Antibiotics Lecture Summary

Introduction

• Discussion on antibiotics and their mechanisms of action.
• Importance of downloading illustrations from the website to follow along.
• Encouraged repetition and self-testing to memorize information.

Mechanisms of Action of Antibiotics

Cell Wall Inhibitors

• Cell Wall Structure: Composed of peptidoglycans cross-linked by tetrapeptides.
• Inhibition Methods:
  • Decrease Peptidoglycan Synthesis:
    • Antibiotics: Vancomycin, Phosphomycin.
  • Reduce Cross-linking:
    • Antibiotics:
      • Natural Penicillins: Penicillin G (IV/IM), Penicillin V (PO).
      • Anti-staphylococcal Penicillins: Oxacillin, Nafcillin (IV), Dicloxacillin (PO).
      • Amino Penicillins: Amoxicillin, Ampicillin.
        • Resistance: Beta-lactamases; use inhibitors like Clavulanate (Augmentin) and Sulbactam (Unison).
      • Anti-pseudomonal Penicillins: Piperacillin (often combined with Tazobactam).
      • Cephalosporins: Five generations.
        • First Gen: Cefazolin, Cephalexin.
        • Third Gen: Ceftriaxone, Ceftazidime.
        • Fourth Gen: Cefepime.
        • Fifth Gen: Ceftaroline.
      • Carbapenems: Doripenem, Meropenem, Ertapenem, Imipenem.
      • Monobactam: Aztreonam.

Cell Membrane Integrity Inhibitors

• Daptomycin: Creates efflux pumps leading to cell lysis.
• Polymyxins: Cationic detergents increasing membrane permeability.

Nucleotide Synthesis Inhibitors

• Folic Acid Pathway: Targeting dihydrofolate synthesis.
  • Sulfonamides (e.g., Sulfamethoxazole).
  • Trimethoprim (inhibits dihydrofolate to tetrahydrofolate).
  • Combined as Bactrim.

DNA Integrity Inhibitors

• Metronidazole: Forms reactive oxygen species damaging DNA.
• Nitrofurantoin: Similar action on DNA and proteins.
• Fluoroquinolones: Inhibit DNA gyrase (e.g., Ciprofloxacin, Levofloxacin).

Protein Synthesis Inhibitors

• 50S Subunit: Macrolides (e.g., Azithromycin, Erythromycin), Clindamycin.
• 30S Subunit: Aminoglycosides (e.g., Gentamicin), Tetracyclines (e.g., Doxycycline).

Bacterial Coverage and Resistance

Gram-positive Coverage

• MSSA: Anti-staphylococcal penicillins, First-gen cephalosporins.
• MRSA: Vancomycin, Linezolid, Daptomycin, Clindamycin.

Gram-negative Coverage

• Common Pathogens: E. coli, Klebsiella, Pseudomonas.
• Coverage: Amino penicillins, Third and fourth gen cephalosporins, Carbapenems, Monobactams.

Anaerobic and Atypical Bacteria

• Anaerobes: Clindamycin, Metronidazole.
• Atypicals: Macrolides, Doxycycline.

Empiric Antibiotic Therapy

• Start with broad-spectrum agents based on the most likely pathogens.
• Adjust based on culture results.
• Addressing specific infections like pneumonia, UTI, skin infections, meningitis, and sepsis.

Adverse Effects of Antibiotics

• Neurotoxicity: Penicillins, Cephalosporins, Carbapenems, Polymyxins.
• Pancytopenia: Penicillins, Cephalosporins, Bactrim, Chloramphenicol.
• Nephrotoxicity: Aminoglycosides, Vancomycin, Bactrim.
• Ototoxicity: Aminoglycosides, Vancomycin.
• Myasthenia Gravis Exacerbation: Fluoroquinolones, Aminoglycosides, Macrolides.

Mechanisms of Resistance

• Decreased Permeability: Via reduced entry of antibiotics into the cell.
• Efflux Pumps: Removing antibiotics from the cell.
• Altered Binding Sites: Changing target proteins of antibiotics.
• Inactivating Enzymes: Beta-lactamases destroying antibiotic structure.

Conclusion

• Importance of understanding antibiotic mechanisms, coverage, adverse effects, and resistance in clinical practice.