Risk factors and challenge outcomes in trimethoprim-sulfamethoxazole hypersensitivity in HIV-negative patients: A multicenter retrospective report

Abstract

Background: Contemporary drug allergy practice parameters suggest performing trimethoprim-sulfamethoxazole (TMP-SMX) challenges in patients with a sulfa allergy label (SAL).

Objective: To evaluate the safety of TMP-SMX challenges and risk factors for confirmed TMP-SMX allergy by challenge in a large cohort.

Methods: Retrospective data review from all consecutive TMP-SMX challenges in patients with HIV-negative SAL performed between 2017 and 2022 across all 4 Mayo Clinic sites. Independent variables included demographics, index reaction history, etc. Univariate and multivariable logistic regression analyses with challenge outcome as the dependent variables were performed.

Results: Among 348 patients (mean age, 58.9 years; 76% female), 29 (8%) had a positive objective challenge result and an additional 33 (9%) reported subjective symptoms. Most patients underwent 2-step challenges (57%). Rash occurred in 8%, and 3 patients (0.9%) received epinephrine. In multivariable analysis, recent index reactions (<5 years) (odds ratio [OR] 3.17; 95% CI, 1.03-8.66) and immediate-onset (<6 hours) reactions (OR 3.67; 95% CI, 1.10-10.62) were independently associated with a positive objective challenge result. For subjective symptoms during challenges, multi-drug intolerance syndrome (OR 3.33; 95% CI, 1.45-7.64) and myalgias (OR 17.43; 95% CI, 1.38-419.36) were significant predictors of a positive subjective challenge result. Two patients (0.6%) required emergency department evaluation post-challenge; 1 for transient epinephrine-related symptoms and 1 for infection concerns requiring brief admission.

Conclusion: In this large cohort, 319 of 348 patients (92%) with a SAL tolerated a TMP-SMX challenge. TMP-SMX challenges are safe with less than 1% of patients receiving intramuscular epinephrine. Patients with SAL with immediate index reactions occurring within 5 years of evaluation were more likely to have TMP-SMX allergy confirmed.