Doses and common adverse effects of medications used to treat nontuberculous mycobacterial (atypical mycobacterial) infections in children and adolescents^[1-6]

Medication	Dose	Route	Usual maximum daily dose	Potential adverse effects and target dose ranges
Amikacin*^¶	15 to 22.5 mg/kg daily or divided in 2 to 3 doses 15 to 25 mg/kg per day in 1 dose for 3 times per week dosing^Δ	IV, IM	1.5 g/day	Dizziness; ataxia; vertigo; tinnitus; hearing loss; nephrotoxicity For every 8 hour dosing: Adjust dose for trough <3 to 5 mcg/mL and peak 20 to 25 mcg/mL For once daily dosing: Adjust dose for trough 0.5 to 1 mcg/mL (at 18 hours) and peak 40 to 50 mcg/mL
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, IV	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)
Cefoxitin^¶	160 mg/kg per day divided in 4 doses	IV, IM	12 g/day	Bone marrow suppression; interstitial nephritis; hypersensitivity (fever, rash); may interfere with serum creatinine assay (falsely elevates creatinine)
Ciprofloxacin^¶	20 mg/kg per day divided in 2 doses	Oral, IV	Oral: 1.5 g/day IV: 1200 mg/day	Tendon damage; prolongation of the QT interval; CNS stimulation; nausea; vomiting; diarrhea
Clarithromycin^¶	15 to 30 mg/kg per day divided in 2 doses (for daily or 3 times per week dosing)^Δ	Oral	1 g/day	Prolongation of the QT interval; nausea; vomiting; diarrhea; taste disturbance; decreased hearing; hepatitis^◊; anterior uveitis^◊; arthralgia^◊; granulocytopenia^◊; significant drug-drug interactions (particularly with rifamycins)
Doxycycline	2 to 4 mg/kg per day in 1 or 2 doses	Oral, IV	200 mg/day	Tooth discoloration in children <8 years; nausea; vomiting; diarrhea; photosensitivity; rash; hyperpigmentation; phlebitis (IV); and injection site pain (IV)
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 dosing^Δ	Oral	Daily: 1 g/day 3 times per week: 2.5 g/day	Optic neuritis (usually reversible)^§; red-green color blindness^¥; gastrointestinal disturbances; hypersensitivity
Imipenem^¶	60 to 100 mg/kg per day in 4 doses Adolescents can receive 500 mg to 1 g 2 or 3 times daily	IV	4 g/day	Nausea; vomiting; diarrhea; hypersensitivity; seizures; confusion; hepatitis; leukopenia; anemia; thrombocytopenia
Isoniazid	5 mg/kg per day for NTM infection 10 to 15^‡mg/kg per day in 1 dose if cannot definitively exclude Mycobacterium tuberculosis	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
Levofloxacin^¶	<5 years: 20 mg/kg per day in 2 doses ≥5 years: 10 mg/kg once daily	Oral, IV	500 mg/day	Tendon damage; CNS stimulation; nausea; vomiting; diarrhea
Linezolid	<12 years: 30 mg/kg per day in 3 doses ≥12 years: 600 mg twice per day	Oral, IV	1200 mg/day	Nausea; vomiting; diarrhea; leukopenia; anemia; thrombocytopenia; pancytopenia; peripheral neuropathy; optic neuritis; serotonin syndrome
Meropenem^¶	<50 kg: 30 to 60 mg/kg per day divided in 3 doses ≥50 kg: 3 g/day in 3 divided doses	IV	3 g/day	May lower seizure threshold; bone marrow suppression; interstitial nephritis
Moxifloxacin	400 mg per day in 1 dose (for adolescents)	Oral	400 mg/day	Tendon damage; CNS stimulation; nausea; vomiting; diarrhea
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 tract upset; hepatotoxicity; hyperuricemia
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; hepatitis^◊; "flu-like" syndrome; thrombocytopenia; renal failure; myalgia; arthralgia^◊; granulocytopenia^◊; anterior uveitis^◊
Rifampin (rifampicin)^†	15 to 20 mg/kg per day in 1 dose (for daily or 3 times per week dosing)	Oral, IV	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; renal failure; multiple significant drug-drug interactions
Streptomycin*^¶	20 to 40 mg/kg per day in 1 dose or in 2 divided doses (preferred for IV) 15 to 25 mg/kg per day in 1 dose for 3 times per week dosing^Δ	IM, IV (if IM not tolerated)	1 g/day	Dizziness; ataxia; vertigo; tinnitus; hearing loss; nephrotoxicity; hypersensitivity reaction Adjust dose for trough <3 to 5 mcg/mL and peak 15 to 30 mcg/mL for every 12 hour dosing*
Tigecycline	8 to 11 years: 2.4 to 4 mg/kg per day in 2 divided doses ≥12 years: 50 mg every 12 hours	IV	100 mg/day	Nausea; anorexia; vomiting; diarrhea; photosensitivity; coagulopathy; tooth discoloration (in children <8 years of age); phlebitis; injection site pain
Tobramycin*^¶	7.5 mg/kg per day in 3 doses or 7 mg/kg once daily	IM, IV	300 mg/day	Dizziness; ataxia; vertigo; tinnitus; hearing loss; nephrotoxicity For every 8 hour dosing: Adjust dose for trough <1 mcg/mL and peak 6 to 8 mcg/mL For once daily dosing: Adjust dose for trough <1 mcg/mL at 18 hours and peak 15 to 22 mcg/mL
Trimethoprim-sulfamethoxazole^¶ (TMP-SMX, cotrimoxazole)	8 to 12 mg/kg per day of the TMP component divided in 2 doses	Oral, IV	320 mg/day of TMP component	Rash; hypersensitivity reaction (fever, rash, Stevens-Johnson syndrome); bone marrow suppression; nausea; vomiting; diarrhea; IV formulation requires substantial dilution, which may result in large volumes (which may be problematic for patients with renal insufficiency or fluid overload)

