What is the recommended dose of amikacin (an aminoglycoside antibiotic) for pediatric patients?

Amikacin Dosing in Pediatric Patients

For infants and children with normal renal function, administer amikacin 15-22.5 mg/kg/day divided every 8 hours (5-7.5 mg/kg every 8 hours), with neonatal dosing stratified by weight and postnatal age. 1

Neonatal Dosing (0-4 weeks of age)

Neonatal dosing requires careful stratification based on both weight and postnatal age to minimize toxicity while achieving therapeutic levels 1:

Weight-based and age-based dosing:

• <1200 g, postnatal age ≤7 days: 7.5 mg/kg every 18-24 hours 1
• <1200 g, postnatal age >7 days: 7.5-10 mg/kg every 8-12 hours 1
• 1200-2000 g, postnatal age ≤7 days: 7.5 mg/kg every 12 hours 1
• 1200-2000 g, postnatal age >7 days: 7.5-10 mg/kg every 8-12 hours 1
• >2000 g, postnatal age ≤7 days: 7.5-10 mg/kg every 12 hours 1
• >2000 g, postnatal age >7 days: 10 mg/kg every 8 hours 1

Alternative FDA-approved neonatal regimen: A loading dose of 10 mg/kg followed by 7.5 mg/kg every 12 hours 2

Infants and Children Dosing

Standard dosing for infants and children: 15-22.5 mg/kg/day divided every 8 hours (equivalent to 5-7.5 mg/kg every 8 hours) 1

FDA-approved alternative: 15 mg/kg/day divided into 2-3 equal doses (7.5 mg/kg every 12 hours or 5 mg/kg every 8 hours), not to exceed 1.5 grams/day 2

Once-Daily Dosing Option

Once-daily dosing of 15 mg/kg is an effective alternative supported by multiple pediatric studies showing comparable or superior efficacy with reduced nephrotoxicity 3, 4, 5. However, a loading dose of 20 mg/kg may be necessary to achieve therapeutic peak concentrations of 30-40 mg/L in the first dose 3.

Clinical evidence for once-daily dosing:

• A randomized trial of 141 pediatric patients showed 83% clinical cure with once-daily dosing versus 66% with twice-daily dosing (P=0.001), with less nephrotoxicity (21% vs 35%, P=0.05) 5
• Once-daily dosing at 15 mg/kg achieved mean peak levels of 31.3 mg/L but required individualized dosing adjustments in 54% of children to maintain therapeutic ranges 3

Special Clinical Situations

High-dose regimens for specific conditions: Initial doses of 30 mg/kg/day divided every 8 hours may be required in patients with documented need based on serum levels, particularly in cystic fibrosis or febrile neutropenic patients 1

Outpatient intramuscular therapy: Once-daily intramuscular amikacin at 15 mg/kg/day for 6 days showed 96% favorable response in treating community-acquired UTIs caused by ESBL-producing E. coli in children aged 2-18 years 4

Therapeutic Drug Monitoring

Mandatory monitoring to prevent toxicity and ensure efficacy 2:

Target levels:

• Peak concentrations: 30-40 mg/L for once-daily dosing 3; avoid exceeding 35 mcg/mL 2
• Trough concentrations: Avoid exceeding 10 mcg/mL 2

Monitoring schedule:

• Measure peak levels 30-90 minutes after infusion 2
• Measure trough levels just prior to next dose 2
• Initial serum monitoring is essential given wide interpatient variability in children 3

Toxicity Considerations

Nephrotoxicity and ototoxicity are the primary concerns requiring vigilant monitoring 2:

• Renal function: Monitor serum creatinine periodically; adjust dosing in renal impairment 2
• Ototoxicity: Instruct patients/families on signs of vestibular toxicity (unsteady gait, tinnitus, diminished hearing); consider baseline and interval audiometry 1
• Duration: Limit treatment to 7-10 days when feasible; if treatment exceeds 10 days, closely monitor amikacin levels and renal, auditory, and vestibular function 2

Pediatric studies show low toxicity rates: No nephrotoxicity was observed in 35 children receiving once-daily dosing 3, and only mild, predominantly reversible high-frequency hearing deficits occurred in 10-25% of patients in comparative studies 6

Critical Pitfalls to Avoid

• Do not use fixed 500 mg doses in pediatrics—this ignores weight entirely and risks treatment failure 7
• Do not exceed 15 mg/kg/day total daily dose by all routes of administration in standard therapy 2
• Do not use every-other-day dosing for IV amikacin—this lacks guideline support and may cause inadequate trough levels 7
• Do not skip therapeutic drug monitoring in children due to high interpatient pharmacokinetic variability 3