Cephalosporin chemical reactivity and its immunological implications

Pérez‐Inestrosa, Ezequiel; Suau, Rafael; Montañez, María Isabel; Rodríguez, Rebeca; Mayorga, Cristobalina; Torres, Marı́a José; Blanca, Miguel

doi:10.1097/01.all.0000173788.73401.69

Cited by 86 publications

(78 citation statements)

References 35 publications

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“…The exact nature of these intermediate products has not been characterized [86,87], but the haptenization mechanism appears slower and possibly more complex than with penicillins [88,89]. Our knowledge of the immunological relevance of cephalosporin hapten-carrier conjugates remains incomplete.…”

Section: Molecular Structurementioning

confidence: 99%

“…Cross-reactivity as a result of antibody recognition is more closely related to side chain homology (and possibly the small beta-lactam fragment linked to the carrier protein during cephalosporin conjugation) rather than the central beta-lactam ring [86][87][88]. Therefore, cefadroxil, cefradine, cefaclor and cefalexin have significant cross-reactivity in patients with a previous history of allergic reaction to ampicillin/amoxicillin because of similarities in side chain structure (table 3a,b) [89].…”

Section: Cross-reactivity Between Cephalosporins and Penicillinsmentioning

confidence: 99%

See 1 more Smart Citation

Management of allergy to penicillins and other beta‐lactams

Mirakian

Leech

Krishna

et al. 2015

Clin Experimental Allergy

216

221

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SummaryThe Standards of Care Committee of the British Society for Allergy and Clinical Immunology (BSACI) and an expert panel have prepared this guidance for the management of immediate and non-immediate allergic reactions to penicillins and other beta-lactams. The guideline is intended for UK specialists in both adult and paediatric allergy and for other clinicians practising allergy in secondary and tertiary care. The recommendations are evidence based, but where evidence is lacking, the panel reached consensus. During the development of the guideline, all BSACI members were consulted using a Web-based process and all comments carefully considered. Included in the guideline are epidemiology of allergic reactions to beta-lactams, molecular structure, formulations available in the UK and a description of known beta-lactam antigenic determinants. Sections on the value and limitations of clinical history, skin testing and laboratory investigations for both penicillins and cephalosporins are included. Cross-reactivity between penicillins and cephalosporins is discussed in detail. Recommendations on oral provocation and desensitization procedures have been made. Guidance for beta-lactam allergy in children is given in a separate section. An algorithm to help the clinician in the diagnosis of patients with a history of penicillin allergy has also been included.Keywords allergy, anaphylaxis, beta-lactam, BSACI, carbapenem, cephalosporin, children, cross-reactivity, desensitization, drug provocation test, epidemiology, hypersensitivity, monobactam, oral challenges, paediatrics, penicillin, serum-specific IgE, skin tests, Standards of Care Committee • This guideline addresses immediate and non-immediate allergic reactions to beta-lactams.• Up to 20% of drug-related anaphylaxis deaths in • Individuals with a positive skin test to an aminopenicillin but negative skin tests to penicillin determinants are likely to be sensitized to the aminopenicillin side chain. (B) In this situation, a cautious challenge to benzyl or phenoxymethyl penicillin can be considered to ascertain whether the patient has a selective penicillin allergy. (D) • If a cephalosporin is required in a patient with a clinical history of penicillin allergy and positive skin tests -the patient should undergo skin testing using a cephalosporin with a different side chain and, if negative, provocation testing should be undertaken to exclude allergy to the specific cephalosporin. (D)• If penicillin is required in a patient with a clinical history of cephalosporin allergy, skin testing should be undertaken with penicillins and, if negative, provocation testing to exclude allergy to penicillin. (B) If skin tests are positive, then penicillin avoidance or desensitization can be considered. (B)• If a cephalosporin is required by a patient with a previous reaction, skin testing to penicillins and the required cephalosporin should be carried out to establish whether sensitization is to the beta-lactam core or side chain. (B) This should be followed by either provo...

