PENICILLIN ALLERGY DELABELLING IN A PEDIATRIC PRIMARY CARE SETTING

Penicillin allergy labels are the most common drug allergy label. The objective of this study was to describe the quality and management of penicillin allergy labels in the pediatric primary care setting. Retrospective chart review of 500 of 18 015 children with penicillin allergy labels born from January 1, 2010 to June 30, 2020 randomly selected from an outpatient birth cohort from Texas Children's Pediatrics and Children's Hospital of Philadelphia networks. Penicillin allergy risk classification ("not allergy," "low risk," "moderate or high risk," "severe risk," "unable to classify") was determined based on documentation within (1) the allergy tab and (2) electronic healthcare notes. Outcomes of allergy referrals and penicillin re-exposure were noted. Half of penicillin allergy labels were "unable to classify" based on allergy tab documentation. Risk classification agreement between allergy tabs and healthcare notes was fair (Cohen's ĸ = 0.35 ± 0.02). Primary care physicians referred 84 of 500 (16.8%) children to an allergist, but only 54 (10.8%) were seen in allergy clinic. All children who were challenged (25 of 25) passed skin testing. Removal of allergy labels was uncommon (69 of 500, 13.8%) but occurred more often following allergy appointments (26 of 54, 48%) than not (43 of 446, 9.6%, P < .001). Children delabeled by primary care physicians were as likely to tolerate subsequent penicillin-class antibiotics as those delabeled by an allergist (94% vs 93%, P = .87). Penicillin allergy documentation within the allergy tab was uninformative, and children were infrequently referred to allergists. Future quality improvement studies should improve penicillin allergy documentation and expand access to allergy services.

Fewer than 5% of patients labeled with a penicillin allergy are truly allergic. The standard of care to remove the penicillin allergy label in adults is specialized testing involving prick and intradermal skin testing followed by an oral challenge with penicillin. Skin testing is resource intensive, limits practice to specialist-trained physicians, and restricts the global population who could undergo penicillin allergy delabeling. To determine whether a direct oral penicillin challenge is noninferior to the standard of care of penicillin skin testing followed by an oral challenge in patients with a low-risk penicillin allergy. This parallel, 2-arm, noninferiority, open-label, multicenter, international randomized clinical trial occurred in 6 specialized centers, 3 in North America (US and Canada) and 3 in Australia, from June 18, 2021, to December 2, 2022. Eligible adults had a PEN-FAST score lower than 3. PEN-FAST is a prospectively derived and internationally validated clinical decision rule that enables point-of-care risk assessment for adults reporting penicillin allergies. Patients were randomly assigned to either direct oral challenge with penicillin (intervention arm) or a standard-of-care arm of penicillin skin testing followed by oral challenge with penicillin (control arm). The primary outcome was a physician-verified positive immune-mediated oral penicillin challenge within 1 hour postintervention in the intention-to-treat population. Noninferiority was achieved if a 1-sided 95% CI of the risk difference (RD) did not exceed 5 percentage points (pp). A total of 382 adults were randomized, with 377 patients (median [IQR] age, 51 [35-65] years; 247 [65.5%] female) included in the analysis: 187 in the intervention group and 190 in the control group. Most patients had a PEN-FAST score of 0 or 1. The primary outcome occurred in 1 patient (0.5%) in the intervention group and 1 patient (0.5%) in the control group, with an RD of 0.0084 pp (90% CI, -1.22 to 1.24 pp). The 1-sided 95% CI was below the noninferiority margin of 5 pp. In the 5 days following the oral penicillin challenge, 9 immune-mediated adverse events were recorded in the intervention group and 10 in the control group (RD, -0.45 pp; 95% CI, -4.87 to 3.96 pp). No serious adverse events occurred. In this randomized clinical trial, direct oral penicillin challenge in patients with a low-risk penicillin allergy was noninferior compared with standard-of-care skin testing followed by oral challenge. In patients with a low-risk history, direct oral penicillin challenge is a safe procedure to facilitate the removal of a penicillin allergy label. ClinicalTrials.gov Identifier: NCT04454229.

