MOA OF AMINOGLYCOSIDE ANTIBIOTICS

MOA                of  Aminoglycoside           Antibiotics

Aminoglycosides exert their bactericidal effect by inhibiting protein synthesis in bacteria and compromising the structure of the bacterial cell wall.

Aminoglycoside Antibiotics

Aminoglycoside antibiotics are used to treat serious infections caused by gram-negative bacteria.

Some commonly used aminoglycosides include:

amikacin (Amikin®); apramycin;

capreomycin; gentamicin (Garamycin®); kanamycin (Kantrex®); neomycin (Mycifradin®); netilmicin

(Netromycin®); paromomycin (Humatin®);

streptomycin; tobramycin (TOBI Solution®, TobraDex®, Nebcin®)

Mode of Action

Although aminoglycosides stop bacteria from making proteins, it is uncertain whether this is the action that results in bacterial cell death.

 

 

Disruption of Protein Synthesis

Aminoglycosides bind to the bacterial 30S ribosomal subunit. Ribosomes are the protein factories of cells. They are composed of two subunits in bacteria, the 30S and a larger 50S. By binding to the ribosome, aminoglycosides inhibit the translocation of

tRNA during translation and leaving the bacterium unable to synthesize proteins necessary for growth.

Although the eukaryotic cells of humans also have ribosomes, these cellular protein factories differ in size and structure from the ribosomes of prokaryotes. That is why aminoglycosides  do not interfere  with  protein synthesis in human cells.

Bacterial Cell Wall Damage

It may not be the inhibition of protein synthesis that produces the bactericidal (bacteria-killing) effect.

Aminoglycosides also appear to displace cations in the bacterial cell biofilm that are responsible for linking the

lipopolysaccharide (LPS) molecules characteristic of

Gram-negative bacterial cell walls.

This creates holes in the cell wall that may kill the bacteria before the aminoglycoside even reaches the ribosome. Because our cells do not have cell walls (some of the chemical structural components of the bacterial cell wall are found only bacteria) human cells are not susceptible to these destructive actions.

Type of Infection Aminoglycosides Are Used Against

Aminoglycosides are most often used in empiric therapy (treatment initiated before a firm diagnosis is made) for serious infections including septicemia, complex infections within the abdominal cavity, severe urinary tract infections, and nosocomial (hospital-acquired) respiratory infections.

Because of their toxicity, aminoglycosides are only given for only a short period of time. Less toxic antibiotics are substituted once the causative agent of infection is positively identified.

Antimicrobial Spectrum of Aminoglycosides

Gram-negative Aerobic Bacteria: Aminoglycosides exert

their antibiotic effect against aerobic (oxygen requiring), gram-negative bacteria,

including Pseudomonas, Acinetobacter, and Enterobacter.

Gram-positive Bacteria: Gram-positive bacterial infections can also be treated with aminoglycosides, but are typically not used because of the toxicity.

Aminoglycosides have a synergistic the effect when combined with beta-lactam antibiotics (penicillins) and have been used to treat streptococcal infections. The ampicillin (a beta-lactam antibiotic) gentamicin combination is referred to as "amp and gent" or "pen and gent" for penicillin and gentamicin.

Mycobacteria: Some species of Mycobacteria, including the causative agent of tuberculosis, are also susceptible to aminoglycosides.

Adverse Effects of Aminoglycosides =Because aminoglycosides are quickly broken down in the stomach, these antibiotics can't be given orally, but instead must be injected.

The adverse effects of aminoglycosides include potential

damage to the ears and kidneys. The risk can be reduced by monitoring blood levels of the drug and maintaining the dose at levels that will kill bacteria without causing harmful side effects.