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Background: Compared to penicillin, cephalosporin allergies are less common in children, and their diagnostic approach is less standardized. A recent European Academy of Allergy and Clinical Immunology position paper provided a risk stratification system for patients with suspected β-lactam hypersensitivity reactions., Objective: This study aimed to evaluate risk stratification and predicting factors for confirmed cephalosporin hypersensitivity., Methods: The case-controlled study included patients with confirmed cephalosporin hypersensitivity (skin tests, n = 53; drug provocation, n = 19). For each patient, 2 age- and gender-matched control subjects were included in the study. Data were retrieved from patients' records and analyzed retrospectively. Risk stratification was performed according to the severity of index reactions, which was initially divided as high and low risk and then further divided as immediate and nonimmediate., Results: According to risk stratification, the patient and control groups were divided as follows: high-risk immediate (66.7% vs. 13%, respectively), high-risk delayed (1.4% vs. 8.3%, respectively), low-risk immediate (16.7% vs. 16%, respectively), and low-risk delayed (15.3% vs. 62.9%, respectively). Immediate reactions (odds ratio [OR]: 12.1, 95% confidence interval [CI]: 9-24.8, p < 0.001) and high-risk reactions (OR: 7.8, 95% CI: 4.1-14.6, p < 0.001) were associated with confirmed cephalosporin hypersensitivity in univariate analysis. Multivariate regression analysis indicated that immediate reactions (OR: 7.5, 95% CI: 3.3-16.8, p < 0.001) and high-risk reactions (OR: 5.2, 95% CI: 2.1-12.9, p < 0.001) were significant risk factors for the prediction of cephalosporin hypersensitivity., Conclusion: This model can be applied in children with suspected cephalosporin allergy. Skin testing provides diagnostic information in high-risk patients with immediate reactions and reduces the need for drug provocation testing in these patients. It is highly likely to confirm the diagnosis of low-risk patients directly with provocation tests without skin tests. High-risk and immediate reactions were found to be predictive factors for confirmed cephalosporin allergy., (© 2021 S. Karger AG, Basel.)

Background: Intradermal testing with delayed reading (IDTdr), used routinely in many centers, may identify delayed reactions to penicillins. However, few studies have compared the results of IDTdr with drug provocation test (DPT). The aim of this study was to examine the proportion of provocation-positive patients testing positive on IDTdr., Methods: Fifty-seven patients with a positive DPT occurring >2 h after intake of penicillin V, dicloxacillin, pivampicillin, or amoxicillin had an IDTdr with penicillin G, amoxicillin, ampicillin, and dicloxacillin. A control group included 18 patients with negative DPTs with the suspected penicillin., Results: In total 25% (n = 14) of provocation-positive patients tested positive on IDTdr. Among patients with positive IDTdr, 9/14 (64%) versus 11/43 (26%) in the IDTdr negative group (p < 0.05) had required oral steroids to treat skin reactions following DPT. No other differences between IDTdr positive and negative groups were found. No controls had a positive IDTdr., Conclusion: Investigating with IDTdr would have identified 25% of patients with a DPT-verified allergy with delayed reactions. It is difficult to target subgroups who will test positive on IDTdr. There were more patients who tested positive on IDT who had received oral steroids after DPT, and this may be an indication that skin reaction severity plays a role in skin testing diagnostics. Further potential predictors for positivity of IDTdr, such as duration of skin symptoms, should be assessed in large studies in order to optimize the investigations of nonimmediate drug allergic reactions., (© 2021 S. Karger AG, Basel.)

