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Background: Ten percent of the population is labeled as allergic to penicillin(s), when in fact 90% of these labels are inappropriate. Recent studies have shown that inpatient delabeling by a direct drug challenge (dDC) is safe in low-risk patients. However, there is a need for outpatient and nonallergist delabeling., Objective: To assess the safety of delabeling low-risk adults by means of dDC in primary care., Methods: We searched the MEDLINE, Embase, and Cochrane Library databases from inception to March 15, 2022 (updated June 5, 2023) for studies performing dDC in adults in primary care or other outpatient settings. Two researchers independently screened studies for eligibility. The data extraction and critical appraisal were performed by 1 reviewer, and we pooled the results in a meta-analysis., Results: Of 2138 results, 12 studies (1070 participants) were eligible for inclusion. Three studies evaluated delabeling in primary care and 9 studies in an outpatient hospital setting. There were no critical adverse events during dDC. No reaction occurred in 97.13% of the 1070 patients, who previously labeled as penicillin-allergic, and were safely delabeled. Ten patients (<1%) developed an immediate reaction: 3 had self-limiting reactions and 7 needed antihistaminics, steroids, epinephrine, and/or salbutamol., Conclusions: No serious allergic reactions are observed during direct amoxicillin challenge in adults in an outpatient setting. However, with the exception of 1 recent report, these studies are of low to moderate quality. Nonspecialist delabeling is promising, but further research is required on correct risk stratification and safety assessment in large cohort studies evaluating dDC in primary care., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Disclosures The authors have no conflicts of interest to report.

Study Objective: To characterize and assess the effects of a preoperative, nurse-driven penicillin allergy risk stratification tool on rates of perioperative cefazolin and second-line antibiotic use., Design: Quasi-experimental quality improvement study of penicillin-allergic surgical patients undergoing procedures for which cefazolin is indicated., Setting: Outpatient Perioperative Care Clinic (PCC) for preoperative surgical patients at a tertiary care center., Patients: 670 and 1371 adult penicillin-allergic PCC attendants and non-attendants, respectively., Intervention: A paper penicillin allergy risk stratification questionnaire was administered during the PCC visit. Nurses were educated on its use., Measurements: Antibiotic (cefazolin, clindamycin, vancomycin) use rates in the 24 months before and 17 months after intervention implementation in November 2020 (November 2018 - April 2022) were assessed in penicillin-allergic PCC attendants with statistical process control charts. Multivariable logistic regression assessed antibiotic use rates pre- and post-intervention adjusting for age, sex, surgical specialty and penicillin allergy history severity. Similar analyses were done in penicillin-allergic PCC non-attendants., Main Results: Of 670 penicillin-allergic PCC attendants, 451 (median [IQR] age, 66 (Sousa-Pinto et al., 2021 [14])) were analyzed pre-intervention and 219 (median [IQR] age, 66 (Mine et al., 1970 [13])) post-intervention. One month after implementation, process measures demonstrated an upward shift in cefazolin use for PCC attendants versus no shift or other special cause variation for PCC non-attendants. There were increased odds of cefazolin use (aOR 1.67, 95% CI [1.09-2.57], P = 0.019), decreased odds of clindamycin use (aOR 0.61, 95% CI [0.42-0.89], P = 0.010) and decreased odds of vancomycin use (aOR 0.56, 95% CI [0.35-0.88], P = 0.013) in PCC attendants post-intervention. This effect did not occur in PCC non-attendants. There was no increase in perioperative anaphylaxis post-intervention., Conclusions: A simple penicillin allergy risk stratification tool implemented in the preoperative setting was associated with increased use of cefazolin and decreased rates of second-line agents post implementation., Competing Interests: Declaration of competing interest none., (Copyright © 2023. Published by Elsevier Inc.)

Competing Interests: Declaration of competing interest The authors declare the following conflicts of interest: Daniel Yo: declares no conflicts of interest. Richard D. Urman: declares unrelated research funding from Merck, AcelRx, and NIH. Marc Philip Tanedo Pimentel: declares no conflicts of interest.

