Long-Term Outcomes Associated With ß-Lactam Allergies.

Importance: ß-lactam (BL) allergies are the most common drug allergy worldwide, but most are reported in error. BL allergies are also well-established risk factors for adverse drug events and antibiotic-resistant infections during inpatient health care encounters, but the understanding of the long-term outcomes of patients with BL allergies remains limited. Objective: To evaluate the long-term clinical outcomes of patients with BL allergies. Design, Setting, and Participants: This longitudinal retrospective cohort study was conducted at a single regional health care system in western Pennsylvania. Electronic health records were analyzed for patients who had an index encounter with a diagnosis of sepsis, pneumonia, or urinary tract infection between 2007 and 2008. Patients were followed-up until death or the end of 2018. Data analysis was performed from January 2022 to January 2024. Exposure: The presence of any BL class antibiotic in the allergy section of a patient's electronic health record, evaluated at the earliest occurring observed health care encounter. Main Outcomes and Measures: The primary outcome was all-cause mortality, derived from the Social Security Death Index. Secondary outcomes were defined using laboratory and microbiology results and included infection with methicillin-resistant Staphylococcus aureus (MRSA), Clostridium difficile, or vancomycin-resistant Enterococcus (VRE) and severity and occurrence of acute kidney injury (AKI). Generalized estimating equations with a patient-level panel variable and time exposure offset were used to evaluate the odds of occurrence of each outcome between allergy groups. Results: A total of 20 092 patients (mean [SD] age, 62.9 [19.7] years; 12 231 female [60.9%]), of whom 4211 (21.0%) had BL documented allergy and 15 881 (79.0%) did not, met the inclusion criteria. A total of 3513 patients (17.5%) were Black, 15 358 (76.4%) were White, and 1221 (6.0%) were another race. Using generalized estimating equations, documented BL allergies were not significantly associated with the odds of mortality (odds ratio [OR], 1.02; 95% CI, 0.96-1.09). BL allergies were associated with increased odds of MRSA infection (OR, 1.44; 95% CI, 1.36-1.53), VRE infection (OR, 1.18; 95% CI, 1.05-1.32), and the pooled rate of the 3 evaluated antibiotic-resistant infections (OR, 1.33; 95% CI, 1.30-1.36) but were not associated with C difficile infection (OR, 1.04; 95% CI, 0.94-1.16), stage 2 and 3 AKI (OR, 1.02; 95% CI, 0.96-1.10), or stage 3 AKI (OR, 1.06; 95% CI, 0.98-1.14). Conclusions and Relevance: Documented BL allergies were not associated with the long-term odds of mortality but were associated with antibiotic-resistant infections. Health systems should emphasize accurate allergy documentation and reduce unnecessary BL avoidance.

Characterizing Antibiotic Allergy Labels in a Large UK Hospital Population to Inform Antimicrobial Stewardship and Delabeling Assessment Strategy.

BACKGROUND: Antibiotic allergy labels are important barriers to treatment and antimicrobial stewardship, but their prevalence in UK hospitals is poorly described. OBJECTIVE: To ascertain the prevalence and characteristics of antibiotic allergy labels in a large UK hospital setting and estimate the proportion of penicillin allergy labels for which point-of-care (POC) delabeling assessment would be appropriate. METHODS: Electronic health records data were analyzed from all patients treated at Cambridge University Hospitals NHS Foundation Trust in 2019. Validated POC delabeling risk stratification criteria were retrospectively applied to penicillin allergy labels. RESULTS: Recorded reactions to antibiotics were present in 11.8% of all patients (32,148 of 273,216), 16.3% of inpatients (13,874 of 85,230), and 9.7% of outpatients (18,274 of 187,986). Penicillins were the commonest reaction precipitant described (9.0% of patients; 24,646 of 273,216), followed by sulfonamides/trimethoprim (1.4%; 3869 of 273,216) and macrolides/lincosamides (1.3%; 3644 of 273,216). A total of 3.9% of inpatients had recorded reactions to >1 antibiotic class (3348 of 85,230). Cutaneous manifestations were the most commonly described reaction features (40.7% of labels; 15,821 of 38,902). Of 15,949 labels describing probable or possible penicillin "allergy" with sufficient detail to allow for the retrospective assessment of POC delabeling suitability, 1702 were deemed suitable for removal or downgrading of the label to "intolerance" without further investigation (10.7%), 11,887 were appropriate for POC assessment using an oral penicillin challenge (OPC) or OPC with prior bedside skin testing (74.5%), and 2360 were identified as unsuitable for any form of POC assessment (14.8%). CONCLUSIONS: Antibiotic allergy labels are highly prevalent in a UK hospital setting. A large proportion of penicillin allergy labels may be suitable for POC delabeling assessment.

