Cross-Reactivity to Cephalosporins and Carbapenems in Penicillin-Allergic Patients: Two Systematic Reviews and Meta-Analyses

Picard, Matthieu; Robitaille, Geneviève; Karam, Fatiha; Daigle, Jean-Marc; Bédard, François; Biron, Éric; Tardif, Maurice; Lacombe-Barrios, Jonathan; Bégin, Philippe

doi:10.1016/j.jaip.2019.05.038

Cited by 73 publications

(44 citation statements)

References 60 publications

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“…All BL compounds can potentially induce a specific immunological response and, due to their wide prescription, BL allergy is nowadays a worldwide health issue with relevant implications [43][44][45]. One of the main issues is establishing the risk of developing an allergic reaction to cephalosporins prescribed in patients previously diagnosed of penicillin IHR, with different unsolved questions like if this risk can be predicted by ST and/or DPT, or the role of the chemical structure, specifically the side chain, in this recognition [10,[46][47][48][49]. The main difficulty is that, despite efforts [28][29][30], the antigenic determinants of cephalosporins are unknown [31].…”

Section: Discussionmentioning

confidence: 99%

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

Bogas

Mayorga

Martín-Serrano

et al. 2020

Clin Transl Allergy

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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.

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Section: Discussionmentioning

confidence: 99%

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

Bogas

Mayorga

Martín-Serrano

et al. 2020

Clin Transl Allergy

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“…4 There are few prospective studies of β-lactam-allergic subjects which assessed cross-reactivity among β-lactams by carrying out allergy tests with β-lactams other than those responsible and, in case of negative results, by performing graded challenges with them. 4,[9][10][11][12] Penicillin-Allergic Subjects Individuals with histories of penicillin allergy are more likely to receive alternative broad-spectrum antibiotics, including vancomycin and quinolones, which can lead to higher costs, prolonged hospitalizations, and elevated number of infection with methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, and Clostridioides difficile (formerly Clostridium difficile). [15][16][17] Although a large number of patients are labeled as allergic to penicillin, more than 95% of them can tolerate penicillin after an appropriate evaluation.…”

Section: Selecting Alternative β-Lactams In β-Lactam-allergic Subjectsmentioning

confidence: 99%

“…In particular, side chains contribute significantly to immunological recognition and therefore the structures are most frequently responsible for allergic cross-reactivity. 1,[7][8][9][10][11][12] In β-lactam-allergic patients, the diagnostic workup with alternative drugs shows the cross-reactivity and, above all, allows to treat patients with safe drugs. 4,13 This review is mainly about prospective studies which assessed the cross-reactivity among β-lactams in penicillin-or cephalosporin-allergic subjects by carrying out in vivo tests and, if available, in vitro ones with alternative β-lactams and, in case of negative results, administering them via graded challenges.…”

mentioning

confidence: 99%

β-Lactam Allergy and Cross-Reactivity: A Clinician’s Guide to Selecting an Alternative Antibiotic

Valluzzi¹,

Colantuono²,

Gaeta³

et al. 2021

JAA

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β-Lactams which include penicillins, cephalosporins, carbapenems, and monobactams are the most common antibiotic classes reported to cause allergic reactions to drugs. This review is mainly about published studies assessing the cross-reactivity among β-lactams in penicillin-or cephalosporin-allergic subjects by carrying out diagnostic tests with alternative β-lactams and, if appropriate, graded challenges. Several studies demonstrated that cross-reactivity connected with the β-lactam ring, causing positive responses to allergy tests with all β-lactams, is infrequent in subjects with an IgE-mediated allergy and anecdotal in those with a T-cell-mediated allergy. Identities or similarities of βlactam side-chain structures are mainly responsible for cross-reactivity among these antibiotics. For example, in aminopenicillin-allergic subjects, cross-reactivity with aminocephalosporins could possibly be over 30%. On the other hand, in a few prospective studies of penicillin-allergic individuals, less than 1% of cases show a cross-reactivity between penicillins and both aztreonam and carbapenems. Particular patterns of allergytest positivity observed in some studies that assessed cross-reactivity among β-lactams seem to indicate that prior exposures may be responsible for coexisting sensitivities. Therefore, pre-treatment skin tests with the related β-lactams are suggested before administering them via graded challenges to β-lactam-allergic patients who need alternative β-lactams.