Background: Machine learning may assist with the identification of potentially inappropriate penicillin allergy labels. Strategies to improve the performance of existing models for this task include the use of additional training data, synthetic data and transfer learning., Aims: The aims of this study were to investigate the use of additional training data and novel machine learning strategies, namely synthetic data and transfer learning, to improve the performance of penicillin adverse drug reaction (ADR) machine learning classification., Methods: Machine learning natural language processing was applied to free-text penicillin ADR data extracted from a public health system electronic health record (EHR). The models were developed by training on various labelled data sets. ADR entries were split into training and testing data sets and used to develop and test a variety of machine learning models. The effect of training on additional data and synthetic data versus the use of transfer learning was analysed., Results: Following the application of these techniques, the area under the receiver operator curve of best-performing models for the classification of penicillin allergy (vs intolerance) and high-risk allergy (vs low-risk allergy) improved to 0.984 (using the artificial neural network model) and 0.995 (with the transfer learning approach) respectively., Conclusions: Machine learning models demonstrate high levels of accuracy in the classification and risk stratification of penicillin ADR labels using the reaction documented in the EHR. The model can be further optimised by incorporating additional training data and using transfer learning. Practical applications include automating case detection for penicillin allergy delabelling programmes., (© 2024 Royal Australasian College of Physicians.)

Allergy to penicillin can occur via any of the 4 types of Gel-Coombs hypersensitivity reactions, producing distinct clinical histories and physical examination findings. Treatments include penicillin discontinuation, and depending on the type of reaction, epinephrine, antihistamines, and/or glucocorticoids. Most beta-lactams may be safely used in penicillin-allergic patients, with the possible exception of first-generation and second-generation cephalosporins. Penicillin testing includes skin testing, patch testing, and graded challenge. The selection of the type of testing depends on the clinical setting, equipment availability, and type of hypersensitivity reaction. Desensitization may be used in some cases where treatment with penicillins is essential., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Approximately 10% of pregnant individuals report a penicillin allergy, yet most are not truly allergic. Allergy verification during pregnancy is safe and recommended; however, many hospitals lack the infrastructure to execute testing. Our aim was to evaluate the cost of developing and implementing a penicillin allergy referral program for pregnant individuals at an academic institution and to compare costs of care between patients who were referred and not referred through the program., Study Design: We conducted an economic analysis of our institution's antepartum penicillin allergy referral program. We prospectively collected detailed resource utilization data and conducted the analysis from the program's perspective, accounting for costs related to program development, allergy verification, antibiotic cost, and delivery hospitalization. Costs were compared between patients who were referred for evaluation versus patients who were not referred using bivariate tests as well as quantile regression adjusting for baseline differences. A sensitivity analysis was performed for allergy testing cost. All cost estimates were inflation adjusted to 2021 U.S. dollars., Results: The startup cost of program development and educational initiatives was $19,920, or 86 per patient. The median allergy evaluation cost was $397 (interquartile range: $303-663). There was no significant difference in maternal (median: $13,579 vs. 13,999, p  = 0.94) or neonatal (median: $3,565 vs. 3,577, p  = 0.55) delivery hospitalization cost or antibiotic cost (median: $1.57 vs. 3.87, p  = 0.10) between referred and nonreferred patients. Overall, the total cost per person did not differ significantly between study groups (median: $18,931 vs. 18,314, p  = 0.69)., Conclusion: The cost of developing a penicillin allergy referral program in pregnancy was modest and did not significantly alter short-term cost of care with potential for long-term cost benefit. Verification of a reported penicillin allergy is an integral part of antibiotic stewardship, and the pregnancy period should be utilized as an important opportunity to perform this evaluation., Key Points: · The cost of developing and implementing an antepartum penicillin allergy referral program is modest.. · Program cost did not significantly alter short-term cost with a potential for long-term cost benefit.. · Penicillin allergy verification is an important part of antibiotic stewardship and should be expanded.., Competing Interests: Funds were paid to Yale University for Moeun Son from Sera Prognostics for being site PI for a study of the PreTRM test. The other authors do not report any potential conflict of interest., (Thieme. All rights reserved.)