Analysis of the Safety of Drug Allergy Workups in a Spanish University Hospital: Drug Characteristics, Type of Reaction, and Patients' Age at the Initial Assessment.

INTRODUCTION: The drug provocation test (DPT) is the gold standard for the drug allergy workup; however, it is not free from severe adverse reactions. Our aim was to obtain robust data that predict a reaction during or after the DPT at the first contact with the patient in the allergy outpatient clinic. METHODS: The population of this cross-sectional study comprised all patients undergoing a drug allergy workup (clinical assessment, specific IgE, or skin tests, or DPT) at University Hospital Fundacion Alcorcon in 2016. DPTs were performed until therapeutic doses were reached, and late reactions were checked. The clinical disorders assessed in our study were classified mainly as absence of allergic reactions, morbilliform rash, urticaria, anaphylaxis, and other cutaneous disorders. RESULTS: Physicians from the Allergy Unit programmed drug allergy workups in 977 patients (median age, 52 years; women, 64.54%). DPTs were not performed for 165 drugs involved in the reactions. Patients who did not undergo DPT were older than patients who did (positive or negative) (p = 0.0001). Positive DPT results were detected in 6.00% of DPTs performed, and most were for amoxicillin and metamizole (15-25% each). Multinomial logistic regression showed that positive reactions were more probable after DPT if the same clinical disorder was diagnosed at the first visit, including the episodes not considered allergic episodes (OR = 0.2, <0.01), except for anaphylaxis, which favored not performing DPTs (OR = 11, p < 0.001). CONCLUSION: We conclude that clinical practice in the diagnosis of drug allergy in our Allergy Department is safe, without over-diagnosis.

Penicillin Allergy Evaluation and Health Equity: A Call to Action.

Allergists have been at the forefront of addressing the burden of unverified penicillin allergy labels. Coordinated national efforts with infectious diseases, antimicrobial stewardship experts, and pharmacy societies to advocate for formal evaluation of patient-reported penicillin allergy have resulted in improvements in delabeling efforts. Given the poorer health outcomes associated with the penicillin allergy label and the potential health benefits that can be gained with delabeling, improving access to penicillin allergy evaluation is of the utmost importance. Health disparities are widely recognized to impact all aspects of health care, and multilevel interventions at the patient, clinician, and systems level are required to ensure equitable care delivery. Structural racism underpins many social determinants of health and is a key driver of racial and ethnic health disparities. In this Rostrum, we use a conceptual framework from the 2015 National Academy of Medicine report Improving Diagnosis in Health Care to explore how inequities are related to the evaluation of penicillin allergy. We use the National Institute on Minority Health and Health Disparities Strategies to Advance Health Disparities to elucidate areas of important study. Building upon existing efforts to address disparities in Allergy/Immunology, we highlight the urgent importance of understanding and eliminating health disparities in penicillin allergy evaluation and delabeling.

A Prospective Study of Costs Associated With the Evaluation of Allergic Reactions to Radiological Contrast Media.

