Aminoglycosides
One-Sentence Definition
Aminoglycosides bind the bacterial 30S ribosome, causing misreading of mRNA — concentration-dependent bactericidal agents used for serious Gram-negative infections and synergistic enterococcal/staphylocidal regimens, with nephro/ototoxicity limits.
Simple Explanation
They punch ribosomes to stop protein synthesis — powerful against many Gram-negatives when combined with β-lactams, but kidneys and ears watch closely.
Detailed Scientific Explanation
| Examples | Role |
|---|---|
| Gentamicin, tobramycin | Gram-negative synergy (endocarditis, sepsis) |
| Amikacin | Broader enzyme stability; resistant GNR |
| Streptomycin | TB (specialized) |
Use patterns
- Synergy with cell-wall agents (Beta-lactams, Glycopeptides) for enterococcal endocarditis
- Gram-negative sepsis combination therapy (local guidelines vary)
- Not monotherapy for most serious staphylococcal infections
PK/PD: concentration-dependent — peak/MIC; extended-interval dosing common; therapeutic drug monitoring.
Resistance: modifying enzymes (AAC, ANT, APH); ribosomal mutations; reduced uptake (biofilm, anaerobes poor activity).
Mechanism
Irreversible 30S binding → faulty peptides → bactericidal effect enhanced by oxygen-dependent uptake (poor in anaerobes).
Clinical Importance
- Once-daily regimens with level monitoring
- Avoid in pregnancy if alternatives exist (ototoxicity risk)
AMR Relevance
- Enzymatic resistance genes on plasmids in Enterobacterales
- Poor activity in Biofilm and abscess anaerobic cores — not a solo fix
Related MOCs
Active Recall Questions
- Why combine with β-lactam for enterococcal endocarditis?
- Why poor anaerobic efficacy?
- Concentration-dependent — TDM focuses on what?