Background: Penicillin "allergy" labels are prevalent but frequently misdiagnosed. Mislabelled allergies are associated with adverse outcomes and increased antimicrobial resistance. With an urgent need to delabel the overwhelming number of mislabeled allergies, nonallergist evaluations have been advocated for low-risk individuals. Despite growing interest in non-allergist-led initiatives, evidence on their effectiveness, safety, and impact by direct comparisons is lacking., Objective: To assess the comparative outcomes of penicillin allergy evaluations conducted by allergists versus nonallergists., Methods: A prospective, multicenter, pragmatic study was conducted at 4 tertiary hospitals (1 allergist- vs 3 non-allergist-led) for low-risk penicillin allergy patients in Hong Kong-the Hong Kong Drug Allergy Delabelling Initiative 2 (HK-DADI2)., Results: Among 228 low-risk patients who underwent testing (32.9% by allergists, 67.1% by nonallergists), only 14 (6.1%) had positive penicillin allergy testing results. Delabeling rates (94.1% vs 93.3%; P = .777), positive skin test results (2.6% vs 2.7%; P > .99), and drug provocation test results (3.3% vs 2.7%; P = 1.000) were similar between allergists and nonallergists. There were no systemic reactions in either cohort. All patients had significant improvements in health-related quality of life (Drug Hypersensitivity Quality of Life Questionnaire scores -5.00 vs -8.33; P = .072). Nonallergist evaluations had shorter waiting times (0.57 vs 15.7 months; P < .001), whereas allergists required fewer consultations with higher rate of completing evaluations within a single visit (odds ratio, 0.04; P < .001)., Conclusions: With training and support, nonallergists can independently evaluate low-risk penicillin allergies. Compared with allergists, evaluation of low-risk penicillin allergy by nonallergists can be comparably effective, safe, and impactful on quality of life. More multidisciplinary partnerships to empower nonallergists to conduct allergy evaluations should be encouraged., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Up to 10% of children are reported to be allergic to penicillin, but many allergy labels are unverified and may require formal testing. Inaccurate drug allergy labels are associated with a range of adverse clinical outcomes. Patients with hematological disorders may experience frequent and severe infections; those who have been incorrectly labeled penicillin allergic may benefit from allergy de-labeling (ADL) efforts to facilitate access to beta-lactam antibiotics. We developed a multidisciplinary, pharmacist-driven process that enabled non-allergist trained providers to assess and de-label penicillin allergies in a pediatric hematology center., Methods: Volunteers, including physicians, advanced practice providers, nurses, and pharmacists, were trained in skin testing and oral challenge procedures. Patients were identified by review of electronic medical records for penicillin or penicillin-derivative allergy. Patient and family interviews were conducted in cases where a true penicillin allergy was deemed uncertain based on chart review. If allergy could not be de-labeled by chart review or interview alone, patients were offered skin and/or oral challenge testing., Results: Fifty-nine patients were initially labeled as penicillin allergic. Allergy labels of 11 (19%) were removed by chart review only, and 15 (25%) after conducting interviews. A total of two (3%) patients were ineligible due to contraindications, and five (9%) declined participation. Twenty-six patients (44%) underwent allergy testing (50% skin testing, 50% oral challenge) of which 23 (88%) were negative., Conclusions: ADL was possible in most patients previously identified as penicillin allergic. Testing was well tolerated with no serious adverse effects., (© 2024 Wiley Periodicals LLC.)

The beta-lactam antibiotics are some of the safest and best-tolerated antibiotic agents; however, many patients have reported allergies against penicillin. All beta-lactam antibiotics are only restrictively prescribed for these patients and alternative antibiotics are increasingly given, which carries the risk of negative clinical results and socioeconomic sequelae; however, over 95% of patients who reported an allergy to penicillin show a negative result in the allergy tests for penicillin and this antibiotic can safely be prescribed. The use of sensitive and specific instruments for identification of false penicillin allergies should be an important topic within the framework of antibiotic stewardship. Anesthesists can play a central role in the reduction of the enormous individual and public health burden associated with the classification of penicillin allergy by taking an appropriate medical history and a risk stratification for the identification of patients with a penicillin allergy. This overview article presents a possible delabelling algorithm within the framework of the clarification of a beta-lactam antibiotic allergy. The focus is on a structured allergy anamnesis using the penicillin allergy, five or fewer years ago, anaphylaxis/angioedema, severe cutaneous adverse reaction (SCAR) and treatment required for allergy episode (PEN-FAST) score., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Purpose: Critically ill patients are vulnerable to penicillin allergy labels that may be incorrect. The validity of skin testing in intensive care units (ICUs) is uncertain. Many penicillin allergy labels are low risk, and validated tools exist to identify those amenable to direct oral challenge. This pilot randomised controlled trial explored the feasibility, safety, and validity of direct enteral challenge for low-risk penicillin allergy labels in critical illness., Methods: Consenting patients with a low-risk penicillin allergy label (PAL) (PEN-FAST risk assessment score < 3) in four ICUs (Melbourne, Australia) were randomised 1:1 to penicillin (250 mg amoxicillin or implicated penicillin) direct enteral challenge versus routine care (2-h post-randomisation observation for each arm). Repeat challenge was performed post -ICU in the intervention arm. Patients were reviewed at 24 h and 5 days after each challenge/observation., Results: We screened 533 patients. 130 (24.4%) were eligible and 80/130 (61.5%) enrolled (age median 64.5 years (interquartile range, IQR 53.5, 74), PEN-FAST median 1 (IQR 0,1)), with 40 (50%) randomised to direct enteral challenge. A positive challenge rate of 2.5% was identified. No antibiotic-associated serious adverse events were identified. 32/40 (80%) received a repeat challenge (zero positive). Post-randomisation, 13 (32%) of the intervention arm and 4 (10%) of the control arm received penicillin (odds ratio, OR 4.33 [1.27, 14.78] p = 0.019)., Conclusion: These findings support the safety, validity, and feasibility of direct enteral challenge for critically ill patients with PEN-FAST assessed low-risk penicillin allergy. The absence of false negative results was confirmed by subsequent negative repeat challenges. A relatively low recruitment to screened ratio suggests that more inclusive eligibility criteria and integration of allergy assessment into routine ICU processes are needed to optimise allergy delabelling in critical illness., (© 2024. The Author(s).)

