Aminoglycosides

The first aminoglycoside, streptomycin, was isolated from the fungus Streptomyces griseus in 1943. Neomycin proved more efficacious against Gram negative aerobic bacilli, but was too toxic to be used systemically.
Gentamicin, isolated in 1963, was the big breakthrough. Safe enough to be used systemically, and active against the Gram negatives, including Pseudomonas aeruginosa.

They work by creating fissures in the outer cell membrane, causing leaking of intracellular contents. This rapid action is responsible for the bactericidal activity.¹ Bacteria need to expend energy to take the aminoglycoside into the cell.

Anaerobes have less available energy for this, and so are less susceptible to aminoglycosides than aerobic bacteria.
They are not absorbed from the gut, so are given intravenously for systemic infections.

• Gentamicin - used most often, low cost, active against Gram negative aerobes²
• Neomycin
• Netilmicin
• Tobramycin
• Amikacin - used when organisms resistant to other aminoglycosides, less susceptible to inactivating enzymes

Aminoglycosides are often used in combination with a beta-lactam antibiotic, to increase their spectrum of activity. They also enhance beta-lactam activity.

Aminoglycosides are active against:

• Escherichia
• Enterobacter
• Klebsiella
• Salmonella
• Serratia
• Shigella
• Proteus (some)
• Pseudomonas aeruginosa
• Staphylococcus aureus

Where possible treatment should be guided by sensitivities from a cultured specimen. Where empirical treatment is necessary the local primary care trust will produce a formulary, based on knowledge of local prevalent pathogens and resistance.

Aminoglycosides should be used with caution in:²

• Pregnancy
• Renal impairment - there are papers recommending dosing in different stages of renal disease, including intermittent haemodialysis⁴
• Infants or the elderly
• Avoid prolonged use i.e. not greater than 7 days
• Conditions characterised by muscular weakness
• They should not be administered at the same time as diuretics e.g. furosemide (increases the potential ototoxicity - if unavoidable, the doses should be separated by as great a time period as possible)

They are CONTRAINDICATED in myasthenia gravis, as they impair neuromuscular transmission.

• Nephrotoxicity
• Ototoxicity - both vestibular and auditory (usually irreversible - netilmicin is less ototoxic than gentamicin, which is important if longer treatment periods are required)
• Neuromuscular blockade
• Hypersensitivity reactions
• Hypomagnesaemia rarely, on prolonged therapy
• Antibiotic associated colitis
• Neomycin may cause increased salivation and stomatitis
• Tobramycin may cause voice alteration and cough when inhaled

• Serum concentrations should be monitored in all patients to avoid both excessive or subtherapeutic concentrations.^2,3,4
• Peak levels should be measured approximately one hour after intramuscular or intravenous administration, and trough levels should be measured just before the next dose. For specific serum concentration measurements see individual drug monographs.
• Although divided daily doses are most common, once daily can be used. Consult local laboratory guidelines for peak and trough measurements.
• Levels MUST be determined in infants, the elderly, obese patients, patients with cystic fibrosis and if high doses are being administered and in renal impairment.
• Patients with normal renal function should have serum concentrations measured after 3 or 4 doses of a multiple daily dose regimen.
• Patients with renal impairment may require earlier and more numerous monitoring.