
| Tuberculous meningitis (TBM)c | Add fourth drug—at least during 2-mo intensive phase. Prolong continuation phase to 10 months (WHO recommendation) Add steroids for 1 mo |
Organism load low; drug penetration variable; risk of severe immune mediated sequelae |
| Severe airway compression | Three- or four-drug regimen depending on extent of lung infiltration/cavities Consider adding steroids for 1 mo |
Organism and drug penetration variabled; inflammation may worsen airway compression |
| Recent exposure/infection No active disease |
Preventive therapy INH (6–9 mo) INH, RMP (3 mo) |
Organism load very low; drug penetration good |
Data adapted from Perez-Velez and Marais 2012.
aHypersensitivity reactions and drug rashes may occur with any drug.
bWHO dosage recommendations for children.
cRecommendations around fourth drug and duration of therapy vary.
dDrug penetration into large cold abscesses may be limited, requiring surgical drainage.