Penicillin Classification
Flucloxacillin is an anti-staphylococcal penicillin (also called penicillinase-resistant penicillin), while ampicillin is an aminopenicillin.
Flucloxacillin: Anti-Staphylococcal Penicillin
Flucloxacillin belongs to the class of penicillinase-resistant penicillins or anti-staphylococcal penicillins. The WHO Expert Committee explicitly notes that "for oral administration, dicloxacillin and flucloxacillin are preferred because of better oral bioavailability among options within the class" of anti-staphylococcal penicillins 1. This class was developed specifically to combat penicillinase-producing Staphylococcus aureus by incorporating an acyl side chain that prevents disruption of the beta-lactam ring 2, 3.
Key Characteristics of Anti-Staphylococcal Penicillins:
- Primary indication: Methicillin-susceptible Staphylococcus aureus (MSSA) infections
- Mechanism: Resistant to staphylococcal beta-lactamases (penicillinase)
- Class members: Flucloxacillin, dicloxacillin, oxacillin, nafcillin, methicillin, cloxacillin 1, 2
Ampicillin: Aminopenicillin
Ampicillin is classified as an aminopenicillin, a semisynthetic penicillin derived from 6-aminopenicillanic acid 4. The aminopenicillins were developed to provide gram-negative antimicrobial activity beyond what penicillin G could offer 2, 3.
Key Characteristics of Aminopenicillins:
- Spectrum: Gram-positive organisms susceptible to penicillin G PLUS certain gram-negative bacteria including E. coli, Proteus mirabilis, Shigella, Salmonella, Listeria, Haemophilus, and Neisseria 4, 2
- Critical limitation: Inactivated by penicillinase, therefore ineffective against penicillinase-producing staphylococci 4
- Class members: Ampicillin, amoxicillin, bacampicillin 2, 3, 5
Clinical Implications
The distinction matters clinically because:
- Flucloxacillin should be used for suspected or confirmed MSSA infections, particularly skin and soft tissue infections 1
- Ampicillin is appropriate for susceptible gram-negative infections but will fail against penicillinase-producing staphylococci 4
- When combined with beta-lactamase inhibitors (ampicillin-sulbactam), aminopenicillins gain activity against some beta-lactamase-producing organisms 1, 2
Important Caveat:
Neither drug is effective against methicillin-resistant S. aureus (MRSA) or Pseudomonas aeruginosa 1, 4.