Aminoglycosides

Aminoglycosides

Aminoglycosides are compounds consisting of at least two amino sugars linked by glycosidic bonds. They bind irreversibly to the ribosome, thereby inhibiting the attachment of tRNA during the initiation and thus the protein synthesis. The inhibition of protein synthesis is based on malformation of the ribosomal complex, causing premature release of the ribosome from the mRNA and misreading of the mRNA. Aminoglycosides act bactericidal and concentration dependent.

Common indications for use of aminoglycosides like gentamicin,tobramycin, amikacin and netilmicin are infections with

Enterobacteriaceae, Pseudomonas and aerobe Gram-negative bacteria. Aminoglycosides are poorly absorbed via gastrointestinal tract (polar cations). The drugs do not distribute well over the whole body. Resistance against aminoglycosides can occur via the following mechanisms: failure of permeation of the antibiotic, low affinity for the bacterial ribosome, and inactivation by microbial enzymes. Nephrotoxicity and ototoxicity are the most important adverse effects.

Gentamicin therapy is used against urinary tract infections, pneumonia, meningitis, and peritonitis.

Population pharmacokinetic parameters for gentamicin:

Clearance: Cl= 0.82 * creatinine Cl + 0.11 ml/min/kg

Volume of distribution: Vd= 0.31 L/kg

Half-life: t1/2= 3,4 h

Population pharmacokinetic parameters for tobramycin:

Clearance: Cl= 0.98 * creatinine Cl + 0.32 ml/min/kg

Volume of distribution: Vd= 0.33 L/kg

Half-life: t1/2= 2,2 h

1

Anaerobes and streptococci are resistant to aminoglycosides. 

2

Aminoglycosides are bacteriostatic. 

3

Aminoglycosides act synergistically with B-lactams against enterococci.

4

A 31-year old woman suffers from high fever and cold shivering. The diagnosis is pyelonephritis with an eventual sepsis. E.coli is the probable infectious agent. Therapy with gentamicin is in this case the most effective treatment. 

5

Ototoxicity caused by aminoglycosides is irreversible.