SULF-FAST may help identify those at low risk of sulfa allergy: JAMA

Trimethoprim-sulfamethoxazole is a first-line treatment for many infections; however, sulfa allergy limits its use. Trimethoprim-sulfamethoxazole is frequently needed by antimicrobial stewardship programs to prevent the use of more restricted antibiotics. Studies with nonstandardized challenge criteria indicate that those with low-risk allergy phenotypes can safely undergo direct oral challenges (OCs); however, no current risk-stratification tool exists to guide challenges.

Jamie L. Waldron, Austin Health, Heidelberg, Victoria, Australia, and colleagues sought to adapt PEN-FAST, a penicillin allergy clinical decision tool, for trimethoprim-sulfamethoxazole allergy.

The research team adapted the PEN-FAST tool for creating SULF-FAST, a clinical decision rule for TMP-SMX (trimethoprim-sulfamethoxazole) allergy. They used two US and Australian datasets to validate the SULF-FAST tool.

The research team defined a positive test result as a positive patch test (PT) result or the occurrence of a clinician-observed or patient-reported presumed immune-mediated reaction following the challenge. The team calculated the PEN-FAST score and its diagnostic performance for each cohort and subgroup based on allergy phenotype.

The study included adult patients aged 18 or above who reported nonsevere sulfa or TMP-SMX allergy and consented to undergo direct oral challenges. The PEN-FAST score and its diagnostic performance were calculated for each cohort and subgroup.

The study led to the following findings:

• The prevalence of positive TMP-SMX allergy test results was 5.2% in Australia and 6.4% in the US.
• The adapted PEN-FAST tool showed good discrimination in determining true allergy in the Australian cohort, with an area under the curve (AUC) of 0.86.
• A low PEN-FAST score (<3) indicated to the team a low allergy risk (<5%), while a score of 3 or more showed a higher allergy risk (>20%).
• The tool had a sensitivity of 66.7% and a specificity of 96.4% in identifying this allergy.
• In the US cohort, the tool was shown to have an AUC of 0.67, with a sensitivity of 38.5% and specificity of 89.5%. The tool also performed well in identifying immediate reactions but had a lower performance for the delayed phenotype.
• Good performance was seen for immediate reactions but lower for the delayed phenotype.
• Of 115 individuals with long-term prescribing data, 45 received a trimethoprim-sulfamethoxazole course without adverse reactions.

"Although the single-dose challenge was protocolized, the high tolerance rate of multiple extended trimethoprim-sulfamethoxazole treatment doses is reassuring for omitting delayed hypersensitivity," the authors wrote. "Further validation is needed for widespread implementation."

Reference:

Waldron JL, Rose M, Vogrin S, et al. Development and Validation of a Sulfa Antibiotic Allergy Clinical Decision Rule. JAMA Netw Open. 2023;6(6):e2316776. doi:10.1001/jamanetworkopen.2023.16776