Amikacin Dosing for Severe Infections
For patients with normal renal function and severe infections, administer amikacin 15 mg/kg once daily (maximum 1.5 g/day), which achieves superior peak concentrations and equivalent or better efficacy compared to divided dosing while potentially reducing nephrotoxicity risk. 1, 2, 3
Standard Dosing Algorithm
For Normal Renal Function:
- Once-daily dosing: 15 mg/kg/day as a single dose (preferred regimen) 1, 2, 3
- Alternative divided dosing: 7.5 mg/kg every 12 hours OR 5 mg/kg every 8 hours 2
- Maximum daily dose: 1.5 g/day regardless of weight 2
- Once-daily dosing achieves peak levels of ~40.9 mg/L (approximately 10× MIC for most gram-negative bacteria), compared to only 24.4 mg/L with twice-daily dosing 3
For Patients >59 Years:
- Reduce dose to 10 mg/kg/day (maximum 750 mg) due to age-related decline in renal function 4
Duration:
- Standard therapy: 7-10 days 2
- Complicated infections: 4-7 days with adequate source control 1
- If treatment beyond 10 days is required, mandatory monitoring includes serum drug levels, renal function, and auditory/vestibular testing 2
Renal Impairment Dosing (Critical)
The most common dosing error is reducing the per-dose amount—never do this. 1, 5, 6
Dosing Principle:
- Maintain full dose of 12-15 mg/kg per administration 4, 1
- Only reduce frequency to 2-3 times per week 4, 5
- This preserves concentration-dependent bactericidal killing while minimizing toxicity 1, 6
Calculation Methods:
Method 1 (Prolonged Interval): Multiply serum creatinine (mg/dL) by 9 to determine dosing interval in hours 2
- Example: Creatinine 2.0 mg/dL → give 7.5 mg/kg every 18 hours 2
Method 2 (Reduced Dose at Fixed Interval):
- Loading dose: 7.5 mg/kg 2
- Maintenance dose every 12 hours = (Observed CrCl/Normal CrCl) × Loading dose 2
Hemodialysis Patients:
- Administer full dose (12-15 mg/kg) after dialysis sessions to prevent premature drug removal and facilitate directly observed therapy 1, 6
Monitoring Requirements
Baseline (Before Starting):
During Therapy:
- Renal function monitoring:
- Serum drug concentrations: Target peak ~20 mg/L for once-daily dosing; trough <5 mg/L 1, 6
- Monthly questioning for auditory/vestibular symptoms 4
- Repeat audiogram if any eighth nerve toxicity symptoms develop 4, 5
Nephrotoxicity Risk Stratification
Overall Risk:
- 8.7% nephrotoxicity rate overall 4, 5
- Only 3.4% in patients without risk factors 4, 6
- Significantly lower (1.076/person-year) in noncritically ill patients with normal baseline renal function 7
High-Risk Patients Requiring Intensive Monitoring:
- Pre-existing renal insufficiency 5
- Age >59 years 5
- Initially elevated creatinine 4, 5
- Concurrent nephrotoxic agents (NSAIDs, vancomycin, loop diuretics) 5, 6
- Volume depletion or hemodynamic instability 5
- Congestive heart failure 5
- Hepatic disease (predisposes to hepatorenal syndrome) 5
Critical Pitfalls to Avoid
Never combine amikacin with NSAIDs (especially diclofenac)—this significantly increases nephrotoxicity beyond the baseline 8.7% 5, 6
Never reduce the mg/kg dose in renal impairment—only extend the interval 1, 5, 6
- Smaller doses reduce efficacy by failing to achieve concentration-dependent killing 4
Use adjusted body weight (lean body mass) for dosing in obese patients, not total body weight 1
Do not use standard unmonitored dosing—6.1% of patients are at risk for toxicity without therapeutic drug monitoring 8
Avoid concurrent loop diuretics (furosemide, ethacrynic acid), which increase both ototoxicity and nephrotoxicity risk 4
Contraindicated in pregnancy due to fetal nephrotoxicity and congenital hearing loss 4
Administration Details
Intravenous:
- Infuse over 30-60 minutes in adults 2
- Infuse over 1-2 hours in infants 2
- Compatible with normal saline, D5W, lactated Ringer's, and other standard IV solutions 2
- Stable for 24 hours at room temperature at concentrations of 0.25-5 mg/mL 2