Multisite Oral Amoxicillin Challenges During Pediatric Emergency Department Visits.

This cohort study assesses differences in children's allergy risk level designation and results of a direct oral challenge via a penicillin allergy delabeling process.

A potential cost savings analysis of a penicillin de-labeling program.

Introduction: Over 95% of patients documented as penicillin allergic can tolerate a penicillin without a reaction. Inaccurate documentation of penicillin allergy leads to more expensive alternative antibiotic prescriptions and an increased incidence of resistant infections. Objective: To understand the potential drug cost savings of a penicillin de-labeling program to a healthcare system. Methods: We evaluated patient visits with documented penicillin allergy who presented to the pediatric Emergency Department (PED) and 22 associated primary care clinics. Patients were included if they were discharged home with a non-penicillin antibiotic when the first-line treatment for the diagnosis would have been a penicillin. The potential cost savings were the sum of all visit-level cost differences between the non-penicillin prescription(s) and a counterfactual penicillin prescription. To factor in a 95% successful patient de-labeling rate, we repeatedly sampled 95% from the patients with the eligible visits 10,000 times to produce an estimate of the potential cost savings. Results: Over the 8-year period, 2,034 visits by 1,537 patients to the PED and 12,349 visits by 6,073 patients to primary care clinics satisfied eligibility criteria. If 95% of the patients could have been successfully de-labeled, it would have generated a cost saving of $618,653 (95% CI $618,617-$618,689) for all the corresponding payers in the system. Conclusions: Implementing a penicillin de-labeling program across a healthcare system PED and its associated primary care clinics would bring significant cost savings. Healthcare systems should rigorously evaluate optimal methods to de-label patients with reported penicillin allergy.

Parental perspective on penicillin allergy delabeling in a pediatric emergency department.

BACKGROUND: Penicillin (PCN) allergy is frequently mislabeled and inaccurately diagnosed in children. Successful implementation of pediatric emergency department (PED) delabeling efforts requires parental understanding and willingness for children to be delabeled as PCN-nonallergic. OBJECTIVE: To describe the parental perspective on allergy delabeling in the PED for children identified as low risk for true PCN allergy. METHODS: This is a cross-sectional survey of parents of children with documented PCN allergy presenting to a single tertiary-care PED. Parents were first approached to complete a PCN allergy identification questionnaire to stratify their child as high- or low-risk for true PCN allergy. Facilitators and barriers to PED-based oral challenge and delabeling were subsequently assessed by parents of low-risk children. RESULTS: A total of 198 participants completed the PCN identification questionnaire. Of 198 children, 49 (25%) screened low risk for true PCN allergy. Of the 49 low-risk children, 29 (59%) parents were uncomfortable with a PED-based PCN oral challenge. Reasons include fear of allergic reaction (72%), availability of adequate alternative antibiotics (45%), and longer PED stay (17%). Reasons for willingness to delabel included PCN's low adverse effect profile (65%) and avoidance of antimicrobial resistance from alternative antibiotics (74%). Participants without a family history (FH) of PCN allergy were more comfortable with PED-based PCN oral challenge (60% vs 11%; P = .001) and delabeling (67% vs 37%; P = .04) compared with those with FH. CONCLUSION: Most parents of children with low-risk PCN allergy are uncomfortable with oral challenge or delabeling in the PED. Before implementing oral challenges in PEDs, efforts should be made to highlight the safety of oral challenging low-risk children, the benefits and risks of alternative antibiotics, and the minimal impact that FH has on PCN allergy.

Management of Children with Reported Penicillin Allergies.

Penicillin allergy is the most commonly reported medication allergy. Reported allergy is associated with increased morbidity and mortality. Risk categorization tools can help determine the optimal testing strategies to delabel patients with reported allergy. Approaches to allergy removal include oral challenge in low-risk patients and skin testing in high-risk patients. Many different locations may be used to test for allergy, including ambulatory care clinics, inpatient units, and emergency departments. Interventions (eg, use of the electronic medical record) are needed to ensure that once the allergy is removed, this information is effectively transmitted to the patient and appropriate providers.

Anaphylaxis knowledge gaps and future research priorities: A consensus report.