BACKGROUND AND OBJECTIVE: The prevalence of hypersensitivity reactions to radiological contrast media (RCM) is increasing owing to the improved performance of diagnostic and therapeutic tests that require RCMs. Objective: We carried out a year-long real-life observational study to prospectively evaluate patients referred to the allergy department from primary care, the emergency department, and other specialties with suspected moderate-to-severe RCM hypersensitivity reactions. METHODS: To study the costs of evaluating RCM hypersensitivity reactions, we systematically recorded direct and indirect costs. RESULTS: Sixty-nine patients with previous reactions to RCM were evaluated in the allergy department from June 1, 2017, to May 31, 2018.Total direct health care costs were €10 715.84, with a mean (SD) cost per patient of €155.30 (77.08). Specifically, direct non-health care costs reached €1605.42 (mean, €23.27 [41.14]), and indirect costs were €6490.85 (mean, €94.07 [110.61]). In summary, the total cost was €18 812.11, that is, a mean cost of €272.64 (164.77). CONCLUSION: Our study shows that the costs of an elective evaluation of hypersensitivity reactions to RCM are low, thus confirming that correct and safe management of affected patients are cost-effective. Therefore, our efforts should be directed toward ensuring the necessary logistics.

Penicillin Allergy Delabeling Program: an exploratory economic evaluation in the Australian context.

BACKGROUND: Internationally, clinical and economic advantages of low-risk penicillin delabelling have been explored, supporting changes to healthcare delivery systems where penicillin delabelling is embedded into inpatient usual care. AIMS: To determine if economic advantages of low-risk inpatient penicillin delabelling, described in the international literature, are realised in the Australian context. METHODS: This explorative economic evaluation had prospective patient data collection between January and August 2019, across two Australian health services. Part 1: determine the cost per effectively delabelled patient for Penicillin Allergy Delabeling Program inpatients (PADP cohort) compared with Outpatient Antibiotic Allergy Testing Service outpatients (OAATS cohort). Part 2: a cost analysis to compare hospital costs for inpatients with low-risk penicillin allergy who did (PADP cohort) and did not (usual care cohort) undergo PADP delabelling. RESULTS: Part 1: the PADP (n = 350) and OAATS (n = 27 patients, n = 36 individual visits) cohorts were comparable. In PADP, costs/proportion delabelled was $20.10/0.98, equating to $20.51 per effectively delabelled patient; in OAATS, it was $181.24/0.50, equating to $362. Compared with OAATS, PADP was associated with savings of $341.97 per effectively delabelled patient, indicating the outpatient testing was the dominated strategy, being more costly and less effective. Part 2: the PADP (n = 218) and usual care (n = 32) cohorts were comparable. Significantly favouring the delabelled PADP cohort, the mean difference per patient was -4.41 days (95% confidence interval: -7.64, -1.18) and -$9467.72 (95% confidence interval: -$15 419.98, -$3515.46). CONCLUSIONS: Consistent with international literature, delabelling low-risk penicillin allergies in the inpatient setting had economic advantages in the Australian context. Fully powered economic evaluations are urgently required to consolidate these findings.

DALES, Drug Allergy Labels in Elective Surgical patients: a prospective, multicentre cross-sectional study of prevalence, nature and anaesthetists' approach to management.