Background: Approximately 15% of patients in sexually transmitted infection (STI) clinics report penicillin allergies, complicating treatment for syphilis and gonorrhea. Nonetheless, >90% do not have a penicillin allergy when evaluated. We developed and validated an algorithm to define which patients reporting penicillin allergy can be safely treated at STI clinics with these drugs., Methods: Randomized controlled trial to assess feasibility and safety of penicillin allergy evaluations in STI clinics. Participants with reported penicillin allergy answered an expert-developed questionnaire to stratify risk. Low-risk participants underwent penicillin skin testing (PST) followed by amoxicillin 250 mg challenge or a graded oral challenge (GOC)-amoxicillin 25 mg followed by 250 mg. Reactions were recorded, and participant/provider surveys were conducted., Results: Of 284 participants, 72 (25.3%) were deemed high risk and were excluded. Of 206 low-risk participants, 102 (49.5%) underwent PST without reactions and 3 (3%) had mild reactions during the oral challenge. Of 104 (50.5%) participants in the GOC, 95 (91.3%) completed challenges without reaction, 4 (4.2%) had mild symptoms after 25 mg, and 4 (4.2%) after 250-mg doses. Overall, 195 participants (94.7%) successfully completed the study and 11 (5.3%) experienced mild symptoms. Of 14 providers, 12 (85.7%) completed surveys and 11 (93%) agreed on the safety/effectiveness of penicillin allergy assessment in STI clinics., Conclusions: An easy-to-administer risk-assessment questionnaire can safely identify patients for penicillin allergy evaluation in STI clinics by PST or GOC, with GOC showing operational feasibility. Using this approach, 67% of participants with reported penicillin allergy could safely receive first-line treatments for gonorrhea or syphilis. Clinical Trials Registration. Clinicaltrials.gov (NCT04620746)., Competing Interests: Potential conflicts of interest. L. A. B. reports research funding support from NIH, Nabriva, Hologic, and SpeeDx, and participation on a Data and Safety Monitoring Board for an NIH-funded study on the Bexsero vaccine (looking at mucosal immunity). C. J. M. reports receiving research funding from BARDA/GSK, the Centers for Disease Control and Prevention, GlaxoSmithKline, Cepheid, Gilead, Hologic, and the National Association of County and CityHealth Officials and consulting honoraria from the Infectious Diseases Society of America, Contraceptive Technologies, Core Concepts in Health, and AHEC (Area Health Education Centers); and participation on a Data Safety Monitoring Board or Advisory Board for the NIH (unpaid) and Advisory Board for Talis Biomedical (payment to their institution); and receipt of study product provided to their institution from Lupin. J. M. Z. reports compensation for service on Data Safety Monitoring Committees for Pfizer. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Using the reaction history in logistic regression and machine learning (ML) models to predict penicillin allergy has been reported based on non-US data., Objective: We developed ML positive penicillin allergy testing prediction models from multisite US data., Methods: Retrospective data from 4 US-based hospitals were grouped into 4 datasets: enriched training (1:3 case-control matched cohort), enriched testing, nonenriched internal testing, and nonenriched external testing. ML algorithms were used for model development. We determined area under the curve (AUC) and applied the Shapley Additive exPlanations (SHAP) framework to interpret risk drivers., Results: Of 4777 patients (mean age 60 [standard deviation: 17] years; 68% women, 91% White, and 86% non-Hispanic) evaluated for penicillin allergy labels, 513 (11%) had positive penicillin allergy testing. Model input variables were frequently missing: immediate or delayed onset (71%), signs or symptoms (13%), and treatment (31%). The gradient-boosted model was the strongest model with an AUC of 0.67 (95% confidence interval [CI]: 0.57-0.77), which improved to 0.87 (95% CI: 0.73-1) when only cases with complete data were used. Top SHAP drivers for positive testing were reactions within the last year and reactions requiring medical attention; female sex and reaction of hives/urticaria were also positive drivers., Conclusions: An ML prediction model for positive penicillin allergy skin testing using US-based retrospective data did not achieve performance strong enough for acceptance and adoption. The optimal ML prediction model for positive penicillin allergy testing was driven by time since reaction, seek medical attention, female sex, and hives/urticaria., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: β-Lactam antibiotics are widely used with increased utilization in hospitalized patients. Of this population, as high as 10-20% report an allergy to β-lactam antibiotics but <5% are at risk of developing clinically significant immunoglobulin E- or T-lymphocyte-mediated reactions. Most of the time, these reported allergies are present during an illness with no previous inquiry of their validity, which makes investigation and possible removal of this allergy label a challenge. Methods: We report a 16-year-old boy who presented with 1 week of night sweats, chills, headaches, and fatigue, followed by 1 day of fever and right knee swelling and who was diagnosed with septic bursitis. Due to concern of a penicillin allergy label, the patient was started on a cefepime infusion. Five minutes into the infusion, the patient reported puffy eyes and itchy throat, followed by a witnessed cascading flat nonpruritic erythematous rash from head to shoulders. This rash went away in 3 minutes after stopping the infusion and the patient being given 50 mg of intravenous diphenhydramine and 10 mg of oral dexamethasone. He was subsequently diagnosed with a cefepime allergy. Results: Allergy/immunology was the speciality consulted, and, by using a screening questionnaire, the patient's reported penicillin allergy was determined to be low risk. Subsequent 1-step oral challenge was the key to providing the patient with the necessary antibiotic course to resolve his infection. Conclusion: Multiple reported antibiotic allergies lead to poor antibiotic stewardship that causes impactful health and financial burden on the patient and health-care system. It is thus important to have an evidence-based systematic approach to de-label penicillin antibiotic allergy labels to reduce these potential harms.

