Indication	First Choice	Alternative	Comments/Special Issues
Prophylaxis Post-exposure	Source Case Drug Susceptible: Isoniazid 10–15 mg/kg body weight (maximum 300 mg/day) by mouth daily for 9 months Source Case Drug Resistant Consult expert and local public health authorities.	If adherence with daily isoniazid cannot be ensured, consider isoniazid 20–30 mg/ kg body weight (maximum 900 mg/day) by mouth 2 times a week by DOT for 9 months Isoniazid 10–15 mg/kg body weight (maximum 300 mg/ day) and rifampin 10–20 mg/ kg body weight (maximum 600 mg/day) by mouth daily for 3–4 months Rifampin 10–20 mg/kg body weight (maximum 600 mg/ day) by mouth daily for 4–6 months	Drug-drug interactions with cART should be considered for all rifamycin containing alternatives. Indication: Positive TST (TST ≥5 mm) or IGRA without previous TB treatment Close contact with any infectious TB case (repeated exposures warrant repeated post-exposure prophylaxis) TB disease must be excluded before starting treatment. No indication for pre-exposure and post- treatment prophylaxis. Criteria for Discontinuing Prophylaxis: Only with documented severe adverse event, which is exceedingly rare. Adjunctive Treatment: Pyridoxine 1–2 mg/kg body weight once daily (maximum 25–50 mg/day) with isoniazid; pyridoxine supplementation is recommended for exclusively breastfed infants and for children and adolescents on meat- and milk-deficient diets; children with nutritional deficiencies, including all symptomatic HIV-infected children; and pregnant adolescents and women.
Treatmen	Intrathoracic Disease Drug-Susceptible TB Intensive Phase (2 Months): Isoniazid, 10–15 mg/kg body weight (maximum 300 mg/day) by mouth once daily, plus Rifampin 10–20 mg/kg body weight (maximum 600 mg/day) by mouth once daily, plus Pyrazinamide 30–40 mg/kg body weight (maximum 2 g/day) by mouth once daily, plus Ethambutol 15–25 mg/kg body weight (maximum 2.5 g/day) by mouth once daily Continuation Phase (7 Months): Isoniazid 10–15 mg/kg body weight (maximum 300 mg/day) by mouth once daily, plus Rifampin 10–20 mg/kg body weight (maximum 600 mg/day) by mouth once daily Extrathoracic Disease: Note: Depends on disease entity Lymph node TB—treat as minimal intrathoracic disease Bone or joint disease–consider extending continuation phase to 10 months (for total duration of therapy of 12 months). TB Meningitis: As alternative to ethambutol or streptomycin, 20–40 mg/kg body weight (maximum 1 g/day) IM once daily—during intensive phase, consider ethionamide, 15– 20 mg/kg body weight by mouth (maximum 1 g/day), initially divided into 2 doses until well tolerated Consider extending continuation phase to 10 months (for total duration of therapy of 12 months). Discuss with an expert. Drug-Resistant TB MDR-TB: Therapy should be based on resistance pattern of child (or of source case where child’s isolate is not available); consult an expert. Treatment Duration: 18–24 months after non- bacteriological diagnosis or after culture conversion; ≥12 months if minimal disease Discuss with an expert.	Alternative for Rifampin Rifabutin 10–20 mg/kg body weight (maximum 300 mg/ day) by mouth once daily (same dose if 3 times a week) Discuss with an expert. Alternative Continuation Phase If Good Adherence and Treatment Response: Isoniazid 20–30 mg/kg body weight (maximum 900 mg/ day) by mouth, plus Rifampin 10–20 mg/kg body weight (maximum 600 mg/ day) three times a week. In children with minimal disease with fully drug- susceptible TB in the absence of significant immune compromise, a 3-drug intensive phase regimen (excluding ethambutol) and a continuation phase of 4 months can be considered (total duration of therapy of 6 months).	Only DOT. If cART-naive, start TB therapy immediately and initiate cART within 2–8 weeks. Already on cART; review to minimize potential toxicities and drug-drug interactions; start TB treatment immediately. Potential drug toxicity and interactions should be reviewed at every visit. Adjunctive Treatment: Co-trimoxazole prophylaxis Pyridoxine 1–2 mg/kg/ body weight/day (maximum 25–50 mg/day) with isoniazid or cycloserine/terizidone or, if malnourished; pyridoxine supplementation is recommended for exclusively breastfed infants and for children and adolescents on meat- and milk-deficient diets; children with nutritional deficiencies, including all symptomatic HIV-infected children; and pregnant adolescents and women. Corticosteroids (2 mg/kg body weight per day of prednisone [maximum, 60 mg/day] or its equivalent for 4–6 weeks followed by tapering) with CNS disease or pericardial effusion; may be considered with pleural effusions, severe airway compression, or severe IRIS. Second-Line Drug Doses: Amikacin 15–30 mg/kg body weight (maximum 1 g/day) IM or IV once daily Kanamycin 15–30 mg/kg body weight (maximum 1 g/day) IM or IV once daily Capreomycin 15–30 mg/kg body weight (maximum 1 g/day) IM once daily Ofloxacin 15–20 mg/kg body weight (maximum 800 mg/day), or levofloxacin 7.5–10 mg/kg body weight (maximum 750 mg/day) by mouth once daily. Because some fluoroquinolones are approved by the FDA for use only in people aged 18 years and older, their use in younger patients necessitates careful assessment of the potential risks and benefits. Cycloserine/Terizidone 10–20 mg/kg body weight (maximum 1 g/day) by mouth once daily Ethionamide/prothionamide, 15–20 mg/ kg body weight (maximum 1 g/day) by mouth in 2–3 divided doses Para-aminosalicylic acid 200–300 mg/kg body weight by mouth divided into 3–4 doses per day (maximum 10 g/day). Thiacetazone can cause severe reactions in HIV-infected children including rash and aplastic anemia, and should not be used.

Key to Acronyms: cART = combined antiretroviral therapy; CNS = central nervous system; DOT = directly observed therapy; FDA = Food and Drug Administration; IGRA = interferon-gamma release assay; IM = intramuscular; IRIS = immune reconstitution inflammatory syndrome; IV = intravenous; MDR-TB = multi-drug-resistant tuberculosis; TB = tuberculosis; TST = tuberculin skin test