Aminoglycosides

Bactericidal antimicrobials that prevent protein synthesis by irreversible binding to the 30S ribosomal subunit, preventing mRNA transcription.

  • As they are large, polar molecules, they must be actively transported into the cell
    • This occurs with an oxygen dependent transporter
      Therefore they are not effective against anaerobes.
  • Transport is inhibited by increased Ca2+, Mg2+, low pH, and low O2
  • Aminoglycoside killing is dependent on the peak concentration over MIC
    Typically peak concentration must be 8-10x MIC.
    • Exposure to aminoglycosides causes bacteria to down-regulate aminoglycoside uptake, and therefore increases MIC
      This effect disappears after ~24 hours, and is one justification for daily dosing of aminoglycosides. Additional justifications include:
      • Allows larger single doses to be used, increasing bactericidal effect
      • Aminoglycosides exhibit a post-antibiotic effect
        Ongoing bactericidal activity even after concentration falls.
Property Gentamicin
Uses/Spectrum Gram negative including pseudomonas, limited gram positive (staph, limited strep), synergistic effects with β-lactams and vancomycin.
Route of Administration IV only.
Dosing 4-7mg.kg-1.
Distribution 70% protein bound. Very small VD of 0.2L.kg-1, which may result in significant pharmacokinetic changes with oedema.
Metabolism Not metabolised.
Elimination Eliminated unchanged, elimination t1/2 prolonged up to 70 hours in renal impairment.
CNS Ototoxicity due to accumulation in perilymph, and is usually permanent. Increased risk with concomitant frusemide use.
MSK Muscle weakness.
Renal Nephrotoxicity due to accumulation in the renal cortex, typically reversible.
Toxic Effects Narrow therapeutic index, requires monitoring and dose reduction in renal impairment.

References

  1. Peck TE, Hill SA. Pharmacology for Anaesthesia and Intensive Care. 4th Ed. Cambridge University Press. 2014.
  2. Stubbings W, Bostock J, Ingham E, Chopra I Mechanisms of the post-antibiotic effects induced by rifampicin and gentamicin in Escherichia coli. J Antimicrob Chemother. 2006 Aug;58(2):444-8.
  3. Deranged Physiology - Kill Characteristics of Antibiotic Agents
Last updated 2017-08-12

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