Aminoglycosides

Mechanism of Action (MOA):

Aminoglycosides bind irreversibly to the 30S ribosomal subunit of bacterial ribosomes, leading to:
	•	Inhibition of protein synthesis.
	•	Misreading of mRNA, causing the production of nonfunctional or toxic proteins.
	•	Disruption of bacterial membrane integrity, ultimately leading to cell death.
This bactericidal activity is concentration-dependent.

Classification:

Aminoglycosides are a class of bactericidal antibiotics. Examples include:
	•	Gentamicin
	•	Tobramycin
	•	Amikacin
	•	Streptomycin
	•	Neomycin

Spectrum of Activity:

Aminoglycosides are primarily effective against:
	•	Gram-negative aerobes: E. coli, Klebsiella spp., Pseudomonas aeruginosa, Proteus spp.
	•	Limited activity against Gram-positive organisms, but often used synergistically with beta-lactams or vancomycin for infections caused by Enterococcus spp. or Staphylococcus aureus.
	•	Ineffective against anaerobic bacteria due to oxygen-dependent uptake.

Dosing:

Dosing varies based on the specific drug, indication, and patient factors (e.g., renal function). Typical approaches include:
	•	Gentamicin/Tobramycin:
	•	Conventional dosing: 1–2 mg/kg every 8 hours.
	•	Once-daily dosing: 5–7 mg/kg once daily.
	•	Amikacin:
	•	15–20 mg/kg once daily.
	•	Adjustments for renal impairment are critical due to nephrotoxicity risks.
	•	Therapeutic drug monitoring (TDM) is often employed to optimize efficacy and minimize toxicity.

Adverse Effects:

Aminoglycosides are associated with significant toxicities, particularly with prolonged use or high doses:
	•	Nephrotoxicity: Reversible damage to renal tubules.
	•	Ototoxicity: Irreversible hearing loss or vestibular dysfunction.
	•	Neuromuscular blockade: Rare but can lead to respiratory paralysis, particularly in patients with underlying neuromuscular disorders or concurrent use of neuromuscular blockers.
	•	Hypersensitivity reactions: Rare.