Antibiotics Overview

In this lecture, we discussed various types of antibiotics, focusing on those that affect bacterial cell walls.

Bacterial Cell Types

• Gram-negative vs. Gram-positive:
  • Gram-negative bacteria:
    • Thin peptidoglycan layer.
    • Surrounded by an outer membrane with porins.
    • Contains lipopolysaccharides (LPS) which can be toxic.
  • Gram-positive bacteria:
    • Thick peptidoglycan layer.
    • No outer cell membrane.

Beta-Lactam Antibiotics

Structure

• Beta-lactams have a unique structure characterized by:
  • A beta-lactam ring (cyclic amide).
  • Composed of a 5-membered and a 4-membered ring.

Types of Beta-Lactams

1. Penicillins
   • Includes Penicillin G and Amoxicillin.
   • Effective against Gram-positive and some Gram-negative bacteria.
   • Resistance due to beta-lactamase which breaks the beta-lactam ring.
2. Cephalosporins
   • Four generations:
     • 1st Generation: Cephalexin (mainly Gram-positive).
     • 2nd Generation: Cefuroxime (also primarily Gram-positive).
     • 3rd Generation: Ceftriaxone (increased Gram-negative coverage).
     • 4th Generation: Cefepime (even broader Gram-negative coverage).

Mechanism of Action

• Penicillins & Amoxicillin:
  • Bind to penicillin binding proteins (PBPs) and stimulate autolytic enzymes, disrupting the cell wall structure.
  • Also inhibit transpeptidase enzymes, preventing cross-linking of peptidoglycan chains.
  • Leads to cell lysis as water enters the cell.
• Amoxicillin:
  • Often combined with clavulanic acid to overcome beta-lactamase resistance.

Coverage

• Penicillin: Effective against Streptococcus spp. and some Staphylococcus spp., and treats syphilis.
• Amoxicillin: Effective against:
  • Urinary tract infections
  • Respiratory tract infections
  • Meningitis
  • Salmonella
  • Otitis media (middle ear infections)
• Cephalosporins:
  • 1st & 2nd generation: Good for Staphylococcus aureus and Streptococcus pyogenes.
  • 3rd & 4th generation: Effective against Pseudomonas aeruginosa, meningitis, and Klebsiella pneumonia.

Other Beta-Lactams

• Examples include Piperacillin-tazobactam (Pip-Tazo) and carbapenems.

Glycopeptide Antibiotics

• Vancomycin:
  • Effective against MRSA (Methicillin-resistant Staphylococcus aureus) and Clostridium difficile (C. diff).
  • Mechanism: Binds to the peptide chains and inhibits peptide bond formation, disrupting cell wall integrity leading to lysis.

Antibiotics for Mycobacterium

• Isoniazid:
  • Used to treat tuberculosis.
  • Inhibits mycolic acid synthase, disrupting the cell wall comprised of mycolic acids, leading to bacterial death.

Conclusion

• The next lecture will cover antibiotics targeting the folic acid pathway.