# Optimizing the diagnostic approach to cephalosporin allergy testing (DACAT Trial)

> **NIH NIH U01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $3,234,536

## Abstract

PROJECT SUMMARY
 In the United States, beta-lactam antibiotics are the leading cause of allergic reactions. Cephalosporin
antibiotics, in particular, are the most common cause of drug-induced anaphylaxis and perioperative allergy.
For penicillin allergy, the mechanism of allergy and the antigenic determinants are known; validated penicillin
skin testing followed by drug challenge has a 100% negative predictive value to exclude an immunoglobulin
(Ig)E-mediated reaction. For cephalosporin allergy, the antigenic determinants and mechanism are not known,
and skin testing is not validated. The diagnostic test characteristics of skin testing with native cephalosporins
remain unclear with no sensitivity nor specificity reported. Although beta-lactam cross-reactivity has been
hypothesized to be from the similarity of the R1 side chains, rather than the beta-lactam ring, cross-reactivity
estimates among beta-lactams vary. Furthermore, it is not known whether the variance in cross-reactivity is
due to true allergy versus sensitization based on positive skin testing, given that drug challenges were not
performed on skin-test-positive patients. While an IgE mechanism is assumed for cephalosporin allergy and
supported by skin testing that has been positive, the biology has yet to be characterized, and some
cephalosporin anaphylaxis can occur on the first exposure, which is inconsistent with an IgE mechanism.
Given the complexity of cephalosporin structures and potential epitopes, there may be several distinct biologic
pathways involved in cephalosporin allergy. Future diagnostics in cephalosporin allergy are reliant on
determination of these biological pathways and finding key haptens.
 Current national practice guidelines related to cephalosporin allergy assessment are considered
conditional and based on low-quality evidence. Our overall goal is to identify the optimal diagnostic approach to
cephalosporin allergy and determine beta-lactam cross-reactivity, while discovering the mechanism and
antigenic determinants of cephalosporin allergy to advance future diagnostics. We will do this through a clinical
trial that will generate empirical evidence through novel trial procedures, double-blind skin testing, and double-
blind placebo-controlled drug challenges. Our specific aims are: 1) To determine the optimal approach to
cephalosporin allergy evaluation; 2) To assess beta-lactam cross-reactivity in cephalosporin-allergic
individuals; and 3) To investigate the antigenic determinants and mechanism of cephalosporin allergy.
 We will achieve these aims through collaboration with an established network of drug allergy
specialists. Our study is the first clinical trial in drug allergy that investigates diagnostic strategies and
mechanisms for a common and important antibiotic class. This project aligns with NIH/NIAID goals to advance
drug allergy research and PAR-21-083 to support high-risk clinical trials with mechanistic studies.

## Key facts

- **NIH application ID:** 10928478
- **Project number:** 1U01AI184071-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Kimberly G. Blumenthal
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $3,234,536
- **Award type:** 1
- **Project period:** 2024-07-10 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10928478

## Citation

> US National Institutes of Health, RePORTER application 10928478, Optimizing the diagnostic approach to cephalosporin allergy testing (DACAT Trial) (1U01AI184071-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10928478. Licensed CC0.

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