BACKGROUND: We sought to define the prevalence and nature of patient-reported drug allergies, determine their impact on prescribing, and explore drug allergy knowledge and attitudes amongst anaesthetists. METHODS: We performed a prospective cross-sectional study in 213 UK hospitals in 2018. Elective surgical patients were interviewed, with a detailed allergy history taken in those self-reporting drug allergy. Anaesthetists completed a questionnaire concerning perioperative drug allergy. RESULTS: Of 21 219 patients included, 6214 (29.3 %) (95% confidence interval [CI]: 28.7-29.9) reported drug allergy. Antibiotics, NSAIDs, and opioids were the most frequently implicated agents. Of a total of 8755 reactions, 2462 (28.1%) (95% CI: 29.2-31.1) were categorised as high risk for representing genuine allergy after risk stratification. A history suggestive of chronic spontaneous urticaria significantly increased the risk of reporting drug allergy (odds ratio 2.68; 95% CI: 2.4-3; P<0.01). Of 4756 anaesthetists completing the questionnaire, 1473 (31%) (95% CI: 29.7-32.3) routinely discuss perioperative allergy risk with patients. Prescribing habits in the presence of drug allergy labels differ depending on the implicated agent. Most anaesthetists (4678/4697; 99.6%) (95% CI: 99.4-99.8) prescribe opioids when reactions are consistent with side-effects, although 2269/4697 (48%) (95% CI: 46.9-49.7) would avoid the specific opioid reported. CONCLUSIONS: Almost 30% of UK elective surgical patients report a history of drug allergies, but the majority of reported reactions are likely to be non-allergic reactions. Allergy labels can impact on perioperative prescribing through avoidance of important drugs and use of less effective alternatives. We highlight important knowledge gaps about drug allergy amongst anaesthetists, and the need for improved education around allergy.

Drug allergy management in the elderly.

PURPOSE OF REVIEW: Drug allergy management has previously not been emphasized in the elderly. However, the geriatric population poses several unique characteristics, challenges for drug allergy testing and considerations in the management. Especially in the era of COVID-19, the elderly population is a vulnerable cohort and reviewing the management during this unprecedented time is both timely and relevant. RECENT FINDINGS: In recent years, larger scale studies focusing on the epidemiology and prevalence trends of drug allergies among older adults has been summarized in this review. Emphasis on anaphylaxis in the older adults has been studied. SUMMARY: There are many implications of these findings. Epidemiological studies are useful in realizing the burden and spectrum of drug allergies on our healthcare system. It has allowed us to identify certain barriers in drug allergy management and develop ways to overcome these challenges through. Lastly, we have proposed an approach to drug allergy management based on previous studies as well as from our perspective and local experience.

Economic Burden of Patient-Reported Penicillin Allergy on Total Hip and Total Knee Arthroplasty.

INTRODUCTION: Self-reported penicillin allergies in patients undergoing total joint arthroplasty often results in the use of second-line prophylactic antibiotics. A higher risk of prosthetic joint infection (PJI) is associated with suboptimal antibiotics vs first generation cephalosporins, which have historically been grouped with other beta-lactam antibiotics such as penicillin for potential allergic reactions. This study evaluates the economic burden of self-reported penicillin allergies in total joint arthroplasty (TJA). METHODS: Data from studies reporting true incidence of IgE-mediated penicillin allergies, infection-free survivorship of TJA, and cost of PJI attributed to use of second-line antibiotics were obtained. Projected cost of preoperative penicillin allergy testing and potentially avoidable PJI associated with second-line antibiotic usage were calculated. This was compared with projected cost of PJI in the current state to estimate cost savings. RESULTS: Implementation of preoperative penicillin allergy testing leads to a potential savings of nearly $37 million to payors in the first year based on 1-year survivorship. This savings increases to $411.6 million over a 10-year span and $1.18 billion over a 20-year span. CONCLUSION: Preoperative penicillin allergy testing or risk stratification via thorough history should be implemented as standard of care for patients with self-reported penicillin allergies before TJA and would result in decreased cost of PJI.

Assessment of the Frequency of Dual Allergy to Penicillins and Cefazolin: A Systematic Review and Meta-analysis.

