Diagnosis Of Penicillin Allergy Research Articles

Evaluation of Penicillin Allergy in the Hospitalized Patient: Opportunities for Antimicrobial Stewardship.

Penicillin allergy is often misdiagnosed and is associated with adverse consequences, but testing is infrequently done in the hospital setting. This article reviews historical and contemporary innovations in inpatient penicillin allergy testing and its impact on antimicrobial stewardship. Adoption of the electronic medical record allows rapid identification of admitted patients carrying a penicillin allergy diagnosis. Collaboration with clinical pharmacists and the development of computerized clinical guidelines facilitates increased testing and appropriate use of penicillin and related β-lactams. Education of patients and their outpatient providers is the key to retaining the benefits of penicillin allergy de-labeling. Penicillin allergy testing is feasible in the hospital and offers tangible benefits towards antimicrobial stewardship. Allergists should take the lead in this endeavor and work towards overcoming personnel limitations by partnering with other health care providers and incorporating technology that improves the efficiency of allergy evaluation.

Frequency and Risk Factors of Penicillin and Amoxicillin Allergy in Suspected Patients with Drug Allergy.

Unconfirmed beta-lactam allergy is a significant public health problem because of the limitations it imposes in drug selection. In this study, we aimed to evaluate patients referred for beta-lactam allergy to determine the frequency of confirmed beta-lactam allergy and identify some risk factors. In a prospective cohort study, all referred patients to Immunology, Asthma and Allergy Research Institute in Tehran University of Medical Sciences (between 2007 - 2009) who suspected to have beta-lactam allergy were entered into this study based on having the inclusion criteria. Follow-up was performed 6 - 8 years after the final diagnosis. Diagnosis of beta-lactam allergy relies on thorough history and specific IgE measurements (ImmunoCAP), skin prick testing (SPT), intradermal testing (IDT), patch testing, and oral drug challenge test. Fifty-one patients with mean age of 24.5 (±18.5) years were enrolled in this study. Based on workups, beta-lactam allergy was confirmed in 16 (31.4%) patients, suspicious in 22 (43.1%) patients and ruled out in 13 (25.5%) patients. During the follow-up, 3 patients with suspicious drug allergy consumed the culprit drug with no reaction so allergy was finally ruled out in 16 (31.4%) patients. Age, sex, atopy and family history of drug allergies were not significantly different between the patients with confirmed or ruled-out diagnosis of penicillin and amoxicillin allergy. At least up to one-third of patients with a history of beta-lactam allergy are proven to be safe using the drug. Also, a clear protocol consists of serum sIgE assay and SPT can be helpful to the physicians in the health care system.

Penicillin allergy evaluation: experience from Kuwait

Results Total of 124 patients were evaluated for penicillin allergy. Mean age was 37.8 (SD 12.7) years, range from 8 to 74 years. 39 (31.5%) male and 85 (68.5%) female patients were included. Diagnosis of penicillin allergy was confirmed in 46 patients (37.1%). Among the 44 confirmed allergic patients by skin evaluation we had 15 (34.1%) positive skin prick test, and 29 (65.9%) positive intradermal testing. Among patients with positive skin testing, 47.7% were positive to PPL, 20.4% to MDM, 50.0% to PG and 40.9% to ampicillin; 13.6% of patients were positive to amoxicillin by skin prick test. One patient had positive RAST and one had a positive challenge test.

Penicillin allergy diagnosis and desensitization.