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Section: Molecular Structurementioning

confidence: 99%

Section: Cross-reactivity Between Cephalosporins and Penicillinsmentioning

confidence: 99%

Management of allergy to penicillins and other beta‐lactams

Mirakian

Leech

Krishna

et al. 2015

Clin Experimental Allergy

216

221

View full text Add to dashboard Cite

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“…Skin testing or in vitro IgE antibody tests using cephalosporin preparations have only limited clinical value [7, 8]. Unlike penicillins, cephalosporin skin tests are performed with the native molecule, as the degradation products of the cephalosporins are not available for testing [9]. This may result in a false-negative skin test and a subsequently high-risk oral challenge test.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Immediate Allergic Reactions to Cephalosporins in Non-Penicillin-Allergic Patients

Somech

Weber

Lavi

2009

Int Arch Allergy Immunol

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Background: Cephalosporins can induce severe or life-threatening IgE-mediated reactions in some individuals. In this study, we wish to describe a group of non-penicillin-allergic patients who were evaluated for immediate allergic reactions to cephalosporins. Methods: The patients were assessed by skin tests with the culprit cephalosporin as well as with other cephalosporins and penicillins. If indicated, oral challenge testing was performed. Results: Six patients were assessed. A total of 42 skin tests and 20 oral challenges were performed. In 4 patients, skin tests included the causative drug; in 2 patients, the diagnosis of a cephalosporin allergy was made by skin test; in 4 patients, the diagnosis of a cephalosporin hypersensitivity was made by oral challenge. In 96.9% of the oral challenges, which were done using medications with no structural side chain similarities to the culprit drug, no adverse reaction occurred. Conclusion: A positive skin test to cephalosporin implies the presence of drug-specific IgE antibodies. Cephalosporins without side chain similarities are suggested to patients with cephalosporin reactions and no β-lactam reactivity.

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“…In the majority of clinically relevant cephalosporins, the presence of a good leaving group at the 3′ position (-CH 2 -R 2 side chain) increases the reactivity of the BL via the elimination of R 2 . However, for other cephalosporins such as cefaclor, ceftizoxime, cefrodaxime, cefadroxil, cephalexin, and cephradine, there is no R 2 group at the 3′ position, but instead a substituent (e.g., chloride, methyl, or methoxy) whose expulsion is not so evident [10]. Regardless of the reactivity of R 2 , there is clinical evidence that the R 1 side chain may form part of the antigenic determinant and contribute to IgE induction and crossreactivity.…”

Section: Bl Antigenic Determinantsmentioning

confidence: 99%

Cross-Reactivity in Betalactam Allergy: Alternative Treatments

Montañez

Ariza

Mayorga

et al. 2015

Curr Treat Options Allergy

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Opinion statementIt was originally thought that, as all betalactams share a four-member ring, they would cross-react, and so the classical recommendation was for allergic patients to avoid all betalactams. However, later studies found that some individuals selectively responded to one betalactam only and tolerated others. This was shown to be more frequent than initially thought, and this finding has led to a change from the initial recommendations of complete avoidance. Selective responses to amoxicillin are mainly due to recognition of the side chain structure, making benzylpenicillin a safe alternative. These amoxicillin-selective responders comprise up to 55 and 90 % of patients with immediate allergic reactions to amoxicillin and amoxicillin-clavulanic, respectively. Additionally, more than 85 % of penicillin-allergic patients can tolerate cephalosporins with different R 1 side chains, decreasing to 65 % if the side chain is identical. It is known that third and fourth generation cephalosporins are well tolerated by penicillin-allergic patients, probably because their chemical structures differ more from penicillins that those from the first generation. In patients with IgE-mediated allergic reactions to cephalosporins, penicillins can be an alternative treatment in up to 75 % of cases. Moreover, 40 % of patients primarily sensitized to a given cephalosporin also react to others, which might be because some cephaloporins have the same (ceftriaxone and cefotaxime) or very similar (ceftriaxone and cefuroxime) side chain structures. Finally, carbapenems and monobactams are good alternative for patients with penicillin and/or cephalosporin allergy because cross-reactivity occurs in G1 % of these cases. For all betalactams, tolerance is higher in T-cell-mediated reactions than IgE-mediated. These results show that alternative treatments for infectious disease are available to patients with allergic reactions to betalactams, from within the same group of antibiotics. Nevertheless, this general rules need to be analyzed patient by patient, and skin tests and graded challenge with the betalactam that is going to be administered are recommended. Keypoints• Patients with IgE-or T-cell-mediated allergy to betalactams can have selective reactions, specific to one betalactam with good tolerance to others, or be crossreactive, recognizing several different chemically related betalactams.• The percentage of selective reactions to the different betalactam compounds is higher than previously reported and patients should be studied in order to increase the treatment options available.

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Cephalosporin chemical reactivity and its immunological implications

Cited by 86 publications

References 35 publications

Management of allergy to penicillins and other beta‐lactams

Management of allergy to penicillins and other beta‐lactams

Evaluation of Immediate Allergic Reactions to Cephalosporins in Non-Penicillin-Allergic Patients

Cross-Reactivity in Betalactam Allergy: Alternative Treatments

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