Importance: Cefazolin is the preoperative antibiotic of choice because it is safer and more efficacious than second-line alternatives. Surgical patients labeled as having penicillin allergy are less likely to prophylactically receive cefazolin and more likely to receive clindamycin or vancomycin, which results in higher rates of surgical site infections. Objective: To examine the incidence of dual allergy to cefazolin and natural penicillins. Data Sources: MEDLINE/PubMed, Web of Science, and Embase were searched without language restrictions for relevant articles published from database inception until July 31, 2020. Study Selection: In this systematic review and meta-analysis, a search of MEDLINE/PubMed, Web of Science, and Embase was performed for articles published from database inception to July 31, 2020, for studies that included patients who had index allergies to a natural penicillin and were tested for tolerability to cefazolin or that included patients who had index allergies to cefazolin and were tested for tolerability to a natural penicillin. A total of 3228 studies were identified and 2911 were screened for inclusion. Data Extraction and Synthesis: Data were independently extracted by 2 authors. Bayesian meta-analysis was used to estimate the frequency of allergic reactions. Main Outcomes and Measures: Dual allergy to cefazolin and a natural penicillin. Results: Seventy-seven unique studies met the eligibility criteria, yielding 6147 patients. Cefazolin allergy was identified in 44 participants with a history of penicillin allergy, resulting in a dual allergy meta-analytical frequency of 0.7% (95% credible interval [CrI], 0.1%-1.7%; I2 = 74.9%). Such frequency was lower for participants with unconfirmed (0.6%; 95% CrI, 0.1%-1.3%; I2 = 54.3%) than for those with confirmed penicillin allergy (3.0%; 95% CrI, 0.01%-17.0%; I2 = 88.2%). Thirteen studies exclusively assessed surgical patients (n = 3884), among whom 0.7% (95% CrI, 0%-3.3%; I2 = 85.5%) had confirmed allergy to cefazolin. Low heterogeneity was observed for studies of patients with unconfirmed penicillin allergy who had been exposed to perioperative cefazolin (0.1%; 95% CrI, 0.1%-0.3%; I2 = 13.1%). Penicillin allergy was confirmed in 16 participants with a history of cefazolin allergy, resulting in a meta-analytical frequency of 3.7% (95% CrI, 0.03%-13.3%; I2 = 64.4%). The frequency of penicillin allergy was 4.4% (95% CrI, 0%-23.0%; I2 = 75%) for the 8 studies that exclusively assessed surgical patients allergic to cefazolin. Conclusions and Relevance: These findings suggest that most patients with a penicillin allergy history may safely receive cefazolin. The exception is patients with confirmed penicillin allergy in whom additional care is warranted.

A Survey on Knowledge Gaps in Assessment and Management of Severe Drug Hypersensitivity Reactions: Multicenter Cross-Sectional Study of Australian Health Care Providers.

Severe drug hypersensitivity reactions (DHRs) are often encountered by health care professionals (HCPs). We evaluated knowledge of doctors and pharmacists in the assessment and management of severe DHRs using a structured questionnaire. A cross-sectional study was conducted in 4 metropolitan hospital networks in Melbourne, Australia. A 13-question, scenario-based multiple-choice questionnaire to assess specific knowledge domains in drug hypersensitivity syndrome recognition, causality attribution, cross-reactivity patterns, appropriate diagnostic tests, and therapy was administered to HCPs of various vocation and specialty groups. Data were analyzed according to profession, self-reported experience, and preparedness in managing severe DHRs. Two hundred thirty-eight participants (45.0% senior doctors, 24.4% junior doctors, and 30.7% pharmacists) across a range of subspecialties achieved an overall median score of 7 (IQR, 5-8)-overall 55.6% correct responses to all questions-with senior doctors outperforming junior doctors and pharmacists (P < .001). The best performance by all participants was in DHR syndrome recognition (60.9%), and the poorest was in diagnostics/therapy (52.0%). HCP group and experience level were significantly associated with better performance in the knowledge domains of cross-reactivity and diagnostics/therapy (P = .003 and < .001, respectively), but not in the domains of syndrome recognition and causality attribution (P > .05). Levels of self-reported preparedness in DHR management were not associated with performance rates in any of the knowledge domains. This study demonstrated significant knowledge gaps in the recognition and management of severe drug hypersensitivity reactions. Targeted multidisciplinary education of staff caring for these patients is needed to improve knowledge gaps.

Perioperative Allergic Reactions: Allergy Assessment and Subsequent Anesthesia.

