RX511 Antibiotic Inhibitors of Protein Synthesis 1

What are the key points of streptomycin?

- First agent against tuberculosis

- Use declined due to resistance and side effects

What are the characteristics of aminoglycosides?

- Polycationic at low pH

- Mostly topical or injectable

- Gram-negative as monotherapy

What are the current uses of aminoglycosides?

- Second-line for tuberculosis

- In combination with beta-lactams

- Last resort for MDR Gram-negative infections

- Plague and tularemia

How do aminoglycosides work?

- Target 30S subunit (16S rRNA decoding and S12 protein

- Aerobic Gram-negative bacilli

- Positive charge helps with entry

- Disrupts protein synthesis

- Oxygen-dependent

How can OH groups on aminoglycosides be modified?

- ANT

- APH

How are NH2 groups on aminoglycosides modified?

AAC

What is gentamicin susceptible to?

- AAC

- ANT

What are the key points of amikacin?

- Inhalation and injection

- Only susceptible to APH

What are the key points of plazomicin?

- Blocks most aminoglycoside-modifying enzymes

- Active against MDR Enterobacteriaceae

How is tobramycin available?

Inhalation, ophthalmic, and injection

How is aminoglycoside entry prevented?

- Mutations of porin genes

- Changes to membrane chemistry and composition

- Changes that affect proton motive force

- Efflux pump overexpression

What 16S rRNA mutations can stop aminoglycosides from binding?

- Single nucleotide mutations

- Methylation

What are the adverse effects of aminoglycosides?

- Ototoxicity

- Nephrotoxicity

- Neuromuscular junction blockade

What are the key points of ototoxicity caused by aminoglycosides?

- Leaky channels allow accumulation

- Permanent hearing loss

- Human mitochondrial ribosomes also have 30S subunits

What are the key points of nephrotoxicity caused by aminoglycosides?

- Dose adjusted in renal impairment

- Phospholipid accumulation results in necrosis

- Renal impairment increases ototoxicity

What are the key points of neuromuscular junction blockade caused by aminoglycosides?

- Polycationic groups block ACh release

- Paralysis-like symptoms

- Myasthenia gravis or Parkinsonism increase risk

What are the key points of neomycin B?

- Oral and topical

- Suppresses urease-producing bacteria

- Treats hepatic encephalopathy