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Antibiotics are the commonest cause of life-threatening immune-mediated drug reactions that are considered off-target, including anaphylaxis, and organ-specific and severe cutaneous adverse reactions. However, many antibiotic reactions documented as allergies were unknown or not remembered by the patient, cutaneous reactions unrelated to drug hypersensitivity, drug-infection interactions, or drug intolerances. Although such reactions pose negligible risk to patients, they currently represent a global threat to public health. Antibiotic allergy labels result in displacement of first-line therapies for antibiotic prophylaxis and treatment. A penicillin allergy label, in particular, is associated with increased use of broad-spectrum and non-β-lactam antibiotics, which results in increased adverse events and antibiotic resistance. Most patients labelled as allergic to penicillins are not allergic when appropriately stratified for risk, tested, and re-challenged. Given the public health importance of penicillin allergy, this Review provides a global update on antibiotic allergy epidemiology, classification, mechanisms, and management., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Idiosyncratic drug reactions are unpredictable reactions that can result in significant morbidity and mortality. Severe reactions are often characterised by fever and internal organ involvement. Despite progress in the identification of reactive metabolites believed to be the cause of idiosyncratic reactions, the basic mechanisms remain elusive. Furthermore, because of the lack of consensus regarding definition of these syndromes, reporting, and therefore epidemiological data, are often unreliable. Research is needed to explore further the pathophysiology of these reactions, so that better diagnostic tests and treatment methods can be developed.

Physicians are often confronted with patients who state that they are "allergic" to a drug or drugs. Knowing which medications can be prescribed safely is therefore difficult, and care of such patients frustrating. The goal of this review is to help physicians develop management plans for patients who present with drug-induced diseases. It provides information that allows physicians to differentiate between reactions that are truly allergic in nature and those that are not immunologically mediated. Relevant information on medical history, physical findings, and laboratory tests that may be helpful in the assessment are discussed, and guidance is provided on when and if a drug may be safely readministered. Unfortunately, however, until we are able to better understand the mechanisms responsible for drug-induced reactions, our management tools will remain limited.