MICI: Antibiotics Pt 2

Overview of Antibiotics Mechanisms of Action (MOA)

• Antibiotics are categorized based on their mechanisms of action targeting essential bacterial processes.

Inhibition of Cell Wall Synthesis

• Beta-lactams (e.g., Penicillin, Methicillin):

  • Prevent cross-linking of NAM subunits in peptidoglycan layer.
  • Disrupt cell wall synthesis by binding to penicillin-binding proteins (PBPs).
  • Resistance: Many bacteria produce beta-lactamase enzymes that break down the antibiotic.
  • Solutions include combination therapies like Piperacillin-Tazobactam with beta-lactamase inhibitors.

• Vancomycin:

  • Targets Gram-positive bacteria by binding to D-alanine-D-alanine termini in peptidoglycan precursors.
  • Resistance arises when bacteria substitute D-alanine with D-lactate.

• Glycopeptides and Bacitracin:

  • Glycopeptides (e.g., Vancomycin) inhibit cross-linking in Gram-positive bacteria.
  • Bacitracin intervenes in the transport of peptidoglycan precursors from cytoplasm to cell wall.

Inhibition of Protein Synthesis

• Aminoglycosides (e.g., Streptomycin):

  • Bind to the 30S ribosomal subunit, causing misreading of mRNA.
  • Resistance through enzymatic modification by bacteria.

• Tetracyclines:

  • Attach to the 30S subunit, blocking tRNA attachment, thus halting protein synthesis.
  • Adverse effects include tooth discoloration and skeletal growth inhibition; contraindicated in young children and pregnant women.

• Macrolides (e.g., Erythromycin):

  • Bind to the 50S subunit, blocking translocation during protein synthesis.
  • Used as an alternative in penicillin-allergic patients and for atypical pathogens.

Inhibition of Nucleic Acid Synthesis

• Quinolones and Fluoroquinolones (e.g., Ciprofloxacin):

  • Inhibit DNA gyrase and topoisomerase IV, preventing DNA replication.
  • Resistance through mutations in target enzymes or efflux pumps.

• Rifamycins (e.g., Rifampin):

  • Inhibit RNA synthesis by binding to bacterial RNA polymerase, commonly used for tuberculosis.

• Metronidazole:

  • Disrupts DNA by generating free radicals, effective particularly in anaerobic bacteria.

Inhibition of Metabolic Pathways

• Sulfonamides (Sulfa drugs):
  • Act as competitive inhibitors of dihydropteroate synthase, blocking folic acid synthesis essential for nucleic acid production.
  • High therapeutic index in humans since they do not synthesize folic acid.

Antibiotic Resistance

• Resistance mechanisms include:
  • Enzyme production such as beta-lactamase, which destroys the beta-lactam ring.
  • Target modification leading to altered PBPs that prevent binding.
  • Efflux pumps that actively expel the drug from bacterial cells.
  • Horizontal gene transfer via transformation, transduction, or conjugation.

Key Concepts for Test Review

• Comparison of Gram-positive and Gram-negative bacteria, focusing on cell wall differences and susceptibility to antibiotics.
• Understanding bacterial growth phases; antibiotics are most effective during the log phase.
• Review the basic structure of bacterial cells, including ribosomes and peptidoglycan layers.

Antibiotic Targeting

• Gram-positive bacteria show higher susceptibility to antibiotics targeting the thick peptidoglycan layer.
• Gram-negative bacteria may exhibit resistance due to their outer membrane, necessitating the use of specific antibiotics like aminoglycosides.

Antibiotic Classes

• Beta-lactams target cell wall synthesis.
• Fluoroquinolones inhibit DNA gyrase.
• Macrolides and Aminoglycosides disrupt protein synthesis differently at ribosomal subunits.

Focus on Case Studies and Practical Examples

• Vancomycin is crucial against MRSA and resistant Gram-positive infections.
• Erythromycin serves as an alternative for those allergic to penicillin and is effective against atypical pathogens.

Common Exam Questions

• Understand targeting mechanisms of fluoroquinolones and macrolides.
• Identify how bacteria develop resistance to beta-lactams.
• Compare Gram-positive and Gram-negative bacteria regarding cell wall structure and antibiotic susceptibility.