Medicine & USMLE

Penicillin Overview

Antibiotics / Antiparasitics
  1. Penicillin Overview
  2. Penicillinase-Sensitive vs. Penicillinase-Resistant Penicillins
  3. Anti-Pseudomonal Penicillins
  4. Cephalosporins Overview
  5. 1st Generation Cephalosporins
  6. 2nd Generation Cephalosporins
  7. 3rd Generation Cephalosporins
  8. 4th Generation Cephalosporins
  9. 5th Generation Cephalosporins
  10. Carbapenems
  11. Monobactams (Aztreonam)
  12. Vancomycin
  13. Aminoglycosides
  14. Tetracyclines
  15. Tigecycline
  16. Chloramphenicol
  17. Clindamycin
  18. Linezolid
  19. Macrolides
  20. Polymyxins
  21. Sulfonamides
  22. Dapsone
  23. Trimethoprim
  24. Fluoroquinolones
  25. Daptomycin
  26. Metronidazole
  27. Rifamycins (Rifampin, Rifabutin)
  28. Isoniazid
  29. Pyrazinamide
  30. Ethambutol
  31. Chloroquine


Penicillins are a group of antibiotics used to treat a variety of bacterial infections. Penicillins are beta-lactam antibiotics, meaning that they possess a beta-lactam ring. This beta-lactam ring is a D-Ala-D-Ala structural analog, mimicking the end parts of the peptidoglycan building blocks that bacteria use in order to build their cell wall. When bacterial transpeptidase enzymes bind penicillin instead of these building blocks, they get inactivated, causing the bacteria to fail in maintaining its cell wall. This kills the bacteria, explaining penicillin's antibacterial effect. Resistance to penicillins develops in two ways: by creating penicillinases that cleave the beta-lactam rings of penicillin, or by mutating the transpeptidases that penicillins target so the penicillin can no longer bind. Clinically, many different types of penicillins exist, and these drugs are used to treat gram-positive organisms as well as some gram negative bacteria. Adverse effects of the penicillin drugs include hypersensitivity reactions, hemolytic anemia, nephrotoxicity, and Clostridium difficile overgrowth. Finally, two forms of pure penicillin are used in the clinical setting: Penicillin G and Penicillin V. Penicillin G is administered in an injected form, while Penicillin V is taken orally.

Key Points

  • Penicillin
    • Drug Names
      • Penicillin G
        • IV and IM (injected) form
      • Penicillin V
        • Oral form
    • Mechanism
      • Original beta-lactam antibiotics
        • D-Ala-D-Ala structural analog
          • Does not actually bind D-Ala-D-Ala (unlike vancomycin), but competes with D-Ala-D-Ala for enzyme
        • Bind penicillin-binding protein (transpeptidases)
          • Prevents cross-linking of cell wall via peptidoglycans
        • Activate autolytic enzymes
    • Clinical Use
      • Mainly gram-positive organisms (Streptococcus spp., Actinomyces)
      • Some gram-negative cocci (N. meningitidis) and spirochetes (T. pallidum)
    • Adverse Effects
      • Hypersensitivity reactions (allergy)
        • Most common side effect of penicillin
        • Usually manifests as rash
      • Direct Coombs-positive hemolytic anemia
      • Drug-induced interstitial nephritis
      • Pseudomembranous colitis (C. difficile)
        • Broad-spectrum antimicrobials can open niche in GI tract for C. difficile overgrowth
    • Resistance
      • Beta-lactamase (penicillinase) cleaves beta-lactam rings
        • May be administered with beta-lactamase inhibitors (e.g. clavulanic acid, sulbactam, tazobactam) to prevent breakdown
      • Mutations in penicillin-binding proteins (PBPs)
        • This is seen in MRSA, where beta-lactam cannot bind to PBPs