Allergy Delabeling Research Articles

The Evolution of Our Understanding of Penicillin Allergy: 1942-2022

This article reviews our evolving understanding of penicillin hypersensitivity at the 80th anniversary of penicillin's clinical introduction. Penicillin breakdown products covalently bond to serum proteins, leading to classic drug hypersensitivity. Penicillin remains the most frequently reported drug "allergy." Adverse reactions were presumed, in retrospect incorrectly, to implicate a risk for anaphylaxis, and therefore skin testing for IgE became the focus. Skin test positivity may wane over time. This insight has led to the radical conclusion that penicillin hypersensitivity may not be "forever." Atopic background, other drug allergies, family history, gender, and race are apparently not risk factors for penicillin hypersensitivity. Confirmed penicillin hypersensitivity has declined since the 1960s, potentially due to "cleaner" penicillin products and lower dose oral, instead of parenteral, use. Avoiding penicillins, without evaluation, caused unanticipated problems that have been appreciated only recently including longer hospital stays, increased cost of care, suboptimal outcomes from serious infections, and greater toxicities and costs with alternative antibiotics. There are personal and public health advantages with broadly implemented penicillin allergy delabeling based on a reaction history-based risk assessment. Limited skin testing followed by an oral challenge, if negative, for higher-risk histories, and direct oral challenges in lower-risk individuals are currently the reference standard tests to confirm current tolerance.

Survey of Obstetric Providers to Assess the Knowledge and Management of a Reported Penicillin Allergy in Pregnant Women.

Penicillin allergy is the most commonly reported drug allergy in the United States; however, less than 10% of individuals labeled with a penicillin allergy are truly allergic. A reported penicillin allergy in pregnancy is associated with adverse maternal and perinatal outcomes. Despite recommendations for penicillin allergy testing in pregnancy, limited literature regarding obstetric providers' comfort and knowledge in addressing penicillin allergy and referral patterns exists. The objective of this study is to survey obstetric providers to assess their clinical practice patterns and baseline penicillin allergy knowledge, identify potential knowledge gaps in the management of pregnant patients with reported penicillin allergy, and measure the impact of an educational intervention on provider knowledge and practice patterns. An anonymous, electronic 23-question survey administered to all obstetric providers at a single academic medical center assessed obstetric provider characteristics, self-reported antibiotic practice patterns, and antibiotic allergy knowledge before (June 19, 2020) and after (September 16, 2020) a penicillin allergy educational intervention, which consisted of multiple small-group educational sessions and a culminating departmental educational session. Discrete knowledge comparison by provider type and experience level of pre- and postintervention was performed using chi-square tests. Of 277 obstetric providers invited, 124 (45%) responded preintervention and 62 (22%) postintervention. In total, 27% correctly identified the percentage of patients labeled penicillin allergic who would tolerate penicillins, 45% identified cephalosporin cross-reactivity, 59% understood penicillin allergies can wane, and 54% identified penicillin skin testing (PST) as a valid allergy verification tool. Among 48 respondents who attended educational sessions and responded postintervention, their knowledge of penicillin allergy waning (79% preeducation vs. 98% posteducation, p < 0.01) and PST as a valid tool for penicillin allergy verification (50% preeducation vs. 83% posteducation, p < 0.01) improved. Knowledge gaps related to penicillin allergy exist among obstetric providers. Educational initiatives may improve provider knowledge, help in the identification of patients requiring penicillin allergy evaluation, and reduce referral barriers. · Obstetric providers lack adequate knowledge of penicillin allergy.. · Educational interventions can improve discrete knowledge.. · Limited knowledge is a barrier to allergy referral for penicillin allergy delabeling..

Hong Kong Drug Allergy Delabelling Initiative (HK-DADI) consensus statements for penicillin allergy testing by nonallergists.

IntroductionPenicillin allergy testing has been traditionally performed by allergists, but there remains a huge deficit of specialists. A multidisciplinary effort with nonallergists would be invaluable to overcome the magnitude of penicillin allergy labels via the Hong Kong Drug Allergy Delabelling Initiative (HK-DADI). These consensus statements (CSs) offer recommendations and guidance to enable nonallergists to screen for low-risk (LR) patients and perform penicillin allergy testing.MethodsCSs were formulated by the HK-DADI Group using the Delphi method. An agreement was defined as greater than or equal to 80% consensus.ResultsA total of 26 CSs reached consensus after multiple rounds of Delphi. CSs were categorized into risk assessment, skin testing, drug provocation testing (DPT), and post-testing management. For risk assessment, the essentials of allergy history and exclusion criteria were detailed. Patients with only LR features can proceed with testing by nonallergists. Skin tests should be performed prior to DPT. Details regarding the timing, preparation, and interpretation of skin tests were elaborated. DPT remains the gold standard to diagnose genuine allergy or tolerance and should be performed when there is a low pretest probability following negative skin testing. Details of DPT preparations, dosing protocols, and interpretation were elaborated. For post-testing management, inaccurate allergy labels should be delabeled following negative DPT with proper patient counseling.ConclusionCSs support penicillin allergy testing by nonallergists in Hong Kong. LR cases can be managed by nonallergists at Spoke Clinics, with training and support of an allergist-led Hub.

Antibiotic Allergy De-Labeling: A Pathway against Antibiotic Resistance.

