Direct Challenges to Penicillin-Based Antibiotics in the Inpatient Setting

Abstract

Background: Direct challenge (DC) is an emerging safe and effective alternative to penicillin skin testing (PST) in patients reporting a low-risk reaction history, but limited data exist for the inpatient setting.

Objective: To demonstrate the safety and efficacy of DC of penicillin-based antibiotics in the inpatient setting in patients with low-risk, cutaneous-only reaction histories more than 20 years ago.

Methods: Adult inpatients reporting penicillin allergy and receiving antibiotics were screened by an infectious disease PharmD for appropriateness for penicillin allergy delabeling. Patients with low-risk, cutaneous-only reaction histories (rash, hives, itching) more than 20 years ago were offered a 3-step DC. Patients with a cutaneous reaction history less than 20 years ago, a history of angioedema, or reactions involving multiple body systems underwent PST followed by a 1-time observed dose of amoxicillin.

Results: A total of 372 patients were screened during the study period, with 100 of these patients undergoing further evaluation, 52 with histories appropriate for PST and 48 with histories appropriate for DC. In the PST group, 44 of 52 (84.6%) patients were PST negative. In the DC group, 47 of 48 (97.9%) patients initially tolerated the DC, with 2 of 48 (4.2%) experiencing a delayed reaction. The sole patient with an immediate DC reaction was treated with an antihistamine alone. Beta-lactam antibiotics were subsequently used in 56 of the 100 total patients. Total direct antibiotic savings was $23,375.27. DC was less costly than PST, at $206.18/patient versus $419.63/patient.

Conclusions: DC is a safe, effective, and less expensive method for penicillin delabeling in adult inpatients with a low-risk, cutaneous-only reaction history more than 20 years ago.

Keywords: Delabeling; Direct challenge; Drug allergy; Graded challenges; Penicillin allergy; Penicillin allergy screening algorithm; Penicillin skin testing; Stewardship.