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

Gador Bogas,Ángela Martín-Serrano,Esther Barrionuevo,Tahía Diana Fernández,Cristobalina Mayorga,María Salas,María José Torres,Isabel M Jiménez-Sánchez,Rubén Fernández-Santamaría,Adriana Ariza,Teresa Posadas,María Isabel Montañez

doi:10.1186/s13601-020-00368-1

Abstract

BackgroundAnalysis 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.MethodsFifty-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.ResultsTolerance 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.ConclusionsCross-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.

Highlights

Analysis of cross-reactivity is necessary for prescribing safe cephalosporins for penicillin allergic patients
From 1393 patients with confirmed BL hypersensitivity evaluated from 1984 to 2019, 994 subjects were confirmed with IHRS to AX, from which we randomly selected 54 patients, whose cross-reactivity to CX and CO was evaluated and flow-charts analysed (Fig. 2)
Regarding skin testing (ST), 2 (4%) cases were positive to Benzylpenicil‐ loyl-poly-L-lysine (PPL)/BP-OL, 4 (8%) to Minor determinant mixture (MDM)/ Minor determinant (MD), and to AX 27 (54%) by Skin prick test (SPT) and 23 (46%) by Intradermal tests (IDT) (Table 2)

Summary

Introduction

Analysis of cross-reactivity is necessary for prescribing safe cephalosporins for penicillin allergic patients. Crossreactivity rate with cephalosporins in penicillin-allergic patients with IgE-mediated reactions ranges from 0% to almost 40% depending on the chemical structure of the BL involved [15,16,17,18,19,20,21,22], on similarity in the R1 side chain [23, 24]. In this context, AX, which shares the same amino R1 side chain with CX (Fig. 1), could have a high cross reactivity [19,20,21]. Several reports have addressed this issue [28,29,30], the antigenic determinants of cephalosporins are currently not wellknown [31]

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