The 2021 AAAAI Foundation Faculty Development awardees

Patients with a penicillin allergy label (PAL) use more and broader-spectrum antibiotics, have worse health outcomes and cost more to treat than patients without a PAL. A significant proportion of penicillin allergy labels are incorrect; here we review the published evidence on the costs, health-related quality of life, and cost-effectiveness of penicillin allergy testing. We conducted a systematic review of published economic evaluations of penicillin allergy testing in accordance with Cochrane guidelines. We searched Medline, Embase, Scopus, Web of Science, EconPapers (RePeC) and the International HTA Database (INAHTA) and included reports of full or partial economic evaluations of costs and/or health benefits of penicillin allergy testing strategies. The outcomes of interest were healthcare resource use, medical costs, and health-related quality of life for patients with a penicillin allergy label and for patients with the label removed, and cost-effectiveness. We evaluated the methodological quality of the studies using a published checklist designed for systematic reviews. The review followed a narrative synthesis. Thirty-six studies met the inclusion criteria. Most studies analysed the effect of testing on the costs of antibiotic use among patients admitted to hospital with a PAL. Studies measured costs of testing (n = 19); antibiotic medication use (n = 23); adverse reactions with penicillin use (n = 4), alternative antibiotic drugs (n = 3); length of hospital stay (n = 5); subsequent health care use episodes (n = 4); and antibiotic medication use in subsequent care episodes (n = 3). The median cost of skin testing plus oral challenge across six primary costing studies was USD 246 (range: 164, 514), which contrasts with the USD 42-258 range of antibiotic cost savings during the initial hospital admission. Two studies presented evidence that penicillin allergy testing is cost-saving in an outpatient setting over 3.5-4.5 years. One model-based study reported that testing in inpatient settings is cost-saving. No reports on the effect of penicillin allergy testing on health-related quality of life were found and the two cost-effectiveness studies that accounted for this outcome employed the opinion of healthcare professional or an assumption of a common generic value for adverse reactions. While penicillin allergy testing shows promise in reducing antibiotic costs, the evidence remains insufficient to definitively establish whether these savings consistently outweigh testing costs across various healthcare settings.

Another Step Forward in the Optimization of Penicillin Allergy Delabeling Strategies in Children

Introduction 2.7 million people are estimated to have a penicillin allergy in United Kingdom but 90% of these people are not allergic.1 In reality, only 1 in 100 patients have a ‘true’ penicillin allergy.2 These patients end up receiving alternative, less effective broad-spectrum antibiotics. This leads to a higher risk of antibiotic resistance, prolonged hospital stays, and increased healthcare costs.3 The root of this issue lies in the confusion between an allergic reaction and side effects. Findings from this audit could be used to inspire substantial cost savings, reduction in unnecessary antibiotic use, improved patient outcomes, and proper antimicrobial stewardship. Aim To undertake an audit with the following criteria and standards, to establish the percentage of patients that have a ‘true’ penicillin allergy as well as checking the accuracy of documentation for penicillin allergies: At least 70% of penicillin-allergic patients will have the nature of allergy documented on the trust’s electronic prescribing (eCare) system; At least 90% of penicillin allergies that are documented on the eCare system will also be documented on the Summary Care Record (SCR) system; 100% of penicillin-allergic patients will not have had penicillin therapy during their current or most recent hospital stay; A penicillin allergy label will be justified by the nature of allergy in at least 90% of patients. Methods This study did not require ethics approval. Data was extracted from the eCare system, consisting of penicillin-allergic patients admitted between 25/1/2023-30/1/2023. Extracted data featured the nature of allergy, reaction status and class, and antibiotic prescribed. A pilot study was undertaken using a day’s worth of data (25/1/2023). The pilot study was successful; therefore, no adjustments were made to the data collection tool. Results 90 patients were included in the study. 63.3% (n=57) of patients had their nature of allergy documented on eCare system. 85.6% (n=77) of patients also had their penicillin allergy documented on SCR. Of the patients taking inpatient antibiotics (n=30), 93.3% (n=28) were not prescribed a penicillin during their hospital stay. 50% (n=45) of patients had a justified penicillin allergy based on the nature of allergy. Discussion/Conclusion None of the four objectives were achieved. This audit study proved that there are fewer patients with a ‘true’ penicillin allergy than expected. More improvement is needed for documenting the nature of allergy on the eCare system as well as justifying penicillin allergy based on the nature of allergy and other relevant factors. This can be actioned by giving training sessions to clinicians, teaching the importance of proper penicillin allergy documentation, creating a new hospital guideline to help deliver a penicillin allergy de-labelling service, and performing a re-audit after 6 months. One limitation of this study was not being able to speak to patients due to time and logistical constraints.

