INFECTION: AMINOGLYCOSIDES

Question 1

AMINOGLYCOSIDES: INDICATIONS

Answer 1

• Severe infections, particularly those caused by Gram-Negative aerobes (Pseudomonas Aeruginosa)
• Severe sepsis, including where the source is unidentified
• Pyelonephritis and complicated urinary tract infection
• Biliary and other intra-abdominal sepsis
• Endocarditis.

Aminoglycosides lack activity against streptococci and anaerobes, so should be combined with penicillin and/or metronidazole when the organism is unknown

Question 2

AMINOGLYCOSIDES: MOA

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

AMINOGLYCOSIDES: ADVERSE EFFECTS

Answer 3

• Nephrotoxicity
• Ototoxicity
• Aminoglycosides accumulate in renal tubular epithelial cells and cochlear and vestibular hair cells where they trigger apoptosis and cell death.

Question 4

AMINOGLYCOSIDES: WARNINGS

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

AMINOGLYCOSIDES: INTERACTIONS

Answer 5

• 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 6

AMINOGLYCOSIDES: EXAMPLES

Answer 6

• gentamicin

- amikacin