Elsevier

The Lancet

Volume 393, Issue 10167, 12–18 January 2019, Pages 183-198
The Lancet

Review
Antibiotic allergy

https://doi.org/10.1016/S0140-6736(18)32218-9Get rights and content

Summary

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.

Introduction

Antibiotics can result in adverse drug reactions (ADRs) and hypersensitivity reactions (HSRs) through a variety of mechanisms. Antibiotic allergies are frequently documented in the electronic health record, which results in changes to the care of future infectious diseases. Inaccurately determined allergies might result in the use of unnecessarily broad-spectrum or inferior antibiotics, posing a threat to patient safety and public health. Despite these threats, the histories associated with documented allergies are rarely reconciled, or acted on, by the health-care team. Ideally, patients at low risk for allergy would have their allergy evaluated without specialist intervention, and high-risk patients would be referred for allergy diagnostic testing and have potential reaction mechanism(s) implicated. Although some allergy investigations are validated diagnostic tests approved by governing bodies globally, many tests for immunologically mediated drug hypersensitivity remain under investigation.

In this Review, we provide a global perspective on antibiotic allergies, with a focus on updated classification, epidemiology, effect on public health, diagnosis, and management. We also advise on the crucial steps required to appropriately combat unverified penicillin allergy labels as an emergent threat for individuals and public health.

Section snippets

Classification, presentation, and mechanism

ADRs include any untoward medication effect experienced at normal therapeutic doses of the drug, and HSRs are ADRs that are immunologically mediated. As our mechanistic understanding of ADRs improves, limitations of previous ADR classifications have become apparent. Consequently, a high-level classification of on-target and off-target reactions, with further categorisation of off-target immune and non-immune reactions has been proposed (figure 1).2, 3 Both on-target and off-target effects can

Adverse drug reactions and hypersensitivity reactions

ADRs account for more than 3% of hospital admissions16 and complicate the inpatient care of 10–20% of hospitalised patients.17, 18 Drug HSRs comprise up to 20% of ADRs and are reported in approximately 8% of general populations.19, 20 Cutaneous reactions, including rash and hives, are the most commonly reported HSRs.21, 22 Although most patients are labelled with an antibiotic allergy at the time of hospital admission, new onset cutaneous HSRs were found to affect approximately 2% of inpatients.

Unverified antibiotic allergy labels

Most patients labelled with a β-lactam allergy are not allergic (ie, they tolerate penicillin and related drugs).57 This mislabel occurs for a variety of reasons. First, the original reaction might not have been an allergy (there could be intolerance, a viral exanthem, or a drug-infection interaction). Even if the original reaction were immunological, it might not recur with re-challenge. IgE-mediated reactions to β-lactams can wane over time; approximately 80% of patients who are positive for

Effect of antibiotic allergy labels

Precise assessment and subsequent documentation of antibiotic allergies is a key mechanism to ensure patients do not receive a medication to which they are allergic. However, most allergy labels are untrue and less than 1% of reported antibiotic allergies globally are interrogated through allergy evaluation methods, despite known negative consequences of allergy mislabels for patients, health-care systems, and communities.

Diagnosis and management of suspected hypersensitivity

The evaluation of patients with antibiotic allergies begins with an allergy history that includes symptom details, timing of reaction, timing since reaction, treatment of the reaction, and relevant ingestions concurrent with, and since, the reaction. When relevant, review of historical details, such as: rash description, photos, and biopsy; concomitant medication list; concomitant diagnoses; laboratory; and imaging details should be obtained. Although allergy specialists widely agree on these

A global call for action

Although penicillin allergy evaluations are recognised as important by a variety of government bodies, foundations, and professional organisations,91, 120, 121, 122 there is no standard approach to penicillin allergy evaluation or documentation. However, a systematic approach to remove the penicillin allergy label is now warranted.

Global implementation of penicillin allergy evaluations must be supported on an international scale to improve the quality and safety of health care delivered to

Conclusions

Although antibiotic ADRs are commonly reported, immunologically mediated hypersensitivity is uncommon and true IgE-mediated antibiotic allergy is verified in only a small minority. For those with true antibiotic HSRs, appropriate specialty assessment is indicated to prevent future ADR-related morbidity and mortality. This assessment includes defining the most likely drug implicated in the allergic reaction, the probable mechanism(s), and the potential cross-reactive drugs that should be avoided

Search strategy and selection criteria

We searched MEDLINE from Jan 1, 2005, to April 30, 2018, but did not exclude commonly referenced landmark articles published before 2005. Primary search terms included: “drug“, “antibiotics”, “drug-induced”, “penicillin”, “beta-lactam”, “sulfonamide”, “nevirapine”, “abacavir”, “antiretroviral”, “rifampin”, “rifamycin”, “vancomycin”, “fluoroquinolone”, “anesthesia”, “itch”, “erythema”, “pruritus”, “rhinitis”, “wheezing”, “urticaria”, “hive”, “angioedema”, “edema”, “swelling”, “anaphylaxis”,

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