The role of IgE recognition in allergic reactions to amoxicillin and clavulanic acid

Torres, Marı́a José; Montañez, María Isabel; Ariza, Adriana; Salas, María; Fernandez, Tahía D.; Barbero, Nekane; Mayorga, Cristobalina; Blanca, Miguel

doi:10.1111/cea.12689

Cited by 40 publications

(56 citation statements)

References 79 publications

(167 reference statements)

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“…As a consequence of increasing allergic reactions to CLV, there is much interest in elucidating the underlying mechanisms and structures involved in its immunological recognition . As other β‐lactams, CLV must bind covalently to carrier proteins to form conjugates with sufficient size to be recognized by the immune system and induce a response .…”

Section: Introductionmentioning

confidence: 99%

Identification of an antigenic determinant of clavulanic acid responsible for IgE‐mediated reactions

Barbero

Mayorga

Martín-Serrano

et al. 2019

Allergy

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Background: Selective reactions to clavulanic acid (CLV) account for around 30% of immediate reactions after administration of amoxicillin-CLV. Currently, no immunoassay is available for detecting specific IgE to CLV, and its specific recognition in patients with immediate reactions has only been demonstrated by basophil activation testing, however with suboptimal sensitivity. The lack of knowledge regarding the structure of the drug that remains bound to proteins (antigenic determinant) is hampering the development of in vitro diagnostics. We aimed to identify the antigenic determinants of CLV as well as to evaluate their specific IgE recognition and potential role for diagnosis.Methods: Based on complex CLV degradation mechanisms, we hypothesized the formation of two antigenic determinants for CLV, AD-I (N-protein, 3-oxopropanamide) and AD-II (N-protein, 3-aminopropanamide), and designed different synthetic analogs to each one. IgE recognition of these structures was evaluated in basophils from patients with selective reactions to CLV and tolerant subjects. In parallel, the CLV fragments bound to proteins were identified by proteomic approaches.Results: Two synthetic analogs of AD-I were found to activate basophils from allergic patients. This determinant was also detected bound to lysines 195 and 475 of CLVtreated human serum albumin. One of these analogs was able to activate basophils in 59% of patients whereas CLV only in 41%. Combining both results led to an increase in basophil activation in 69% of patients, and only in 12% of controls.

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Section: Introductionmentioning

confidence: 99%

Identification of an antigenic determinant of clavulanic acid responsible for IgE‐mediated reactions

Barbero

Mayorga

Martín-Serrano

et al. 2019

Allergy

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“…Reaction patterns have been changing in accordance with consumption trends 2. Nowadays, BLs are the most highly consumed antibiotics worldwide, followed by macrolides and quinolones 3.…”

Section: Introductionmentioning

confidence: 99%

“…Nowadays, allergy to new cephalosporins are also being reported 1011. Reactions to clavulanic acid (CLV) have emerged in the last few years and are progressively increasing,12 though AX is still the most frequent inducer of reactions 210…”

Section: Introductionmentioning

confidence: 99%

In Vitro Diagnostic Testing for Antibiotic Allergy

Doña

Torres

Montañez

et al. 2017

Allergy Asthma Immunol Res

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Allergy to antibiotics is an important worldwide problem, with an estimated prevalence of up to 10% of the population. Reaction patterns for different antibiotics have changed in accordance with consumption trends. Most of the allergic reactions to antibiotics have been reported for betalactams, followed by quinolones and macrolides and, to a lesser extent, to others, such as metronidazole clindamycin and sulfonamides. The diagnostic procedure includes a detailed clinical history, which is not always possible and can be unreliable. This is usually followed by in vivo, skin, and drug provocation tests. These are not recommended for severe, potentially lifethreaten reactions or for drugs that are known to produce a high rate of false positive results. Given the limitations of in vivo tests, in vitro test can be helpful for diagnosis, despite having suboptimal sensitivity. The most highly employed techniques for diagnosing immediate reactions to antibiotics are immunoassays and basophil activation tests, while lymphocyte transformation tests are more commonly used to diagnose non-immediate reactions. In this review, we describe different in vitro techniques employed to diagnose antibiotic allergy.

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“…AMX-C used in skin testing is limited to a concentration of 20 mg/ml due to a possible irritant effect in higher concentrations, hence reducing the sensitivity of the test [25,26]. …”

Section: Discussionmentioning

confidence: 99%

The Importance of Amoxicillin and Amoxicillin-Clavulanate Determinants in the Diagnosis of Immediate Allergic Reactions to β-Lactams

Confino‐Cohen

Rosman

Lachover

et al. 2016

Int Arch Allergy Immunol

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Background: Immediate allergic reactions to β-lactam antibiotics are considered to be one of the most important drug hypersensitivities. A positive skin test (ST) with a combination of major and minor penicillin determinants is usually sufficient to recommend avoidance of the culprit drug, whereas a negative ST is usually followed by an oral challenge test (OCT). Recently, concern has been raised regarding the role of amoxicillin (AMX) ST in the diagnosis of AMX allergy. Objective: The aim of this study was to examine the additive value of AMX determinants in STs of patients with immediate hypersensitivity reactions to AMX or AMX-clavulanate (AMX-C). Methods: Patients with a history of immediate AMX or AMX-C allergy underwent an ST using a combination of penicilloyl-polylysine (PPL) and minor determinants as well as AMX. An ST with AMX-C was added when appropriate. Results: Thirty-one patients were evaluated. Eight patients, all of them with a history of AMX allergy, had positive reactions only to the AMX component. Two patients with AMX-C allergy had a positive ST reaction only to the AMX-C component. Moreover, only 14 patients (13 with AMX and 1 with AMX-C allergy) had a positive reaction to PPL, whereas most patients (54.8%) had positive reactions to other determinants. One patient, who was positive for AMX, developed several urticarial lesions after the test. Conclusions: Skin testing with AMX and AMX-C is mandatory in patients with immediate allergy to these drugs. Failure to perform it may result in a false-negative ST jeopardizing these patients with anaphylactic reactions during a hazardous OCT.

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The role of IgE recognition in allergic reactions to amoxicillin and clavulanic acid

Cited by 40 publications

References 79 publications

Identification of an antigenic determinant of clavulanic acid responsible for IgE‐mediated reactions

Identification of an antigenic determinant of clavulanic acid responsible for IgE‐mediated reactions

In Vitro Diagnostic Testing for Antibiotic Allergy

The Importance of Amoxicillin and Amoxicillin-Clavulanate Determinants in the Diagnosis of Immediate Allergic Reactions to β-Lactams

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