Lecture on Cephalosporins

Overview

• Cephalosporins are a class of beta-lactam antibiotics.
  • Characterized by a beta-lactam ring.
• Names start with prefixes: CEF or CEPH.
• Mechanism: Inhibit cell wall synthesis by binding to penicillin-binding proteins on bacteria.

Adverse Effects and Contraindications

• Adverse Effects:
  • Skin rashes, pruritis, Stevens-Johnson syndrome.
  • Nausea, vomiting, diarrhea, risk of seizures (especially with cefepime).
  • Nephrotoxicity and allergic reactions.
• Contraindications:
  • Hypersensitivity to cephalosporins or other beta-lactam antibiotics.
  • Potential cross-reactivity in individuals allergic to penicillin.

Generations of Cephalosporins

First Generation

• Drugs: Cephalexin (oral), Cefazolin (IV/IM).
• Coverage:
  • Good for gram-positive bacteria (aerobic cocci, Group A/B Streptococci, MSSA).
  • Limited gram-negative coverage (E. coli, Proteus, Klebsiella).
  • Inadequate for H. influenzae, Moraxella catarrhalis, Bacteroides fragilis.
• Uses:
  • Uncomplicated community-acquired skin and soft-tissue infections.
  • Uncomplicated UTIs.
  • Surgical wound prophylaxis.

Second Generation

• Drugs: Cefotetan, Cefuroxime, Cefprozil, Cefoxitin.
• Coverage:
  • Similar gram-positive as the first generation but less for staphylococci.
  • Increased gram-negative coverage (Neisseria meningitidis, Moraxella catarrhalis).
  • Cefoxitin and Cefotetan: increased coverage for oral anaerobes like Bacteroides fragilis.
• Uses:
  • Respiratory tract infections, uncomplicated UTIs.
  • Surgical wound prophylaxis, pneumococcal pneumonia.

Third Generation

• Drugs: Ceftriaxone, Cefotaxime, Cefixime, Ceftazidime.
• Coverage:
  • Cross blood-brain barrier.
  • Increased gram-negative activity, less gram-positive than previous generations.
  • Ceftazidime: covers Pseudomonas.
• Uses:
  • Gram-negative meningitis, pneumococcal infections.
  • Hospital-acquired and complicated community-acquired infections.

Fourth Generation

• Drugs: Cefepime, Cefpirome.
• Coverage:
  • Similar to third generation but includes Pseudomonas.
  • Improved activity against "SPACE" organisms (Serratia, Proteus, Acinetobacter, Citrobacter, Enterobacter).
• Uses:
  • Pseudomonas infections, antibiotic-resistant infections.
  • Gram-negative meningitis.

Fifth Generation

• Drug: Ceftaroline.
• Coverage:
  • Active against MRSA, less against gram-negative.
  • No activity against Pseudomonas, less effective against "SPACE" organisms compared to fourth generation.

Summary

• Generational Changes:
  • First generation: More gram-positive, little gram-negative.
  • Second generation: Slightly more gram-negative, less gram-positive.
  • Third generation: Rapidly increases gram-negative, loses some gram-positive.
  • Fourth generation: Even better gram-negative, increased gram-positive.
  • Fifth generation: Increased gram-positive, decreased gram-negative.

Additional Resources

• Recommended to explore more on other antibiotics like fluoroquinolones from pharmacology playlists.