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)
- Note that, in order for aminoglycosides to reach this target, it requires an oxygen-dependent transport system
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