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Guideline on Diagnostic Procedures for Suspected Hypersensitivity to Beta-Lactam Antibiotics

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Guideline on Diagnostic Procedures for Suspected Hypersensitivity to Beta-Lactam Antibiotics published by: guidelines Allergo J Int https://doi.org/10.1007/s40629-019-0100-8 Guideline on diagnostic procedures for suspected hypersensitivity to beta-lactam antibiotics Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) in collaboration with the German Society of Allergology (AeDA), German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Contact Dermatitis Research Group (DKG), the Austrian Society for Allergology and Immunology (ÖGAI), and the Paul-Ehrlich Society for Chemotherapy (PEG) Gerda Wurpts · Werner Aberer · Heinrich Dickel · Randolf Brehler · Thilo Jakob · Burkhard Kreft · Vera Mahler · Hans F. Merk · Norbert Mülleneisen · Hagen Ott · Wolfgang Pfützner · Stefani Röseler · Franziska Ruëff · Helmut Sitter · Cord Sunderkötter · Axel Trautmann · Regina Treudler · Bettina Wedi · Margitta Worm · Knut Brockow © The Author(s) 2019 Electronic supplementary material The online version of this article (https://doi.org/10.1007/s40629-019-0100-8) contains supplementary material, which is available to authorized users. Dr. G. Wurpts () · H. F.Merk · S. Röseler V. Ma h l e r Clinic for Dermatology and Allergology, Aachen Paul-Ehrlich Institute, Langen, Germany Comprehensive Allergy Center (ACAC), Uniklinik RWTH Department of Dermatology, University Hospital Erlangen, Aachen, Pauwelsstraße 30, 52074 Aachen, Germany Erlangen, Germany [email protected] N. Mülleneisen W. Aberer Asthma and Allergy Centre, Leverkusen, Germany Department of Dermatology, Graz Medical University, Graz, Austria H. Ott Division of Pediatric Dermatology and Allergology, Auf der H. Dickel Bult Children’s Hospital, Hannover, Germany Department of Dermatology, Venereology and Allergology, St. Josef Hospital, University Hospital of the Ruhr University W. Pfützner Bochum, Bochum, Germany Department of Dermatology and Allergology, University Hospital Gießen und Marburg, Marburg Site, Marburg, R. Brehler Germany Department of Dermatology, University Hospital Münster, Münster, Germany F.Ruëff Department of Dermatology and Allergy, University T. Jakob Hospital, LMU Munich, Munich, Germany Department of Dermatology and Allergology, University Hospital Gießen und Marburg, Gießen Site, Gießen, H. Sitter Germany Institute of Surgical Research, Philipps University Marburg, Marburg, Germany B. Kreft · C. Sunderkötter Department of Dermatology and Venereology, University A. Trautmann Hospital Halle (Saale), Halle (Saale), Germany Department of Dermatology and Allergy, Allergy Center Mainfranken, University Hospital Würzburg, Würzburg, Germany K Guideline on diagnostic procedures for suspected hypersensitivity to beta-lactam antibiotics guidelines Abstract This guideline on diagnostic procedures for Here again, further studies are required to extend the suspected beta-lactam antibiotic (BLA) hypersensi- present state of knowledge. Performing allergy testing tivity was written by the German and Austrian pro- for suspected BLA hypersensitivity is urgently rec- fessional associations for allergology, and the Paul- ommended not only in the interests of providing the Ehrlich Society for Chemotherapy in a consensus patient with good medical care, but also due to the procedure according to the criteria of the German immense impact of putative BLA allergies on society Association of Scientific Medical Societies. BLA such as a whole. as penicillins and cephalosporins represent the drug group that most frequently triggers drug allergies. Keywords Beta-lactam antibiotics · Allergy · However, the frequency of reports of suspected al- Penicillin·Cephalosporin·Drughypersensitivity lergy in patient histories clearly exceeds the number of confirmed cases. The large number of suspected Abbreviations BLA allergies has a significant impact on, e.g., the AGEP Acute generalized exanthematous pus- quality of treatment received by the individual patient tulosis and the costs to society as a whole. Allergies to BLA AMP Ampicillin are based on different immunological mechanisms AX Amoxicillin and often manifest as maculopapular exanthema, BAT Basophil activation test as well as anaphylaxis; and there are also a num- BL Beta-lactams ber of less frequent special clinical manifestations of BLA Beta-lactam antibiotic/beta-lactam an- drug allergic reactions. All BLA have a beta-lactam tibiotics ring. BLA are categorized into different classes: peni- BP Benzylpenicillin cillins, cephalosporins, carbapenems, monobactams, BPO Benzyl penicilloyl and beta-lactamase inhibitors with different chemi- BP-OL Benzylpenicilloyl octa-L-lysine cal structures. Knowledge of possible cross-reactiv- CAST Cellular allergen stimulation test ity is of considerable