Secondary prevention with penicillin aims to prevent further episodes of acute rheumatic fever and subsequent development of rheumatic heart disease (RHD). Penicillin allergy, self-reported by 10% of the population, can affect secondary prevention programs. We aimed to assess the role for (i) routine penicillin allergy testing and the (ii) safety of penicillin allergy delabeling approaches in this context. We searched MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, WHO ICTRP, ISRCTN, and CPCI-S to identify the relevant reports. We found 2419 records, but no studies addressed our initial question. Following advice from the WHO-Guideline committee and experts, we identified 6 manuscripts on allergy testing focusing on other populations showing that the prevalence of allergy confirmed by testing was low and the incidence of life-threatening reactions to BPG was very low (< 1-3/1000 individuals treated). A subsequent search addressed penicillin allergy delabeling. This found 516 records, and 5 studies addressing the safety of direct oral drug challenge vs. skin testing followed by drug administration in patients with suspected penicillin allergy. Immediate allergic reactions of minor severity were observed for a minority of patients and occurred less frequently in the direct drug challenge group: 2.3% vs. 11.5%; RR = 0.25, 95%CI 0.15-0.45, P < 0.00001, I 2  = 0%. No anaphylaxis or deaths were observed. Severe allergic reactions to penicillin are extremely rare and can be recognized and dealt by trained healthcare workers. Confirmation of penicillin allergy diagnosis or delabeling using direct oral drug challenge or penicillin skin testing seems to be safe and is associated with a low rate of adverse reactions., (© 2024. The Author(s).)

The Standards of Care Committee of the British Society for Allergy and Clinical Immunology (BSACI) and a committee of experts and key stakeholders have developed this guideline for the evaluation and testing of patients with an unsubstantiated label of penicillin allergy. The guideline is intended for UK clinicians who are not trained in allergy or immunology, but who wish to develop a penicillin allergy de-labelling service for their patients. It is intended to supplement the BSACI 2015 guideline "Management of allergy to penicillin and other beta-lactams" and therefore does not detail the epidemiology or aetiology of penicillin allergy, as this is covered extensively in the 2015 guideline (1). The guideline is intended for use only in patients with a label of penicillin allergy and does not apply to other beta-lactam allergies. The recommendations include a checklist to identify patients at low risk of allergy and a framework for the conduct of drug provocation testing by non-allergists. There are separate sections for adults and paediatrics within the guideline, in recognition of the common differences in reported allergy history and likelihood of true allergy., (© 2022 John Wiley & Sons Ltd.)