BACKGROUND: Evidence-based guidelines are needed in the United States to improve evaluation of perioperative allergic reactions including recommendations for subsequent anesthesia. OBJECTIVE: To identify causative agent(s) and evaluate patients' tolerability of subsequent anesthesia in patients evaluated by Allergy/Immunology (A/I) at Massachusetts General Hospital. METHODS: We performed a retrospective review of patients referred to the outpatient A/I clinic for perioperative allergic reactions between October 2003 and May 2017. Patient demographics, atopic history, and prior adverse drug reactions were reviewed. Patients underwent a comprehensive evaluation with testing including skin testing (ST), drug challenges (when appropriate), tryptase level measurement, and specific IgE to latex measurement. Tolerance of subsequent procedures requiring anesthesia was assessed. RESULTS: Of 123 patients referred, 74 (60%) were female and the mean age was 46 (±18) years. At least 1 causative agent was identified in 28 patients (24%, n = 28 of 118). Seventeen of 28 (61%) patients were ST positive to an antibiotic, including 13 (46%) positive to cefazolin; 3 patients (11%) had a positive latex specific IgE. Of 85 patients who had subsequent anesthesia with a known outcome, 78 (91%) did not have another perioperative allergic reaction. Two of 5 patients with an elevated baseline tryptase level did not tolerate subsequent anesthesia. CONCLUSION: The majority of patients safely received subsequent anesthesia after comprehensive A/I evaluation for their perioperative allergic reactions; however, improved algorithmic care is needed in the United States. Among ST-positive patients (24%), antibiotics (especially cefazolin) were the most common culprits. An elevated baseline tryptase level was associated with an increased risk of recurrent perioperative allergic reactions.

Penicillin Allergy Assessment in Pregnancy: Safety and Impact on Antibiotic Use.

BACKGROUND: Penicillin and other beta-lactam antibiotics are recommended for group B Streptococcus and cesarean section prophylaxis, but approximately 10% of pregnant patients report a penicillin allergy. OBJECTIVE: To assess the safety and impact of penicillin allergy evaluation in pregnant patients. METHODS: In this retrospective study of obstetrician-ordered Allergy/Immunology (AI) electronic consultations (e-consults) from September 20, 2017 through December 31, 2019, we reviewed the electronic health record for e-consult recommendation; patient demographic, obstetric, and allergy histories; and peripartum antibiotic utilization with indication. For patients whose electronic consultation recommended an in-person AI evaluation, testing outcomes were determined, and multivariable logistic regression models were used to compare antibiotic use between patients who did and did not receive an in-person AI evaluation. RESULTS: Of 389 obstetrician-ordered e-consults, 363 (93%) recommended an in-person AI evaluation; of these, 222 (61%) patients received an in-person AI evaluation. Of 220 (99%) patients skin tested, 209 (95%) had their penicillin allergy label safely removed. Compared with patients who did not receive an in-person AI evaluation despite it being recommended (n = 141), patients with in-person AI evaluation (n = 222) had reduced peripartum vancomycin (adjusted odds ratio [aOR], 0.07; 95% CI, 0.01-0.33), clindamycin (aOR, 0.17; 95% CI, 0.08-0.34), and gentamicin (aOR, 0.39; 95% CI, 0.19-0.78) use and increased penicillin (aOR, 18.0; 95% CI, 6.30-51.2) use. The fully AI evaluated patients had increased first-line antibiotic prophylaxis for group B Streptococcus (aOR, 26.9; 95% CI, 6.32-114) and cesarean section (aOR, 1.94; 95% CI, 1.06-3.52). CONCLUSIONS: In a sample of 220 pregnant patients with penicillin allergy histories and in-person AI evaluation, penicillin allergy testing was safe and associated with significantly reduced broad-spectrum antibiotic use and increased first-line beta-lactam antibiotic use.

The impact of antibiotic allergy labels on antibiotic exposure, clinical outcomes, and healthcare costs: A systematic review.

