A Comparative Analysis Between Antibiotic- and Nonantibiotic-Associated Delayed Cutaneous Adverse Drug Reactions

Trubiano, Jason A; Aung, Ar Kar; Nguyen, Mary; Fehily, Sasha; Graudins, Linda V; Cleland, Heather; Padiglione, Alex; Peleg, Anton Y.

doi:10.1016/j.jaip.2016.04.026

Cited by 44 publications

(38 citation statements)

References 24 publications

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“…1,2,23–27 At present, PT and delayed skin testing in isolation are hampered by uncertain availability and poor sensitivity. 23,24 Ex vivo techniques such as ELISpot assay have shown promise in small cohorts; however, their availability and performance have not been validated in large-scale high-throughput clinical laboratories against a clinical probability score.…”

Section: Discussionmentioning

confidence: 99%

“…AMP, ampicillin; CEF, ceftriaxone; CEFZ, cefazolin; FLU, flucloxacillin; MER, meropenem; MET, metronidazole; PIP-TAZ, piperacillin-tazobactam; TEIC, teicoplanin; VAN, vancomycin; TMP, trimethoprim. a In patients beta-lactam implicated in SCAR causality a standard panel employed for IDT (DAP-major, DAP -minor, PENG, FLU, AMP, PIP-TAZ, CEFX, CEF) in addition to implicated beta-lactam at recommended concentrations 1 . For all other drugs the implicated antibiotic was tested via either patch testing (PT) or delayed intradermal testing (IDT).…”

Section: Figurementioning

confidence: 99%

“…Severe cutaneous adverse reactions (SCARs), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS), are associated with significant mortality and short-term and long-term morbidity 1,2 and may be caused by a range of medications including antibiotics. 1 SJS and TEN are considered the same condition representing different severities across a spectrum.…”

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confidence: 99%

“…1 SJS and TEN are considered the same condition representing different severities across a spectrum. The hallmarks of SJS/TEN are skin detachment (1%-10% for SJS, 10%-30% for SJS/TEN overlap, and >30% for TEN) and blistering of mucous membranes accompanied by other serious manifestations of systemic involvement.…”

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confidence: 99%

“…1,2 Current diagnostic options such as in vivo patch testing (PT) or delayed intradermal skin testing (IDT) have been limited by lack of experience, lack of validated concentrations and approaches, limited availability to providers, and poor sensitivity. 4–6 Ex vivo and in vitro testing using a range of research platforms including lymphocyte transformation testing and IFN-g release enzyme-linked immunoSpot (ELISpot) assay have been used in small cohorts of antibiotic-associated (AA) delayed hypersensitivities with varied success.…”

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confidence: 99%

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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

Strautins

Redwood

et al. 2018

The Journal of Allergy and Clinical Immunology: In Practice

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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-g release from CD4D and CD8D 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-g release enzyme-linked immunoSpot assay, with an overall reported sensitivity of 52% (95% CI, 29-76) and specificity of100% (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.

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Section: Discussionmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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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

Strautins

Redwood

et al. 2018

The Journal of Allergy and Clinical Immunology: In Practice

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A Survey on Knowledge Gaps in Assessment and Management of Severe Drug Hypersensitivity Reactions: Multicenter Cross‐Sectional Study of Australian Health Care Providers

Mazzoni

Tee

Menezes

et al. 2020

The Journal of Clinical Pharma

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Severe drug hypersensitivity reactions (DHRs) are often encountered by health care professionals (HCPs). We evaluated knowledge of doctors and pharmacists in the assessment and management of severe DHRs using a structured questionnaire. A cross-sectional study was conducted in 4 metropolitan hospital networks in Melbourne, Australia. A 13-question, scenario-based multiple-choice questionnaire to assess specific knowledge domains in drug hypersensitivity syndrome recognition, causality attribution, cross-reactivity patterns, appropriate diagnostic tests, and therapy was administered to HCPs of various vocation and specialty groups.Data were analyzed according to profession,self-reported experience,and preparedness in managing severe DHRs. Two hundred thirty-eight participants (45.0% senior doctors, 24.4% junior doctors, and 30.7% pharmacists) across a range of subspecialties achieved an overall median score of 7 (IQR, 5-8)-overall 55.6% correct responses to all questions-with senior doctors outperforming junior doctors and pharmacists (P < .001). The best performance by all participants was in DHR syndrome recognition (60.9%), and the poorest was in diagnostics/therapy (52.0%). HCP group and experience level were significantly associated with better performance in the knowledge domains of cross-reactivity and diagnostics/therapy (P = .003 and < .001, respectively), but not in the domains of syndrome recognition and causality attribution (P > .05). Levels of self-reported preparedness in DHR management were not associated with performance rates in any of the knowledge domains. This study demonstrated significant knowledge gaps in the recognition and management of severe drug hypersensitivity reactions. Targeted multidisciplinary education of staff caring for these patients is needed to improve knowledge gaps.

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Antibacterial antibiotic-induced drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome: a literature review

Sharifzadeh

Mohammadpour

Tavanaee

et al. 2020

Eur J Clin Pharmacol

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Background Drug reaction with eosinophilia and systemic symptoms syndrome (DRESS) is a delayed infrequent potentially lifethreatening idiosyncratic drug reaction. Aromatic anticonvulsants and allopurinol are the most frequent causative agents. However, various reports of antibiotic-induced DRESS are available. In this review, we try to summarize reports of antibacterial antibiotic-induced DRESS focusing on characteristics of DRESS induced by each antibiotic group. Methods The data were collected by searching PubMed/MEDLINE and ScienceDirect. The keywords used as search terms were "DRESS syndrome," "drug-induced hypersensitivity syndrome (DIHS)," "antibiotics," "antimicrobial," and names of various antimicrobial groups. Finally, 254 relevant cases with a definite or probable diagnosis of DRESS based on RegiSCAR criteria were found until 30 May 2020 and reviewed. Results and conclusion Totally, 254 cases of antibacterial antibiotic-induced DRESS are reported. Most of them are related to antituberculosis drugs, vancomycin, and sulfonamides, respectively. Rash and fever were most frequent clinical findings. Eosinophilia and liver injury were the most reported hematologic and visceral organ involvement, respectively. Most of the patients are managed with systemic corticosteroids. The death occurred in 16 patients which most of them experienced liver or lung involvement. The reactivation of various viruses especially HHV-6 is reported in 33 cases. The mean latency period was 29 days. It is necessary to perform thorough epidemiological, genetic, and immunological studies, also systematic case review and causality assessment, as well as well-designed clinical trials for better management of antibiotic-induced DRESS.

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A Comparative Analysis Between Antibiotic- and Nonantibiotic-Associated Delayed Cutaneous Adverse Drug Reactions

Cited by 44 publications

References 24 publications

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 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

A Survey on Knowledge Gaps in Assessment and Management of Severe Drug Hypersensitivity Reactions: Multicenter Cross‐Sectional Study of Australian Health Care Providers

Antibacterial antibiotic-induced drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome: a literature review

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