What is the coverage and dosage of Amikacin (generic name) for treating Gram-negative bacterial infections?

Amikacin Coverage and Dosage for Gram-Negative Bacterial Infections

Amikacin is an effective aminoglycoside antibiotic for treating various gram-negative bacterial infections, with recommended dosage of 15 mg/kg/day divided into 1-2 doses for adults with normal renal function, requiring therapeutic drug monitoring to avoid toxicity. 1

Spectrum of Coverage

• Amikacin is effective against a wide range of gram-negative bacteria, including those resistant to other aminoglycosides (gentamicin, tobramycin) 2, 3

• Particularly effective against:

  • Carbapenem-resistant Enterobacterales (CRE) 4
  • Pseudomonas aeruginosa 5, 6
  • Escherichia coli 5
  • Serratia species 2
  • Acinetobacter species (including Mycobacterium abscessus) 4
  • HACEK group organisms 4

• In China, CRE isolates show significantly higher susceptibility to amikacin than to gentamicin 4

Standard Dosing for Adults with Normal Renal Function

• FDA-approved dosing: 15 mg/kg/day divided into 2-3 equal doses (7.5 mg/kg q12h or 5 mg/kg q8h) 1
• Once-daily dosing alternative: 15 mg/kg IV once daily - practical, efficacious and safe in critically ill patients 5, 6
• Maximum daily dose: Should not exceed 1.5 grams/day 1
• Duration: Typically 7-10 days; limit to short-term whenever feasible 1

Dosing in Special Populations

Renal Impairment

• Creatinine clearance >80 ml/min: 15 mg/kg once daily 5
• Creatinine clearance 50-80 ml/min: 12 mg/kg once daily 5
• Creatinine clearance <50 ml/min: 8 mg/kg once daily 5
• Alternative method: Calculate interval by multiplying serum creatinine by 9 hours (e.g., serum creatinine 2 mg/dL = administer every 18 hours) 1

Pediatric Dosing

• Children and older infants: 15-22.5 mg/kg/day IV divided every 8 hours or once daily 4
• Neonates: Varies by gestational and postnatal age 4
  • Gestational age <30 weeks:
    • Postnatal age <14 days: 15 mg/kg/dose IV q48h
    • Postnatal age >14 days: 15 mg/kg/dose IV q24h

Therapeutic Drug Monitoring (TDM)

• TDM is strongly recommended to optimize dosing regimen, improve efficacy, and reduce toxicity 4
• Target levels:
  • Peak concentrations (30-90 minutes after injection): <35 μg/mL 1
  • Trough concentrations (just before next dose): <10 μg/mL 1
• TDM-guided aminoglycoside treatment is associated with shorter hospital stays, lower mortality rates, and reduced nephrotoxicity compared to non-TDM guided therapy 4

Clinical Applications

Carbapenem-Resistant Gram-Negative Bacilli

• Recommendation: Amikacin-containing combination therapy is suggested for treatment of CRE infections in patients without contraindications to aminoglycosides (conditional recommendation, very low quality evidence) 4
• Combination therapies containing amikacin showed 59 fewer deaths per 1000 patients and 417 fewer clinical treatment failures per 1000 patients compared to non-aminoglycoside combinations 4

Specific Infections

• Bloodstream infections: Amikacin 15 mg/kg/day IV once daily, typically for 7-14 days 4
• Complicated urinary tract infections: Amikacin 15 mg/kg/day IV once daily for 5-7 days 4
• Mycobacterium abscessus infections:
  • Amikacin 10-15 mg/kg daily IV (lower dose for patients >50 years or requiring >3 weeks therapy) 4
  • Alternative: 25 mg/kg three times weekly (may be difficult to tolerate >3 months) 4
  • Combined with other agents (cefoxitin, imipenem, macrolides) for at least 4 months 4

Adverse Effects and Precautions

• Major toxicities: Ototoxicity and nephrotoxicity 4, 7
• Monitoring recommendations:
  • Regular assessment of renal function 1
  • Avoid concomitant nephrotoxic drugs 4
  • Consider audiometric testing for prolonged therapy 7
• Contraindications: History of serious hypersensitivity reactions to aminoglycosides 1

Combination Therapy

• Often used in combination with other antibiotics for synergistic effects:
  • With beta-lactams (ceftazidime, cefepime) for Pseudomonas and other gram-negative infections 5
  • With carbapenems, tigecycline, or polymyxins for CRE infections 4
  • With macrolides and other parenteral agents for Mycobacterium abscessus 4

Pitfalls and Caveats

• Therapeutic window is narrow - underdosing risks treatment failure while overdosing increases toxicity risk 1
• Renal function must be monitored throughout treatment 1
• Susceptibility testing is essential as resistance patterns vary geographically 4
• Avoid in pregnancy if possible due to potential fetal ototoxicity 1
• Not effective as monotherapy for serious mixed infections - always consider appropriate combination therapy 4, 5