Category:Aminoglycosides

From IDWiki

Background

Mechanism of Action

  • Requires electron transport chain (ETC) to cross over the membrane
    • Anaerobes are therefore inherently resistant
  • Reversibly binds 30S ribosomal subunit, which stops proofreading and causes accumulation of bad proteins

Spectrum of Activity

  • Good coverage of Gram-negative aerobes
    • Except Stenotrophomonas and Burkholderia
  • Streptomycin also covers mycobacterium
  • Some protozoal coverage
  • Can cover Gram-positives if cell wall is disrupted (e.g. by beta-lactam)

Mechanisms of Resistance

Pharmacokinetics and Pharmacodynamics

  • Poor membrane penetration, therefore doesn't cross over into lungs and CSF
  • Half-life 2-3 hours (longer in CKD)
  • Excreted 99% unchanged in urine
  • Displays concentration-depedent killing with a prolonged post-antibiotic effect (2-13 hours)

Dosing

Initial Dose

$$ABW = IBW + 0.4 \times (actual BW - IBW)$$

Traditional Dosing

Extended Interval Dosing

  • Q24H dosing, which is safer but less well-studied
  • 7mg/kg (15mg/kg amikacin) IV, frequency depends on CrCl
  • Use Hartford nomogram with a random level (but remember to halve the amikacin level first)

Dialysis Dosing

  • Pre-HD levels with post-HD doses, though this may change

Synergy

  • 1mg/kg divided q8-12h, peak target 3-5, trough <2

Monitoring

Peak

  • 30 minutes after third dose
  • Response is based on peak:MIC ratio, target is 8-10 times
  • If below target, increase dose

Trough

  • Prior to 4th dose, or a random level at 24 to 48h in renal failure
  • Side effects are predicted by trough levels
  • Tobramycin <0.5 (extended) or <2 (traditional)
  • Amikacin <1 (extended) or <?? (traditional)
  • If above target, increase interval

Hartford Nomogram

Hartford nomogram.png

  • Dosing interval is whichever is the line just above the random level
  • Double the concentration for amikacin

Safety

Adverse Drug Reactions

  • Nephrotoxicity (0-50%), usually non-oliguric AKI with decreased Ca/Mg resorption, often reversible
    • Decreased protein synthesis
    • Decreased cellular respiration
    • Increased apoptosis
    • Necrosis in proximal tubules
  • Ototoxicity (0-60%), irreversible
    • Cumulative effect
    • Distribute into the perilymph of the ear, and cause free radical formation causing apoptosis of hair cells
    • Needs hearing tests, because it can be subclinical
      • Monitor audiometry weekly
  • Vestibulotoxicity (0-20%), irreversible
  • Rarely, neuromuscular blockade

Monitoring

  • Trough levels
  • Creatinine
  • Weekly audiometry

Pages in category "Aminoglycosides"

The following 3 pages are in this category, out of 3 total.