Risk factors and challenge outcomes in trimethoprim-sulfamethoxazole hypersensitivity in HIV-negative patients: A...

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

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

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.

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.

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.