Penicillins
Work in Progress Updated Jan 31, 2026
Core Concepts
Approximately 10% of the US population reports an allergy to penicillin.
Less than 5% are clinically significant immediate or delayed immune-mediated drug reactions.
Over 95% of patients are actually tolerant because:
- The index reaction was likely a benign delayed rash.
- IgE-mediated allergy wanes over time (80% tolerance after a decade).
- The reaction may have been an intolerance or caused by the underlying infection.
These individuals are more likely to receive broad-spectrum antibiotics, increasing the risk for:
- Antimicrobial resistance (MRSA, VRE)
- C. difficile infection
- Surgical site infections (due to non-beta-lactam perioperative prophylaxis)
Epstein-Barr virus.
About 0.5% to 2.0%
Potentially due to the decrease in use of parenteral penicillins in the outpatient setting.1
The NPV of penicillin skin testing is > 95% when performed with only benzylpenicilloyl polylysine plus penicillin G or with benzylpenicilloyl polylysine plus full panel of minor derterminants.
Skin Testing
| Reagent | Description |
|---|---|
| Penicilloyl polylysine (PrePen®) | Major antigenic determinant (95% of penicillin degradation). Complexed with polylysine to constitute a multivalent skin test reagent. Acts as the carrier for the penicilloyl hapten in vivo. |
| Minor determinant mixture (MDM) | Contains Penicillin G, penicilloate, and penilloate. Not commercially available in the US. |
| Penicillin G | Also called benzylpenicillin. |
| Ampicillin | Differs from Penicillin G by the presence of an amino group (-NH2). |
Selective IgE-mediated reactions to aminopenicillins are rare in North America (e.g. 3-5% in the United States) versus 25-50% of skin test positive patients in Europe.
The polylysine carrier has ~40 lysine repeats.
Oral Penicillin = Penicillin VK IM/IV Penicillin = Penicillin G Amino group = -NH3
Aminopenicillins = Amoxicillin, Ampicillin Aminocephalosporins = Cephalexin, Cefadroxil, Cefprozil and Cefaclor
Chapter 77 Middleton’s Drug Allergy