Antibiotics Lecture Notes

Introduction

• Lecture focuses on antibiotics and their mechanisms of action.
• Importance of downloading illustrations from the website to follow along.
• Emphasizes self-testing to memorize information.

Mechanism of Action of Antibiotics

Cell Wall Synthesis Inhibition

• Cell wall structure: Made of peptidoglycans cross-linked by tetrapeptides.
• Key components: Penicillin-binding proteins, transpeptidases.

Types of Inhibitors

• Inhibit peptidoglycan synthesis:

  • Vancomycin: Reduces synthesis of peptidoglycan layers.
  • Phosphomycin: Used for acute cystitis.

• Inhibit cross-linking:

  • Natural Penicillins:
    • Penicillin G (IM/IV)
    • Penicillin V (PO)
  • Anti-Staphylococcal Penicillins:
    • Oxacillin (IV)
    • Nafcillin (IV)
    • Dicloxacillin (PO)
  • Aminopenicillins:
    • Amoxicillin, Ampicillin
    • Combination with beta-lactamase inhibitors (e.g., clavulanate, sulbactam).
  • Anti-Pseudomonal Penicillins:
    • Piperacillin (commonly used with tazobactam).

Cephalosporins

• Generations:
  • 1st Gen: Cefazolin, Cephalexin
  • 3rd Gen: Ceftriaxone, Cefotaxime
  • 4th Gen: Cefepime
  • 5th Gen: Ceftaroline (covers MRSA).

Other Antibiotic Classes

• Carbapenems:
  • Dori, Imi, Meropenem, Ertapenem
• Monobactam:
  • Aztreonam (good for penicillin allergic patients).

Glycopeptides

• Vancomycin: Inhibits peptidoglycan synthesis, effective against MRSA.
• Phosphomycin: Another option for treating specific UTIs.

Antibiotics that Alter Cell Membrane Integrity

• Daptomycin: Forms efflux pumps, increases permeability leading to lysis.
• Polymyxins: Cationic detergent action, used as a last resort for multi-drug resistant bacteria.

Metabolic Inhibitors

• Folic Acid Pathway Inhibitors:
  • Sulfonamides (e.g., Sulfamethoxazole)
  • Trimethoprim: Often combined to treat UTIs.

DNA and RNA Synthesis Inhibitors

• Metronidazole: Generates reactive oxygen species, effective mainly against anaerobes.
• Fluoroquinolones: Inhibit DNA gyrase and topoisomerase IV, resulting in fragmented DNA.

Protein Synthesis Inhibitors

• 50s Ribosomal Subunit Inhibitors:
  • Macrolides (Azithromycin, Erythromycin)
  • Clindamycin, Chloramphenicol, Linezolid
• 30s Ribosomal Subunit Inhibitors:
  • Aminoglycosides (Gentamicin, Tobramycin)
  • Tetracyclines (Doxycycline, Minocycline)

Bacterial Coverage and Empiric Therapy

Gram-positive Bacteria

• Common pathogens include MSSA, MRSA, Strep pneumoniae.
• Antibiotic options vary based on the type of infection (community or hospital-acquired).

Gram-negative Bacteria

• Important to understand common organisms (e.g., E. coli, Klebsiella, Pseudomonas).
• Coverage often requires broad-spectrum antibiotics, especially in nosocomial infections.

Adverse Effects and Contraindications

Common Adverse Effects

• Neurotoxicity: Seizures, myoclonus from penicillins, cephalosporins, carbapenems, polymyxins.
• Pancytopenia: Found with penicillins, cephalosporins, trimethoprim-sulfamethoxazole, chloramphenicol.
• Nephrotoxicity: Particularly aminoglycosides and vancomycin.
• Ototoxicity: Also aminoglycosides and vancomycin.
• Worsening Myasthenia Gravis: Fluoroquinolones and aminoglycosides.

Mechanisms of Antibiotic Resistance

Common Mechanisms

• Decreased Permeability: Common in Vancomycin, Aminoglycosides, Tetracyclines, Beta-lactams.
• Efflux Pumps: Seen in Fluoroquinolones, Aminoglycosides, Tetracyclines, Macrolides.
• Target Site Alteration: Affects Fluoroquinolones, Aminoglycosides, Tetracyclines, Beta-lactams, Macrolides, Linezolid.
• Inactivation by Enzymes: Particularly Beta-lactams and Aminoglycosides via beta-lactamases and modifying enzymes.

Summary

• Antibiotics play crucial roles in treating infections by targeting specific bacterial mechanisms.
• Understanding their mechanisms of action, coverage, adverse effects, and resistance mechanisms is important for effective treatment.