What is the recommended dose of amikacin (an aminoglycoside antibiotic) for adults with normal renal function?

Amikacin Dosing in Adults

Standard Dosing for Normal Renal Function

For adults with normal renal function, administer amikacin 15 mg/kg/day (maximum 1 gram/day) as a single daily dose via intramuscular or intravenous route. 1

Primary Dosing Regimens

• Single daily dosing (preferred): 15 mg/kg once daily is the standard approach, administered as a 30-60 minute IV infusion or IM injection 2, 1
• Alternative divided dosing: 7.5 mg/kg every 12 hours OR 5 mg/kg every 8 hours can be used, though once-daily dosing demonstrates superior clinical outcomes 1, 3
• Maximum daily dose: Do not exceed 1.5 grams/day regardless of weight 1

Evidence Supporting Once-Daily Dosing

Once-daily administration achieves better clinical outcomes compared to divided dosing. In a randomized trial of 348 critically ill patients, once-daily dosing resulted in an 83% clinical cure rate versus 66% with twice-daily dosing (P=0.001), and nephrotoxicity occurred in only 21% versus 35% with twice-daily dosing (P=0.05) 3. The concentration-dependent bactericidal effect of aminoglycosides makes single daily dosing both more effective and safer 2, 4.

Age-Related Dose Adjustments

• Patients >59 years: Reduce dose to 10 mg/kg/day (maximum 750 mg) due to age-related decline in renal function and increased risk of ototoxicity and nephrotoxicity 2, 5, 6
• Standard adult dosing applies to ages 18-59 years 2, 1

Renal Impairment Dosing

Critical principle: In renal insufficiency, maintain the mg/kg dose at 12-15 mg/kg but reduce the dosing frequency to 2-3 times per week—never reduce the individual dose. 2, 5

Dosing Interval Adjustment Method

• Calculate extended interval by multiplying serum creatinine (mg/dL) by 9 hours 1
• Example: If serum creatinine = 2 mg/dL, administer 7.5 mg/kg every 18 hours 1
• For hemodialysis patients, administer the full dose (12-15 mg/kg) after dialysis to prevent premature drug removal 2, 5

Rationale for Maintaining Dose

Smaller doses reduce drug efficacy by failing to achieve the concentration-dependent bactericidal effect that aminoglycosides require 2. The pharmacodynamic benefit comes from high peak concentrations, not prolonged exposure 4.

Obesity Dosing

• Use ideal body weight plus 40% of excess weight for dose calculation 5, 7
• Do not use actual body weight in obese patients as this leads to excessive dosing and toxicity 5

Therapeutic Drug Monitoring

Target Levels

• Peak (daily dosing): 25-35 mg/L 5, 7
• Peak (three times weekly): 65-80 mg/L 5, 7
• Trough: <5 mg/L to prevent toxicity 5, 7, 1

Monitoring Schedule

• Measure peak levels within the first week of therapy 7
• Check trough levels weekly for 4 weeks, then every 2 weeks when stable 7
• Serum drug concentration monitoring is essential to avoid toxicity, particularly in renal impairment 2, 1

Baseline and Ongoing Monitoring

Baseline Assessment

• Audiogram 2, 5, 6
• Vestibular testing 2, 5, 6
• Romberg testing 2, 5
• Serum creatinine measurement 2, 5, 6

Monthly Monitoring

• Renal function assessment 2, 5, 6
• Question patient about auditory symptoms (hearing loss, tinnitus) 2, 5, 6
• Question patient about vestibular symptoms (dizziness, imbalance) 2, 5, 6
• Repeat audiogram and vestibular testing if any symptoms of eighth nerve toxicity develop 2, 5, 6

Duration of Therapy

• Standard duration: 7-10 days 1
• Extended therapy: If treatment beyond 10 days is necessary, re-evaluate the indication and intensify monitoring of amikacin serum levels, renal function, and auditory/vestibular function 1
• Tuberculosis: Initially give 5-7 days/week, then reduce to 2-3 times weekly after 2-4 months or culture conversion 2, 6

Toxicity Considerations

Nephrotoxicity

• Occurs in 8.7% of patients overall, but only 3.4% in those without risk factors 2, 5
• Risk factors include baseline renal impairment, higher cumulative doses, and concurrent nephrotoxic agents 2, 5
• Amikacin may be more nephrotoxic than streptomycin 2

Ototoxicity

• High-frequency hearing loss occurs in 1.5-24% of patients, with higher rates in longer treatment courses and higher doses 2, 5
• Amikacin causes primarily cochlear toxicity (deafness) with less vestibular dysfunction than streptomycin 2
• Risk increases with age, concurrent loop diuretics, higher single doses, and cumulative doses above 100-120 grams 6

Absolute Contraindications

• Pregnancy: Amikacin is absolutely contraindicated due to risk of fetal nephrotoxicity and congenital hearing loss 2, 5, 7

Common Pitfalls to Avoid

• Do not reduce the mg/kg dose in renal impairment—extend the dosing interval instead while maintaining 12-15 mg/kg per dose 2, 5
• Do not use fixed 500 mg doses regardless of weight—this risks underdosing in larger patients and treatment failure 5
• Do not continue therapy beyond 10 days without reassessing drug levels and monitoring for toxicity 5, 1
• Do not use actual body weight in obese patients—use adjusted body weight (IBW + 40% excess) 5

Special Clinical Context: CNS Infections

• Amikacin has poor CSF penetration even with meningitis, which may necessitate higher systemic doses or alternative agents 2, 6
• Only low concentrations reach the CSF, though slightly higher in active meningitis 2