BACKGROUND: Despite a better understanding of the epidemiology, pathogenesis, and management of patients with anaphylaxis, there remain knowledge gaps. Enumerating and prioritizing these gaps would allow limited scientific resources to be directed more effectively. OBJECTIVE: We sought to systematically describe and appraise anaphylaxis knowledge gaps and future research priorities based on their potential impact and feasibility. METHODS: We convened a 25-member multidisciplinary panel of anaphylaxis experts. Panelists formulated knowledge gaps/research priority statements in an anonymous electronic survey. Four anaphylaxis themed writing groups were formed to refine statements: (1) Population Science, (2) Basic and Translational Sciences, (3) Emergency Department Care/Acute Management, and (4) Long-Term Management Strategies and Prevention. Revised statements were incorporated into an anonymous electronic survey, and panelists were asked to rate the impact and feasibility of addressing statements on a continuous 0 to 100 scale. RESULTS: The panel generated 98 statements across the 4 anaphylaxis themes: Population Science (29), Basic and Translational Sciences (27), Emergency Department Care/Acute Management (24), and Long-Term Management Strategies and Prevention (18). Median scores for impact and feasibility ranged from 50.0 to 95.0 and from 40.0 to 90.0, respectively. Key statements based on median rating for impact/feasibility included the need to refine anaphylaxis diagnostic criteria, identify reliable diagnostic, predictive, and prognostic anaphylaxis bioassays, develop clinical prediction models to standardize postanaphylaxis observation periods and hospitalization criteria, and determine immunotherapy best practices. CONCLUSIONS: We identified and systematically appraised anaphylaxis knowledge gaps and future research priorities. This study reinforces the need to harmonize scientific pursuits to optimize the outcomes of patients with and at risk of anaphylaxis.

Skin Testing for Penicillin Allergy: a Review of the Literature.

PURPOSE OF REVIEW: Self-reported penicillin allergies are frequently reported, though more than 95% of those are not truly allergic when challenged. These patients are more likely to receive alternative antibiotic regimens resulting in the use of broad-spectrum antibiotics that may be less effective, more toxic, and/or more expensive than preferred agents. Given the significant burden on patient outcomes and the healthcare system, the ability to reconcile an allergy and broaden future antibiotic options is essential. RECENT FINDINGS: This is a narrative review describing risk stratification for penicillin skin testing, practical advice for implementation, and future directions. A summary of studies within the last 5 years is provided. The trend over the past several years has been to offer oral drug challenges to low-risk patients and skin testing to high-risk patients with a reported penicillin allergy. This review provides support for risk stratification assessment of reported penicillin allergy to optimize antibiotic use and prevent emergence of antimicrobial resistance.

Severity grading system for acute allergic reactions: A multidisciplinary Delphi study.

BACKGROUND: There is no widely adopted severity grading system for acute allergic reactions, including anaphylactic and nonanaphylactic reactions, thus limiting the ability to optimize and standardize management practices and advance research. OBJECTIVE: The aim of this study was to develop a severity grading system for acute allergic reactions for use in clinical care and research. METHODS: From May to September 2020, we convened a 21-member multidisciplinary panel of allergy and emergency care experts; 9 members formed a writing group to critically appraise and assess the strengths and limitations of prior severity grading systems and develop the structure and content for an optimal severity grading system. The entire study panel then revised the grading system and sought consensus by utilizing Delphi methodology. RESULTS: The writing group recommended that an optimal grading system encompass the severity of acute allergic reactions on a continuum from mild allergic reactions to anaphylactic shock. Additionally, the severity grading system must be able to discriminate between clinically important differences in reaction severity to be relevant in research while also being intuitive and straightforward to apply in clinical care. Consensus was reached for all elements of the proposed severity grading system. CONCLUSION: We developed a consensus severity grading system for acute allergic reactions, including anaphylactic and nonanaphylactic reactions. Successful international validation, refinement, dissemination, and application of the grading system will improve communication among providers and patients about the severity of allergic reactions and will help advance future research.

PEMCRC anaphylaxis study protocol: a multicentre cohort study to derive and validate clinical decision models for the emergency department management of children with anaphylaxis.

INTRODUCTION: There remain significant knowledge gaps about the management and outcomes of children with anaphylaxis. These gaps have led to practice variation regarding decisions to hospitalise children and length of observation periods following treatment with epinephrine. The objectives of this multicentre study are to (1) determine the prevalence of and risk factors for severe, persistent, refractory and biphasic anaphylaxis, as well as persistent and biphasic non-anaphylactic reactions; (2) derive and validate prediction models for emergency department (ED) discharge; and (3) determine data-driven lengths of ED and inpatient observation prior to discharge to home based on initial reaction severity. METHODS AND ANALYSIS: The study is being conducted through the Pediatric Emergency Medicine Collaborative Research Committee (PEMCRC). Children 6 months to less than 18 years of age presenting to 30 participating EDs for anaphylaxis from October 2015 to December 2019 will be eligible. The primary outcomes for each objective are (1) severe, persistent, refractory or biphasic anaphylaxis, as well as persistent or biphasic non-anaphylactic reactions; (2) safe ED discharge, defined as no receipt of acute anaphylaxis medications or hypotension beyond 4 hours from first administered dose of epinephrine; and (3) time from first to last administered dose of epinephrine and vasopressor cessation. Analyses for each objective include (1) descriptive statistics to estimate prevalence and generalised estimating equations that will be used to investigate risk factors for anaphylaxis outcomes, (2) least absolute shrinkage and selection operator regression and binary recursive partitioning to derive and validate prediction models of children who may be candidates for safe ED discharge, and (3) Kaplan-Meier analyses to assess timing from first to last epinephrine doses and vasopressor cessation based on initial reaction severity. ETHICS AND DISSEMINATION: All sites will obtain institutional review board approval; results will be published in peer-reviewed journals and disseminated via traditional and social media, blogs and online education platforms.

