Aminoglycosides

Snapshot

  • A 24-year-old woman presents to the emergency room for abdominal pain and foul-smelling discharge from her vagina. About 4 days ago, she gave birth to twins via C-section and was sent home without complications. Yesterday, she developed a fever as well as abdominal pain. On physical exam, there is significant tenderness to palpation. She is started on intravenous antibiotic therapy with 2 agents, covering both anaerobes and aerobic gram-negative organisms. (Postpartum endometritis)

Introduction

  • Drugs
    • amikacin
    • gentamicin
    • neomycin
    • streptomycin
    • tobramycin
  • Mechanism of action 
    • irreversibly binds to 30S subunit of bacterial ribosomes   
      • prevents initiation complex from forming
      • causes misreading of genetic code
    • requires oxygen for uptake and is effective only against aerobes
    • works synergistically with beta-lactams
    • bactericidal
  • Mechanism of resistance 
    • bacterial enzymes inactivate the drug by modifying it through adenylation, acetylation, or phosphorylation
  • Clinical use
    • severe aerobic gram-negative rod infections
      • including Pseudomonas aeruginosa, Acinetobacter, Nocardia, and Actinomycetes
      • P aeruginosa resistant to gentamicin and tobramycin are often susceptible to amikacin
    • neomycin for bowel surgery
    • topical neomycin for superficial skin infections
  • Adverse effects
    • irreversible ototoxicity (cochlear and vestibular) 
      • increased with loop diuretics
    • nephrotoxicity
      • increased with cephalosporins
    • neuromuscular blockade
    • teratogen