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“…In terms of cross-reactivity between beta-lactams in the context of delayed hypersensitivities, 18.7-31.2% of the patients tested presented a reaction to amino-penicillins and amino-cephalosporins (Dash, 1975) predicted by the presence of shared R1 and R2 side chains (Buonomo et al, 2014;Romano et al, 2016). Also, in patients with a delayed penicillin type reaction, delayed IDT to beta-lactams has allowed to confirm tolerance to cephalosporins (Picard et al, 2019;Trubiano et al, 2020), carbapenems (Gaeta et al, 2015;Picard et al, 2019) and monobactams (Buonomo et al, 2011). Other classes of interest are currently being studies with no evidence of cross-reactivity such as glycopeptides (Empedrad et al, 2003a), antibiotic and non-antibiotic sulfonamides (Empedrad et al, 2003a;Lammintausta and Kortekangas-Savolainen, 2005), drugs in the rifampin class (Lammintausta and Kortekangas-Savolainen, 2005) and aromatic and non-aromatic anticonvulsants (Heinzerling et al, 2013).…”

Section: Intradermal Testingmentioning

confidence: 99%

“…Putting aside the demanding and time-consuming laboratory manipulations and the use of radioactivity and specialist equipment, the LTT can be an interesting support in drug hypersensitivity diagnosis but is still only used as a research tool (Pichler and Tilch, 2004;Nagao-Dias et al, 2009). The largest study describes LTT in 923 patients with suspected hypersensitivity among which only 100 patients had a confirmed drug hypersensitivity reaction and 58/78 penicillin allergy labeled patients presented a positive LTT (Picard et al, 2019). In the last 10 years, aside from case reports or small cases series (Kim et al, 2013;Cabanas et al, 2014;Dias de Castro et al, 2015;Tomida et al, 2016), very few studies have focused solely on the LTT method for diagnosis.…”

Section: Lymphocyte Transformation Testmentioning

confidence: 99%

An Updated Review of the Diagnostic Methods in Delayed Drug Hypersensitivity

Copaescu

Gibson

et al. 2021

Front. Pharmacol.

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Delayed drug hypersensitivity reactions are clinically diverse reactions that vary from isolated benign skin conditions that remit quickly with no or symptomatic treatment, drug discontinuation or even continued drug treatment, to the other extreme of severe cutaneous adverse reactions (SCARs) that are associated with presumed life-long memory T-cell responses, significant acute and long-term morbidity and mortality. Diagnostic “in clinic” approaches to delayed hypersensitivity reactions have included patch testing (PT), delayed intradermal testing (IDT) and drug challenges for milder reactions. Patch and IDT are, in general, performed no sooner than 4–6 weeks after resolution of the acute reaction at the maximum non-irritating concentrations. Functional in vitro and ex vivo assays have largely remained the province of research laboratories and include lymphocyte transformation test (LTT) and cytokine release enzyme linked ImmunoSpot (ELISpot) assay, an emerging diagnostic tool which uses cytokine release, typically IFN-γ, after the patient’s peripheral blood mononuclear cells are stimulated with the suspected drug(s). Genetic markers such as human leukocyte antigen have shown recent promise for both pre-prescription screening as well as pre-emptive and diagnostic testing strategies.

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Cross-Reactivity to Cephalosporins and Carbapenems in Penicillin-Allergic Patients: Two Systematic Reviews and Meta-Analyses

Cited by 73 publications

References 60 publications

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

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

β-Lactam Allergy and Cross-Reactivity: A Clinician’s Guide to Selecting an Alternative Antibiotic

An Updated Review of the Diagnostic Methods in Delayed Drug Hypersensitivity

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