Background: Patients with penicillin allergy have been shown to have suboptimal antibiotics prescribed for infections as well as an increased risk of adverse effects. However, it is currently unknown at what rate patients with penicillin allergy are prescribed antibiotics after hospitalization. Objective: The purpose of this study was to determine the rate at which patients with penicillin allergy are prescribed antibiotics after hospitalization and if this rate differs from that of patients without penicillin allergy. Methods: This was a retrospective case-control study that evaluated subsequent courses of antibiotics after hospitalization in patients with and those without penicillin allergies. Subsequent courses of antibiotics were compared between patients who with penicillin allergy and patients who were not allergic to penicillin for the 15 months after hospitalization by using the incidence rate ratio of new antibiotics prescribed. Results: Patients in the penicillin allergy group received significantly more outpatient antibiotics in the 15 months after hospitalization compared with patients with no penicillin allergy. The incidence rate ratio between the two groups was 1.27 (95% confidence interval, 1.10-1.48); p = 0.0014. There was no difference between the subsequent courses of inpatient antibiotic courses during the same time period. Conclusion: Patients with a penicillin allergy in the current evaluation received significantly more outpatient courses of antibiotics than did the patients without a penicillin allergy. These data provide more evidence for the importance of penicillin allergy de-labeling to provide patients with the most appropriate antibiotics for their respective infections.

Penicillin allergy is the most frequently reported allergy in hospitalized patients, although rarely confirmed. Given the negative outcomes associated with incorrect penicillin allergy diagnoses, implementation of programmatic delabeling strategies is important for successful antibiotic stewardship. This systematic review evaluates the effectiveness of different delabeling strategies and highlights elements and settings that facilitate or constrict their implementation. Following the PRISMA-statement PubMed/MEDLINE, EMBASE, Cochrane Library, and grey literature databases "Worldcat" and "OpenGrey" were searched for studies reporting on interventions to identify, evaluate, or rule out incorrect penicillin allergy in hospitalized adults. Data extraction included settings, intervention types, and their effectiveness, barriers, facilitators, and regulatory factors. This review included 42 studies, involving 6269 patients undergoing penicillin allergy delabeling, with 5017 (80%) successfully delabeled. Effectiveness varied from 32% to 99%. Skin testing had the highest success rate at 87%, followed by a combination of skin testing and oral challenge (84%), and direct oral challenges (77%). Direct delabeling alone had a lower effectiveness (67%), which improved to 80% when paired with oral challenges. Key facilitators included standardized algorithms and involvement of interdisciplinary teams. Barriers included patient refusal, staff resistance, time constraints, and financial limitations, particularly in smaller hospitals. Dependent on financial and staffing resources, oral challenges and direct delabeling after risk stratification may be alternatives to resource-intensive methods, such as skin testing, for successful delabeling. To address barriers to widespread delabeling implementation, patient and provider education must be improved, interprofessional collaboration enhanced, and standardized protocols developed.

Background: Pneumonia is the most common reason for pediatric hospitalizations. The impact of penicillin allergy labels among children with pneumonia has not been well studied. Objective: This study assessed the prevalence and impact of penicillin allergy labels among children admitted with pneumonia over a 3-year period at a large academic children's center. Methods: Inpatient charts of pneumonia admissions with a documented allergy to a type of penicillin from January to March in 2017, 2018, and 2019 were reviewed and compared with pneumonia admissions without the label over the same time with regard to days of antimicrobial treatment, route of antimicrobial therapy, and days of hospitalization. Results: There were 470 admissions for pneumonia during this time period, of which 48 patients (10.2%) carried a penicillin allergy label. Hives and/or swelling comprised 20.8% of the allergy labels. Other labels included nonpruritic rashes, gastrointestinal GI symptoms, unknown/undocumented reactions, or other reasons. There were no significant differences between those with a penicillin allergy label to those without regarding days of antimicrobial treatment (inpatient and outpatient), route of antimicrobial therapy, and days of hospitalization. Those with a penicillin allergy label were less likely to be prescribed a penicillin product (p < 0.002). Of the 48 patients who were allergy labeled, 23% (11/48) were given a penicillin medication without adverse reaction. Conclusion: Ten percent of pediatric admissions for pneumonia had a label of penicillin allergy, similar to the overall population. The hospital course and clinical outcome were not significantly affected by the penicillin allergy label. The majority of documented reactions were of low risk for immediate allergic reactions.

