Perioperative Penicillin and Cephalosporin Antibiotic Allergy Assessment and Testing: The PREPARE Pilot Randomized Clinical Trial

Abstract

Importance: Antibiotic allergy labels (AALs) impact patient health and perioperative outcomes. Antibiotic allergy delabeling could improve antibiotic prescribing and infection-related outcomes perioperatively.

Objective: To assess the feasibility and safety of antibiotic allergy assessment and delabeling in anesthesiologist-led preoperative assessment clinics and expand delabeling efforts outside of specialist allergy clinics.

Design, setting, and participants: This randomized clinical trial was a multicenter, phase 2 feasibility and safety trial conducted between December 14, 2020, and October 31, 2023, at outpatient preoperative anesthesiologist-led clinics at 3 tertiary hospitals in Melbourne, Australia. Participants were adults (age ≥18 years) with a reported β-lactam AAL likely to require intravenous antibiotic therapy for perioperative prophylaxis. Randomization was carried out on a 1:1 basis.

Interventions: Enhanced allergy assessment by anesthesiologists using a smartphone application with a decision support algorithm adapted from a validated antibiotic allergy assessment tool. Risk scores guided antibiotic allergy testing: direct oral challenge (low risk) or skin testing followed by oral challenge (medium to high risk).

Main outcomes and measures: The 2 primary feasibility outcomes were the proportion of patients randomized to intervention who received intervention per protocol and proportion of patients consenting to participate out of all eligible. The primary safety outcome was the proportion of the intervention group experiencing an antibiotic-associated adverse event (AE) within 90 days postsurgery.

Results: Of 150 patients enrolled, 74 were randomly assigned to receive the intervention and 76 to control. The median age was 67 years (range, 28-89 years); 78 (52%) were female and 72 (48%) were male. For feasibility of recruitment, 150 of 511 patients (29.4%; 95% CI, 25.4%-33.5%) with eligible AALs were enrolled. For feasibility of intervention delivery, 47 of 74 patients (63.5%; 95% CI, 51.5%-74.4%) randomized to intervention had allergy testing; 28 of 30 patients (93%) assessed as low risk and 19 of 44 patients (43%) assessed as moderate/high risk proceeded to allergy testing. Antibiotic-related AE were reported in 4 of 74 intervention patients (5.4%, 95% CI, 1.5%-13.3%), 1 event was immune mediated (benign rash) without a delay to surgery. There was less restricted antibiotic use in the intervention group (6 patients; 10.7%) compared with the control group (10 patients; 17.9%).

Conclusions and relevance: Low-risk β-lactam AAL were successfully evaluated and delabeled by anesthesiologists in the preoperative clinic using the intervention. The absence of severe AE after the intervention provides reassurance that antibiotic allergy delabeling can be achieved as part of a preoperative workup without delaying surgery and may improve the choice of preferred β-lactam prophylaxis.

Trial registration: anzctr.org.au Identifier: ACTRN12620001295932.