Introduction: Beta-lactams (BLs) are one of the most frequent causes of drug hypersensitivity reactions (HRs), and cephalosporins are a widely used subclass of BLs, especially in children. The aim of this study was to evaluate the clinical features and diagnostic test results of pediatric patients evaluated for suspected cephalosporin allergy., Methods: This study included patients who presented to our pediatric allergy clinic with a history of reactions attributed to cephalosporins between January 1, 2011, and December 31, 2019, and whose diagnostic tests were completed for the diagnosis., Results: This study included 120 pediatric patients and 69 (57.5%) of them were girls. The median age was 38.63 (interquartile range 10.5-85.7) months. Reactions occurring within 1 h of drug intake were reported in 33 patients (27.5%). Reactions were maculopapular rash in 55 (45.8%) patients, urticaria and/or angioedema in 49 (40.8%), anaphylaxis in 11 (9.2%), severe cutaneous drug reaction in 4 (3.3%), and fixed drug reaction in 1 patient (0.83%). The most frequently suspected agent was cefixime in 41 patients (34.2%). In total, 30 (25%) patients were diagnosed as having cephalosporin hypersensitivity. Confirmation of HRs was also significantly more frequent among patients who were older (p: 0.000), who had taken the drug parenterally (p: 0.000) and with immediate reactions (p: 0.000)., Conclusion: Cephalosporin allergy has been confirmed in approximately one-fourth of the patients evaluated for suspected cephalosporin allergy. Confirmation of HRs was significantly more common among patients who were older, had immediate reactions, and had taken the drug parenterally., (© 2021 S. Karger AG, Basel.)

Background: Perioperative use of cefazolin has been associated with severe allergic reactions, and patients are usually labelled as allergic to penicillin afterwards. The aim of our study was to describe a group of patients with immediate reactions to cefazolin, with proven selective hypersensitivity reactions., Methods: Systematic review of all patients followed at our drug centre with cefazolin-related reactions, between January 2012 and December 2016. All patients were investigated according to the European Network for Drug Allergy (ENDA) recommendations through skin testing (major and minor penicillin determinants, penicillin, amoxicillin, cefazolin, cefuroxime and ceftriaxone) and oral challenges tests., Results: We included 7 patients (median age 40 years) with perioperative anaphylactic reactions immediately after cefazolin injection, 4 with hypotension and 1 with Kounis syndrome (KS) type I. The presence of a selective IgE-mediated hypersensitivity through positive skin tests to cefazoline has been proven in all patients. Two patients experienced systemic reactions during skin testing. All patients were successfully challenged with amoxicillin, and they tolerated cefuroxime., Conclusions: Cefazolin can be responsible for immediate severe allergic reactions in perioperative setting, including KS. Allergological workup is essential for an accurate diagnosis and to explore cross-reactivity between cefazolin and other beta-lactams. Our experience confirmed that patients with IgE-mediated hypersensitivity reactions to cefazolin can tolerate other beta-lactams. This selective pattern of clinical reactivity may be explained by its particular chemical structure, whose R1 side-chain is different from other beta-lactams., (© 2018 S. Karger AG, Basel.)

Immediate hypersensitivity (IHS) reactions to macrolides and to macrolide-derived antibiotics like pristinamycin are uncommon. In this context, there is little data available to appreciate the true value of biological tools regarding the diagnosis of immediate allergy to pristinamycin. Here we assess the clinical usefulness of the basophil activation test (BAT) to differentiate allergic from nonallergic IHS to pristinamycin. Thirty-six patients were tested with skin tests as the gold standard and BAT. The BAT achieved a sensitivity of 76% and a specificity of 100%, implying an absence of false positive results. Multicenter studies remain to be performed to better define the sensitivity, specificity and interlaboratory variation of BAT in the diagnosis of allergy to pristinamycin and macrolides., (© 2015 S. Karger AG, Basel.)

