What is the protocol for skin testing antibiotics in children?

Antibiotic Skin Testing in Children: A Risk-Stratified Approach

For pediatric patients with a history of benign cutaneous reactions (maculopapular rash or urticaria without systemic symptoms) to penicillins, proceed directly to a single-dose oral amoxicillin challenge without prior skin testing. 1

When to Skip Skin Testing (Direct Challenge Approach)

Most children labeled as "penicillin allergic" are not truly allergic - only 1.98% of children with reported β-lactam allergy have confirmed reactions upon testing. 1 This is substantially lower than the 7.78% rate seen in adults. 1

Low-Risk Criteria for Direct Challenge (No Skin Testing Needed):

• Mild cutaneous reactions only: maculopapular exanthem or urticaria without systemic involvement 1
• No history of: respiratory symptoms, cardiovascular symptoms, anaphylaxis, angioedema, blistering, or exfoliative eruptions 1
• Remote reactions: reactions occurring >1 year ago have 98.4% negative predictive value for true IgE-mediated allergy 1
• Viral illness context: rash during concurrent infection (especially Epstein-Barr virus, where 30-100% develop non-allergic rash with amoxicillin) 1, 2

The 2022 practice parameter provides a strong recommendation against routine penicillin skin testing before direct amoxicillin challenge in these low-risk pediatric patients. 1

When Skin Testing IS Indicated

Perform skin testing before challenge in children with:

• Severe index reactions: anaphylaxis, angioedema, serum sickness-like reactions, or severe cutaneous adverse reactions (SCAR) 1
• Recent severe reactions: particularly if <1 year ago and involved systemic symptoms 1
• Documented reactions by healthcare personnel: reactions observed and documented in hospital/emergency settings are more likely to represent true allergy 1
• Known culprit drug requiring re-exposure: when the specific penicillin that caused the reaction must be used again 1

Skin Testing Protocol When Indicated:

Reagents and technique: 1

• Penicilloyl-polylysine (PPL/Pre-Pen) at 6×10⁻⁵ mol/L as major determinant
• Penicillin G at 10,000 units/mL as minor determinant
• Consider testing with the specific culprit antibiotic if available in IV form

Interpretation criteria: 1

• Positive test: wheal ≥3 mm greater than negative control with flare ≥5 mm
• Perform prick/puncture test first, followed by intradermal testing if negative

Safety profile: Skin testing is safe with <2% of skin test-positive patients experiencing systemic reactions, and very few being anaphylactic. 1

Challenge Protocol for Children

Single-Dose Challenge (Preferred):

For low-risk patients: 1

• Administer full therapeutic dose of amoxicillin (or culprit antibiotic)
• Observe for 60-90 minutes post-administration
• Single-day challenges are sufficient - multiple-day challenges are unnecessary and expose children to antibiotics when not needed 1

For moderate-risk patients: 1

• Two-step challenge: 1/10 dose followed by full dose
• 30-minute observation between doses
• Minimum 60-minute observation after final dose

Extended Observation:

• Contact patients at 5 days to assess for delayed reactions 1
• Delayed reactions occur in approximately 5-10% but are typically mild 1
• Most delayed reactions manifest within 7 days of a single challenge 1

Critical Pitfalls to Avoid

Do NOT routinely skin test children without a history of penicillin allergy - this practice has no scientific basis and is not performed in evidence-based medicine. 3

Do NOT permanently label children as "penicillin allergic" based solely on:

• Rash during viral illness (especially mononucleosis) 2
• Gastrointestinal symptoms, headache, or other non-immune reactions 1
• Family history of penicillin allergy alone 1

Do NOT perform "test doses" - this practice does not protect against anaphylaxis and has no scientific basis. 3

Do NOT repeat skin testing after successful challenge or delabeling unless a new reaction occurs - resensitization is rare in children. 1

Risk Factors That Increase Likelihood of True Allergy

When evaluating whether to proceed with direct challenge versus skin testing first, consider: 1

• Shorter interval since reaction (<1 year) increases odds of true allergy
• Cephalosporin reactions have 2.96-fold higher odds of confirmed allergy versus penicillin reactions
• Severe reactions (anaphylaxis, angioedema) are independently associated with true hypersensitivity
• Healthcare-observed reactions are more likely to be confirmed as true allergies

Post-Evaluation Management

After negative testing/challenge: 1

• Inform families the child has the same baseline risk as general population for developing new penicillin allergy
• Remove "penicillin allergy" label from medical records
• No routine repeat testing needed unless new reaction occurs 1
• Can safely receive penicillins orally or intravenously in future 1

Documentation requirements: 1

• Record specific symptoms of reaction, timing, concurrent medications, and comorbidities
• Document drug name, route, dose, and temporal relationship
• Note setting, time to resolution, and management provided