Aminoglycosides

crop_square Key points

  • check_circle Bactericidal antibiotics with an aminocyclitol core
  • check_circle Inhibit bacterial protein synthesis by binding to the 30S ribosomal subunit
  • check_circle Synergistic effect with beta-lactam and glycopeptide antibiotics
  • check_circle Most active against gram-negative rods, mycobacteria
  • check_circle Narrow therapeutic range, nephrotoxicity, ototoxicity

crop_square Background and biochemistry

Aminoglycoside antibiotics where isolated from bacteria of the Actinomycetia class. The two bacterial genera relevant to aminoglycoside antibiotics are Streptomyces (suffix -mycin: streptomycin, tobramycin, neomycin, kanamycin) and Micromonospora (suffix -micin: gentamicin, amikacin, netilmicin). It does get slightly more complicated though as there are antibiotics (e.g., vancomycin, erythromycin) which were derived from Streptomyces bacteria but are not aminoglycosides with entirely different mechanisms of actions. Molecular structures of aminoglycosides are complex, however, all antibiotics in this class are polar molecules with amino sugars linked to a carbon ring (aminocyclitol). Aminoglycosides are more active at a higher pH (more alkaline) than at a lower pH (more acidic).

crop_square Mechanism of action

Aminoglycosides bind to a specific site on the 16S rRNA (ribosomal RNA) of the 30S subunit of the bacterial ribosome. This interferes with bacterial protein biosynthesis resulting in non-functional bacterial proteins causing cell damage. Aminoglycosides are bactericidal antibiotics. Various resistance mechanisms against aminoglycosides are known, including mutations affecting the ribosomal binding site and cell wall structure, drug efflux from the bacterial cell and enzymatic inactivation. Aminoglycosides work well in combination with beta-lactam and glycopeptide antibiotics. The synergistic effect of these antibiotic drug combinations is more than the sum of its parts. Aminoglycosides work better against aerobic bacteria as the lack of oxygen in an anaerobic environment inhibits active drug uptake into the bacterial cell. A post-antibiotic effect is seen, which means that even after the drug has been removed from the body, growth of susceptible organisms will still be inhibited for a few hours.

crop_square Drugs and spectrum of activity

  • Strepto­mycin
  • Neo­mycin
  • Kana­mycin
  • Tobra­mycin
  • Genta­micin
  • Amikacin
  • Netil­micin

Aminoglycosides are strong against aerobic gram-negative rods. They are usually given with synergistic antibiotics (see above) in septic patients and in endocarditis caused by enteric gram-negative organisms. Systemic aminoglycoside monotherapy is uncommon. Aminoglycosides are active against mycobacteria with streptomycin being a second-line treatment for tuberculosis.

crop_square Pharmacokinetics

Aminoglycosides are rapidly distributed in the extracellular fluid after intravenous administration. They do not sufficiently cross the blood-brain barrier. Aminoglycosides are not hepatically metabolised and cleared by the kidneys. Half-life of aminoglysides is approximately 2h in patients with normal renal funtion. Patients often receive a loading dose based on their ideal body weight.

crop_square Adverse drug effects

Managing patients on aminoglycosides can be challenging because of the narrow therapeutic range. Drug levels need to be monitored. Underdosing may lead to insufficient drug concentrations, while overdosing may cause dangerous well-known toxic adverse effects. These are mainly nephrotoxicity, though the kidney function tends to recover after drug discontinuation, and ototoxicity, which can be irreversible.