Gentamicin

R.A.S HEMAT, MB;BCh, FRCSI, DUL.

Amainoglycosides were developed in 1940s, and since they became a mainstay antimicrobial therapy. Gentamicin was discovered in 1963.
Aminoglycosides diffuse passively through the outer bacterial membrane and then require energy dependent transport across the inner lipid membrane into the cytosol. Pharmacodynamic synergism occurs as well when high serum levels of aminoglycosides cause a first pass effect with unusually efficient bacterial killing.
Mechanisms of aminoglycoside resistance:
1- Plasmid mediated resistance (bacterial killer enzymes inactivating the drug).
2- Chromosomal mediated resistance (decreased gentamicin transport through the inner bacterial cell membrane by mutations in bacterial transport proteins).
3- Plasmid mediated mutations (gentamicin binding to the 30-S ribosomal subunit).
4- Adaptive resistance (decreases temporarily gentamicin transport across intracellular membrane).

1-55% of patients exhibits nephrotoxicity after a full course of gentamicin therapy. Aminoglycoside accumulation results in lysosomal rupture and leakage of phospholipases, causing phospholiposis, mitochondrial damage and cell necrosis. Gentamicin interferes with vitamin B6 metabolism. Aminoglycoside affects gut flora resulting in diarrhoea, superinfection by nonsusceptible organisms and malabsorption syndrome after prolonged administration.
Gentamicin is water soluble, containing 40 mg/ml, 100% absorbed after intramuscular administration; but this may be delayed by shock, in the elderly, and when the same injection site is used repeatedly.
Aminoglycosides are poorly absorbed from the GIT because they are highly positively charged at the pH level of the small intestine.
Standard gentamicin dosing (multiple daily dosing) is affected by body habitus, type of illness and susceptibility of target organisms. Single daily dosing (extended interval, once daily and skip dosing) is based on the higher peak and lower trough levels achieve more effective microbial killing while reducing toxicity. Single daily dosing has less toxicity, as the uptake into the kidney and ear is a saturation process.
Poorly functioning kidneys excrete less aminoglycosides, such as unilateral obstructive uropathy or reflux nephropathy.

Find more in Urotext, E. Book simplifying Urology.

Dr. R.A.S HEMAT declares no conflicts of interest or financial interests in any product or service mentioned in this article, including grants, employment, stock holdings, gifts, or honoraria.