British Journal of Hospital MedicineVol. 75, No. Sup7 What You Need To Know AboutPenicillin allergy diagnosis and desensitizationIman Nasr, Ignatius Chua, Saima Alam, Giuseppina Rotiroti, Miguel Blanca, Joanna LukawskaIman NasrSearch for more papers by this author, Ignatius ChuaSearch for more papers by this author, Saima AlamSearch for more papers by this author, Giuseppina RotirotiSearch for more papers by this author, Miguel BlancaSearch for more papers by this author, Joanna LukawskaSearch for more papers by this authorIman Nasr; Ignatius Chua; Saima Alam; Giuseppina Rotiroti; Miguel Blanca; Joanna LukawskaPublished Online:4 Jul 2014https://doi.org/10.12968/hmed.2014.75.Sup7.C98AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View article References Antunez C, Blanca-Lopez N, Torres MJ et al. 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Am J Med 121: 572–6 (doi: https://doi.org/10.1016/j.amjmed.2007.12.005) Crossref, Medline, Google Scholar FiguresReferencesRelatedDetailsCited ByEvaluation of desensitization protocols to betalactam antibiotics24 November 2021 | Journal of Clinical Pharmacy and Therapeutics, Vol. 47, No. 5 1 July 2014Volume 75Issue Sup7ISSN (print): 1750-8460ISSN (online): 1759-7390 Metrics History Published online 4 July 2014 Published in print 1 July 2014 Information© MA Healthcare LimitedPDF download

Penicillin allergy evaluation: experience from a drug allergy clinic in an Arabian Gulf Country, Kuwait.

BackgroundHypersensitivity to penicillin has been studied worldwide, but data regarding patterns of sensitization in Arabian Gulf countries are scarce.ObjectiveTo describe the patterns of penicillin hypersensitivity during a 6-year study in Kuwait in terms of demographics, type of the culprit drug, in vivo and in vitro allergy testing.MethodsOne hundred and twenty-four patients referred to the drug allergy clinic for penicillin allergy were fully evaluated by skin prick and intradermal testing. Drug provocation test was done on patients with negative results.ResultsA total of 124 patients were evaluated for penicillin allergy. Mean age was 37.8 (standard deviation, 12.7) years, range from 8 to 74 years. Thirty-nine male (31.5%) and 85 female patients (68.5%) were included. Diagnosis of penicillin allergy was confirmed in 46 patients (37.1%). Among the 44 confirmed allergic patients by skin evaluation we had 15 (34.1%) positive skin prick test, and 29 (65.9%) positive intradermal testing. Among patients with positive skin testing, 47.7% were positive to major determinant benzylpenicilloyl poly-L-lysine, 20.4% to minor determinant mixture, 50.0% to penicillin G and 40.9% to ampicillin; 13.6% of patients were positive to amoxicillin by skin prick test. One patient had a positive radioallergosorbent test and one had a positive challenge test.ConclusionPenicillin allergy is a common problem with an incidence of about one third in our study subjects.

Diagnosis of penicillin allergy revisited: the value of case history, skin testing, specific IgE and prolonged challenge

Skin testing in duplicate, correlation between case history of immediate and nonimmediate reactions and challenge outcome and prolonged oral treatment with penicillin in the diagnostic evaluation of allergic reactions to β-lactam antibiotics, mimicking real-life situations, have only been addressed in few studies. A total of 342 patients suspected of having β-lactam allergy were investigated according to the European Network for Drug Allergy (ENDA) guidelines and patients found to be negative in the ENDA program were supplemented with a 7-day oral treatment with penicillin. Skin testing with penicillins was performed in duplicate. Patients with case histories of reactions to other β-lactams were also subsequently challenged with the culprit drug. Nineteen patients were IgE-sensitized to penicillin. Then, intracutaneous tests (ICTs) were performed, in which 35 patients tested positive for allergy, 21 with delayed and 14 with immediate reactions. Only three patients tested positive for the major (PPL) and/or minor (MDM) penicillin determinants, all being positive for penicillin G in ICT. The remaining 291 patients were challenged with penicillin: 10 tested positive in single-dose challenge and 23 tested positive in the 7-day challenge. A total of 17 of 78 patients with a negative penicillin challenge tested positive during challenges with other β-lactams. We found no correlation between case histories of immediate and nonimmediate reactions and reaction time during challenge. The data suggest that case history is often insufficient to discriminate between immediate reactors and nonimmediate reactors. A 7-day challenge with the culprit β-lactam may yield more positive reactions than the accepted one- or 2-day challenge. Interpretation of skin testing should be made with caution.

