Monday, November 19, 2007

Chapter 45: Aminoglycosides

- active ingredient - hexose ring attaching to amino sugars
- works in synergism with B-lactams + vancomycin
- MOA: irresible protein synthesis inhibitor - exact mechanism unknown

  • passive diffusion via porin channel across outer membrane (see B-lactamase cell wall)
  • actively transported into cytoplasm
  • binds to 30S subunit ribosomal protein
  • inhibit protein synthesis
- resistance - NO activity against anaerobes

  1. production of transferase enzyme/enzyme that inactivate aminoglycoside
  2. impaired entry into cell --> mutation/deletion of porin protein
  3. receptor protein on 30S ribosomal subunit deleted/altered
- pharmacokinetics

  • poorly absorbed po unless has ulcers
  • IM or IV
  • cencentration-dependent killing + has postantibiotic effects (several hours) --> hence can be given OD rather than traditional TDS in smaller doses
- aminoglycoside toxicity

  • concentration and time dependent
  • toxic threshold achieved --> once the concentration achieved --> the time above the threshold becomes critical
  • usually look at trough - hence the monitoring of genta at 12hrs post abx
  • with OD dosing - unncessary to measure serum level in 3 days
- SE

  • ototoxic - neomycin, kanamycin, amikacin
  • nephrotoxic - neumycin, tobra, genta
  • vestibulotoxic - streptomycin and genta
  • likely to be encountered for therapy >5 days
  • loop diuretics --> potentiate kidney damage
  • don't use with concurrent nephrotoxic abx (vancomycin, amphotericin B)
- water soluble, cannot mix with B-lactams with administration

- alternative rx for gonorrhoea allerg to penicillin

- isolated from Micromonospora purpurea
- g+ve and g-ve - inhibit staph and coliform and g-ve
- synergistic with B-lactams against pseudomonas, proteus, enterobacter, klebsiella, serratia, stenetrophomonas
- resistance
  • strep and enterococci - failure of drug to enter cell --> add vanco or penicillin (break down cell wall)
  • ribosomal resistance is rare
  • mostly from plasmid - encoded aminoglycoside-modifying enzymes --> this type of resistance will be susceptible to amikacin
- clinical use
  • IM/IV
  • topical - infected burns/wounds/skin lesion
  • intrathecal - g-ve meningitis
- similar to genta in dose, frequency, chemical
- slightly different
  • genta covers serratia better
  • tobra covers pseudomonas
  • E. faecalis susceptible to both
  • E. faecium only to genta
  • otherwise can interchange
- can be given via neb for Pseudomonas rx

- works with g-ve that are resistant to genta and tobra --> proteus, pseudomonas, enterobacter, serratia

Neomycin & kanamycin
- paromomycin member of the group
- active g+ve and g-ve but not strep and pseudomonas
- widespread use in bowel prep --> resistance
- limited to topical (joint injection/infected surfaces) or oral use

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