What is the recommended dosing regimen for amikacin (an aminoglycoside antibiotic)?

Amikacin Dosing Recommendations

The recommended dosing regimen for amikacin in adults with normal renal function is 15 mg/kg/day, administered either as a single daily dose or divided into 2-3 doses at equally-divided intervals. 1

Adult Dosing

Normal Renal Function

• Single daily dosing: 15 mg/kg once daily (preferred approach)
• Divided dosing: 7.5 mg/kg every 12 hours or 5 mg/kg every 8 hours
• Maximum daily dose: Should not exceed 1.5 grams per day 1

Target Serum Levels

• Peak concentration:
  • 25-35 mg/kg for daily dosing
  • 65-80 mg/kg for three times weekly dosing 2
• Trough concentration: <5 mg/kg (critical to avoid toxicity) 2, 3
• Timing of samples:
  • Trough: Just before next dose
  • Peak: 90-120 minutes after infusion ends 2

Impaired Renal Function

Two approaches are recommended:

1. Normal dose at prolonged intervals:

   • Calculate interval (hours) = patient's serum creatinine × 9
   • Example: If serum creatinine is 2 mg/dL, administer 7.5 mg/kg every 18 hours 1

2. Reduced dose at fixed intervals:

   • Dosing should be adjusted based on creatinine clearance
   • Serum amikacin concentrations should be monitored 1

Pediatric Dosing

Normal Renal Function

• Infants and children: 15-22.5 mg/kg/day divided every 8 hours 2
• Higher doses: Some experts recommend initial doses of 30 mg/kg/day divided every 8 hours in specific conditions (cystic fibrosis, febrile neutropenia) 2

Neonatal Dosing

Based on weight and postnatal age:

• <1200g, 0-4 weeks: 7.5 mg/kg every 18-24 hours
• 1200-2000g, ≤7 days: 7.5 mg/kg every 12 hours
• >2000g, ≤7 days: 7.5-10 mg/kg every 12 hours
• <1200g, >7 days: 7.5-10 mg/kg every 8-12 hours
• >2000g, >7 days: 10 mg/kg every 8 hours 2

Special Indications

Complicated Urinary Tract Infections

• Standard dose: 15 mg/kg/day IV once daily 2
• Alternative: For uncomplicated UTIs, 250 mg twice daily may be used 1

Non-tuberculous Mycobacterial Pulmonary Disease

• Daily dosing: 15 mg/kg once daily
• Three times weekly dosing: 15-25 mg/kg three times per week 2

Monitoring Recommendations

Frequency of Monitoring

• Serum levels:
  • Peak level in first week, repeat if poor response
  • Trough levels weekly for first 4 weeks, then fortnightly when stable 2, 3
• Renal function: Twice weekly during first month, then monthly 3
• Auditory function: Regular audiometric testing 3

Adjustments Based on Levels

• High trough level: Extend dosing interval
• High peak level: Reduce dose
• Low peak level: Increase dose 2

Important Considerations

Administration

• Dilute in 100-200 mL of compatible solution
• Administer over 30-60 minutes (longer for infants) 3

Safety Concerns

• Nephrotoxicity: More common with prolonged treatment, higher doses, concurrent diuretics, advanced age, and pre-existing renal insufficiency 3
• Ototoxicity: Irreversible vestibulocochlear nerve damage can occur 2
• Endocrine effects: Hypocalcemia, hypomagnesemia, and hypokalemia 2

Evidence for Once-Daily Dosing

Recent research supports once-daily dosing as it:

• Provides higher peak concentrations for better bactericidal activity
• Results in higher clinical cure rates (83% vs 66% for twice-daily dosing) 4
• Demonstrates lower nephrotoxicity (21% vs 35% for twice-daily dosing) 4

For severe sepsis or septic shock, higher loading doses (≥25 mg/kg) may be needed due to increased volume of distribution, though standard maintenance doses are typically sufficient afterward 5.