Aminoglycosides

Gentamicin, Tobramycin, Neomycin

Structure and efficacy

• Composed of an essential 6-membered ring with amino-group substitutions
• Excellent activity against aerobic gram-negative organisms including enterobacteriaceae (e.g. E coli, Klebsiella, Proteus), also Pseudomona aeruginosa
• Can be used in combination with beta-lactams and glycopeptides for synergy against Staphylococci and Streptococci (gram-positive)
• Not effective against anaerobic organisms

Mechanism

• Interferes with bacterial protein synthesis by binding to the 30S ribosomal subunit.
  • Note that, in order for aminoglycosides to reach this target, it requires an oxygen-dependent transport system
    • this is inhibited by divalent cations e.g. Ca2+ and Mg2+; low pH; anaerobic conditions and hyperosmolarity
  • However, once achieved, these are rapidly bactericidal (efficacy increases with concentration).  They also continue to kill bacteria after levels have dropped
    • Once daily dosing is adequate (see prescribing below)

Pharmacokinetics

• Poor GI absorption- IV route needed
• Distributed well into the urine, kidney (nephrotoxic), inner ear (ototoxic), bone, synovial and peritoneal fluids.  Generally poor CSF levels.
• Majority excreted by the kidneys

Prescribing

See Gentamicin prescribing protocol for NHS tayside

(Also the Hartford Gentamicin Calculator)

Side effects

• Nephrotoxicity- requires eGFR and U&Es monitoring (usually reversible)
• Ototoxicity- usually irreversible (early symptoms include tinnitus, vertigo)
• Neuromuscular blockade- gentamicin is contraindicated in patients with e.g. myaesthenia gravis
  • reversed by calcium gluconate