For people who have low-risk reaction histories in an inpatient setting, direct oral challenges may be a safe, effective, and less expensive option for penicillin allergy delabeling compared with penicillin skin testing, according to results of a study published in The Journal of Allergy and Clinical Immunology: In Practice.

The penicillin allergy is the most commonly reported drug allergy with 10% of outpatients and >15% of inpatients reporting a history of this allergy. The harms of the penicillin allergy label include an increased length and cost of hospital stay, decreased infection cure rates, increased risk for infection recurrence, and increased risk for adverse events from second-line antibiotic use. In addition, the penicillin allergy is associated with higher healthcare costs and an increased antimicrobial resistance. As a result, many organizations, including the Centers for Disease Control and Prevention, recommend penicillin allergy delabeling.

Historically, penicillin allergy delabeling was performed through penicillin skin testing and followed by an oral challenge. However, in those with low-risk reaction histories, an emerging safe and effective alternative to penicillin skin testing is direct oral challenge. Most safety data on direct oral challenge has been evaluated in the outpatient setting, resulting in a lack of inpatient data. Therefore, this single-center, prospective study demonstrated the safety and efficacy of direct oral challenge of penicillin-based antibiotics in the in-patient settings in patients with low-risk, cutaneous-only reaction histories >20 years ago.

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In total, 100 patients were included. The patients who were offered a 3-step direct oral challenge had low-risk, cutaneous-only reaction histories (eg, rash, hives, itching), occurring >20 years ago. Patients who had a cutaneous reaction history <20 years ago, a history of angioedema, or reactions involving multiple body systems received penicillin skin testing and a one-time observed dose of amoxicillin. In total, 52 patients had histories appropriate for penicillin skin testing and 48 patients had histories appropriate for direct oral challenge.

The primary objective was to demonstrate the safety and feasibility of direct oral challenge in the inpatient setting in patients with a low-risk penicillin allergy history. Secondary outcomes included pre- and post-evaluation of antibiotic use, days of antibiotic therapy that were avoided, direct antibiotic cost-savings after the penicillin allergy evaluation, and cost of penicillin skin testing compared with direct oral challenge.

Results suggested that direct oral challenge may be a safe, effective, and less expensive method for penicillin delabeling. In the penicillin skin testing group, 44 (84.6%) patients were penicillin skin testing negative. In the direct oral challenge group, 47 (97.9%) patients initially tolerated direct oral challenge with 2 (4.2%) patients having a delayed reaction. The 1 patient who had an immediate reaction to direct oral challenge was treated with an antihistamine. In the penicillin skin testing group, hives and angioedema (23.1%), anaphylaxis (19.2%), and angioedema alone (13.5%) were the most common reactions reported. In the direct oral challenge group, rash (45.8%), hives (41.7%), and itching (4.2%) were the most common reactions reported.

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For both groups and all 100 included patients, 56 patients transitioned to penicillin-based antibiotics, 13 patients were transitioned to a non-β-lactam antibiotic, 10 patients transitioned to a first- or second-generation cephalosporin, 4 patients were transitioned to a third-generation cephalosporin. In total, 783 days of second-line antibiotic therapy were avoided based on antibiotic indication and recommended length of therapy. Results also demonstrated that direct oral challenge was a cheaper option than penicillin skin testing ($206.18/patient vs $419.63/patient).

Overall, the study authors concluded that, “[direct oral challenge] is a safe, effective, and less expensive method for penicillin de-labeling in adult inpatients with a low risk, cutaneous-only reaction history >20 years ago.”


Ramsey A, Mustafa SS, Holley AM, Staicu ML. Direct challenges to penicillin-based antibiotics in the inpatient setting [published online March 7, 2020]. J Allergy Clin Immunol Pract. doi:10.1016/j/jaip.2020.02.033

This article originally appeared on Infectious Disease Advisor