Objective(s): The objective of the study was to validate a clinical aid to guide the assessment and management of a patient's listed beta-lactam antibiotic allergy for use in rural areas of Australia., Design: Rural generalists, pharmacists and junior doctors completed an online assessment of eight patient case studies using the tool., Setting: The study was conducted in the Southern Downs, QLD., Participants: Twenty-seven rural generalists, nine pharmacists and eight junior doctors., Main Outcome Measures: The sensitivity of the selected allergy phenotype and management option for each case study was calculated by profession and overall. Hazardous responses were reported by management category and profession., Results: The sensitivity overall for phenotype selection was 82.4% (95% CI, 78.0-86.2) and for management 88.1% (95% CI, 84.2-91.2). The sensitivity for phenotype selection was lower for junior doctors than other professions 73.4% (95% CI, 60.9-83.7), but did not reach statistical significance (p = 0.08). A total of 10/308 responses for management recommended the least restrictive option of direct delabelling or oral challenge, where the correct answer was skin prick testing or referral to an allergist., Conclusion(s): With further education the tool could be a key component of increased antimicrobial stewardship in rural areas in Australia., (© 2022 National Rural Health Alliance Ltd.)

Introduction: Penicillin allergies are highly prevalent in the healthcare setting and associated with the prescription of second-line inferior antibiotics. More than 85% of all penicillin allergy labels can be removed by skin testing and 96%-99% of low-risk penicillin allergy labels can be removed by direct oral challenge. An internally and externally validated clinical assessment tool for penicillin allergy, PEN-FAST, can identify a low-risk penicillin allergy without the need for skin testing; a score of less than 3 has a negative predictive value of 96.3% (95% CI, 94.1 to 97.8) for the presence of a penicillin allergy. It is hypothesised that PEN-FAST is a safe and effective tool for assessing penicillin allergy in an outpatient clinic setting., Methods and Analysis: This is an international, multicentre randomised control trial using the PEN-FAST tool to risk-stratify penicillin allergy labels in adult outpatients. The study's primary objective is to evaluate the non-inferiority of using PEN-FAST score-guided management with direct oral challenge compared with standard care (defined as prick and intradermal skin testing followed by oral penicillin challenge). Participants will be randomised 1:1 to the intervention arm (direct oral penicillin challenge) or standard of care arm (skin testing followed by oral penicillin challenge, if skin testing is negative). The sample size of 380 randomised patients (190 per treatment arm) is required to demonstrate non-inferiority., Ethics and Dissemination: The study will be performed according to the guidelines of the Helsinki Declaration and is approved by the Austin Health Human Research Ethics Committee (HREC/62425/Austin-2020) in Melbourne Australia, Vanderbilt University Institutional Review Board (IRB #202174) in Tennessee, USA, Duke University Institutional Review Board (IRB #Pro00108461) in North Carolina, USA and McGill University Health Centre Research Ethics Board in Canada (PALACE/2022-7605). The results of this study will be published and presented in various scientific forums., Trial Registration Number: NCT04454229., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Patients with self-reported antibiotic allergies have a higher cost of care, more frequent infections with resistant bacteria and worse health outcomes than patients without antibiotic allergies. Ultimately, less than 5% of patients who report a penicillin allergy have a clinically significant immune-mediated hypersensitivity reaction when tested. As 10%-30% of the population of pregnant patients are colonised for group B Streptococcus (GBS) and guidelines recommend penicillin as the treatment of choice for GBS, current recommendations support penicillin allergy testing in pregnant patients who report an allergy., Methods and Intervention: In this quality improvement project, nursing staff used an algorithm outlining inclusion and exclusion criteria to determine which patients were eligible to have penicillin allergy testing completed. Penicillin allergy testing consisted of a skin test using benzylpenicilloyl polylysine (Pre-Pen), penicillin G potassium, amoxicillin and alkaline hydrolysis mix (penicilloate) as a prick skin test, followed by intradermal skin test and finally an oral challenge with either amoxicillin or penicillin. Patient outcomes were analysed to evaluate the impact of the intervention., Results: Of the 1266 patients receiving prenatal care during the intervention, 236 (19%) reported a history of penicillin allergy, and 212 if these were eligible for testing. 150 of the eligible patients were offered penicillin allergy testing. 101 patients (67%) completed testing and 49 (33%) declined testing. Seven patients (7%) had positive penicillin allergy testing, while 94 patients (93%) had negative penicillin allergy testing and were immediately de-labelled as penicillin allergic. Seventeen of the de-labelled patients subsequently tested positive for GBS colonisation, and all received intrapartum penicillin without adverse events., Conclusions: Pursuing penicillin allergy testing for pregnant patients with reported penicillin allergy is a safe and feasible approach, allowing for allergy de-labelling and safe, guideline-driven antimicrobial therapy during subsequent labour and delivery hospitalisations. Cost-effectiveness of the allergy testing and impact on later episodes of care should be further investigated., Competing Interests: Competing interests: RT has research funding and know-how agreements with HeraMed, unrelated to this project., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Penicillin allergy can be risk stratified in the hospital or outpatient setting to identify low-, moderate-, and high-risk phenotypes. Following ascertainment of risk, dedicated penicillin allergy testing strategies can be deployed successfully for each risk type-direct oral challenge (low risk), skin testing and oral challenge (moderate risk), and specialist review and/or skin testing (high risk)., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Penicillin is the most common reported drug allergy. Previous literature suggests that there is increased prevalence of penicillin drug allergy in female patients in the outpatient setting. However, this is poorly described in the inpatient setting. Objective: This study was performed to determine whether female sex is an independent risk factor for penicillin allergy in the inpatient setting. Methods: A retrospective review of electronic medical records (January 1, 2001-December 31, 2017) was performed for patients with a history of penicillin allergy who underwent penicillin skin testing (PST). Each chart review included the age at initial skin testing, sex, medications, and medical co-morbidities. The study was approved by the institutional review board. Results: 30,883 patients underwent PST with 29,354 and 1,529 occurring in the outpatient and inpatient setting respectively. 170 patients tested positive with a ≥ 5x5 wheal. Of the 170 positive patients, 122 were female (72%) and 48 were male (28%). 15 patients tested positive in the inpatient setting. Of the 1506 adult patients tested in the inpatient setting, 809 were female and 697 were male. 12 females (92.3%) and 1 one male (7.7%) tested positive with a ≥ 5x5 wheal (OR-10.5; 95% CI-1.4-80.8; p-value=0.02). 23 pediatric patients were tested in the inpatient setting. Two pediatric male patients were positive and no female pediatric patients tested positive (OR-1.7; 95% CI-0.5-5.9; p-value=0.5). Conclusion: In the inpatient setting, adult females are 10 times more likely to have a positive PST compared to males. Female sex may be a potential risk factor for objective penicillin drug allergy in the inpatient setting.

