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Title
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Beta-lactam hypersensitivity : epidemiology and optimized diagnosis
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Author
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Abstract
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| Unverified and false “β-lactam allergies”, mainly to the first-line preparations natural penicillin and aminopenicillins, have evolved into a worldwide plague with serious medical and financial consequences. From this thesis it appears that as much as 12% of the individuals attending the outpatients’ clinic of Allergology and Pediatric Allergology of the Antwerp University Hospital claim to have a “penicillin allergy”. However, in 91% of these individuals this claim appears to be false, as they tolerated these antibiotics during a controlled drug challenge. Importantly, as these cases could be safely delabelled, we were able to improve their antibiotic stewardship, mainly by safeguard them against the unnecessary risk for use of suboptimal and expensive second-line treatments. From the literature and our own experience it is clear that judicious diagnostic work-up by a trained physician is absolutely necessary in every case of both witnessed or self-reported “penicillin allergy”. However, diagnosis of β-lactam hypersensitivity reactions is not always straightforward and optimization of the diagnostic approach of β-lactam hypersensitivities is needed. Therefore, we studied the performance of new or recently introduced diagnostics. First, in the context of nonimmediate hypersensitivity reactions to amoxicillin and amoxicillin clavulanic acid, we showed that a CD154-based flow cytometric lymphocyte activation test is a safe and quick diagnostic test, especially in cases with mild cutaneous nonimmediate drug hypersensitivity reactions to amoxicillin or amoxicillin clavulanic acid, and that a prolonged drug challenge extending over several consecutive days is of limited use. In our country cefazolin has evolved to one of the major causes of perioperative anaphylaxis. We explored the performance of a recently developed specific (s)IgE assay to cefazolin. We observed that neither sIgE to cefazolin nor a sIgE/tIgE ratio were of added value in the diagnosis of cefazolin hypersensitivity. Finally, it is known that cross-reactivity among β-lactam antibiotics is unpredictable but mostly related to the R1-side chain. However, we demonstrated that fine structural differences in the R1-side chain can suffice to explain absence of cross-reactivity and clinical tolerance. Clearly, molecules with a similar, but not identical R1-side chain, should not be precluded or administered using a desensitization protocol, provided they test negative in skin testing. In conclusion, self-reported “penicillin allergy” has grown into a vast epidemic with unacceptable consequences for the individual patient and the society. Further efforts are required to optimize and harmonize a cost-conscious diagnostic approach of “penicillin allergy” and “β-lactam allergy” in general. |
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Language
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English
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Publication
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Antwerp
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University of Antwerp, Faculty of Medicine & Health sciences
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2020
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ISBN
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978-90-5728-652-0
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Volume/pages
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169 p.
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Note
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Ebo, D.G. [Supervisor]
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Sabato, V. [Supervisor]
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Hagendorens, M.M. [Supervisor]
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Full text (publisher's version - intranet only)
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