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J Allergy Clin Immunol Pract. 2018 Jul - Aug;6(4):1287-1296.e1. doi: 10.1016/j.jaip.2017.09.004. Epub 2017 Oct 31.

The Combined Utility of Ex Vivo IFN-γ Release Enzyme-Linked ImmunoSpot Assay and In Vivo Skin Testing in Patients with Antibiotic-Associated Severe Cutaneous Adverse Reactions.

Author information

1
Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia; Department of Infectious Diseases, Peter MacCallum Cancer Centre, Parkville, Victoria, Australia; National Centre for Infections in Cancer, National Health and Medical Research Council Centre of Research Excellence, Peter MacCallum Cancer Centre, Department of Oncology, University of Melbourne, Parkville, Victoria, Australia; Department of Medicine, University of Melbourne, Parkville, Victoria, Australia. Electronic address: Jason.trubiano@austin.org.au.
2
Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia.
3
Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Centre, Nashville, Tenn.
4
Department of General Medicine and Infectious Diseases, Alfred Health and Monash University, Melbourne, Victoria, Australia.
5
Department of Infectious Diseases, Peter MacCallum Cancer Centre, Parkville, Victoria, Australia.
6
Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia; Department of Medicine, University of Melbourne, Parkville, Victoria, Australia.
7
Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia; Departments of Medicine & Pharmacology, Vanderbilt University, Nashville, Tenn.

Abstract

BACKGROUND:

For severe cutaneous adverse reactions (SCARs) associated with multiple antibiotics dosed concurrently, clinical causality is challenging and diagnostic approaches are limited, leading to constricted future antibiotic choices.

OBJECTIVE:

To examine the combined utility of in vivo and ex vivo diagnostic approaches at assigning drug causality in a cohort of patients with antibiotic-associated (AA)-SCARs.

METHODS:

Patients with AA-SCARs were prospectively recruited between April 2015 and February 2017. In vivo testing (patch testing or delayed intradermal testing) was performed to the implicated antibiotic(s) at the highest nonirritating concentration and read at 24 hours through 1 week. Ex vivo testing used patient peripheral blood mononuclear cells (PBMCs) stimulated with a range of pharmacologically relevant concentrations of implicated antibiotics to measure dose-dependent IFN-γ release from CD4+ and CD8+ T cells via an enzyme-linked immunoSpot assay.

RESULTS:

In 19 patients with AA-SCARs, combined in vivo and ex vivo testing assigned antibiotic causality in 15 (79%) patients. Ten patients (53%) with AA-SCARs were positive on IFN-γ release enzyme-linked immunoSpot assay, with an overall reported sensitivity of 52% (95% CI, 29-76) and specificity of 100% (95% CI, 79-100), with improved sensitivity noted in acute (within 1 day to 6 weeks after SCAR onset) testing (75%) and in patients with higher phenotypic scores (59%). There was increased use of narrow-spectrum beta-lactams and antibiotics from within the implicated class following testing in patients with a positive ex vivo or in vivo test result.

CONCLUSIONS:

We demonstrate the potential utility of combined in vivo and ex vivo testing in patients with AA-SCARs to assign drug causality with high specificity.

KEYWORDS:

Antibiotic allergy; Delayed hypersensitivity; Stevens-Johnson syndrome; drug reaction with eosinophilia and systemic symptoms; toxic epidermal necrolysis

PMID:
29100867
PMCID:
PMC5930120
DOI:
10.1016/j.jaip.2017.09.004
[Indexed for MEDLINE]
Free PMC Article

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