Direct Oral Challenge for Low-Risk Sulfonamide Allergy: Safety and Antimicrobial Stewardship Impacts in Hospitalised Patients.

Abstract

Aim Sulfonamide antibiotic allergy affects 2% of the population and impacts antimicrobial prescribing. Trimethoprim-sulfamethoxazole is commonly prescribed in antimicrobial stewardship (AMS) programs and is the preferred drug for Pneumocystis jiroveci pneumonia (PJP) prophylaxis in immunocompromised hosts. In this prospective cohort study, we evaluated the safety and antimicrobial prescribing impacts of trimethoprim-sulfamethoxazole direct oral challenge (DOC) for low-risk sulfonamide allergy in hospitalised patients. Methods Using an antibiotic allergy assessment tool and validated clinical decision rule, adult inpatients with a sulfonamide, ‘sulfa’ or trimethoprim-sulfamethoxazole allergy were evaluated during a pharmacist-led AMS allergy ward round at Austin Health. Patients with a low-risk phenotype, or SULF-FAST score < 3, were offered a single-dose trimethoprim-sulfamethoxazole DOC. Sulfonamide antibiotic prescribing and relabelling rates were evaluated three months post-DOC. Results Between 23rd March 2022 and 24th April 2024, 57 inpatients with a low-risk sulfonamide, ‘sulfa’ or trimethoprim-sulfamethoxazole allergy underwent DOC. Twenty-four (42%) patients had a history of immunocompromise. The most common phenotypes were: non-severe cutaneous reactions > 10 years ago (75%), unknown reactions > 5 years ago (14%), and non-immune mediated reactions that requested delabelling via DOC (11%). Fifty-seven (100%) patients had a negative DOC and were delabelled. Fourteen (25%) patients were prescribed trimethoprim-sulfamethoxazole within three months of DOC, of which nine (64%) were prescribed directed therapy based on microbiological culture result, and five (36%) were prescribed PJP prophylaxis in the setting of immunosuppression. No patients had the allergy label reinstated in the medical record three months post-DOC. Conclusion Trimethoprim-sulfamethoxazole DOC in hospitalised patients with a low-risk sulfonamide allergy is safe and improves antimicrobial prescribing in patients requiring trimethoprim-sulfamethoxazole directed or prophylactic therapy. Impact In hospitalised patients with low-risk sulfonamide allergy, oral challenge is a low-resource testing strategy, removes the requirement for outpatient skin testing, and improves antibiotic choice, importantly in immunocompromised patients.