Aminoglycosides

Question 1

Example of Aminoglycoside

Answer 1

Gentamicin

Question 2

How does Gentamicin work?

Answer 2

Aminoglycosides bind irreversibly to bacterial ribosomes (30S subunit) and inhibit protein synthesis. They are bactericidal (i.e. they kill bacteria), although this effect is likely to be due to additional mechanisms that are incompletely understood. Their spectrum of action includes Gram-negative aerobic bacteria, staphylococci and mycobacteria (for example, streptomycin was one of the first effective treatments for tuberculosis).
Aminoglycosides enter bacterial cells via an oxygen-dependent transport system. Streptococci and anaerobic bacteria do not have this transport system, so have innate aminoglycoside resistance. Other bacteria acquire resistance through reduced cell membrane permeability to aminoglycosides or acquisition of enzymes that modify aminoglycosides to prevent them from reaching the ribosomes. As penicillins weaken bacterial cell walls, they may enhance aminoglycoside activity by increasing bacterial uptake.

Question 3

Indications for Gentamicin

Answer 3

Severe sepsis, including where the source is unidentified.

Pyelonephritis and complicated urinary tract infection.

Biliary and other intra-abdominal sepsis.

Endocarditis.

Question 4

Contraindications of Gentamicin

Answer 4

Aminoglycosides are renally excreted. Monitoring of plasma drug concentrations with careful dose adjustment is essential to prevent renal, cochlear and vestibular damage, particularly in neonates and the elderly who are most susceptible and in patients with renal impairment. Aminoglycosides can impair neuromuscular transmission so should not be given to people with myasthenia gravis unless absolutely necessary.

Question 5

Side effects of Gentamicin

Answer 5

Important: nephrotoxicity and ototoxicity.

Aminoglycosides accumulate in renal tubular epithelial cells and cochlear and vestibular hair cells where they trigger apoptosis and cell death. Nephrotoxicity presents as reduced urine output and rising serum creatinine and urea and is potentially reversible.

Ototoxicity is often not noticed until after resolution of the acute infection, when the patient may complain of hearing loss, tinnitus (cochlear damage) and/or vertigo (vestibular damage). Ototoxicity may be irreversible.

Question 6

Interactions of Gentamicin

Answer 6

Ototoxicity is more likely if aminoglycosides are co-prescribed with loop diuretics (e.g. furosemide) or vancomycin.

Nephrotoxicity is more likely if aminoglycosides are co-prescribed with ciclosporin, platinum chemotherapy, cephalosporins or vancomycin.

Question 7

Elimination of Gentamicin

Answer 7

Renal

Question 8

Patient information on Gentamicin

Answer 8

Explain that the aim of treatment is to get rid of infection and improve symptoms. Ask the patient daily if they have noticed any change in their hearing, ringing in their ears or dizziness and advise them to let you know if this occurs. Ensure that the prescription clearly indicates that dosing depends on plasma concentrations and that measurement and recording of these has been organised, particularly at weekends.