Is a skin test for ampicillin (antibiotic) allergy suitable for a 5-month-old patient?

Skin Testing for Ampicillin Allergy in a 5-Month-Old Infant

Skin testing for ampicillin allergy can be performed at any age, including in a 5-month-old infant, but is generally unnecessary for most pediatric reactions and should be reserved for specific high-risk scenarios. 1

When Skin Testing Is Appropriate

Skin testing should be considered in infants only when:

• The infant had an immediate-onset reaction (within 1 hour) with urticaria, angioedema, or anaphylaxis 1
• There were severe cutaneous reactions including blistering, skin exfoliation, or mucosal involvement (Stevens-Johnson syndrome, toxic epidermal necrolysis) 1
• Ampicillin or another beta-lactam antibiotic is essential for treatment and no alternative exists 1

The CDC specifically states that penicillin skin testing can be performed at any age, including infants, when penicillin is essential, with full battery testing identifying 90-97% of allergic patients. 1 However, this recommendation applies primarily when the antibiotic is medically necessary and the reaction history suggests true IgE-mediated allergy.

When Skin Testing Should Be Avoided

Skin testing has limited utility and should NOT be performed for:

• Maculopapular rashes (the most common presentation in children, accounting for 36% of reactions) 1
• Delayed-onset rashes occurring days after starting the antibiotic 2
• Non-severe, non-immediate reactions 2
• Vague or unspecified rashes 2

The British Society for Allergy and Clinical Immunology specifically recommends against performing penicillin skin testing for non-IgE-mediated maculopapular rash, as it has limited utility and poor sensitivity/specificity for delayed reactions. 1 Reactions in childhood, typically delayed onset and unspecified rashes, are only rarely associated with positive skin or drug provocation testing. 2

Alternative Approach: Direct Drug Challenge

For low-risk reactions in infants, a direct oral drug provocation test (without prior skin testing) is the preferred approach when future antibiotic use is needed. 2

Recent evidence demonstrates that:

• Over 90% of children with reported amoxicillin rashes tolerate the drug on re-exposure 1
• In pediatric studies, 818 children underwent amoxicillin challenge without skin testing, with 94% tolerating amoxicillin and all immediate reactions being mild 2
• Direct drug provocation testing in children aged 5-17 years showed only 1.5-2.6% with objective reactions, none life-threatening 2
• A 2025 study successfully performed drug provocation tests without skin testing in children, including those with immediate reactions, without major complications 3

Important Clinical Caveats

Common pitfalls to avoid:

• Do not permanently label an infant as "penicillin allergic" based solely on a maculopapular rash during a viral illness 1, 4. In infants with viral infections, 30-100% may develop rashes when given amoxicillin, representing a virus-drug interaction rather than true allergy. 1

• Skin testing has reduced sensitivity over time 2. The longer the interval since the reaction, the less reliable skin testing becomes for diagnosing immediate reactions.

• The positive predictive value of skin testing is less than 50% 2. Even when skin tests are positive, patients are not offered drug provocation tests for ethical reasons, but many would likely tolerate the drug.

Practical Algorithm for a 5-Month-Old

Step 1: Characterize the reaction

• Immediate (within 1 hour) with urticaria/angioedema/anaphylaxis → Consider skin testing if ampicillin is essential 1
• Severe cutaneous reactions with blistering/mucosal involvement → Permanent avoidance, no testing needed 1
• Maculopapular rash or delayed reaction → Skip skin testing, consider direct challenge when needed 1, 4

Step 2: Assess necessity

• If ampicillin is not immediately needed, defer evaluation until the infant requires antibiotics in the future 2
• If ampicillin is essential now and reaction was high-risk, proceed with skin testing followed by desensitization if negative 1

Step 3: Future antibiotic use

• For low-risk reactions (maculopapular rash >1 year ago), perform direct oral challenge without skin testing when antibiotics are next needed 2, 1
• Monitor for 5-10 days during extended challenges, as delayed reactions can occur at a mean of 6 days into treatment 1

The evidence strongly supports that most infants labeled as ampicillin-allergic are not truly allergic, and unnecessary labeling leads to use of broader-spectrum, less effective antibiotics with increased antibiotic resistance. 1, 5