Penicillin Allergy Delabeling: A Multidisciplinary Opportunity.

The penicillin allergy label has been consistently linked with deleterious effects that span the health care spectrum, including suboptimal clinical outcomes, the emergence of bacterial resistance, and increased health care expenditures. These risks have recently motivated professional organizations and public health institutes to advocate for the implementation of penicillin allergy delabeling initiatives; however, the burden of delabeling millions of patients is too expansive for any one discipline to bear alone. This review presents the unique perspectives and roles of various stakeholder groups involved in penicillin allergy diagnosis, assessment, and delabeling; we emphasize opportunities, barriers, and promising areas of innovation. We summarize penicillin allergy methods and tools that have proven successful in delabeling efforts. A multidisciplinary approach to delabeling patients with reported penicillin allergy, bolstered by evidence-based clinical practices, is recommended to reduce the risks that associate with the penicillin allergy label.

Persistent, refractory, and biphasic anaphylaxis: A multidisciplinary Delphi study.

BACKGROUND: The use of inconsistent definitions for anaphylaxis outcomes limits our understanding of the natural history and epidemiology of anaphylaxis, hindering clinical practice and research efforts. OBJECTIVE: Our aim was to develop consensus definitions for clinically relevant anaphylaxis outcomes by utilizing a multidisciplinary group of clinical and research experts in anaphylaxis. METHODS: Using Delphi methodology, we developed agenda topics and drafted questions to review during monthly conference calls. Through online surveys, a 19-member panel consisting of experts in allergy and/or immunology and emergency medicine rated their level of agreement with the appropriateness of statements on a scale of 1 to 9. A median value of 1.0 to 3.4 was considered inappropriate, a median value of 3.5 to 6.9 was considered uncertain, and a median value of 7.0 to 9.0 was considered appropriate. A disagreement index was then calculated, with values less than 1.0 categorized as "consensus reached." If consensus was not reached after the initial survey, subsequent surveys incorporating the aggregate de-identified responses from prior surveys were sent to panel members. This process was repeated until consensus was reached or 4 survey rounds had been completed, after which the question was categorized as "no consensus reached." RESULTS: The panel developed outcome definitions for persistent, refractory, and biphasic anaphylaxis, as well as for persistent and biphasic nonanaphylactic reactions. There was also consensus among panel members regarding the need to develop an anaphylaxis severity grading system. CONCLUSION: Dissemination and application of these definitions in clinical care and research will help standardize the terminology used to describe anaphylaxis outcomes and serve as the foundation for future research, including research aimed at development of an anaphylaxis severity grading system.

Children with reported penicillin allergy: Public health impact and safety of delabeling.

OBJECTIVE: To review the relevant literature related to children with reported penicillin allergy and highlight the different ways in which children could be delabeled and to evaluate the public health impact that a penicillin allergy has for children. DATA SOURCES: Data for this review were obtained via PubMed searches and then retrieval of articles from their respective journals for further review. STUDY SELECTIONS: Studies regarding the safety of different ways to evaluate penicillin allergy in children were identified via PubMed searches. Any study that reported different ways of testing (3-tier, direct oral challenge, 5-day oral challenges) were included. This same format was used when selecting relevant articg:les related to the costs, prescription patterns, and stewardship trends associated with a penicillin allergy label. RESULTS: This review found that penicillin allergy testing is a safe and effective way to delabel those with reported allergy. In children with low-risk allergy symptoms, a direct oral challenge approach may be optimal. In those children with a history of high-risk allergy symptoms, a 3-tiered approach is ideal. The review also found that there is a significant cost associated with reported penicillin allergy and that there are increased negative health benefits to those children with reported allergy. CONCLUSION: Penicillin allergy is overdiagnosed, often incorrectly, and the label is frequently first applied during childhood. Targeting children for the removal of the incorrect penicillin allergy label provides a mechanism to reduce the use of broader-spectrum and less effective antibiotics.

