Penicillinase-Sensitive vs. Penicillinase-Resistant Penicillins



Penicillinase-sensitive penicillins or PSPs, and Penicillinase-Resistant Penicillins, or PRPs, are both groups of beta-lactam antibiotics in the penicillin family.

Penicillinase-sensitive penicillins, as their name suggests, are penicillins sensitive to cleavage by beta-lactamases, and important drugs of this group include Amoxicillin and Ampicillin. The PSPs have broad-spectrum coverage of both gram-positive and gram-negative organisms and are often combined with beta-lactamase inhibitors to offset their susceptibility to cleavage and inactivation..

Penicillinase-Resistant Penicillins include Nafcillin, Methicillin, and Oxacillin. Since these drugs have bulky chemical structures that block access to their beta-lactam rings, they are resistant to cleavage by penicillinase enzymes. PRPs provide narrow spectrum coverage and are primarily used to treat infections by Staph aureus.

Key Points

  • Penicillinase-resistant Penicillins
    • Drug Names
      • Nafcillin
      • Methicillin
      • Oxacillin
      • Dicloxacillin
    • Mechanism
      • Same as Penicillin
    • Clinical Use
      • Narrow-spectrum coverage
        • Usually used for S. aureus (except MRSA)
    • Adverse Effects
      • Same as Penicillin
    • Resistance
      • Resistant to penicillinase (beta-lactamase)
        • This is obvious by the class name
        • Bulky R-group blocks access of beta-lactamase to beta-lactam ring
      • Altered penicillin-binding protein
        • e.g. MRSA
    • Penicillinase-Sensitive Penicillins
      • Also known as the aminopenicillins
      • Drug Names
        • Amoxicillin
          • Has greater oral availability
        • Ampicillin
      • Mechanism
        • Same as Penicillin
      • Clinical Use
        • Broader-spectrum coverage against gram-negative species
          • H. influenzae
          • H. pylori
          • E. Coli
          • Listeria monocytogenes
          • Proteus mirabilis
          • Salmonella
          • Shigella
          • Enterococci
      • Adverse Effects
        • Same as Penicillin
      • Resistance
        • Sensitive to penicillinase (beta-lactamase)
          • Obvious by class name
          • Enzymes produced by bacteria that cleave beta-lactam ring
          • May be administered with beta-lactamase inhibitors (e.g. clavulanic acid, sulbactam, tazobactam) to prevent breakdown