OBJECTIVE: A growing body of evidence suggests that antibiotic allergy labels as documented in medical records are a risk factor for poor clinical outcomes. In this systematic review, we aimed to determine how antibiotic allergy labels influence 3 domains: antibiotic use and exposure, clinical outcomes, and healthcare-related costs. DESIGN: We performed a systematic review to identify studies reporting outcomes in patients with antibiotic allergy labels compared to nonallergic counterparts. The search included PubMed, EMBASE, Cochrane CENTRAL, EBSCO, Cochrane Database of Abstracts of Reviews of Effects and Web of Science. Two reviewers independently screened studies for inclusion and abstracted data. Studies were graded using the Newcastle-Ottawa quality assessment scale. Study outcomes included antibiotic use, clinical outcomes, and economic outcomes. RESULTS: In total, 41 studies met our criteria for inclusion. These studies varied in medical specialty, patient population, healthcare delivery system, and design, but most were conducted among adults age >18 years (85%) in the inpatient setting (82.5%). Among 34 studies examining antibiotic exposure, 32 (94%) found that patients with antibiotic allergy labels received more broad-spectrum antibiotics. Moreover, 31 studies examined clinical outcomes such as length of hospitalization, ICU admission, hospital readmission, multidrug-resistant or opportunistic infection, or mortality, and 27 (87%) found that allergy-labeled patients had at least 1 negative outcome. Of 9 studies examining healthcare costs, 7 (78%) found that allergy-labeled patients incurred significantly higher drug or hospital-related costs. CONCLUSIONS: Antibiotic allergy labels have negative effects on antibiotic use, clinical outcomes, and economic outcomes in a variety of clinical settings and populations.

Drug hypersensitivity in the fast lane: What clinicians should know about phenotypes, endotypes, and biomarkers.

OBJECTIVE: To review novel concepts in drug hypersensitivity and the management of immediate hypersensitivity reactions. DATA SOURCES: English language literature on MEDLINE and Embase surrounding drug hypersensitivity and desensitization. STUDY SELECTIONS: References were selected based on relevance, date of publication, and originality. RESULTS: There are numerous citations looking at categorizing drug reactions, pathogenesis, biomarkers, and desensitization. Current understanding supports the use of a phenotype-endotype-biomarker model for categorizing immediate hypersensitivity reactions. Drug desensitization is a powerful therapeutic strategy that enables temporary induction of tolerance to medications that triggered immediate reactions. CONCLUSION: Immediate hypersensitivity reactions are diverse in presentation and pathogenesis. Drug desensitization is an effective intervention with sufficient evidence to support its more widespread availability.

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.

High-cost, high-need patients: the impact of reported penicillin allergy.

OBJECTIVES: More than 90% of patients who report a penicillin allergy have the allergy disproved when tested. Unnecessary use of alternative (non-beta-lactam) antibiotics can result in more treatment failures and adverse reactions. We described the prevalence and impact of a reported penicillin allergy in high-cost, high-need (HCHN) patients. STUDY DESIGN: Retrospective cohort. METHODS: We identified HCHN patients in a care management program of an urban academic medical center (January 1, 2014, to December 31, 2016). We used multivariable logistic regression models to determine the association between a reported penicillin allergy and antibiotic use. We used multivariable Poisson regression models to determine the association between a reported penicillin allergy, with or without multiple drug intolerance syndrome (MDIS; ≥3 reported drug allergies), and healthcare resource utilization (HRU). RESULTS: Of 1870 HCHN patients, 383 (20%) reported penicillin allergy, 835 (45%) had MDIS, and 290 (16%) had both. HCHN patients reporting penicillin allergy had an increased odds of beta-lactam alternative antibiotic use (adjusted odds ratio, 3.84; 95% CI, 2.17-6.80). HRU was significantly higher for patients reporting a penicillin allergy alone (adjusted relative risk [aRR], 1.13; 95% CI, 1.03-1.25) and with concurrent MDIS (aRR, 1.20; 95% CI, 1.08-1.34). CONCLUSIONS: HCHN patients had a high burden of reported drug allergy. A reported penicillin allergy conferred a 4-fold increased odds of beta-lactam alternative antibiotic use. Reporting penicillin allergy, with and without MDIS, was associated with significantly more HRU. HCHN care management programs should consider systematic drug allergy evaluations to optimize antibiotic use in these fragile patients.

