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Doses and common adverse effects of medications used to treat suspected or confirmed MAC lymphadenitis in children and adolescents

Doses and common adverse effects of medications used to treat suspected or confirmed MAC lymphadenitis in children and adolescents
Medication Dose Route Usual maximum daily dose Potential adverse effects and target dose ranges
Azithromycin
  • 5 to 10 mg/kg per day in 1 dose for daily dosing
  • 10 mg/kg per day in 1 dose for 3 times per week dosing
 Oral
  • Daily: 300 mg/day
  • 3 times per week: 500 mg/day
  • Prolongation of the QT interval; nausea; vomiting; diarrhea; decreased hearing; dizziness; hepatitis; phlebitis (IV)
Clarithromycin*
  • 15 to 30 mg/kg per day divided in 2 doses (for daily or 3 times per week dosing)
 Oral
  • 1 g/day
  • Prolongation of the QT interval; nausea; vomiting; diarrhea; taste disturbance; decreased hearing; hepatitisΔ ; anterior uveitisΔ ; arthralgiaΔ ; granulocytopeniaΔ ; inhibits hepatic drug metabolism causing significant drug-drug interactions (particularly with rifamycins)
Ethambutol*
  • 15 mg/kg per day in 1 dose for daily dosing
  • 25 mg/kg per day in 1 dose for 3 times per week dosingΔ
 Oral
  • Daily: 1 g/day
  • 3 times per week: 2.5 g/day
  • Optic neuritis (usually reversible)◊; red-green color blindness§; gastrointestinal disturbances; hypersensitivity
Rifabutin*¥
  • 10 to 20 mg/kg per day in 1 dose (for daily or 3 times per week dosing)
 Oral
  • 300 mg/day
  • Orange discoloration of secretions (may stain soft contact lenses), urine, and stool; gastrointestinal disturbance; hepatitisΔ; "flu-like" syndrome; thrombocytopenia; kidney failure; myalgia; arthralgiaΔ; granulocytopeniaΔ; anterior uveitisΔ
Rifampin (rifampicin)¥
  • 15 to 20 mg/kg per day in 1 dose (for daily or 3 times per week dosing)
 Oral
  • Children weighing <50 kg: 450 mg/day
  • Children weighing ≥50 kg: 600 mg/day
  • Orange discoloration of secretions (may stain soft contact lenses), urine, and stool; gastrointestinal disturbance; hepatitis; "flu-like" syndrome; thrombocytopenia; kidney failure; induces hepatic drug metabolism causing multiple significant drug-drug interactions
Medications that may be added if Mycobacterium tuberculosis cannot be excluded
Isoniazid
  • 10 to 15‡ mg/kg per day in 1 dose
 Oral, IM
  • 300 mg/day
  • Mild hepatic enzyme elevation; hepatitis‡; peripheral neuritis; hypersensitivity (fever, rash); diarrhea and gastric irritation (caused by vehicle in syrup)
  • Pyridoxine supplementation of 1 to 2 mg/kg per day (up to 50 mg/day) is suggested to prevent peripheral neuropathy in exclusively breastfed infants, children and adolescents on meat- and milk-deficient diets, children with nutritional deficiencies, children and adolescents with symptomatic HIV infection, and pregnant adolescents
Pyrazinamide*
  • 30 to 40 mg/kg per day for daily dosing
  • 50 mg/kg per day for twice weekly dosing
 Oral
  • 2 g/day
  • Arthralgia; gastrointestinal
Surgical excision without antimicrobial therapy is the preferred treatment for NTM lymphadenitis; antimycobacterial therapy is an alternative for children who are not candidates for surgery or patients/families who wish to avoid surgery. MAC is the most common cause of NTM lymphadenitis in the United States. If M. tuberculosis is not a concern, a typical empiric regimen for MAC lymphadenitis includes a macrolide (azithromycin or clarithromycin) in combination with ethambutol and/or rifampin (or rifabutin). Patients are typically treated until symptoms resolve (eg, 3 to 6 months). If M. tuberculosis is a concern, isoniazid (and possibly pyrazinamide) is added. Refer to UpToDate topic on NTM lymphadenitis in children for details.

IM: intramuscular; IV: intravenous; MAC: Mycobacterium avium complex; NTM: nontuberculous mycobacterial infection (also known as atypical mycobacterial infection).

* Doses are for children with normal kidney function.

¶ Clinical data in adults indicate that 3 times weekly therapy is as effective as daily therapy, with reduced toxicity, for mild to moderate disease.

Δ Anterior uveitis, arthralgia, neutropenia, and liver function abnormalities may occur when clarithromycin is used in combination with rifabutin.

◊ Rare at doses of 15 to 25 mg/kg in children with normal kidney function.

§ Rarely occurs in children, who metabolize ethambutol more rapidly than adults.

¥ Dose may require modification based upon drug-drug interactions, particularly with clarithromycin.

‡ The incidence of hepatotoxicity may be increased when isoniazid doses >10 mg/kg are used in combination with rifampin.

References:
  1. American Academy of Pediatrics. Tables of antibacterial drug dosages. In: Red Book: 2021-2024 Report of the Committee on Infectious Diseases, 32nd ed, Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH (Eds), American Academy of Pediatrics, Itasca, IL 2021. p.876.
  2. American Academy of Pediatrics. Tuberculosis. In: Red Book: 2021-2024 Report of the Committee on Infectious Diseases, 32nd ed, Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH (Eds), American Academy of Pediatrics, Itasca, IL 2021. p.786.
  3. Donald PR, Maher D, Maritz JS, Qazi S. Ethambutol dosage for the treatment of children: Literature review and recommendations. Int J Tuberc Lung Dis 2006; 10:1318.
  4. Griffith DE, Aksamit T, Brown-Elliott BA, et al. An official ATS/IDSA statement: Diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med 2007; 175:367.
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