II. Background

  1. More than 90% of patient reported Penicillin Allergy is not a true allergy

III. History: Reaction

  1. How old were you when you had the reaction?
  2. Did Type 1 Hypersensitivity Reaction symptoms occur?
    1. Anaphylaxis
    2. Hypotension
    3. Laryngeal edema (Wheezing or Stridor)
    4. Angioedema
    5. Urticaria
  3. Did a Severe Type 4 Hypersensitivity Reaction Occur?
    1. Stevens Johnson Syndrome
    2. Toxic Epidermal Necrolysis
  4. How soon after the medication did the reaction start?
    1. Within one hour suggests Type 1 Hypersensitivity
  5. Was the Penicillin given orally or Parenterally?
  6. Did the reaction resolve after stopping the medication?
  7. Have you taken related medications and did you react?
    1. Amoxicillin or Augmentin?
    2. Cephalosporin

IV. Evaluation: PEN-FAST Penicillin Allergy Decision Rule

  1. Indications
    1. Penicillin Allergy reported by patient
  2. Criteria: FAST
    1. Score 2 Points (F)
      1. Five years or less since reaction
    2. Score 2 Points (AS)
      1. Anaphylaxis or Angioedema OR
      2. Severe cutaneous adverse reaction
        1. Stevens Johnson Syndrome
        2. Toxic Epidermal Necrolysis
        3. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS Syndrome)
        4. Acute Generalized Exanthematous Pustulosis
        5. Severe delayed rash with mucosal involvement
    3. Score 1 Point (T)
      1. Treatment required for reaction
  3. Interpretation
    1. Total Score 0 Points
      1. Very low risk of positive Penicillin Allergy test (<1%)
    2. Total Score 1-2 Points
      1. Low risk of positive Penicillin Allergy test (5%)
    3. Total Score 3 Points
      1. Moderate risk of positive Penicillin Allergy test (20%)
    4. Total Score 4-5 Points
      1. High risk of positive Penicillin Allergy test (50%)
  4. Efficacy
    1. PEN-FAST Total Score 0
      1. Negative Predictive Value (NPV): 99.4%
    2. PEN-FAST Total Score <3
      1. Negative Predictive Value (NPV): 96.3%
  5. Precautions
    1. IV Penicillin reactions were not fully evaluated in study
    2. Rule has not be evaluated in ethnically diverse populations
    3. Other serious reaction histories (e.g. Interstitial Nephritis, Serum Sickness) were not evaluated in the study
  6. References
    1. Trubiano (2020) JAMA Intern Med 180(5): 745-52 [PubMed]

V. Management

  1. Cephalosporins have cross reactivity with Penicillins
    1. Cross reactivity was originally over-estimated as high as 10% in the 1960s
      1. Attributed to cross contamination
      2. Co-production of Cephalosporins and Penicillins in the same factory
    2. Cephalosporin reaction when Penicillin Allergy
      1. Penicillin Allergy and allergy to first and Second Generation Cephalosporins: 1%
      2. Penicillin Allergy and allergy to Third Generation Cephalosporins: Negligible
      3. Aminopenicillins (Amoxicillin and Ampicillin) allergy
        1. Cross-reactivity to first and Second Generation Cephalosporins: High
        2. R1-side chain of Aminopenicillins are similar to first and Second Generation Cephalosporins
        3. Reaction rate is as high as 27% for Cefadroxil
      4. Campagna (2012) J Emerg Med 42(5): 612-20 [PubMed]
    3. Penicillin Allergy when Cephalosporin allergic: >25%
    4. Cephalosporin cross reactivity risk factors
      1. Type I Hypersensitivity to Penicillin
      2. Positive Penicillin skin test (5% risk)
      3. First or Second Generation Cephalosporin
      4. Atopic Dermatitis
  2. Type 1 Hypersensitivity Reaction (IgE-mediated immediate reaction with 6 hours)
    1. More than 80% of those with non-anaphylactic, IgE-mediated reaction history will not react after 10 years
    2. Obtain Penicillin Skin Testing for allergy
    3. Penicillin skin test negative (80-95% of cases)
      1. Cephalosporins may be used (1.3% risk of reaction)
      2. Continue to avoid Penicillins unless otherwise directed by allergist
    4. Penicillin skin test positive
      1. Avoid Penicillins and Cephalosporins
      2. Risk of Cephalosporin reaction: 4.4%
      3. Consider cephalosporin Desensitization
  3. Reaction consistent with NON-Type 1 Hypersensitivity (e.g. Delayed, Type 4 Hypersensitivity Reaction)
    1. Includes severe delayed reactions (e.g. Stevens Johnson Syndrome, Toxic Epidermal Necrolysis, DRESS Syndrome)
    2. Consider Penicillin Skin Testing for allergy
    3. Continue to avoid Penicillins unless otherwise directed by allergy Consultation
    4. Cephalosporins may be used
      1. Some recommend penicillin Skin Testing before use
      2. Kelkar (2001) N Engl J Med 345:804-9 [PubMed]

VI. Complications

  1. Documented Penicillin Allergy is associated with adverse events due to alternative antibiotic use
    1. Confirm allergy and document actual Penicillin reaction
      1. Document the specific medication, the specific reaction (e.g. rash) and the management (e.g. home or ED)
    2. Adverse effects
      1. Results in overuse of broad spectrum agents
      2. Associated with longer hospital stay and increased C. Diff and MRSA Infections
    3. References
      1. Macy (2014) J Allergy Clin Immunol 133(3): 790-6 +PMID:24188976 [PubMed]

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