Mechanism of Action

They bind to the bacterial ribosome causing a change that interferes with mRNA translation. This results in error-prone protein synthesis, allowing for incorrect amino acids to assemble into a polypeptide that is subsequently released to cause damage to the bacterial cell membrane and elsewhere. Some aminoglycosides can also impact protein synthesis by blocking elongation or by directly inhibiting initiation. The exact mechanism of binding and the subsequent downstream effects varies by chemical structure, but all aminoglycosides are rapidly bactericidal.

A ‘post-antibiotic’ effect (PAE) is seen with these drugs due to the level in the bacteria remaining therapeutic even after the blood levels have fallen. The PAE has also been shown to be directly related to the length of time that the bacteria take to recover from the inhibition of protein synthesis. It is hypothesised that this is dependent on the eventual disassociation of the antibiotic from its target and exit from the cell.

How they exert their antibiotic effect

Aminoglycosides display concentration-dependent killing, i.e. a higher peak concentration of drug kills more bacteria. As once-a-day dosing gives a higher peak concentration, this has become the preferable UK administration regimen. A once-daily, high-dose regimen of an aminoglycoside should be avoided in patients with: endocarditis (due to Gram-positive bacteria), HACEK endocarditis, burns of more than 20% of the total body surface area, or creatinine clearance less than 20 mL/minute.

Aminoglycosides show synergistic activity with cell wall active agents such as beta-lactams and are often used in combination with these agents.