DAP: New Products for Skin Tests Diagnosis of Penicillin Allergy

DAP: New Products for Skin Tests Diagnosis of Penicillin Allergy

False-positive penicillin immunoassay: An unnoticed common problem

False-positive penicillin immunoassay: An unnoticed common problem

One-week Oral Challenge with Penicillin in Diagnosis of Penicillin Allergy

Many patients experience reactions during penicillin treatment. The diagnosis may be difficult and is mainly based on short-term tests. The European Network for Drug Allergy (ENDA) guidelines proposed for diagnosing penicillin allergy do not include long-term challenge. In this study a total of 405 patients were evaluated. The ENDA guidelines were extended, to include a 7-day oral treatment (p.o.7) with penicillin for all patients who were negative in the ENDA programme. Among the 405 patients; 85 had an immediate reaction to penicillin, and a further 13 reacted during p.o.7. Among the 307 patients with a negative outcome, 88 had a case history of reaction to other β-lactam antibiotics and were subsequently tested with the culprit drug. Thirteen patients had a positive outcome: 3 on single-dose challenge and 10 during p.o.7. The extended penicillin diagnostic work-up was positive in 111 patients, 30.0% showed immediate reactions and 5.7% reacted during p.o.7. Approximately 20% of all patients with positive outcome during penicillin challenge are detected by adding p.o.7 with penicillin to the original ENDA guidelines.

The need for a biological diagnosis of penicillin allergy

According to the Nomenclature Review Committee of the World Allergy Organization, drug allergies refer to drug hypersensitivity reactions where a definite immunological mechanism [1] can be demonstrated. The prevalence of self-reported penicillin allergy is high; indeed, a crosssectional survey in Portugal found a 4.5% adult population self-reported penicillin allergy [2]. The prevalence rate of true penicillin allergy is, however, much lower [3, 4], and therefore a firm diagnosis is needed [5]. The clinical picture of drug allergy is very heterogeneous, encompassing distinct diseases such as morbilliform or bullous exanthema, urticaria and angiooedema, pustular exanthemas, fixed drug eruptions, anaphylaxis, blood cell dyscrasia, fever, interstitial lung disease, hepatitis, nephritis, vasculitis, DRESS (drug reaction with eosinophilia and systemic symptoms) and various forms of autoimmune diseases. However, it is important to distinguish between immediate and non-immediate reactions. The former occur within the first hour after the last drug administration and are manifested clinically by urticaria, angiooedema, rhinitis, bronchospasm or anaphylactic shock. The diagnosis of drug allergy often relies on clinical histories, skin tests and a few validated in vitro tests, such as serum-specific IgE assays, which are available only for a few drugs. The sensitivity of these tests is not 100% and, in selected cases, provocation tests are therefore necessary. However, new diagnostic tools, such as the basophil activation test (BAT), have been developed and are still under validation. Their routine use could increase the sensitivity of diagnostic work-ups, thus reducing the need for drug provocation tests and filling the gap between the high number of non-allergic drug allergy suspicions and the lack of specialized centres in all countries, which would enable confirmation or elimination of the diagnosis. There is evidence now that the BAT can contribute to the diagnosis of anaphylactic reactions due to several drugs, particularly muscle relaxants and b-lactams [6, 7]. At present, the most commonly used antigens in BATs are CD63 and CD203c. CD63, the gp53 or lysosyme-associated membrane protein (LAMP)-3, is one of the most reported markers for flow cytometric determination of basophil activation. CD63 is deeply anchored into the basophilic intracytoplasmic granules and is generally weakly expressed on the surface of basophils, monocytes, macrophages and platelets. In cases of allergic inflammation, as a result of fusion between the granule and the plasma membrane, CD63 is expressed with a high density on activated basophils and mirrors histamine release [8]. This up-regulated expression of basophilic CD63 can be detected by multi-colour flow cytometry using specific monoclonal antibodies [9]. As far as b-lactams are concerned, the CD63-based BAT was first evaluated in two studies [7, 10] including, respectively, 58 and 70 patients with immediate reactions to these antibiotics. BAT sensitivity was about 50% and specificity was over 90%. However, unlike the study by Sanz et al. [7], the one by Torres et al. [10] assessed not only patients with positive histories and positive skin tests and/or CAP-FEIA but also patients negative to both these tests and positive to challenges. It is interesting to note that one of the seven patients of the latter group was BAT positive. This group of patients with true allergy and negative skin tests is of crucial importance. They account for up to 33% of b-lactam-allergic patients and are only diagnosed by potentially harmful and cumbersome oral provocation tests [11]. Another more basophil-specific marker, CD203c (neural cell surface differentiation antigen E-NPP3, ecto-nucleotide pyrophosphatase/phosphodiesterase 3), is a multifunctional ectoenzyme exclusively and constitutively expressed on the surface of basophils [12]. Five years Correspondence: Prof. Pascal Demoly, Allergy Department, Hopital Arnaud de Villeneuve, University Hospital of Montpellier and Inserm U657, 34295 Montpellier, Cedex 5, France. E-mail: pascal.demoly@inserm.fr doi: 10.1111/j.1365-2222.2008.02981.x Clinical and Experimental Allergy, 38, 869–871

