What is the recommended amikacin dosing regimen for an adult with a confirmed or suspected Acinetobacter infection and normal renal function?

Amikacin Dosing for Acinetobacter Infections

For adults with normal renal function and confirmed or suspected Acinetobacter infection, administer amikacin 15–20 mg/kg intravenously once daily, targeting peak serum concentrations of 65–80 mg/L and trough levels below 5 mg/L. 1, 2, 3

Standard Dosing Regimen

Once-daily dosing at 15–20 mg/kg is the preferred approach for Acinetobacter pneumonia and other serious infections in hemodynamically stable patients with normal renal function. 1, 3 This regimen achieves peak concentrations around 40.9 mg/L with standard dosing, though higher peaks (65–80 mg/L) may be targeted for optimal concentration-dependent bacterial killing. 2, 3

Critical Illness and Hemodynamic Instability

• In patients with unstable hemodynamics or septic shock, administer a full loading dose immediately (25–30 mg/kg) to rapidly achieve therapeutic levels, as fluid resuscitation expands extracellular volume and increases the volume of distribution. 2, 4
• The loading dose is independent of renal function; only maintenance dosing requires renal adjustment. 2
• For critically ill patients, 25 mg/kg may be insufficient in 30–39% of cases, particularly in those with positive fluid balance or low BMI. 5, 6

Combination Therapy for Acinetobacter

Amikacin should be combined with other anti-Acinetobacter agents rather than used as monotherapy:

• Carbapenem-sensitive strains: Combine amikacin with imipenem 500 mg IV q6h or meropenem 1 g IV q8h (consider extended infusion). 1
• Carbapenem-resistant strains: Combine amikacin with colistin 5 mg/kg IV loading dose, then 2.5 mg × (1.5 × CrCl + 30) IV q12h, plus a carbapenem or ampicillin/sulbactam 3 g IV q6h. 1
• Adjunctive inhaled colistin (1.25–15 MIU daily divided q8–12h) may be added for pneumonia caused by polymyxin-only-sensitive strains. 1

Therapeutic Drug Monitoring

Measure both peak and trough concentrations to ensure efficacy while minimizing toxicity:

• Peak levels: Draw 60–120 minutes after infusion ends (90–120 min preferred for accuracy). Target 65–80 mg/L for three-times-weekly dosing or 25–35 mg/L for daily dosing. 2, 7
• Trough levels: Draw immediately before the next dose. Target < 5 mg/L to minimize nephrotoxicity (< 10 mg/L is acceptable for divided dosing). 2, 7
• Timing: Obtain a peak level during the first week of therapy; measure troughs weekly for 4 weeks, then every 2 weeks once stable. 2, 8
• Inadequate initial peaks are linked to clinical failure—ensure appropriate dosing and early TDM. 2

Renal Impairment Adjustments

Never reduce the mg/kg dose in renal impairment—this is a critical pitfall that leads to therapeutic failure. 3, 8

• Maintain the full 12–15 mg/kg per dose and extend the dosing interval (e.g., every 2–3 days or 2–3 times weekly). 3, 8
• For hemodialysis patients, administer 12–15 mg/kg after each dialysis session to facilitate directly observed therapy and prevent premature drug removal. 3, 8
• Alternative method: If creatinine clearance is known and the patient is stable, calculate the dosing interval in hours by multiplying serum creatinine (mg/dL) by 9. 7

Special Populations

Obesity

• Calculate adjusted body weight (ideal body weight + 40% of excess weight) to avoid underdosing in markedly obese patients. 2
• Low BMI (< 22–25 kg/m²) is a risk factor for underdosing, particularly in the first quarter of therapy or with positive fluid balance. 5, 6

Elderly Patients

• For patients ≥ 50–59 years old or those requiring ≥ 3 weeks of therapy, reduce the dose to 10 mg/kg once daily to lower toxicity risk while maintaining efficacy. 2, 8

Positive Fluid Balance

• Positive 24-hour fluid balance is an independent predictor of insufficient peak concentrations. 5, 6
• Consider increasing the dose to 30–35 mg/kg in patients with ongoing fluid resuscitation or low BMI to achieve target peaks. 6

Duration and Monitoring for Toxicity

• Duration: Limit therapy to 7–10 days for uncomplicated infections; re-evaluate if treatment beyond 10 days is needed. 7
• Nephrotoxicity: Occurs in 8.7% overall but only 3.4% in patients without risk factors; monitor serum creatinine closely, especially in those with pre-existing renal impairment or concurrent nephrotoxic agents (NSAIDs, vancomycin, loop diuretics). 3, 4
• Ototoxicity: High-frequency hearing loss occurs in approximately 24% with prolonged therapy; perform baseline audiogram and vestibular testing before starting amikacin, then monthly monitoring for auditory or vestibular symptoms. 8
• Monitor electrolytes for hypocalcemia, hypomagnesemia, and hypokalemia during therapy. 2

Common Pitfalls

• Do not reduce the per-dose amount in renal insufficiency—only extend the interval while maintaining 12–15 mg/kg per dose. 3, 8
• Avoid concurrent nephrotoxic agents whenever possible, as this significantly increases nephrotoxicity risk. 3
• Do not use monotherapy—amikacin must be combined with other agents for Acinetobacter infections. 1
• Ensure adequate loading doses in critically ill patients with expanded volumes of distribution from fluid resuscitation. 2, 4