Amikacin 

Introduction

Amikacin is a  aminoglycoside antibiotic widely used in ICU settings for severe Gram-negative infections, especially when resistance to gentamicin or tobramycin is suspected.

It is a concentration-dependent bactericidal drug therefore (Once-Daily High-Dose Strategy preferred) with a significant post-antibiotic effect (PAE), making it highly valuable in septic shock and ventilator-associated infections.


Key Pharmacodynamic Features

  • Concentration-dependent killing
  • High Peak/MIC ratio (>8–10 desired)
  • Significant post-antibiotic effect
  • Synergistic with beta-lactams


 Spectrum of Activity

Strong Activity Against:

  • Enterobacterales (E. coli, Klebsiella, Enterobacter)
  • Pseudomonas aeruginosa
  • Acinetobacter species
  • Serratia
  • Citrobacter
  • Proteus

Moderate/Variable:

  • Staphylococcus aureus (including some MRSA strains, synergistic use)

Not Active Against:

  • Anaerobes
  • Streptococci (poor penetration unless synergistic use)


 Clinical Indications (ICU-Relevant)

1️⃣ Severe Sepsis / Septic Shock

Used empirically with beta-lactam in:

  • Suspected MDR Gram-negative sepsis
  • ESBL infections
  • Carbapenem-resistant organisms (as combination therapy)

2️⃣ Ventilator-Associated Pneumonia (VAP)

3️⃣ Intra-abdominal Sepsis (Combination therapy)

4️⃣ Complicated UTI / Pyelonephritis


Pharmacokinetics 

Absorption

  • Not absorbed orally
  • IV or IM administration only

Distribution

  • Poor CSF penetration (unless meningitis)
  • Poor lung epithelial lining fluid penetration
  • Accumulates in:
    • Renal cortex
    • Inner ear

 Infusion Duration

  • Infuse over 30–60 minutes
  • Avoid rapid bolus (risk of neuromuscular blockade)


 Adverse Effects 

1️⃣ Nephrotoxicity

  • Causes acute tubular necrosis

Reversible if detected early.


2️⃣ Ototoxicity

Irreversible.

Two types:

  • Vestibular toxicity → Vertigo, imbalance
  • Cochlear toxicity → Hearing loss
  • Avoid in pregnancy (ototoxic risk to fetus)

3️⃣ Neuromuscular Blockade

Rare but dangerous.

Mechanism:

  • Inhibits acetylcholine release

Risk:

  • Myasthenia gravis
  • Concurrent neuromuscular blockers

Reversed with calcium.

Trough is most important to prevent toxicity.


 Resistance Mechanisms

  1. Aminoglycoside-modifying enzymes
  2. Ribosomal mutation
  3. Reduced permeability
  4. Efflux pumps

Amikacin is resistant to many enzymes that inactivate gentamicin.


Combination Therapy Role

Common ICU combinations:

  • Piperacillin-tazobactam + Amikacin
  • Meropenem + Amikacin
  • Colistin + Amikacin (for MDR organisms)

Used for:

  • Broad empirical coverage
  • Synergy
  • Preventing resistance