Aminoglycosides
Aminoglycosides are potent bactericidal antibiotics, especially useful against aerobic Gram-negative infections. Their toxicity profile requires careful monitoring.
Pharmacodynamics
- Mechanism: Binds irreversibly to 30S ribosomal subunit → misreading of mRNA → abnormal proteins → cell death Bactericidal, concentration-dependent killing
- Key Point: The higher the peak concentration/MIC ratio, the more effective the drug.
- Spectrum of Activity:
- Gram-negative aerobes: E. coli, Klebsiella, Pseudomonas, Enterobacter, Proteus
- Some Gram-positive: Staphylococcus, used in synergy (e.g., with β-lactams)
- Mechanisms of Resistance:
- Enzymatic modification (e.g., acetylation, phosphorylation)
- Reduced uptake / Efflux pumps
- Ribosomal modification
Drug Interactions
- Vancomycin, loop diuretics → ↑ nephrotoxicity
- Cisplatin → ↑ ototoxicity
- Neuromuscular blockers → ↑ risk of respiratory depression
Therapeutic Uses
Used for serious infections, especially Gram-negative aerobic bacteria:
- Septicemia
- Hospital-acquired pneumonia
- Complicated UTI
- Intra-abdominal infections
- Endocarditis (synergy with β-lactams)
- Meningitis (only in combination)
Recap Questions
- 1. What is the mechanism of action of aminoglycosides?
- 2. Which bacterial group is primarily targeted by aminoglycosides?
- 3. Name two major toxicities associated with aminoglycosides.
- 4. Why are aminoglycosides not effective for anaerobic infections?
- 5. Which aminoglycoside is often used topically?