How Good Is an Oral Provocation Challenge to Confirm Amoxicillin Allergies in Children?

Summary and Comment |
April 15, 2016

How Good Is an Oral Provocation Challenge to Confirm Amoxicillin Allergies in Children?

  1. Louis M. Bell, MD

An oral provocation challenge to confirm either an immediate or nonimmediate allergic reaction to amoxicillin was found to be safe and more accurate than skin testing.

  1. Louis M. Bell, MD

Some children who develop a rash while taking amoxicillin are labeled as “allergic” to the antibiotic with no further evaluation. In an observational study, researchers offered a graded oral provocation test to all children referred to an allergy clinic in Montreal with suspected allergy to amoxicillin. Children were given 10% of the therapeutic dose of amoxicillin, observed for 20 minutes, then given 90% of the therapeutic dose and observed for at least 1 hour. Parents were instructed to report reactions that occurred the next week.

Of 818 participants (mean age, 1.7 years), 94% tolerated the provocation test and therefore were not allergic to amoxicillin. Of the others, 2% had immediate reactions (within 1 hour of the last dose) — all mild urticaria that resolved with antihistamines — and 4% had nonimmediate reactions (median of 12 hours after the last dose) — all mild maculopapular rash. Only 1 of the 17 children with immediate reactions tested positive on skin prick and intradermal testing 2 to 3 months later.

History of a rash lasting longer than 7 days and parental history of drug allergy were associated with nonimmediate reactions on the provocation test (adjusted odds ratios, 5 and 3, respectively); history of allergic reaction within 5 minutes was associated with immediate reactions (AOR, 10). During 3-year follow-up of children who tolerated the test, 55 received a subsequent full course of amoxicillin and 6 (11%) had nonimmediate reactions. All patients with reactions to amoxicillin tolerated cefixime.


The finding that some children who were tolerant on the oral challenge developed a nonimmediate reaction (rash) after a subsequent full course of amoxicillin suggests the oral challenge might miss some allergic children, but all such reactions were mild. Therefore, the oral provocation test seems to be a positive step forward and will help us to feel comfortable using amoxicillin as the safe narrow-spectrum antibiotic of choice in the vast majority of children who previously were labeled as being allergic.

Editor Disclosures at Time of Publication

  • Disclosures for Louis M. Bell, MD at time of publication Grant / Research support NIH Institutional Clinical and Translational Science Award; Agency for Healthcare Research and Quality National Center for Pediatric Practice Based Research Learning; Patient-Centered Outcomes Research Institute Editorial boards Current Problems in Pediatric Adolescent Healthcare (Associate Editor)


Reader Comments (2)

Harvey Harris Physician, Pediatrics/Adolescent Medicine, Outpatient

Until a larger test group result is published, it is safer using an allergist to perform such testing. Much less stressful than in busy primary care settings. Desensitization in hospitals when urgently necessary is reasonable for suspected or known penicillin allergy. Depending on accurate outpatient parental reports, without examining skin eruptions, is too risky.
Glad to see the true allergic group is smaller than old reports of 50% not allergic when formally tested as adults.

michael posner Physician, Pediatrics/Adolescent Medicine, charter high school

nice to know, but i personally would avoid testing with oral medication if a history of rapid onset urticaria, etc is well described. many small offices are not really ready to deal with anaphylaxis. i am not that brave.

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