II. Background
- More than 90% of patient reported Penicillin Allergy is not a true allergy
- Prevalance (U.S.): 10% are labeled as Penicillin allergic
- Of children with Penicillin Allergy, 75% are diagnosed age <3 years
- Of these children labeled allergic, 90% are able to tolerate Penicillin on drug challenge
III. History: Reaction
- How old were you when you had the reaction?
- Did Type 1 Hypersensitivity Reaction symptoms occur?
- Anaphylaxis
- Hypotension
- Laryngeal edema (Wheezing or Stridor)
- Angioedema (lip or Tongue swelling)
- Urticaria (present <24 hours per location)
- Did a Severe Type 4 Hypersensitivity Reaction Occur?
- How soon after the medication did the reaction start?
- Within one hour suggests Type 1 Hypersensitivity
- More than 24 hours is typically due to non-medication related or Fixed Drug Eruption
- Was the Penicillin Given orally or Parenterally?
- Did the reaction resolve after stopping the medication?
- Have you taken related medications and did you react?
IV. Evaluation: PEN-FAST Penicillin Allergy Decision Rule
- Indications
- Penicillin Allergy reported by patient
- Criteria: FAST
- Score 2 Points (F)
- Five years or less since reaction
- Score 2 Points (AS)
- Anaphylaxis or Angioedema OR
- Severe cutaneous adverse reaction
- Stevens Johnson Syndrome
- Toxic Epidermal Necrolysis
- Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS Syndrome)
- Acute Generalized Exanthematous Pustulosis
- Severe delayed rash with mucosal involvement
- Score 1 Point (T)
- Treatment required for reaction
- Score 2 Points (F)
- Interpretation
- Total Score 0 Points
- Very low risk of positive Penicillin Allergy test (<1%)
- Total Score 1-2 Points
- Low risk of positive Penicillin Allergy test (5%)
- Total Score 3 Points
- Moderate risk of positive Penicillin Allergy test (20%)
- Total Score 4-5 Points
- High risk of positive Penicillin Allergy test (50%)
- Total Score 0 Points
- Efficacy
- PEN-FAST Total Score 0
- Negative Predictive Value (NPV): 99.4%
- PEN-FAST Total Score <3
- Negative Predictive Value (NPV): 96.3%
- PEN-FAST Total Score 0
- Precautions
- IV Penicillin reactions were not fully evaluated in study
- Rule has not be evaluated in ethnically diverse populations
- Other serious reaction histories (e.g. Interstitial Nephritis, Serum Sickness) were not evaluated in the study
- References
V. Management
-
Cephalosporins have cross reactivity with Penicillins
- Cross reactivity was originally over-estimated as high as 10% in the 1960s
- Attributed to cross contamination
- Co-production of Cephalosporins and Penicillins in the same factory
- Cephalosporin reaction when Penicillin Allergy
- Penicillin Allergy and allergy to first and Second Generation Cephalosporins: 1%
- Penicillin Allergy and allergy to Third Generation Cephalosporins: Negligible
- Aminopenicillins (Amoxicillin and Ampicillin) allergy
- Cross-reactivity to first and Second Generation Cephalosporins: High
- R1-side chain of Aminopenicillins are similar to first and Second Generation Cephalosporins
- Reaction rate is as high as 27% for Cefadroxil
- Campagna (2012) J Emerg Med 42(5): 612-20 [PubMed]
- Penicillin Allergy when Cephalosporin allergic: >25%
- Cephalosporin cross reactivity risk factors
- Type I Hypersensitivity to Penicillin
- Positive Penicillin skin test (5% risk)
- First or Second Generation Cephalosporin
- Atopic Dermatitis
- Cross reactivity was originally over-estimated as high as 10% in the 1960s
- Type 1 Hypersensitivity Reaction (IgE-mediated immediate reaction with 6 hours)
- More than 80% of those with non-anaphylactic, IgE-mediated reaction history will not react after 10 years
- Obtain Penicillin Skin Testing for allergy
- Penicillin skin test negative (80-95% of cases)
- Cephalosporins may be used (1.3% risk of reaction)
- Continue to avoid Penicillins unless otherwise directed by allergist
- Penicillin skin test positive
- Avoid Penicillins and Cephalosporins
- Risk of Cephalosporin reaction: 4.4%
- Consider cephalosporin Desensitization
- Reaction consistent with NON-Type 1 Hypersensitivity (e.g. Delayed, Type 4 Hypersensitivity Reaction)
- Includes severe delayed reactions (e.g. Stevens Johnson Syndrome, Toxic Epidermal Necrolysis, DRESS Syndrome)
- Consider Penicillin Skin Testing for allergy
- Continue to avoid Penicillins unless otherwise directed by allergy Consultation
- Cephalosporins may be used
- Some recommend penicillin Skin Testing before use
- Kelkar (2001) N Engl J Med 345:804-9 [PubMed]
- Low risk, non-severe reactions (Non-Type 1, Non-Type 4 reactions)
- Consider Amoxicillin challenge (give a single dose and observe for 1 hour)
VI. Complications
- Documented Penicillin Allergy is associated with adverse events due to alternative Antibiotic use
- Confirm allergy and document actual Penicillin reaction
- Document the specific medication, the specific reaction (e.g. rash) and the management (e.g. home or ED)
- Adverse effects
- Results in overuse of broad spectrum agents
- Associated with longer hospital stay and increased C. Diff and MRSA Infections
- References
- Confirm allergy and document actual Penicillin reaction
VII. References
- (2017) Presc Lett 24(3)
- Ravi (2024) Mayo Clinic Pediatric Days, Attended 1/15/2024
- Kelkar (2001) N Engl J Med 345:804-9 [PubMed]
- Salkind (2001) JAMA 285:2498-505 [PubMed]