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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

Trubiano, J.A., Strautins, K., Redwood, A.J., Pavlos, R., Konvinse, K.C., Aung, A.K., Slavin, M.A., Thursky, K.A., Grayson, M.L. and Phillips, E.J. (2018) 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. The Journal of Allergy and Clinical Immunology: In Practice, 6 (4). pp. 1287-1296.

Link to Published Version: https://doi.org/10.1016/j.jaip.2017.09.004
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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.

Item Type: Journal Article
Murdoch Affiliation: Institute for Immunology and Infectious Diseases
Publisher: Elsevier
Copyright: © 2017 American Academy of Allergy, Asthma & Immunology
URI: http://researchrepository.murdoch.edu.au/id/eprint/41546
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