Prevalence and management of aspirin hypersensitivity in a cardiology practice.

Background: Data are lacking with concern to the prevalence and management of aspirin (ASA) hypersensitivity. Objective: To study the prevalence, different types of reactions, and implications for clinical management of ASA hypersensitivity in a cardiology practice. Methods: We conducted an electronic medical record review of 11,375 individuals, 5052 (44%) in the ambulatory setting, and 6323 (56%) admitted for percutaneous coronary intervention (PCI), from January 2012 to December 2013. Results: The prevalence of ASA hypersensitivity was 1.88% (n = 214). Skin reactions were the most common (40 [19%]), followed by angioedema (10 [4.6%]), respiratory (9 [4.2%]), and anaphylaxis (6 [2.8%]). No records were found for 74 patients (34.5%), and 69 patients (32.2%) were mistakenly labeled as allergic for having gastrointestinal symptoms. Of the 214 patients who had documented ASA hypersensitivity, 108 individuals (50.46%) had coronary artery disease. The medications at discharge were the following: ASA (30 [14%]), thienopyridine (48 [22%]), a combination of ASA and thienopyridine (13 [6%]), anticoagulation only (26 [12%]), and no antiplatelet (97 [43%]). Conclusion: ASA hypersensitivity is often not documented correctly or is often misdiagnosed or not appropriately managed. There is a need for improved management of ASA hypersensitivity, including appropriate referral for ASA desensitization and combating unnecessary avoidance in patients with intolerance due to adverse effects.

Hypersensitivity reactions with allopurinol and febuxostat: a study using the Medicare claims data.

OBJECTIVE: To assess the risk of hypersensitivity reactions (HSRs) with allopurinol and febuxostat in a population-based study. METHODS: We used the 5% Medicare beneficiary sample (≥65 years) from 2006 to 2012 to identify people with a newly filled prescription for allopurinol, febuxostat or colchicine. We used multivariable-adjusted Cox regression analyses to compare the hazard ratio (HR) of incident HSRs with allopurinol or febuxostat use versus colchicine use; separate analyses were done in people exposed to allopurinol. Propensity-matched analyses (5:1) compared hazards with allopurinol versus febuxostat. RESULTS: Crude incidence rates of HSRs were as follows: allopurinol, 23.7; febuxostat, 30.7; and colchicine, 25.6 per 1000 person-years. Compared with colchicine, allopurinol, febuxostat and febuxostat+colchicine were associated with significantly higher HRs of HSRs, 1.32 (95% CI: 1.10 to 1.60) and 1.54 (95% CI: 1.12 to 2.12) and 2.17 (95% CI: 1.18 to 3.99), respectively. In propensity-matched analyses, febuxostat did not significantly differ from allopurinol; HR for HSRs was 1.25 (95% CI: 0.93 to 1.67). Compared with allopurinol start dose <200 mg/day, allopurinol start dose ≥300 mg/day, diabetes and female sex were associated with significantly higher hazard of HSRs, 1.27 (95% CI: 1.12 to 1.44), 1.21 (95% CI: 1.00 to 1.45) and 1.32 (95% CI: 1.17 to 1.48), respectively. The majority (69%) of HSRs occurred in the outpatient setting. CONCLUSIONS: Compared with colchicine, allopurinol and febuxostat similarly increased the risk of HSRs. Allopurinol and febuxostat did not differ from each other. In allopurinol users, starting dose, female sex and diabetes increased this risk, findings that need further study.