Fréquence de l’allergie à la pénicilline autodéclarée dans le département de Seine-Saint-Denis

Purpose Penicillin allergy is a well-known notion among the general population. Because it is rarely questioned, many patients carry this label unnecessarily and cannot use this efficient and cheap antibiotic family. In previous studies, 8–10% subjects declare a penicillin allergy. But these data came mainly from studies done in hospitals and we found interesting to evaluate a general non-hospitalised population. Methods We set up a study in ambulatory patients of Seine-Saint-Denis (French geographic area in the north east of Paris). It was a transversal study, on a single day, in March 2005. Hundred general practitioners were randomised in this geographic area. All their patients from that day were included and were asked to complete a simple questionnaire. Results Among 1057 patients who participated, 99 (9.4%) declared to be allergic to penicillin. Penicillin A was the most cited antibiotic. The most frequently reported clinical manifestations were skin rash (58.6%) and 13 patients (13.1%) reported some severe signs (coma or emergency hospitalisation) of which 11 were anaphylactic shock; eight patients (8.8%) reported digestive signs less compatible with an allergic mechanism. Asthma and eczema appeared to be significantly reported to penicillin allergy in our population sample. Conclusion The percentage of self-declared allergy found in this study is similar to previous publications. Among penicillins, Penicillin A is the most frequently involved. This study also shows the importance of meticulously questioning patients as it can correct a false diagnosis of penicillin allergy.

Allergy to beta-lactams in pediatrics: a practical approach

To present a practical approach to the diagnosis and management of allergy to beta-lactam antibiotics. Allergy journals indexed in MEDLINE and LILACS, as well as seminal studies and texts. Allergy to penicillin is commonly reported. In many cases, this results in the decision not to use this drug. About 10% of drug allergy reports are confirmed. The clinical manifestations due to allergic reaction to penicillin vary widely, with emphasis on skin disorders. Gell & Coombs' four hypersensitivity mechanisms are involved in allergic reactions. Penicillin is degraded to a major (95%) and minor determinants (5%). Immediate IgE-mediated reactions causing anaphylaxis are associated with minor determinants in 95% of the cases. Hypersensitivity to these products can be assessed using cutaneous tests performed with major and minor determinants, thus avoiding anaphylactic shock in allergic individuals. The present article underscores the basic body of knowledge on allergy to penicillin, providing support for a more accurate diagnosis of this event and for the choice of management in cases of suspected beta-lactam allergy. The incorrect diagnosis of penicillin allergy frequently leads to the exclusion of this drug as a therapeutic option. A better recognition of these situations will enable the use of penicillin and reduce the risks associated with hypersensitivity.

