Aminoglycosides

Examples

• gentamicin

• tobramycin

• netilmicin

Others

• streptomycin - used only in combination in multi-drug resistant tuberculosis and NEVER on its own

• neomycin - too toxic systemically, can be used topically in eye, ear

• amikacin - in resistant strains

Mechanism of action

• irreversible binding to 30S ribosomal proteins

• produces aberrant proteins, interrupts protein synthesis

Properties

• broad-spectrum

• bactericidal

• relatively toxic - effects on hearing, balance, kidney if blood levels too high

• chemically stable - so useful in developing countries where refrigeration not needed

Activity

• Pseudomonas

• Enterobacter

• most hospital pathogens

• NOT anaerobes

• poorly active against streptococci - minimum inhibitory concentration 10-20 times higher than for sensitive organisms

• Gram positive organisms don't respond that well so change when sensitivities known

Selection

• (gentamicin, tobramycin, netilmicin) doesn't matter - activity and toxicity closely associated so depends what stocked by hospital pharmacy

Dosage

• see BNF

• 1 /day found to be less toxic and as active

Monitoring

• Peak levels should be no more than 4x MIC e.g. 8µg/ml for E.coli

• Allow 48-72 hours for steady state to develop

• trough level just before dose, peak level 30 mins after dose

Resistance

• anaerobes resistant because take up of aminoglycosides is aerobic-energy dependent

• streptococci, enterococci naturally resistant because aminoglycosides unable to penetrate cell wall (can treat with combination of aminoglycoside and inhibitor of cell wall synthesis)

Acquired

• enzymatical inactivation of the aminoglycosides most common- gentamicin / tobramycin / netilmicin equally

  • plasmid-encoded

  • organisms usually remain sensitive to amikacin

• Enterococcus may mutate binding site

• Pseudomonas, anaerobes may inhibit transport into bacterial cell

Adverse Effects

• vestibular / auditory damage
• nephrotoxicity
• hypomagnesaemia
• antibiotic-associated colitis
• nausea
• vomiting
• rash

Streptomycin

• deafness
• vertigo
• ataxia
• renal damage