Background: Penicillin allergy is the most reported adverse drug reaction (ADR). Being labelled with 'penicillin allergy' is associated with suboptimal antibiotic therapy and poor patient outcomes. Most labelled with 'penicillin allergy' are at low risk of harm from penicillins and guidelines recommend testing for accurate diagnosis. Although skin testing is recommended to exclude immunoglobulin E (IgE)-mediated reactions, there is limited access in most settings., Aims: To evaluate oral amoxicillin challenge without prior skin testing for patients labelled with 'penicillin allergy' assessed as low risk during hospital admission., Methods: General Medical inpatients with a 'penicillin allergy' label were assessed. For those who had tolerated a penicillin since the index event, the ADR label was removed. Those assessed as 'low risk' were administered 250 mg amoxicillin orally without prior skin testing. The durability of de-labelling was subsequently assessed by review of clinical records., Results: Of 224 patients with a history of a penicillin ADR, 162 (72%) were low risk. A further 12 were excluded and of the remaining 150, 56 (37%) had tolerated penicillins since their index reaction and were de-labelled without challenge, 15 (10%) with a non-allergic history were de-labelled. The remaining 79 were offered an oral amoxicillin challenge; 38 declined and 41 tolerated amoxicillin. Overall, 112 of the 224 (50%) patients had their ADR label removed., Conclusions: A careful ADR history enables de-labelling of many patients. An oral amoxicillin challenge without prior skin testing is safe and feasible for low-risk penicillin allergic patients while in hospital., (© 2020 Royal Australasian College of Physicians.)

Background: Of the US population, 10% reports a penicillin allergy but more than 90% can ultimately tolerate penicillin. Confirmation of these allergies in the pediatric population may improve future health outcomes and decrease costs. Referring patients for confirmatory testing is the first step in clarifying penicillin allergies., Objective: To increase the number of referrals of patients with listed penicillin allergies from the University of California, San Diego academic general pediatrics clinics to Rady Children's Hospital allergy clinics using an educational session and a best practice advisory (BPA) in the electronic medical record., Methods: An educational session with attendings and 3 plan-do-study-act (PDSA) cycles were completed using a BPA alert that triggered for all patients with a documented penicillin-class drug allergy to draw attention and facilitate referral. The BPA was modified at each PDSA cycle based on physician input., Results: At baseline, 1.9% of referrals to the allergy clinic were for penicillin-class drug allergies. After an attending physician educational session, the percentage increased to 13.7%. The BPA was implemented with further increase to 27.8% of all allergy referrals in the course of 3 PDSA cycles. Not all patients with penicillin-class drug allergies were referred, and the reasons were documented when the physicians dismissed the BPA. Physicians did not refer 35% of the time because of time constraints, as opposed to patient or parent disinterest, which was 8% of the time., Conclusion: Referrals to the allergist for confirmatory testing in patients with listed penicillin allergies increased by more than 10 fold. This study illustrates successful tools to support delabeling., (Copyright © 2021. Published by Elsevier Inc.)