Alergia a beta-lactâmicos na clínica pediátrica: uma abordagem prática

OBJETIVO: Apresentar uma abordagem pratica ao diagnostico e conduta na alergia a antibioticos beta-lactâmicos. FONTES DOS DADOS: Periodicos da area de alergia indexados nas bases MEDLINE e LILACS, alem de estudos e textos classicos que tratam do tema. SINTESE DOS DADOS: A alergia a penicilina e relatada com frequencia, em muitos casos resultando na exclusao desse medicamento do arsenal terapeutico. Cerca de 10% dos relatos de alergia a drogas sao confirmados. As manifestacoes clinicas decorrentes da reacao alergica a penicilina sao bastante amplas, destacando-se os quadros cutâneos. Os quatro mecanismos de hipersensibilidade de Gell & Coombs estao envolvidos nas reacoes alergicas. A penicilina e degradada em determinante maior (95% dos produtos) e em determinantes menores (5% dos produtos). As reacoes imediatas, mediadas por IgE, e que determinam quadros de anafilaxia, estao relacionadas aos determinantes menores em 95% dos casos. A hipersensibilidade a esses produtos pode ser avaliada atraves de testes cutâneos realizados com os determinantes maior e menores, permitindo, assim, evitar o choque anafilatico em individuos alergicos. O texto ressalta conhecimentos basicos sobre a alergia a penicilina, propiciando um diagnostico mais adequado desse evento e a conduta em casos de suspeita de alergia a beta-lactâmicos. CONCLUSAO: O diagnostico de alergia a penicilina tem sido feito de forma inadequada, resultando em sua exclusao do arsenal terapeutico. O melhor reconhecimento dessas condicoes permitira o uso da penicilina com diminuicao dos riscos decorrentes da hipersensibilidade.

Importance of repeat testing in the diagnosis of penicillin allergy

Conflicts of interest: none declared. Sir, In the May 2005 issue of this Journal Lammintausta and Kortekangas‐Savolainen1 presented an interesting article about the usefulness of skin tests in determining drug hypersensitivity. We have found the results to be very helpful as there are only few reported works about the prevalence of positive skin tests in the context of allergic reactions. However, we have some points of contention. Although both patch tests (PTs) and intradermal tests (IDTs) are used for the diagnosis of nonimmediate reactions to aminopenicillins, and both tests appear to be valuable, delayed‐reading IDTs appear to be somewhat more sensitive2 than PTs, but also less specific.3 In the report by Lammintausta and Kortekangas‐Savolainen, beta‐lactam antibiotics were the drugs more often suspected and tested. However, IDTs with major and minor determinants were carried out only in 31 of 342 patients with suspected penicillin allergy and none of them elicited a positive reaction. The European Network for Drug Allergy (ENDA) recommends testing in most patients in whom penicillin allergy is suspected.4 In fact, most diagnoses of penicillin allergy have recently been reported to be obtained by means of the IDT.5, 6 Between January 2002 and June 2005 we evaluated 604 patients with suspected beta‐lactam allergy. In all of them, after written informed consent, skin prick tests and IDTs were performed with benzylpenicilloyl polylysine (PPL), minor determinants mixture (MDM; including benzylpenicillin, benzylpenicilloic acid and sodium benzylpenicilloate), penicillin G and the suspect drug if it was other than penicillin. PPL and MDM were purchased from two different companies (Allergopen®; Allergopharma, Reinbeck, Germany and Diater SA, Madrid, Spain). If the skin tests were negative, controlled drug challenge was performed under strict supervision. After 15 days the skin tests and drug challenge were repeated, as recommended by ENDA.4 After completing the study, 66 patients were diagnosed with beta‐lactam allergy, 60 by skin testing and 10 of those in the repeat tests. From 1108 challenges with beta‐lactams in 554 patients, there were only six positives following a previously negative skin test.

Basophilenaktivierungstests in der Diagnostik von Arzneimittelreaktionen

Over the past 10 years a number of studies on basophil activation tests (BAT) have been published which focus on their use as diagnostic methods in clarifying IgE-mediated hypersensitivity reactions to various allergens including drugs. These BAT are based on flow cytometric quantification of allergen- induced CD63 or CD203 expression or measurement of sulfo leukotriene release by ELISA. In the diagnosis of penicillin allergy, the combined use of the CD63-BAT and specific IgE increases sensitivity. The role of BAT in the diagnosis of non-IgE-mediated reactions to non-steroidal anti- inflammatory drugs remains to be clarified. This article focuses on (1) the principles of BAT, (2) technical aspects, (3) clinical applications and (4) recommendations for further development.

Skin tests in the diagnosis of penicillin allergy

Skin tests in the diagnosis of penicillin allergy

Utility of major and minor determinants in the diagnosis of penicillin allergy

Utility of major and minor determinants in the diagnosis of penicillin allergy

The rational clinical examination. Is this patient allergic to penicillin? An evidence-based analysis of the likelihood of penicillin allergy.

