What is the recommended use and dosage of amikacin (an aminoglycoside antibiotic) for treating infections?

Amikacin Dosage and Administration Guidelines

Amikacin should be administered at 15 mg/kg/day as a single daily dose for 7-10 days for most serious bacterial infections, with dose adjustments required for patients with renal impairment and careful monitoring of serum levels to prevent toxicity. 1

Standard Dosing Recommendations

Adult Dosing

• Standard dose: 15 mg/kg/day as a single daily dose 1, 2
• Alternative regimen: 15 mg/kg/day divided into 2-3 equal doses (7.5 mg/kg q12h or 5 mg/kg q8h) 1
• Maximum daily dose: 1.5 grams regardless of weight 1
• Duration: 7-10 days for most infections 1, 2
• Uncomplicated UTIs: 250 mg twice daily may be sufficient 1

Pediatric Dosing

• Children and older infants: 15 mg/kg/day divided into 2-3 equal doses 1
• Newborns: Initial loading dose of 10 mg/kg followed by 7.5 mg/kg every 12 hours 1
• Single daily dosing option: 20 mg/kg once daily has shown efficacy and safety in pediatric patients with severe gram-negative infections 3

Special Population Considerations

Renal Impairment

Two approaches for dosing in renal impairment 1:

1. Normal dose at prolonged intervals:

   • Calculate interval (hours) = patient's serum creatinine × 9
   • Example: For serum creatinine of 2 mg/dL, give 7.5 mg/kg every 18 hours

2. Reduced dose at fixed intervals:

   • Start with normal loading dose (7.5 mg/kg)
   • Reduce maintenance doses based on creatinine clearance
   • Monitor serum levels closely

Elderly Patients

• For patients >59 years old, reduce dose to 10 mg/kg/day 4

Weight Considerations

• For obese patients, calculate dose using ideal body weight plus 40% of excess weight 2

Administration Routes

• Intramuscular: Standard administration route 1
• Intravenous: Administer over 30 minutes 5

Therapeutic Monitoring

Target Serum Levels

• Peak levels: 25-35 μg/mL (measured 30-90 minutes after infusion) 2, 1
• Trough levels: <5-10 μg/mL (measured just before next dose) 2, 1
• Warning: Peak concentrations above 35 μg/mL and trough concentrations above 10 μg/mL should be avoided 1

Monitoring Schedule

• Peak levels: Measure in first week and repeat if poor response 2
• Trough levels: Measure weekly for 4 weeks, then every 2 weeks when stable 2
• Renal function: Regular assessment of serum creatinine and creatinine clearance 1

Specific Clinical Applications

Tuberculosis Treatment

• For drug-resistant tuberculosis: 15 mg/kg/day (maximum 1.0 g/day) as a single daily dose initially 4
• After 2-4 months or culture conversion, reduce to 2-3 times per week 4

Nontuberculous Mycobacterial Infections

• For M. abscessus infections: 10-15 mg/kg daily to achieve peak serum levels in low 20 μg/mL range 4
• Consider three-times-weekly dosing at 25 mg/kg for long-term therapy (>3 months) 4

Gram-Negative Infections

• Particularly effective against gentamicin-resistant organisms 6, 7
• For serious infections, combine with a β-lactam antibiotic 5

Endocarditis

• Used in combination with other antibiotics for gram-negative enteric bacilli endocarditis 4

Adverse Effects and Monitoring

Major Toxicities

1. Ototoxicity:

   • Monitor for hearing loss, vestibular dysfunction
   • Higher risk with longer treatment duration and higher doses 4
   • Perform baseline audiogram and vestibular testing 4

2. Nephrotoxicity:

   • More nephrotoxic than streptomycin 4
   • Risk factors: pre-existing renal impairment, older age, higher cumulative dose, concurrent nephrotoxic agents 4, 1

Risk Reduction Strategies

• Use single daily dosing when possible (may reduce nephrotoxicity) 5
• Administer after hemodialysis in patients requiring dialysis 4
• Limit treatment duration to shortest effective course 1
• Avoid concurrent use of other nephrotoxic or ototoxic drugs when possible

Treatment Failure Considerations

• If no clinical response within 3-5 days, reevaluate therapy 1
• Consider antibiotic susceptibility testing and possible surgical drainage of septic foci 1

Contraindications

• Pregnancy (risk of fetal nephrotoxicity and congenital hearing loss) 4
• Known hypersensitivity to aminoglycosides

Amikacin remains a valuable antibiotic for serious gram-negative infections, particularly those caused by multidrug-resistant organisms, but requires careful dosing and monitoring to maximize efficacy while minimizing toxicity.