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Background: There are marked geographical as well as temporal differences in patient sensitization profiles to β-lactams (BL)., Objective: To determine the utility of skin test reagents and identify a cohort of patients where skin testing can be safely omitted in a cohort of patients referred to a UK tertiary referral center., Methods: A retrospective study of the clinical characteristics of 1092 patients referred for BL allergy testing was analyzed using multivariate regression analysis. The effectiveness of skin test reagents was also evaluated., Results: Multivariate logistic regression identified that a history of anaphylaxis (odds ratio [OR] 10.98, P = .001) and the patients' recall of the index drug (apart from ampicillin and meropenem, OR 3.51-12.43, P < .05) were independent predictors of type I BL allergic status and a time of less than 1 year elapsed since index reaction significantly increasing the odds of a patient with a history of anaphylaxis, having a type I BL allergy (OR 38.66, P = .003). An absence of anaphylactic severity, unknown name of the index drug and a reaction occurring more than 1 year before testing, has a negative predictive value (NPV) of 98.4%, which was similar to the NPV of skin testing of 98.9% for type I BL allergy. The NPV of skin testing with benzylpenicillin + amoxicillin ± index BL was similar with (98.9%) or without (98.1%) the use of benzylpenicillin polylysine and minor determinant for type I BL allergy., Conclusion: We identified a "low risk" cohort of patients where the history is of similar reliability to skin testing in predicting nonallergic status for BL allergy., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

European Network on Drug Allergy (ENDA) has proposed an algorithm for diagnosing immediate beta-lactam (BL) allergy. We evaluated its performance in real life. During 1994-2014, 1779 patients with suspected immediate reactions to BL were evaluated following ENDA's short diagnostic algorithm. Five hundred and nine patients (28.6%) were diagnosed of BL hypersensitivity. Of them, 457 (25.7%) were at first evaluation [403 by skin tests (ST), 12 by positive IgE and 42 by controlled provocation tests (CPT)]. At second evaluation (SE), 52 additional patients (10.2% of allergic patients) were diagnosed, [50 (2.8%) by ST and 2 (0.1%) by CPT]. Time between reaction and study was significantly longer in patients diagnosed at SE (median 5 vs 42 months; IQR 34 vs 170; P < 0.0001). Anaphylaxis was significantly associated with a diagnosis at SE. European Network on Drug Allergy/EAACI protocol was appropriate and safe when evaluating BL immediate reactions. Re-evaluation should be performed, particularly when anaphylaxis and long interval to diagnosis are present., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (© 2016 S. Karger AG, Basel.)

Hypersensitivity reactions to β-lactam antibiotics are commonly reported. They can be classified as immediate or non-immediate according to the time interval between the last drug administration and their onset. Immediate reactions occur within one hour after the last drug administration and are manifested clinically by urticaria and/or angioedema, rhinitis, bronchospasm, and anaphylactic shock; they may be mediated by specific IgEantibodies. Non-immediate reactions occur more than one hour after the last drug administration. The most common manifestations are maculopapular exanthemas; specific T lymphocytes may be involved in this type of manifestation. In the diagnostic evaluation of hypersensitivity reactions to β -lactam antibiotics, the patient's history is fundamental. The allergy examination is based on in vitro and in vivo tests selected on the basis of the clinical features and the type of reaction, immediate or non-immediate. Immediate reactions can be assessed in vitro by serum specific IgE assays and basophil activation tests and in vivo by immediate-reading skin tests and, in selected cases, drug provocation tests (DPTs). Non-immediate reactions can be evaluated mainly by delayed-reading skin tests, patch tests, and DPTs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: beta-Lactams are the drugs most frequently involved in hypersensitivity reactions mediated by immunoglobulin (Ig) E., Objective: To evaluate a population of patients with suspected B-lactam allergy using a validated algorithm that includes specific IgE antibodies, skin testing, and/or a drug provocation test., Methods: A total of 1032 patients with symptoms compatible with B-lactam allergy were evaluated by means of their clinical history, specific immunoglobulin (Ig) E antibody determinations (benzylpenicillin, ampicillin, and amoxicillin), and skin tests with major determinants (penicilloyl-polylysine) and minor determinants (minor determinant mixture) of benzylpenicillin, penicillin G, ampicillin, and amoxicillin-clavulanic acid. Patients whose skin test results were negative were challenged with amoxicillin-clavulanic acid. Only immediate hypersensitivity reactions were evaluated. All patients with negative study results and for whom a reaction occurred more than 1 year before were retested using the same protocol., Results: A total of 170 patients (16.4%) were finally confirmed as having immediate allergic reactions to beta-lactams (62.3% by skin testing, 16.5% by specific IgE, and 21.2% by drug provocation test). The mean age of these patients was 43.3 years, and the drug most frequently involved in the reaction was amoxicillin (41.1%), followed by the combination amoxicillin-clavulanic acid (36.4%). In the remaining 22.5%, different beta-lactams were involved or the culprit drug was not known. Only mild reactions were observed after the drug provocation test. A retest was required in 23% of patients in order to confirm their hypersensitivity., Conclusions: These results indicate that a diagnostic protocol based on the combination of skin testing and in vitro determination of specific IgE antibodies plus, if required, drug provocation testing is an appropriate procedure for evaluating immediate hypersensitivity reactions to beta-lactams. Because the sensitivity of skin testing and in vitro IgE assays is not optimal and a considerable proportion of patients are tolerant, drug provocation tests are necessary to achieve the diagnosis or confirm tolerance. A large percentage of patients (23%) were diagnosed using retest.