Clinicians frequently withhold antibiotics that contain penicillin based on patients' self-reported clinical history of an adverse reaction to penicillin and the clinicians' own misunderstandings about the characteristics of a true penicillin allergy. To determine the likelihood of true penicillin allergy with consideration of clinical history and to evaluate the diagnostic value added by appropriate skin testing. MEDLINE was searched for relevant English-language articles dated 1966 to October 2000. Bibliographies were searched to identify additional articles. We included original studies describing the precision of skin testing in diagnosis of penicillin allergy. We excluded studies that did not use both minor and major determinants, provide an explicit definition of penicillin allergy, or list the specific criteria necessary for a positive skin test result. Fourteen studies met the inclusion criteria. Three authors independently reviewed and abstracted data from all articles and reached consensus about any discrepancies. Patients' self-reported history has low accuracy for diagnosis of true penicillin allergy. By evaluating studies comparing clinical history to the skin test for penicillin allergy among patients with and without a positive history for penicillin allergy, positive and negative likelihood ratios were calculated. History of penicillin allergy had a positive likelihood ratio of 1.9 (95% confidence interval [CI], 1.5-2.5), while absence of history of penicillin allergy had a negative likelihood ratio of 0.5 (95% CI, 0.4-0.6). Only 10% to 20% of patients reporting a history of penicillin allergy are truly allergic when assessed by skin testing. Taking a detailed history of a patient's reaction to penicillin may allow clinicians to exclude true penicillin allergy, allowing these patients to receive penicillin. Patients with a concerning history of type I penicillin allergy who have a compelling need for a drug containing penicillin should undergo skin testing. Virtually all patients with a negative skin test result can take penicillin without serious sequelae.

Lack of allergic cross-reactivity to cephalosporins among patients allergic to penicillins.

There are some contradicting data about clinical allergic cross-reactivity to cephalosporins among patients who have had a previous allergic reaction to penicillins. The purpose of this study was to assess the safety of administering cephalosporins to penicillin-allergic patients. The diagnosis of penicillin allergy was made by positive skin tests to penicillin reagents and/or provocation tests with the penicillin suspected of causing the allergic reaction. To assess the clinical tolerance to cephalosporins, 41 well-characterized penicillin allergic patients diagnosed by positive skin tests and/or provocation tests were challenged with three cephalosporins that do not share the same side chain to the penicillin that induced the reactions: cephazoline, cefuroxime and ceftriaxone. Skin prick and intradermal tests with all cephalosporins tested were negative. All penicillin-allergic patients tolerated therapeutic doses of the three cephalosporins tested (cephazoline, cefuroxime and ceftriaxone) without any ill effect. These results indicate that the risk of suffering from an allergic reaction on administering cephalosporins to penicillin-allergic patients seems to be very low, provided that cephalosporins with a different side chain to the penicillin responsible for the allergic reaction are used.

Assessment of histamine release from basophils in whole blood by benzylpenicilloyl poly-L-lysine in penicillin-sensitized patients.

Histamine release from basophil granulocytes in whole blood by benzylpenicilloyl poly-L-lysine (PPL) was investigated in 7 patients with penicillin allergy. All patients presented with systemic immediate hypersensitivity reactions after i.v. administration of penicillin G. Total histamine (of 7 patients) ranged from 27.5 ng/ml to 62.1 ng/ml (mean 43.2 ng/ml). The spontaneous histamine release ranged from 0.15% to 5.1% (mean 1.8%) of the total content. Addition of PPL in various concentrations resulted in values between 0.8 and 9.6%. Although PPL is a reliable allergen for prick- and intradermal testing in the diagnosis of penicillin allergy--demonstrating a histamine liberation in the skin--the in vitro experiment using the same allergen showed no histamine release above 10%. Using a threshold of 5% out of 7 patients, 4 (57%) would show a positive histamine release. Therefore it might indicate that in penicillin allergy a threshold of 5% must be used. In addition, basophils in whole blood and skin mast cells may be activated differently.