What is the recommended amikacin injection dosage for adults, including loading dose for severe infections and adjustments for renal impairment?

Amikacin Injection Dosage

For adults with normal renal function, administer amikacin 15 mg/kg once daily (maximum 1.5 grams/day) as an intravenous infusion over 30-60 minutes, with dose adjustments required for patients over 59 years (reduce to 10 mg/kg/day) and those with renal impairment (maintain 12-15 mg/kg but extend dosing interval to 2-3 times weekly). 1, 2, 3

Standard Adult Dosing

Daily Regimen:

• 15 mg/kg once daily is the preferred dosing strategy for most adults, administered as a single dose 5-7 days per week initially 1, 2, 4
• Maximum daily dose should not exceed 1.5 grams regardless of weight 1
• Alternative dosing: 7.5 mg/kg every 12 hours or 5 mg/kg every 8 hours for divided dosing 1, 2

Intermittent Dosing:

• After the first 2-4 months or culture conversion, frequency can be reduced to 15-25 mg/kg three times per week depending on efficacy of other drugs in the regimen 2

Loading Dose for Severe Infections:

• For critically ill patients, a loading dose of 20-25 mg/kg may be administered initially, followed by standard maintenance dosing 5, 6
• This higher loading dose is particularly important in septic patients to rapidly achieve therapeutic peak concentrations 6

Age-Related Adjustments

Elderly Patients (>59 years):

• Reduce dose to 10 mg/kg/day (maximum 750 mg) due to increased risk of ototoxicity and nephrotoxicity 2, 3, 4
• This population often has reduced creatinine clearance even with normal serum creatinine 7

Pediatric Dosing:

• Children and older infants: 15-30 mg/kg/day as a single daily dose (maximum 1 gram/day) 2, 4, 1
• Newborns: Loading dose of 10 mg/kg, followed by 7.5 mg/kg every 12 hours 1

Renal Impairment Adjustments

Critical Principle:

• Do not reduce the mg/kg dose—instead extend the dosing interval to maintain concentration-dependent bactericidal activity 2, 4
• Maintain dose at 12-15 mg/kg but reduce frequency to 2-3 times per week 2, 4

Practical Calculation Methods:

Method 1 - Interval Extension:

• Multiply patient's serum creatinine (mg/dL) by 9 to determine dosing interval in hours 1
• Example: If serum creatinine is 2 mg/dL, administer normal dose (7.5 mg/kg) every 18 hours 1

Method 2 - Creatinine Clearance-Based:

• Maintenance dose every 12 hours = (Observed CrCl / Normal CrCl) × Calculated loading dose 1

Hemodialysis Patients:

• Administer dose after dialysis to facilitate directly observed therapy and avoid premature drug removal 4
• Use 12-15 mg/kg dosing 2-3 times weekly 2

Obesity Adjustments

Dosing Weight Calculation:

• Use ideal body weight plus 40% of excess weight for markedly obese patients 2
• Male IBW (kg) = 50 + (2.3 × height in cm above 152.4)/2.54 2
• Female IBW (kg) = 45.5 + (2.3 × height in cm above 152.4)/2.54 2
• This adjustment accounts for decreased distribution of extracellular fluids in adipose tissue 2

Therapeutic Drug Monitoring

Target Concentrations:

• Peak levels: 25-35 mg/L for daily dosing OR 65-80 mg/L for three-times-weekly dosing 2, 4
• Trough levels: <5 mg/L to prevent toxicity 2, 4
• Peak concentrations above 35 mcg/mL and trough above 10 mcg/mL should be avoided 1

Timing of Samples:

• Peak: Draw 60-120 minutes after infusion ends 2
• Trough: Draw immediately before next dose 2
• For optimal assessment, draw levels at 90-120 minutes and 6 hours post-infusion, plot on semilogarithmic paper, and extrapolate back to time=0 for true peak 2

Monitoring Frequency:

• Peak serum level in first week, repeat if poor response 2
• Trough levels weekly for 4 weeks, then can reduce to fortnightly when stable 2
• In septic patients requiring higher doses, TDM should guide daily adjustments to achieve peak/MIC ratio ≥8 6

Safety Monitoring

Baseline Assessment:

• Audiogram, vestibular testing, Romberg testing 3, 4
• Serum creatinine and creatinine clearance 3, 4

Ongoing Monitoring:

• Renal function: Twice weekly during month 1, weekly during month 2, then fortnightly 2
• Increase frequency if evidence of renal impairment develops 2
• Auditory/vestibular symptoms: Question monthly and perform audiogram if symptoms develop 3, 4
• Ototoxicity defined as 20 dB loss at any one frequency or 10 dB loss at two adjacent frequencies 2

Duration of Therapy:

• Usual duration is 7-10 days 1
• If treatment beyond 10 days is considered, re-evaluate necessity and intensify monitoring of serum levels, renal function, and auditory/vestibular function 1

Administration Details

Intravenous Preparation:

• Add 500 mg vial to 100-200 mL of sterile diluent (0.9% sodium chloride or 5% dextrose) 1
• Infuse over 30-60 minutes in adults 1
• Infuse over 1-2 hours in infants 1
• Do not physically premix with other drugs 1

Stability:

• Stable for 24 hours at room temperature at concentrations of 0.25-5 mg/mL in standard IV solutions 1

Critical Pitfalls to Avoid

Common Errors:

• Never use fixed 500 mg doses regardless of weight—this risks underdosing and treatment failure 4
• Never reduce the mg/kg dose in renal impairment—extend the interval instead to maintain bactericidal effect 2, 4
• Never continue beyond 10 days without reassessing drug levels and toxicity monitoring 4, 1
• Never use in pregnancy—absolutely contraindicated due to fetal nephrotoxicity and congenital hearing loss 2, 4

High-Risk Situations:

• Patients with pre-existing renal impairment are at higher risk for further decline in renal function during therapy 6
• Concurrent use of loop diuretics significantly increases ototoxicity risk 2
• CNS infections require awareness that amikacin has poor CSF penetration even with meningitis, potentially necessitating higher systemic doses 3, 4

Clinical Efficacy Considerations

Once-Daily vs. Divided Dosing:

• Once-daily dosing demonstrates superior clinical cure rates (83% vs. 66%) and bacteriological cure rates (81% vs. 58%) compared to twice-daily dosing 5
• Once-daily regimen also associated with less nephrotoxicity (21% vs. 35%) 5
• Early achievement of optimal peak/MIC ratio ≥8 significantly improves clinical and microbiological responses 6

Treatment Response Timeline:

• Uncomplicated infections should respond within 24-48 hours 1
• If no definite clinical response within 3-5 days, discontinue and recheck antibiotic susceptibility 1