Competing Interests: None

Betalactams are the most widely used antimicrobials for their safety and efficacy. These include the penicillins, cephalosporins, carbapenems, and monobactams. Penicillin allergy ranks first in relation to drug allergy. 10 to 20 % of the population is labeled as allergic to it, often wrongly. Cross reaction is reported in 2 to 5 % between penicillins and cephalosporin. There is no cross reaction between penicillins and aztreonam, but there is with ceftazidime. All the mechanisms of the Gell and Coombs classification are included in the pathophysiology of hypersensitivity reactions to penicillin. Stratification according to risk allows us to take the most objective behavior to label the patient as allergic to. In the natural history of penicillin allergy, 80-90 % of patients lose this sensitivity by 10 years. If necessary, the patient can undergo a desensitization protocol. The immuno-allergist is a key piece in the selection of the patient, the elaboration of the challenge and desensitization protocols, in a controlled environment.

Background: Patients who report a penicillin allergy are often given second-line antibiotic prophylaxis during total joint arthroplasty (TJA), with only a minority of patients undergoing additional consultations and allergy testing. In an effort to increase the use of cephalosporin prophylaxis in TJA, the present study aimed to assess the effectiveness of a simple, protocol-driven penicillin allergy screening program without the need for additional work-up., Methods: Following implementation of a questionnaire-based screening protocol in May 2019, all patients scheduled for primary TJA were risk-stratified into low or high-risk categories. The low-risk cohort received cefazolin, and the high-risk cohort received non-cefazolin antibiotics. Patients were monitored prospectively, and data on antibiotic usage and adverse outcomes were documented. The protocol group (n = 2,078) was propensity score matched 1:1 with a control group that included patients who underwent TJA in the same institution prior to implementation of the protocol. The primary end point was the efficacy of the protocol in reducing unnecessary use of non-cephalosporin antibiotics for prophylaxis. Secondary outcomes included the rate of surgical site infections and allergic reactions to the administered antibiotic., Results: A total of 357 patients (17.2%) reported a penicillin allergy in the protocol group compared with 310 patients (14.9%) with a recorded allergy in the control group (p = 0.052). The number of patients who received non-cephalosporin antibiotics was significantly lower in the protocol group (5.7% compared with 15.2% in the control group; p < 0.001), whereas there was no difference in the rate of total allergic reactions (0.8% compared with 0.7%, respectively; p = 0.857). Of the 239 low-risk patients (66.9%) in the protocol group, only 3 (1.3%) experienced a mild cutaneous reaction following cefazolin administration. There were no differences in the rates of superficial wound, deep periprosthetic, or Clostridioides difficile infections between the protocol and control groups., Conclusions: A simple screening protocol allowed two-thirds of patients with a self-reported allergy to receive cefazolin without the need for additional consultations or testing. We believe this protocol can be safely implemented to increase the rate of cefazolin usage without a corresponding increase in the number of allergic reactions., Level of Evidence: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/G739)., (Copyright © 2021 by The Journal of Bone and Joint Surgery, Incorporated.)

Patients and Methods: An allergy work-up was performed on adult patients with a history of a penicillin allergy seen by primary medical care in Monastir (Tunisia) between July 2016 and February 2018. Patients with negative skin tests were challenged with amoxicillin. Patients who were delabelled were contacted by phone after 6 months to determine outcomes after any therapeutic penicillin-class antibiotic intake., Results: A total of 39 patients were evaluated and 33 (84.6%) were delabelled. Five patients were penicillin skin-test positive and one was oral challenge positive. We succeeded in contacting 33 delabelled patients at 6 months. Twenty-two patients tolerated a subsequent therapeutic course of amoxicillin, eight patients did not retake penicillin due to a lack of therapeutic indication, and three patients refused an indicated penicillin use fearful of another reaction., Conclusion: This study highlights the importance of allergy work-up in the diagnosis of beta-lactam hypersensitivity. Most patients were excessively labelled as beta-lactam allergic and this mislabelling could increase healthcare costs and lead to the development of drug resistance by the use of wide-spectrum antibiotics., (© 2021 British Pharmacological Society.)