- 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
- production of transferase enzyme/enzyme that inactivate aminoglycoside
- impaired entry into cell --> mutation/deletion of porin protein
- receptor protein on 30S ribosomal subunit deleted/altered
- 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
- 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
- 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)
Spectinomycin
- alternative rx for gonorrhoea allerg to penicillin
Gentamicin
- 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
- 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
Amikacin
- works with g-ve that are resistant to genta and tobra --> proteus, pseudomonas, enterobacter, serratia
- MDRTB
Netilmicin
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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