Penicillin and cephalosporin cross-reactivity: role of side chain and synthetic cefadroxil epitopes

Autor: Maria Salas, Isabel M. Jiménez-Sánchez, Angela Martin-Serrano, Gador Bogas, Maria I. Montañez, Esther Barrionuevo, Cristobalina Mayorga, Teresa Posadas, María José Torres, Ruben Fernandez-Santamaria, Tahia D. Fernandez, Adriana Ariza
Přispěvatelé: [Bogas,G, Mayorga,G, Martín-Serrano,A, Fernández-Santamaría,R, Jiménez-Sánchez,IM, Ariza,A, Barrionuevo,E, Posadas,T, Salas,M, Fernández,TD, Torres,MJ, Montañez,MI] Allergy Research Group, Instituto de Investigación Biomédica de Málaga- IBIMA, Hospital Civil, Málaga, Spain. [Bogas,G, Torres,MJ] Allergy Unit, Hospital Regional Universitario de Málaga, Hospital Civil, Málaga, Spain. [Mayorga,G, Montañez,MI] Nanostructures for Diagnosing and Treatment of Allergic Diseases Laboratory, Andalusian Center for Nanomedicine and Biotechnology-BIONAND, Málaga, Spain. [Fernández,TD] Departamento de Biología Celular, Genética y Fisiología, Universidad de Málaga, Málaga, Spain. [Torres,MJ] Departamento de Medicina, Universidad de Málaga, Facultad de Medicina, Málaga, Spain., The present study has been supported by the Institute of Health ‘‘Carlos III’’ (ISCIII) of MINECO (Grants cofunded by ERDF: ‘‘Una manera de hacer Europa’’: Grant ns. PI12/02529, PI15/01206, CP15/00103, PI17/01237, PI18/00095, RETIC ARADYAL RD16/0006/0001, Euronanomed Program AC19/00082, Andalusian Regional Ministry of Economy and Knowledge (Grants cofunded by ERDF: ‘‘Andalucía se mueve con Europa’’: Grant No. CTS-06603), Andalusian Regional Ministry of Health (Grant Nos. PI-0699–2011, PI-0179–2014, PE-0172–2018 cofunded by ERDF), and ‘‘Premio UNICAJA a la innovación en biomedicina y salud.’’ C.M. holds ‘Nicolas Monardes’ research contract by Andalusian Regional Ministry Health (Grant No. C-0044–2012 SAS2013). G.B. holds a 'Juan Rodes' Grant (JR18/00054), M.I.M. holds a ‘‘Miguel Servet I’’ Grant (CP15/00103), and A.A. holds a ‘‘Sara Borrell’’ Grant (CD17/0146), all by ISCIII of MINECO (grants cofunded by European Social Fund: ‘‘El FSE invierte en futuro’’). R.F.S. holds a predoctoral Grant (PE-0172–2018) cofunded by ERDF.
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Pulmonary and Respiratory Medicine
medicine.drug_class
Chemicals and Drugs::Amino Acids
Peptides
and Proteins::Proteins::Globulins::Serum Globulins::Immunoglobulins::Antibodies::Immunoglobulin Isotypes::Immunoglobulin E [Medical Subject Headings]
Immunology
Cephalosporin
Phenomena and Processes::Immune System Phenomena::Immune System Processes::Antigen-Antibody Reactions::Cross Reactions [Medical Subject Headings]
Cefalosporinas
Antigenic determinant
Pharmacology
medicine.disease_cause
Benzylpenicillin
Group A
Cross-reactivity
Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings]
03 medical and health sciences
Chemicals and Drugs::Organic Chemicals::Amides::Lactams::beta-Lactams::Penicillins::Penicillin G::Ampicillin::Amoxicillin [Medical Subject Headings]
0302 clinical medicine
Reacciones cruzadas
medicine
Chemicals and Drugs::Organic Chemicals::Amides::Lactams::beta-Lactams [Medical Subject Headings]
Immunology and Allergy
030304 developmental biology
Amoxicilina
Epítopos
0303 health sciences
medicine.diagnostic_test
business.industry
Radioallergosorbent test
Research
Amoxicillin
Betalactam
Drug allergy
Beta-lactamas
Chemicals and Drugs::Biological Factors::Antigens::Epitopes [Medical Subject Headings]
Chemicals and Drugs::Organic Chemicals::Amides::Lactams::beta-Lactams::Cephalosporins [Medical Subject Headings]
Penicillin
Specific IgE
030228 respiratory system
Inmunoglobulina E
Cefadroxil
Diseases::Immune System Diseases::Hypersensitivity::Drug Hypersensitivity [Medical Subject Headings]
Hipersensibilidad a las Drogas
business
Cefuroxime
medicine.drug
Zdroj: Clinical and Translational Allergy
ISSN: 2045-7022
Popis: Background Analysis of cross-reactivity is necessary for prescribing safe cephalosporins for penicillin allergic patients. Amoxicillin (AX) is the betalactam most often involved in immediate hypersensitivity reactions (IHRs), and cefadroxil (CX) the most likely cephalosporin to cross-react with AX, since they share the same R1 side chain, unlike cefuroxime (CO), with a structurally different R1. We aimed to analyse cross-reactivity with CX and CO in patients with confirmed IHRs to AX, including sIgE recognition to AX, CX, CO, and novel synthetic determinants of CX. Methods Fifty-four patients with confirmed IHRs to AX based on skin test (ST) and/or drug provocation test (DPT) were included. Serum sIgE to AX and benzylpenicillin was determined by Radioallergosorbent test (RAST). Two potential determinants of CX, involving intact or modified R1 structure, with open betalactam ring, were synthesised and sIgE evaluated by RAST inhibition assay. Results Tolerance to CX (Group A) was observed in 64.8% cases and cross-reactivity in 35.2% cases (Group B). Cross-reactivity with CO was only found in 1.8% cases from Group B. ST to CX showed a negative predictive value of 94.6%. RAST inhibition assays showed higher recognition to CX as well as to both synthetic determinants (66% of positive cases) in Group B. Conclusions Cross-reactivity with CX in AX allergic patients is 35%, being ST not enough for prediction. R1, although critical for recognition, is not the unique factor. The synthetic determinants of CX, 1-(HOPhG-Ser-Bu) and 2-(pyrazinone) are promising tools for determining in vitro cross-reactivity to CX in AX allergic patients. Background Betalactams (BLs) are the drugs most frequently involved in immediate (IgE-mediated) hypersensitivity reactions (IHRs) [1,2,3], which could be explained by their ability to act as haptens due to their high chemical reactivity against proteins [4, 5]. BL chemical structure is formed by a 4-membered ring (the so-called BL ring) that in penicillins is fused to a 5-membered thiazolidine ring, and in cephalosporins to a 6-membered dihydrothiazine ring (Fig. 1). These drugs have a side chain (R1) bound to the BL ring; besides, cephalosporins have a second side chain (R2) bound to the dihydrothiazine ring, whose chemical structures distinguish the different compounds [6, 7]. Yes
Databáze: OpenAIRE
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