Combinations of 2 to 4 of the above agents are selected based upon type of NTM infection and susceptibility testing. Consultation with a specialist in infectious diseases is recommended. Refer to UpToDate topics on NTM infections in children for details.

IV: intravenous; IM: intramuscular; CNS: central nervous system; NTM: nontuberculous mycobacterial infection (also known as atypical mycobacterial infection); HIV: human immunodeficiency virus.
* Monitor drug levels to ensure efficacy and avoid toxicity. The targeted range varies depending upon the clinical syndrome, patient characteristics (eg, cystic fibrosis), and the institution. Consultation with an infectious diseases specialist or pharmacist regarding the appropriate therapeutic range is suggested. Aminoglycoside toxicity is dependent upon duration of treatment and aminoglycoside-free period of dosing interval. (Refer to UpToDate topic on aminoglycosides.)
¶ Doses are for children with normal renal function.
Δ Clinical data in adults indicate that 3 times weekly therapy is as effective as daily therapy, with reduced toxicity, for mild to moderate disease.
◊ Anterior uveitis, arthralgia, neutropenia, and liver function abnormalities may occur when clarithromycin is used in combination with rifabutin.
§ Usually reversible; rare at doses of 15 to 25 mg/kg in children with normal renal function.
¥ Rarely occurs in children, who metabolize ethambutol more rapidly than adults.
‡ The incidence of hepatotoxicity may be increased when isoniazid doses >10 mg/kg are used in combination with rifampin.
† Dose may require modification based upon drug-drug interactions, particularly with clarithromycin. Many experts recommend a daily dose of at least 20 mg/kg per day for infants and toddlers and for serious tuberculosis disease (eg, meningitis, disseminated disease).

References:

American Academy of Pediatrics. Tables of antibacterial drug dosages. In: Red Book: 2021-2024 Report of the Committee on Infectious Diseases, 32^nd ed, Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH (Eds), American Academy of Pediatrics, Itasca, IL 2021. p.876.
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.
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.
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.
Daley CL, Iaccarino JM, Lange C, et al. Treatment of nontuberculous mycobacterial pulmonary disease: An official ATS/ERS/ESCMID/IDSA clinical practice guideline. Clin Infect Dis 2020; 71:e1.
Department of Health and Human Services. Panel on opportunistic infections in HIV-exposed and HIV-infected children. Guidelines for the prevention and treatment of opportunistic infections in HIV-exposed and HIV-infected children. Mycobacterium avium complex disease. Available at: https://clinicalinfo.hiv.gov/en/guidelines/pediatric-opportunistic-infection/mycobacterium-avium-complex-disease. Accessed on June 16, 2021.

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Doses and common adverse effects of medications used to treat nontuberculous mycobacterial (atypical mycobacterial) infections in children and adolescents[1-6]

Doses and common adverse effects of medications used to treat nontuberculous mycobacterial (atypical mycobacterial) infections in children and adolescents^[1-6]