What is an aminoglycoside antibiotic?

Aminoglycoside Antibiotics: Mechanism, Uses, and Considerations

Aminoglycosides are a class of bactericidal antibiotics that inhibit protein synthesis by binding to the 30S ribosomal subunit of bacteria, primarily effective against aerobic gram-negative bacteria and some gram-positive organisms. 1, 2

Mechanism of Action

• Aminoglycosides bind to the aminoacyl site (A) of the 16S RNA within the bacterial 30S ribosomal subunit, inhibiting protein synthesis and causing bacterial cell death 1
• They exhibit concentration-dependent bactericidal activity, meaning their killing power increases with higher concentrations 3
• Aminoglycosides demonstrate a post-antibiotic effect, allowing for continued antibacterial activity even after serum concentrations become undetectable 3

Common Aminoglycosides

• Gentamicin - most commonly used aminoglycoside for general purposes 3
• Tobramycin - slightly more effective against Pseudomonas aeruginosa infections 3
• Amikacin - most resistant to degradation by bacterial enzymes that cause resistance 3, 2
• Netilmicin - considered to have the lowest toxicity profile among aminoglycosides 3

Antimicrobial Spectrum

• Highly effective against many gram-negative bacteria including:
  • Pseudomonas aeruginosa
  • Escherichia coli
  • Klebsiella species
  • Enterobacter species
  • Proteus species
  • Serratia species
  • Acinetobacter species 1, 2
• Limited activity against gram-positive bacteria, except for Staphylococcus aureus 1
• Generally ineffective against Streptococcus pneumoniae, Streptococcus pyogenes, and enterococci 1
• Demonstrate synergistic effects when combined with beta-lactam antibiotics, particularly against Enterococcus faecalis and severe gram-negative infections 2, 3

Clinical Applications

• Treatment of severe infections including:
  • Complicated urinary tract infections 4, 5
  • Intra-abdominal infections 4
  • Bacteremia and sepsis 3
  • Respiratory infections, particularly in cystic fibrosis patients with Pseudomonas aeruginosa 4, 6
  • Infective endocarditis (in combination with cell wall-active agents) 4
• Ideal for single-dose treatment of uncomplicated lower UTIs due to high urinary concentrations 4, 5
• Used in combination therapy for synergistic effects against resistant organisms 6

Dosing Considerations

• Single daily dosing is now preferred over traditional multiple daily dosing for most indications due to:
  • Equal or better efficacy
  • Reduced toxicity risk
  • Cost-effectiveness 4, 3, 7
• Exceptions where traditional multiple daily dosing may still be recommended:
  • Infective endocarditis
  • Immunocompromised patients 3, 7
• In cystic fibrosis, higher doses are often needed due to altered pharmacokinetics and the endobronchial location of infections 4, 6

Toxicity and Monitoring

• Major adverse effects include:
  • Nephrotoxicity (kidney damage) - usually reversible 8, 9
  • Ototoxicity (hearing loss) - often irreversible 8, 9
  • Vestibular toxicity (balance disorders) 6, 9
• Risk factors for toxicity include:
  • Prolonged therapy
  • Volume depletion
  • Concomitant nephrotoxic medications
  • Pre-existing renal impairment
  • Advanced age 8, 7
• Monitoring recommendations:
  • Drug level monitoring when treatment exceeds 24-48 hours 4
  • For multiple daily dosing: monitor after 24 hours 4
  • For single daily dosing: monitor after 48 hours 4
  • Baseline and periodic assessment of renal function 4, 5
  • Consider baseline audiogram for extended therapy 5

Resistance Mechanisms

• Bacterial resistance to aminoglycosides occurs through:
  • Production of aminoglycoside-modifying enzymes
  • Alteration of the ribosomal target via 16S rRNA methyltransferases
  • Upregulation of efflux pumps
  • Reduced permeability into bacterial cells 1, 10
• Amikacin often remains effective against bacteria resistant to other aminoglycosides 2, 10

Special Considerations

• Not recommended as first-line therapy for community-acquired intra-abdominal infections due to toxicity concerns 4
• Should be avoided when suitable, less nephrotoxic alternatives are available 4
• Topical or local applications (e.g., respiratory aerosols) are preferred over systemic administration when feasible 4
• In pregnancy, aminoglycosides should be avoided if possible due to potential eighth cranial nerve damage in the fetus 6
• Aminoglycosides are poorly absorbed from the gastrointestinal tract, requiring parenteral administration for systemic infections 1