Self-reported beta-lactam intolerance: not a class effect, dangerous to patients, and rarely allergy.

Introduction: About 8% of the United States population carries an unconfirmed penicillin 'allergy' in their medical record. Many physicians needlessly avoid other beta-lactam use in individuals with unconfirmed penicillin allergies. There is a significantly increased risk of developing serious antibiotic-resistant infections, and increased morbidity and mortality in those who report penicillin allergy. Areas covered: Within this study, we reviewed the relevant literature on self-reported beta-lactam allergy. We discuss how the myth of serious allergy to penicillin developed and then discuss and in detail clinically significant immunologically mediated hypersensitivity reactions. Following this discussion, we delineate the risks of not using a beta-lactam when it is the drug of choice and then discuss the epidemiology of beta-lactam-associated anaphylaxis, serious cutaneous adverse reactions, and serious systemic immunologically mediated reactions. Following these topics, we further discuss the consensus current best practices to de-label patients with reported penicillin allergy. Expert opinion: An unconfirmed allergy to penicillin offers considerable harm to patients. Many patients have low-risk allergy symptoms to penicillin who could likely tolerate the medication without having an allergic reaction. The current best practices to de-label reported penicillin allergy is the utilization of a single dose oral challenge, with 1 h of observation, in low-risk patients.

Reported Knowledge and Management of Potential Penicillin Allergy in Children.

BACKGROUND: Pediatric emergency medicine (PEM) and primary care provider (PCP) providers are the most likely physicians to initially label a child as allergic to penicillin. Differences in knowledge and management of reported penicillin allergy between these 2 groups have not been well characterized. METHODS: A cross-sectional, 20-question survey was administered to PEM and PCPs to ascertain differential knowledge and management of penicillin allergy. Knowledge regarding high- and low-risk symptoms for true allergy and extent of history taking regarding allergy were compared between the 2 groups using t tests, Chi-square, and Wilcoxon tests. RESULTS: In total, 182 PEM and 54 PCPs completed the survey. PEM and PCPs reported that 74.1 ± 19.5% and 69.0 ± 23.8% of patients with remote low-risk symptoms of allergy could tolerate penicillin without an allergic reaction. PEM and PCPs incorrectly identified low-risk symptoms of allergy as high-risk, including vomiting with medication administration and delayed skin rash. PCPs took more detailed allergy histories when compared with PEM providers. In total, 143 (78.5%) of PEM providers and 51 (94.4%) PCPs were interested in using a penicillin allergy questionnaire to segregate children into high- or low-risk categories. CONCLUSIONS: Most pediatric providers believe that children with a remote history of low-risk allergy symptoms could tolerate penicillin without an allergic reaction; however, this is infrequently acted upon. Both PEM and PCP providers were likely to classify low-risk symptoms as high-risk and infrequently referred children for further detailed allergy assessment. Both groups were receptive to decision support measures to facilitate improved penicillin allergy classification and labeling and support antibiotic appropriateness in their patients.

Antibiotic Use After Removal of Penicillin Allergy Label.

BACKGROUND: Penicillin allergy is commonly reported in the pediatric emergency department. We previously performed 3-tier penicillin allergy testing on children with low-risk symptoms, and 100% tolerated a penicillin challenge without an allergic reaction. We hypothesized that no serious allergic reactions would occur after re-exposure to penicillin and that prescription practices would change after testing. METHODS: We performed a follow-up case series of 100 children whose test results were negative for penicillin allergy. Research staff administered a brief follow-up phone survey to the parent and primary care provider of each patient tested. We combined the survey data and summarized baseline patient characteristics and questionnaire responses. We then completed a 3-tier economic analysis from the prescription information gathered from surveys in which cost savings, cost avoidance, and potential cost savings were calculated. RESULTS: A total of 46 prescriptions in 36 patients were reported by the primary care provider and/or parents within the year after patients were tested for penicillin allergy. Twenty-six (58%) of the prescriptions filled were penicillin derivatives. One (4%) child developed a rash 24 hours after starting the medication; no child developed a serious adverse reaction after being given a penicillin challenge. We found that the cost savings of delabeling patients as penicillin allergic was $1368.13, the cost avoidance was $1812.00, and the total potential cost savings for the pediatric emergency department population was $192 223.00. CONCLUSIONS: Children with low-risk penicillin allergy symptoms whose test results were negative for penicillin allergy tolerated a penicillin challenge without a severe allergic reaction developing. Delabeling children changed prescription behavior and led to actual health care savings.