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Role of the side chain in cross-reactivity between penicillins and cephalosporins, and design of novel cefadroxil epitopes.
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  • Gador Bogas,
  • Cristobalina Mayorga,
  • Angela Martin,
  • Ruben Fernandez,
  • Isabel Jimenez,
  • Adriana Ariza,
  • Esther Barrionuevo,
  • Teresa Posadas,
  • Tahia Fernandez,
  • Maria Salas,
  • Maria Torres,
  • Maria Isabel Montanez
Gador Bogas
IBIMA–Regional University Hospital of Malaga–UMA
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Cristobalina Mayorga
IBIMA-Regional University Hospital of Malaga
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Angela Martin
Instituto de Investigación Biomédica de Málaga-IBIMA
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Ruben Fernandez
Instituto de Investigación Biomédica de Málaga-IBIMA
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Isabel Jimenez
Andalusian Center for Nanomedicine and Biotechnology-BIONAND
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Adriana Ariza
IBIMA-Regional University Hospital of Malaga-UMA
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Esther Barrionuevo
IBIMA-Hospital Regional Universitario de Málaga
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Teresa Posadas
IBIMA-Regional University Hospital of Malaga-UMA
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Tahia Fernandez
Carlos Haya Hospital-Fundacion Imabis.
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Maria Salas
IBIMA-Regional University Hospital of Malaga, UMA
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Maria Torres
Regional University Hospital of Malaga-IBIMA-UMA-BIONAND-ARADyAL
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Maria Isabel Montanez
Instituto de Investigación Biomédica de Málaga-IBIMA
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Abstract

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 (CX), 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. 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 88.2%. 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.