Background: Diagnosing immediate hypersensitivity to β-lactam antibiotics is still a significant problem. Recently, a new penicillin testing reagent was introduced to the market. In this study, the recommendations of the European Network of Drug Allergy (ENDA) for the diagnosis of immediate reactions to β-lactams were followed, and the negative predictive value of this approach with currently available reagents was assessed., Methods: Eighty patients (age range: 6-74 years) with a history of immediate reactions to β-lactams were included. All cases underwent skin testing with benzylpenicilloyl-polylysine (PPL) and minor determinant mixture (MDM), followed by the culprit drug if necessary. If this step was negative, a drug provocation test was offered. If this step also yielded a negative result, then the patients were recommended to use β-lactam antibiotics in future whenever their use was indicated., Results: Overall, 29 patients (36.2%) were diagnosed as β-lactam allergic. The majority of the cases (72.4%) were diagnosed by positive skin tests to either PPL or MDM, whereas 10.3% were diagnosed by skin testing with culprit drugs and 17.2% with drug provocation tests. Regarding the use of the tested drug in the long term, almost half of the contacted patients had had an indication to use the tested drug and the majority had taken the whole course without problems., Conclusions: Although currently available new penicillin tests provide sufficient allergy data, all the steps recommended by ENDA should be followed in the diagnosis of immediate reactions to β-lactams. If these steps are negative, the patients usually tolerate β-lactams and only a few develop mild, non-life-threatening reactions in the long term., (Copyright © 2011 S. Karger AG, Basel.)

Penicillins and cephalosporins are the most widely used antibiotics for the treatment of common infections, and they are the two main classes of β-lactams. On the basis of the time of appearance of the reaction after drug intake and for diagnostic purposes, hypersensitivity reactions to β-lactams have been classified as immediate or non-immediate. The diagnostic evaluation of allergic reactions to β-lactams has changed over the last decade, for several reasons. In many countries, major and minor determinants for skin testing are not available. In immediate allergic reactions, the sensitivity of skin testing is decreasing. For non-immediate reactions, skin testing appears to be less sensitive than previously reported. The drug provocation test is still necessary for diagnosis. In this education review series, we described three cases of β-lactam allergy: first, a child with an IgE-mediated allergy to benzyl-penicillin; second, a child with a non-allergic hypersensitivity to amoxicillin; and in the third patient, we will discuss about cross-reactivity between penicillins and cephalosporins. These cases are correlated with the practical management of evaluating β-lactam allergy., (© 2011 John Wiley & Sons A/S.)

Purpose of Review: The aim of this study was to confirm the applicability of the basophil activation test (BAT) in the in-vitro diagnosis of drug allergy reactions., Recent Findings: The results obtained in terms of sensitivity and specificity with BAT are encouraging and in significant number of cases can establish the diagnosis., Summary: BAT sensitivity in beta-lactam allergy was 50%, and specificity ranged from 89 to 97%. There are several studies to validate the BAT in allergy to muscle relaxants showing a sensitivity ranging from 54 to 64% with a specificity of 100 and 93%. The sensitivity of a test for evaluating immediate allergic reactions to drugs may decrease over time. To date, the BAT is the only in-vitro diagnostic method that has been validated for the diagnosis of both IgE-mediated and hypersensitivity reactions to NSAIDs. With respect to other drugs, they are nonetheless interesting as they include the evaluation of allergy to drugs that cannot be studied by other in-vitro techniques. All these data suggest that although a full validation of the test is required, BAT is a potential diagnostic method for evaluating immediate allergic reactions to drugs and NSAID hypersensitivity reactions.

