Antibiotics Lecture Notes

Introduction

• Overview of antibiotics and importance of understanding their mechanisms of action.
• Urged students to download illustrations for better understanding and follow along.

Mechanism of Action of Antibiotics

• How antibiotics work against bacteria:
  • Target different structures such as cell wall, cell membrane, and metabolic pathways.
  • Categorization based on the structure and type of bacteria (Gram-positive, Gram-negative, anaerobic, atypical).

1. Cell Wall Synthesis Inhibitors

• Peptidoglycan is a key component of bacterial cell walls.
  • Inhibition types:
    • Reducing peptidoglycan synthesis (e.g., Vancomycin, Phosphomycin).
    • Reducing cross-linking (e.g., Penicillins, Cephalosporins).
  • Penicillin Group:
    • Natural Penicillins: Penicillin G, Penicillin V.
    • Anti-Staphylococcal: Oxacillin, Nafcillin, Dicloxacillin.
    • Aminopenicillins: Amoxicillin, Ampicillin.
    • Anti-Pseudomonal: Piperacillin.
  • Cephalosporins:
    • Five generations, vary in Gram-positive to Gram-negative coverage.
    • Common ones: Cefazolin (1st Gen), Ceftriaxone (3rd Gen), Ceftazidime (3rd Gen).
  • Carbapenems: Broad spectrum, e.g., Doripenem, Meropenem.
  • Monobactams: Aztreonam for Gram-negative coverage, especially for penicillin-allergic patients.

2. Cell Membrane Integrity Inhibitors

• Daptomycin: Creates efflux pumps, increases membrane permeability.
• Polymyxins: Cationic detergents that disrupt membrane integrity.

3. DNA and RNA Synthesis Inhibitors

• Folic Acid Synthesis: Sulfonamides (Sulfamethoxazole) and Trimethoprim (Bactrim).
• DNA Integrity: Metronidazole, Nitrofurantoin create reactive oxygen species damaging DNA.
• RNA Polymerase Inhibitors: Rifampin for tuberculosis.
• DNA Gyrase Inhibitors: Fluoroquinolones (Ciprofloxacin, Levofloxacin).

4. Protein Synthesis Inhibitors

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

Bacterial Coverage of Antibiotics

• Gram-Positive Bacteria:
  • Treatments: Beta-lactams, Vancomycin for MRSA, Clindamycin.
• Gram-Negative Bacteria:
  • HENS PECK: Haemophilus, Enterobacter, Neisseria, Serratia, Proteus, E. coli, Klebsiella.
  • Treatments: Aminopenicillins, 3rd and 4th generation cephalosporins, carbapenems.
• MRSA: Limited treatments, use Vancomycin, Linezolid, or Daptomycin.
• Anaerobes: Metronidazole, Clindamycin for above diaphragm; Carbapenems for below diaphragm.
• Atypicals: Doxycycline, Macrolides for Mycoplasma, Chlamydia, Legionella.

Adverse Effects of Antibiotics

• Neurotoxicity: Penicillins, Cephalosporins (seizures), Linazolid.
• Pancytopenia: Penicillins, Cephalosporins, Bactrim, Chloramphenicol, Linezolid.
• Nephrotoxicity: Aminoglycosides, Vancomycin.
• Ototoxicity: Aminoglycosides, Vancomycin.
• Teratogenicity: Tetracyclines, Bactrim.
• Disulfiram Reaction: Metronidazole, Ceftriaxone.
• QT Prolongation: Fluoroquinolones, Macrolides.

Mechanisms of Antibiotic Resistance

• Resistance mechanisms:
  • Decreased permeability (e.g., Vancomycin, Aminoglycosides).
  • Efflux pumps (e.g., Fluoroquinolones, Macrolides).
  • Altered target sites (e.g., Beta-lactams, Vancomycin).
  • Inactivating enzymes (e.g., Beta-lactamases).

Antibiotic Susceptibility Testing

• Methods: Kirby-Bauer method, broth microdilution, macro dilution to determine MIC.
• Interpreting Results: Adjust therapy based on culture results and susceptibility.

Case Studies

1. Pneumonia: Start with empiric therapy based on community-acquired pathogens. Adjust once cultures return.
2. Urinary Tract Infection: Use Aminopenicillins or Vancomycin if Enterococcus is present.
3. Skin Infections: Use anti-staphylococcal penicillins or cephalosporins. Adjust for MRSA if needed.
4. Sepsis: Start with Vancomycin and Piperacillin/Tazobactam. Adjust based on cultures.

Conclusion

• Antibiotics are complex but essential in treating infections.
• Importance of understanding mechanisms, coverage, adverse effects, and resistance to ensure effective treatment.