clinical significance. Whereas CAST-ELISA Cellular antigen stimulation test-en- allergy to the common beta-lactam ring occurs in zyme linked immunosorbent assay only a small percentage of all BLA allergic patients, CLV Clavulanic acid cross-reactivity due to side chain similarities, such DIHS Drug-induced hypersensitivity syn- as aminopenicillins and aminocephalosporins, and drome even methoxyimino cephalosporins, are more com- DPT Drug provocation test mon. However, the overall picture is complex and DRESS Drug reaction with eosinophilia and its elucidation may require further research. Diag- systemic symptoms nostic procedures used in BLA allergy are usually EM Erythema multiforme made up of four components: patient history, labo- ELISpot Enzyme linked immunosorbent spot ratory diagnostics, skin testing (which is particularly assay important), and drug provocation testing. The di- FDE Fixed drug eruption agnostic approach—even in cases where the need FEIA Fluorescence enzyme immunoassay to administer a BLA is acute—is guided by patient HRT Histamine release test history and risk–benefit ratio in the individual case. HSA Human serum albumin IDT Intradermal test IgE Immunoglobulin E IFN-γ Interferon-gamma IL Interleukin R. Treudler LTT Lymphocyte transformation test Department of Dermatology, Venereology, and MD(M) Minor determinant (mixture) Allergology and Leipzig Interdisciplinary Center for MPE Maculopapular exanthema Allergology—LICA-CAC, University of Leipzig, Leipzig, Germany MRSA Methicillin-resistant Staphylococcus aureus B. Wedi NORA Network of severe allergic reactions Department of Dermatology and Allergy, Comprehensive NPV Negative predictive value Allergy Center, Hannover Medical School, Hannover, Germany PA Penicillenic acid PPL Benzylpenicilloyl poly-L-lysine M. Worm RAST Radioallergosorbent test Department of Dermatology, Venereology, and Allergology, SDRIFE Symmetrical drug-related intertrigi- Charité University Hospital Berlin, Allergy Center Charité (ACC), Berlin, Germany nous and flexural exanthema sIgE Specific immunoglobulin E K. Brockow SJS Stevens-Johnson syndrome Department of Dermatology and Allergology am TEN Toxic epidermal necrolysis Biederstein, School of Medicine, Technical University of Munich, Munich, Germany VRE Vancomycin-resistant enterococci Guideline on diagnostic procedures for suspected hypersensitivity to beta-lactam antibiotics K guidelines Aim of diagnostic procedures in suspected BLA quently used as in the past and has been superseded allergies by aminopenicillins in terms of trigger frequency. Cephalosporins also frequently cause immediate re- The aim of allergy testing is to establish whether actions. Likewise, clavulanic acid has recently been a patient with a history of hypersensitivity reaction reported as a trigger of allergic reactions [1, 8–10]. to BLA actually has an allergy. Knowing that they Impact: The high number of BLA allergies reported have a confirmed allergy would protect the allergic in patient histories hampers treating physicians to patients from further allergic reactions. A progno- a significant extent to select an appropriate antibi- sis shall be given, which antibiotics not have to be otic. Patients are often unable to receive the antibi- avoided in the future, and the current hypersensi- otic of first choice and physicians are forced to resort tivity shall be investigated. to broad-spectrum antibiotics in many cases [11–13]. Qualified allergy testing in patients with a history The treatment costs for patients with a history of BLA allergytooneormoreBLAmakesitpossibletose- allergy are higher than for those of non-allergic pa- lect tolerated BLA antibiotics for affected patients tients. The reasons for this include, e.g., the higher in order to more effectively treat bacterial infec- cost of broad-spectrum antibiotics and a higher num- tions. This enables patients to be more frequently ber of hospital days in this patient group [7, 13, 14]. treated with the antibiotic of first choice. An infec- Moreover, the greater use of broad-spectrum an- tion requiring treatment can be better controlled, tibiotics increases bacterial resistance [15], mediated resulting in the faster recovery of the patient and in particular by “collateral damage”. This term refers fewer infection-related sequelae, not least in terms to the suppression of the normal flora and the se- of patients’ life expectancy. lection of antibiotic-resistant microorganisms even at Targeted treatment of infections reduces the use sites far from the actual infection, e.g., in the region of broad-spectrum antibiotics, and thus also the of the intestines colonized by bacteria [16]. Thus, selection of resistant bacteria. Antibiotic resistance patients with an—unconfirmed—history of BLA al- can be reduced. lergy more frequently exhibited colonization or infec- The cost to the population as
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