Penicillin Skin Testing in Infants: Age Recommendations
Penicillin skin testing can be safely performed at any age, including in infants and neonates, when clinically indicated—there is no minimum age requirement. 1
Evidence-Based Age Guidelines
The CDC guidelines from 1993 through 2002 explicitly state that penicillin skin testing may be performed in children of any age, including infants, when penicillin therapy is essential (such as for congenital syphilis). 1
Full battery skin testing (major determinant Pre-Pen plus minor determinants) identifies 90-97% of allergic patients across all pediatric age groups. 1
Modern Approach: Skin Testing Is Often Unnecessary
For most infants with reported antibiotic reactions, direct oral challenge without prior skin testing is now the preferred strategy. 2, 1
When to Skip Skin Testing in Infants
Low-risk reactions (maculopapular rash or urticaria without systemic symptoms, blistering, exfoliation, or anaphylaxis) should proceed directly to supervised oral amoxicillin challenge without skin testing. 2, 1
Over 90% of children with reported amoxicillin rashes tolerate the drug on re-exposure, and only 1.98% of children labeled as penicillin-allergic are truly allergic when properly tested. 1
In a study of 818 children who underwent direct amoxicillin challenge without skin testing, 94% tolerated the antibiotic with all immediate reactions being mild. 2
When Skin Testing Is Indicated in Infants
High-risk reactions requiring skin testing before challenge include: 2, 1
- Immediate-onset urticaria, angioedema, or anaphylaxis (within 1 hour of drug exposure)
- Severe cutaneous reactions with blistering, skin detachment, or mucosal involvement
- Reactions occurring within the past year with concerning features
When penicillin is essential (e.g., for congenital syphilis or other serious bacterial infections where no alternative exists), skin testing should be performed at any age with appropriate monitoring and resuscitation equipment available. 1
Practical Algorithm for Infants
For Non-Urgent Situations (Infant Not Currently Requiring Antibiotics)
Defer evaluation until the infant actually needs antibiotics in the future. 3
When antibiotics are next needed, perform a direct supervised oral challenge (single dose under observation) for low-risk reactions without prior skin testing. 3, 1
For Urgent Situations (Penicillin Essential Now)
Perform skin testing immediately at any age if the infant has a history suggesting possible IgE-mediated allergy (immediate urticaria, angioedema, anaphylaxis). 1
If skin testing is negative, proceed with desensitization before administering therapeutic doses. 3
Critical Limitations of Skin Testing in Infants
Skin testing has no utility for delayed-onset rashes (maculopapular eruptions appearing days after starting the antibiotic), which represent the majority of reported reactions in infants. 2, 3, 1
The positive predictive value of skin testing is less than 50%, meaning many infants with positive skin tests would actually tolerate the antibiotic. 3
Skin testing sensitivity decreases over time—the longer the interval since the reaction, the less reliable the test becomes. 3
Common Pitfalls to Avoid
Do not perform skin testing for delayed maculopapular rashes during viral illnesses, as these are typically benign virus-drug interactions rather than true allergies. 3, 1
Do not permanently label infants as penicillin-allergic based solely on a rash during a viral illness—this leads to unnecessary use of broader-spectrum antibiotics and increased antimicrobial resistance. 3, 4
Do not assume skin testing is required before all challenges—for low-risk reactions, direct challenge is safer, faster, and more cost-effective. 2, 1
Do not delay essential penicillin therapy in infants with serious bacterial infections while awaiting allergy evaluation—skin testing can be performed at any age when the antibiotic is truly needed. 1