Background: Quinolone hypersensitivity reactions are being more frequently reported. Skin tests in investigations of patients are known to not be fully reliable. The provocation test thus remains the gold standard in the definitive diagnosis of allergy, despite the risks involved. The aim of this study was to evaluate basophil activation tests (BATs) in the diagnosis of immediate-type reactions to quinolones., Methods: Thirty-four patients who presented an immediate-type hypersensivity reaction less than an hour after quinolone administration were studied. The allergologic workup of these patients consisted of a careful clinical history, a skin test and a BAT with the culprit quinolone. If not contraindicated, and in the case of high probability of a nonallergic reaction, provocation tests were performed to assess the nonimmunologic nature of the hypersensitivity., Results: Among the 34 patients studied, 17 (50%) presented a negative BAT to the suspected quinolone, while the other 17 (50%) patients presented a positive BAT for quinolone at the time of their reaction. Among the 17 patients with negative BATs, 15 (2 of whom had had positive skin tests) had quinolone successfully reintroduced., Conclusions: Our report suggests that the BAT, if negative for the culprit quinolone, is a valuable tool in the decision whether or not to perform provocation tests in patients with a history of immediate-type reaction to quinolones, in order to exclude an allergic reaction., (Copyright © 2011 S. Karger AG, Basel.)

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.)

Objective: In patients sensitized to beta-lactams, a safe beta-lactam alternative is often needed. The objective was to assess the safety of cefuroxime in patients with a proven beta-lactam allergy., Design: Using the Drug Allergy and Hypersensitivity Database cohort, patients with a proven beta-lactam allergy and tested for cefuroxime between September 1996 and April 2007 were selected. The European Network of Drug Allergy recommendations were followed. Prevalence of sensitization to cefuroxime (as an alternative) was established in patients with a proven beta-lactam allergy., Results: Amongst the 650 subjects tested, 143 (22.0%) presented at least one beta-lactam sensitization other than cefuroxime [39-27.3% male, median age at test 44.0 (32.0-56.0) years]. One hundred and eighteen (82.5%) were sensitized to penicillins, 8 (5.6%) to cephalosporins and 17 (11.9%) to both penicillins and cephalosporins. Nine (6.3%) patients were sensitized to cefuroxime (6 diagnosed by provocation test): 5 (55.6%) in the penicillin-only allergic group and 4 (44.4%) in the penicillin and cephalosporin allergic group. Prevalence of cefuroxime hypersensitivity reaction in patients sensitized to beta-lactams was 6.3% (95% CI 2.3-10.3%) and in those sensitized to penicillin 4.2% (95% CI 0.6-7.9). This rate decreased to 2.9% (95% CI 0-6.9) in patients with prior histories involving a penicillin only (without any history involving an unknown beta-lactam)., Conclusion: Cefuroxime appeared to be a safe alternative in beta-lactam-allergic patients after testing. The risk of giving cefuroxime being not null, a thorough drug allergy work-up, including provocation test, is still needed., (Copyright (c) 2010 S. Karger AG, Basel.)

Background: In clinical practice, clindamycin is increasingly used because of its good tolerability and high efficacy with excellent tissue penetration. However, with increased application of clindamycin, the frequency of side effects such as skin eruptions rises and the need for diagnostic testing to identify clindamycin allergy increases. The aim of this retrospective analysis was to demonstrate the results of skin and challenge tests in cases of clinically suspected clindamycin allergy., Methods: We evaluated 33 patients with a history of a skin reaction in temporal relation to treatment with clindamycin using standardized patch and prick skin testing. In the case of negative skin tests, oral challenges were performed., Results: Clindamycin hypersensitivity was excluded in 20 patients by negative skin tests and subsequently tolerated oral challenge tests. In 5 patients, positive skin tests strongly suggested delayed-type non-IgE-mediated allergic clindamycin hypersensitivity. In 6 skin test-negative patients (2 patients refused challenge tests), a rash was provoked by controlled challenge tests., Conclusions: The evaluation of patients with clindamycin-associated skin reactions should include appropriate allergologic tests establishing or excluding the diagnosis of clindamycin hypersensitivity. Combined testing, i.e. skin tests and subsequent challenge tests, appears to be necessary to definitely confirm or rule out the presence of allergic clindamycin hypersensitivity.

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 beta-lactam reactivity., (Copyright 2009 S. Karger AG, Basel.)