What are the guidelines for amikacin dosage and monitoring in nontuberculous mycobacteria (NTM) infections?

Amikacin Dosage and Monitoring Guidelines for NTM Infections

For NTM infections, amikacin should be administered intravenously at 10-15 mg/kg once daily or 15-25 mg/kg three times per week, with mandatory therapeutic drug monitoring to minimize toxicity while ensuring efficacy. 1

Dosing Recommendations

Intravenous Administration

• Daily dosing: 10-15 mg/kg once daily 1
• Intermittent dosing: 15-25 mg/kg three times per week 1
• Alternative dosing: 7.5 mg/kg twice daily (less commonly used) 1

Dose Adjustments

• Obesity: Use adjusted body weight calculation:
  • Male ideal body weight (kg) = 50 + (2.3 × height in cm above 152.4)/2.54
  • Female ideal body weight (kg) = 45.5 + (2.3 × height in cm above 152.4)/2.54
  • Adjusted weight = Ideal body weight + 40% of excess weight 1
• Age: Use lower dose (10 mg/kg) for patients >50 years 1
• Renal impairment: Requires dose reduction or interval extension based on creatinine clearance 1, 2

Therapeutic Drug Monitoring

Target Levels

• Trough level: <5 mg/L (critical to avoid toxicity) 1
• Peak level:
  • Daily dosing: 25-35 mg/L
  • Three times weekly dosing: 65-80 mg/L 1

Timing of Samples

• Trough: Immediately before next dose
• Peak: 60-90 minutes after infusion ends 1

Monitoring Frequency

• Peak serum level in first week, repeat if poor response
• Trough levels weekly for first 4 weeks, then fortnightly when stable 1
• Adjust dose if:
  • Trough level high: Extend dosing interval
  • Peak level high: Reduce dose
  • Peak level low: Increase dose 1

Toxicity Monitoring

Audiometric Testing

• Baseline audiometry before starting therapy
• Regular follow-up testing during treatment (every 1-2 months) 1, 3
• Note: Subjective hearing changes often don't correlate with objective findings 3

Renal Function

• Baseline creatinine and estimated GFR
• Weekly monitoring initially, then at least monthly 1, 2
• BUN is less reliable for monitoring renal function 2

Vestibular Function

• Regular clinical assessment for balance issues, vertigo, dizziness 1, 3

Specific Considerations for NTM Species

M. avium Complex (MAC)

• Amikacin is not recommended as part of initial treatment regimen 4
• Add amikacin after at least six months of failed guideline-based therapy 4, 5
• Consider liposomal amikacin inhalation (590 mg/day) for refractory cases 1

M. abscessus

• Amikacin is a critical component of treatment regimens 1
• Should be combined with macrolides and at least one other parenteral agent (cefoxitin or imipenem) 1
• Minimum 2-4 months of amikacin therapy recommended for initial phase 1

Risk Factors for Toxicity

Ototoxicity

• Female sex (OR 4.96) 6
• Higher cumulative dose per kg body weight 3, 6
• Advanced age 3
• Longer duration of therapy 2
• East Asian ethnicity appears protective (OR 0.24) 6

Nephrotoxicity

• Concurrent nephrotoxic medications
• Pre-existing renal impairment
• Dehydration 2

Treatment Outcomes

Despite optimal therapy with amikacin:

• Culture conversion rates range from 38-49% 7, 6
• Clinical improvement occurs in approximately 68-76% of patients 7, 6

Important Cautions

• Never combine amikacin with other aminoglycosides (streptomycin, kanamycin) as there is no clinical benefit and increased toxicity risk 1
• Avoid concurrent use of other nephrotoxic or ototoxic drugs (cisplatin, furosemide, vancomycin) 2
• Do not nebulize intravenous amikacin formulation mixed with other nebulized drugs 1
• Contraindicated in myasthenia gravis and pregnancy (risk of fetal ototoxicity) 1, 2

The balance between efficacy and toxicity is challenging in NTM treatment. Close monitoring is essential, as studies show significant rates of ototoxicity (7-39%) even with careful dosing and monitoring 3, 7, 6.