DALES, Drug Allergy Labels in Elective Surgical patients: a prospective multicentre cross-sectional study of incidence, risks, and attitudes in penicillin de-labelling strategies

Patient Perceptions of Penicillin Allergy Testing in a Public Health System

Drug Allergies in Immunodeficiencies: a Single-Center Experience in Southern California

Background: Allergy to penicillin is commonly reported in many countries and is an overwhelming global public health concern. Penicillin allergy labels can lead to the use of less effective antibiotics and can be associated with antimicrobial resistance. Appropriate assessment of suspected penicillin allergy (often including skin testing, followed by drug provocation testing [DPT] performed by allergists) can prevent the unnecessary restriction of penicillin or delabelling. Many countries in the Asia Pacific (AP) have very limited access to allergy services, and there are significant disparities in the methods of evaluating penicillin allergy. Therefore, a clinical pathway for the management of penicillin allergy is essential. Objectives: To develop a risk-stratified clinical pathway for delabeling penicillin allergy, taking into account the distinct epidemiology, patient/sensitization profiles, and disparities of allergy services or facilities within the AP. Methods: A risk-stratified penicillin allergy delabeling clinical pathway was formulated by the Drug Allergy Committee of the Asia Pacific Association of Allergy, Asthma and Clinical Immunology. and members of the Penicillin Allergy Disparities survey in AP each representing one country/region of the AP. The clinical pathway was tested based on a database of anonymized patients who were sequentially referred for and completed penicillin allergy evaluation in Hong Kong. Results: The clinical pathway was piloted employing a “hub-and-spoke” approach to foster multidisciplinary collaboration between allergists and nonallergists. A simulation run of the algorithm on a retrospective Hong Kong cohort of 439 patients was performed. Overall, 367 (84%) of patients were suitable for direct DPT and reduced the need for skin testing or specialist’s care for 357 (97%) skin test-negative individuals. Out of the skin test-negative patients, 345 (94%) patients had a negative DPT. Conclusions: This risk-stratification strategy for direct oral DPT can reduce the need for unnecessary skin testing in patients with low-risk penicillin allergy histories. The hub and spoke model of care may be considered for further piloting and validation in other AP populations that lack adequately trained allergists.

Penicillin allergy labels influence clinical decision-making, yet most children who are labeled do not have type 1 hypersensitivity allergic reactions and instead have a history of predictable adverse reactions or unspecified illness symptoms while receiving penicillin for viral infections. Studies describing penicillin allergy labeling in the pediatric outpatient setting are lacking. To describe the epidemiology and factors associated with penicillin allergy labels across 2 large US pediatric primary care networks. This retrospective, longitudinal birth cohort study was conducted in 90 primary care pediatric practices serving a diverse population of children across Houston, Texas, Austin, Texas, Philadelphia, Pennsylvania, and parts of New Jersey. Participants were children born between January 2010 and June 2020 who had a health care visit in the first 14 days of life and at least 2 additional visits in the first year of life at one of 90 primary care pediatric practices. Censoring criteria were additionally applied to exclude data from children no longer seeking health care in the 90 clinics over time. Statistical analysis was performed from February to May 2021. Basic patient demographics, health care utilization, penicillin exposure, and primary clinic location. Addition of penicillin allergy label in the electronic medical record. Among 334 465 children in the birth cohort, 164 173 (49.1%) were female; 72 831 (21.8%) were Hispanic, 59 598 (17.8%) were non-Hispanic Black, and 148 534 (44.4%) were non-Hispanic White; the median (IQR) age at censoring was 3.8 (1.7-6.6) years; 18 015 (5.4%) were labeled as penicillin allergic, but the prevalence of penicillin allergy labeling ranged from 0.9% to 10.2% across practices. Children were labeled at a median (IQR) age of 1.3 (0.9-2.3) years. Non-Hispanic White children were more likely to be labeled compared with non-Hispanic Black children after controlling for potential confounders (adjusted odds ratio, 1.7 [95% CI, 1.6-1.8]). There were 6797 allergic children (37.7%) labeled after receiving 1 penicillin prescription and 1423 (7.9%) labeled after receiving 0 penicillin prescriptions. In this cohort study of more than 330 000 children, penicillin allergy labeling was common and varied widely across practices. Children were labeled early in life, and almost half were labeled after receiving 1 or 0 penicillin prescriptions. These findings raise questions regarding the validity of penicillin allergy labels. Future work exploring the fidelity of and outcomes associated with penicillin allergy-labeling in children is warranted.

ObjectivesApproximately 10% of the general population are reported to have a penicillin allergy, but more than 90% of these patients are able to tolerate penicillins after formal assessment. Patients with...