D1.384 - Safe Sulfonamide Delabeling in HIV-Negative Adults: Real-World Evidence with TMP-SMX Oral Challenge and SULF-FAST

This study aimed to evaluate the safety of oral provocation testing (OPT) with trimethoprim–sulfamethoxazole (TMP-SMX) in HIV-negative adults carrying a sulfonamide antibiotic allergy label (SAL) and examined the applicability of the SULF-FAST clinical risk score for delabeling patients with a history of TMP-SMX hypersensitivity following diagnostic evaluation.

Between January 2020 and January 2026, 29 patients with a history of an immediate hypersensitivity reaction to TMP-SMX were included for diagnostic evaluation. In eligible cases, OPT with TMP-SMX was performed under physician supervision. Patients with physician-confirmed anaphylaxis underwent basophil degranulation testing (BDT). SULF-FAST scores were calculated and compared with provocation outcomes.

The median age at the time of the index reaction was 54 years (IQR:41.5-65), and 25 patients were female. Among 26 patients who underwent OPT, 21 had negative results. OPT was not performed in three patients due to a history of anaphylaxis; instead, BDT was performed and yielded negative results in all cases. Notably, all five patients with positive OPT results had experienced their index hypersensitivity reaction within the preceding one year. The median SULF-FAST score was 3 (IQR: 1–3); 41.4% of patients (n=12) classified as intermediate risk and 24.1% (n=7) as high risk. According to the risk stratification proposed in the original study, application of the SULF-FAST cut-off ≥3, 19 patients were categorized as intermediate or high risk, of whom 5 had a positive OPT. At this threshold, the score demonstrated 100% sensitivity and 42.9% specificity for predicting a positive provocation result, with a positive predictive value of 29.4% and a negative predictive value of 100% (n=26).

OPT remains essential for delabeling in HIV-negative adults with a TMP-SMX allergy label and cannot be replaced by clinical risk scores alone. While SULF-FAST demonstrated high sensitivity in identifying patients with positive provocation results, its clinical utility appears greatest when the index hypersensitivity reaction occurred relatively close to the time of provocation testing. Therefore, SULF-FAST may serve as a supportive risk stratification tool, but confirmation through OPT is required for accurate delabeling.