Aminoglycosides and Tetracyclines: Two Important Groups of Antibiotics

Aminoglycosides and Tetracyclines: Two Important Groups of Antibiotics

# How do antibiotics affect bacteria?

Aminoglycosides and tetracyclines are both groups of antibiotics that target the process of translation, the protein synthesis of bacteria.

# Aminoglycosides (AG)

• Mechanism of action:

• AGs act on the 30S subunit of bacterial ribosomes, specifically at the 16S site.

• AGs cause errors in the binding of mRNA and tRNA, leading to errors in the amino acid sequence of the polypeptide chain.

• At high concentrations, AGs completely inhibit protein synthesis, leading to bacterial death.

• AGs can also damage the bacterial cell membrane.

• Composition:

• Streptomycin, Neomycin, Kanamycin, Sisomicin, Netilmicin

• Other commonly used antibiotics include: Amikacin, Gentamicin, Tobramicin.

• Characteristics:

• Highly soluble in water.

• Not administered orally, primarily administered intravenously.

• Oral administration is possible for intestinal infections (e.g., Paramomycin).

• Favorable in alkaline pH environments.

• Transported across the bacterial membrane via oxygen (co-transport with oxygen).

• Synergistic action with beta-lactams and vancomycin.

• Spectrum of action:

• Effective against aerobic Gram-negative bacteria.

• Used to treat nosocomial infections: bacteremia, pneumonia, pericarditis.

• Often combined with other drugs to increase effectiveness.

• Short-term treatment.

• Resistance mechanisms:

• Production of AG-resistant enzymes (clinically significant).

• Destruction of the 30S receptor site.

• Structural alterations, changes in drug transport channels.

• Pharmacokinetics:

• AGs are cations, not absorbed through the digestive tract.

• Poor tissue penetration.

• Low plasma protein binding.

• Can enter cerebrospinal fluid, pericardial fluid, or inflamed tissues.

• AGs can be degraded by Fe2+ and Fe3+, prone to decomposition.

• Cause ototoxicity and nephrotoxicity.

• Toxicity:

• Ototoxicity (irreversible).

• Nephrotoxicity (potentially reversible).

• Monitor blood drug levels to prevent accumulation (trough concentration > 2 mcg/ml).

• Use in therapy:

• Combined with other drugs like beta-lactams and vancomycin.

• Administered in high doses (once daily) to achieve optimal concentration, reduce toxicity, and maintain effectiveness.

• Drug concentrations:

• Gentamicin, Netilmicin, Tobramicin:

• Peak concentration: 30-40 mg/l.

• Trough concentration: < 0.5 mg/l.

• Amikacin:

• Peak concentration: 60-80 mg/l.

• Trough concentration: < 2.5 mg/l.

# Tetracyclines

• Composition:

• Tetracycline, Doxycycline, Minocycline.

• Administration:

• Oral administration, systemic action.

• Mechanism of action:

• Binding to the bacterial cell membrane: passive transport.

• Binding to ribosomes: active transport via transport proteins.

• Binding and inhibiting the 30S subunit of ribosomes, particularly at the 16S site.

• Inhibiting tRNA binding to ribosomes.

# Summary

Aminoglycosides and tetracyclines are two important groups of antibiotics used to treat bacterial infections. Both groups act on bacterial ribosomes, inhibiting protein synthesis. However, they have different mechanisms of action, spectrums of action, and pharmacokinetic properties. It is essential to be aware of the toxicity of these drugs and to use them under the guidance of a physician.