Background: Allergic reactions to beta-lactams are the most frequent cause of adverse drug reactions mediated by specific immunologic mechanisms. They can be explored by in vivo and/or in vitro tests. The measurement of serum-specific immunoglobulin E (IgE) presents several advantages: safety, simplicity, and availability to nonallergologist physicians., Objectives: To establish the diagnostic value of specific IgE determination in the diagnosis procedure of immediate beta-lactam allergy., Methods: The in vitro determination of beta-lactam-specific IgE antibodies was compared in three well-defined groups of patients (n=45): one with negative skin tests and a positive drug provocation test, another with positive skin tests, and a third control exposed population with good tolerance. Two techniques were used: the CAP-FEIA system (Phadia) commercially available and a homemade radioallergosorbent test (RAST)., Results: The specificity of CAP-FEIA ranged from 83.3% to 100% and sensitivity from 0% to 25% depending on initial clinical manifestations. The specificity of RAST was between 66.7% and 83.3% and sensitivity 42.9% and 75%. In the subgroup of patients with an anaphylactic shock and negative skin tests, the sensitivity and specificity of RAST were 75%. Positive and negative predictive values were 45.5% and 77.1% with CAP-FEIA and 38.5% and 81.5% with RAST, respectively., Conclusion: These results indicate that, although the specificity of beta-lactam-specific IgE measurement is good, sensitivity is low. Immunoglobulin E measurement should be limited to patients with a clinical history of anaphylactic shock and negative skin tests in order to avoid a drug provocation test. More sensitive assays should be developed.

Immediate hypersensitivity reactions to betalactams are IgE mediated and constitute the most frequent allergic reactions mediated by specific immunological mechanisms. IgE responses to benzyl penicillin (BP), the first antibiotic producing the benzyl penicilloyl structure (BPO), are characterized by a quick release of inflammatory mediators, resulting in anaphylactic shock, urticaria and angioedema. With the progressive appearance of other structures, comprising cephalosporins, carbapenems, monobactams and clavulanic acid, IgE selective responses and cross-reactivity reactions were observed. The diagnosis of betalactam hypersensitivity, classically based on skin testing with major and minor determinants of benzyl penicillin or in vitro IgE antibodies to BP, has been modified by the inclusion of different determinants generated from these compounds, for which amoxicillin (AX) is the most relevant, followed by cephalosporins. Some subjects develop positive responses to several betalactams, mostly within the same family, but others develop a selective response. These are relevant for the appropriate selection of antimicrobial drugs in patients who have immediate hypersensitivity to betalactams.

Allergic reactions to penicillin and cephalosporin antibiotics are common. The mechanisms involved are heterogeneous and not yet completely understood. However, clinical and immunologic studies suggest that type I (IgE-mediated) and type IV (cell-mediated) pathogenic mechanisms are involved in most immediate and non-immediate reactions, respectively. The diagnostic procedure has recently been standardized under the aegis of the European Network for Drug Allergy and the European Academy of Allergy and Clinical Immunology interest group on drug hypersensitivity. In this review, we describe the general guidelines for evaluating subjects in whom there is suspicion of allergic reactions to beta-lactams.

Background: beta-Lactam drugs may induce both cellular and humoral allergic reactions, and there is evidence that T cells play an important role in the pathogenesis of these reactions. The aim of this work was to assess the sensitivity and specificity of the lymphocyte transformation test (LTT) as an in vitro diagnostic tool, in patients with either an immediate or a nonimmediate reaction to penicillin G and/or amoxicillin., Methods: Fifty patients with a well-documented history of allergic reactions to beta-lactams (31 immediate and 19 nonimmediate) were studied by means of skin tests (prick and intradermal), radioallergosorbent test (RAST), and, when necessary, controlled administration of the drug. Twenty-eight healthy subjects with good tolerance to penicillins served as controls. LTT was performed in all subjects., Results: Skin tests were positive in 77.4% of the patients with immediate reactions and in 36.8% of those with nonimmediate reactions. The overall sensitivity of LTT in the allergic patients was 62%, but, when analyzed separately, sensitivity was 64.5% for the immediate group and 57.9% for the nonimmediate group. The LTT specificity was 92.8%., Conclusion: The LTT should be considered a useful in vitro diagnostic tool to identify subjects allergic to penicillins, especially patients with nonimmediate reactions where the LTT has a better diagnostic value than skin tests. Interestingly, positive T-cell proliferative responses can be observed 10 or more years after the occurrence of the reaction without further exposure to the drug.