Comparing Direct Challenge to Penicillin Skin Testing for the Outpatient Evaluation of Penicillin Allergy: A Randomized Controlled Trial

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Direct challenge (DC) may be a safe and effective alternative to penicillin skin testing (PST) in low-risk patients.


To complete a prospective, randomized, controlled trial comparing PST followed by a challenge to amoxicillin versus a 2-step DC to amoxicillin without preceding skin testing in a predefined low-risk patient population.


Penicillin allergy histories were reviewed in patients presenting to an outpatient allergy/immunology practice from April 2018 to August 2018. Patients 5 years or older with a cutaneous-only or unknown reaction (>1 year ago for those aged 5-17 years, >10 years ago for those 18 years or older) were randomized 1:1 to PST or 2-step DC. All children younger than 5 years underwent DC, and patients with extracutaneous reaction histories underwent PST. All groups were monitored 30 minutes after administration of amoxicillin.


Penicillin allergy was reported in 363 of 2465 (14.7%) patients, of which 185 consented to further evaluation. Thirteen patients younger than 5 years underwent DC; all were negative. Thirteen patients with angioedema and/or extracutaneous symptoms underwent PST; 2 of 13 patients had positive PST result. A total of 159 patients were randomized to DC (49.7%) or PST (50.3%). PST result was negative in 70 of 80 (87.5%) patients. All 70 patients had a negative amoxicillin challenge. DC was negative in 76 of 79 (96.2%) patients; positive DC reactions were minor. Average time for patients undergoing PST was 72.7 ± 5.3 minutes and for patients undergoing DC was 66.7 ± 4.8 minutes.


In low-risk patients, DC provided a safe and effective alternative to PST in delabeling penicillin allergy. Compared with PST, DC may also take less time, cost less money, and lead to fewer penicillin allergy evaluations with false-positive results.



This study was presented as a poster at the American Academy of Allergy, Asthma, and Immunology Annual Meeting, San Francisco, CA, February 23, 2019.

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