Antibiotics are one of the most frequently prescribed drugs. Unfortunately, they also are the most common cause for self-reported drug allergy, limiting the use of effective therapies. However, evidence shows that more than 90% of patients labeled as allergic to antibiotics are not allergic. Importantly, the label of antibiotic allergy, whether real or not, constitutes a major public health problem as it directly impacts antimicrobial stewardship: it has been associated with broad-spectrum antibiotic use, often resulting in the emergence of bacterial resistance. Therefore, an accurate diagnosis is crucial for de-labeling patients who claim to be allergic but are not really allergic. This review presents allergy methods for achieving successful antibiotic allergy de-labeling. Patient clinical history is often inaccurately reported, thus not being able to de-label most patients. In vitro testing offers a complementary approach but it shows limitations. Immunoassay for quantifying specific IgE is the most used one, although it gives low sensitivity and is limited to few betalactams. Basophil activation test is not validated and not available in all centers. Therefore, true de-labeling still relies on in vivo tests including drug provocation and/or skin tests, which are not risk-exempt and require specialized healthcare professionals for results interpretation and patient management. Moreover, differences on the pattern of antibiotic consumption cause differences in the diagnostic approach among different countries. A multidisciplinary approach is recommended to reduce the risks associated with the reported penicillin allergy label.

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

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. To determine if economic advantages of low-risk inpatient penicillin delabelling, described in the international literature, are realised in the Australian context. 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. 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). 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.

Improving routine prenatal penicillin allergy testing for reported penicillin allergy

BackgroundPatients 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%...

Feasibility of a Centralized, Pharmacy-Led Penicillin Allergy Delabeling Program.

Penicillin allergy labels are often inaccurate in children and removing unnecessary labels results in improved outcomes and lower health care costs. Although the hospital setting is a frequent point of contact for children, strategies to evaluate penicillin allergies in the hospital are lacking. We performed a prospective pilot study to determine the feasibility of a centralized, pharmacy-led approach to penicillin allergy evaluation. Children with a reported history of penicillin allergy admitted to our children's hospital were risk-stratified and those stratified as low-risk underwent a single-dose oral challenge by a central pharmacist, regardless of the need for antibiotics. After the completion of each patient's delabeling process, surveys were distributed to health care personnel involved in the patient's care to collect perceptions on the acceptability, appropriateness, and feasibility of this intervention. Measures were scored by using a 5-point Likert scale. Of the 23 patients who screened as low-risk, 20 underwent a penicillin allergy evaluation and an oral challenge. Of these, the penicillin allergy label was removed in 19 (95%) patients (Fig 1). The median age was 7 years (range 11 months-18 years). Participants rated the risk stratification and delabeling favorably overall, with high ratings on all 3 implementation measures: acceptability (mean 4.55, ± standard deviation [STD] 0.65), appropriateness (mean 4.58, STD ± 0.6), and feasibility (mean 4.51, STD ± 0.73). Measures of acceptability, appropriateness, and feasibility remained high when stratified by health care worker type and provider type. Our findings provide support for systemic implementation of penicillin allergy delabeling strategies in hospitalized children.

An ultra-sensitive homologous chemiluminescence immunoassay to tackle penicillin allergy

Penicillin is one of the most widely used antibiotics to treat bacterial infections in clinical practice. The antibiotic undergoes degradation under physiological conditions to produce reactive compounds that in vivo bind self-proteins. These conjugates might elicit an immune response and trigger allergic reactions challenging to diagnose due to the complex immunogenicity. Penicillin allergy delabeling initiatives are now part of antibiotic stewardship programs and include the use of invasive and risky in vivo tests. Instead, the in vitro quantification of specific IgE is highly useful to confirm immediate allergy to penicillins. However, discrepant results associated with the low sensitivity and accuracy of penicillin allergy in vitro tests have limited their routine diagnostic use for delabeling purposes. We aimed to develop a homologous chemiluminescence-based immunochemical method for the reliable determination of specific IgE to penicillin G, using unprecedented synthetic human-like standards. The synthetic standard targets the major antigenic determinant of penicillin G and the paratope of Omalizumab, acting as human-like specific IgE. It is a potent calibrator, highly stable, easy, and inexpensive to produce, overcoming the limitations of the pooled human serum preparations. The developed method achieved a good agreement and strong positive relationship, reaching a detection limit below 0.1 IU mL−1 and excellent reproducibility (RSD <9%). The clinical sensitivity of the assay significantly increased (66%), doubling the accuracy of the reference method with an overall specificity of 100%. The new diagnostic strategy compares favorably with results obtained by the standard procedure, paving the way towards the standardization of penicillin allergy testing, and enhancing the detection sensitivity of specific IgE in serum to tackle reliably β-lactam allergy delabeling.

Racial and ethnic differences in penicillin allergy reporting and allergist referral

Background: Antimicrobial resistance (AMR) is a global public health crisis. A key strategy to combat AMR is to use targeted antibiotics, which is difficult in patients who report an allergy to penicillin. Increased risk for resistant infections, mortality, and healthcare costs are associated with penicillin allergies; however, up to 90% of those with a reported penicillin allergy do not have a true allergy. We investigated racial and ethnic differences related to penicillin allergy delabeling by analyzing rates of penicillin allergy reporting and referral for allergist consultation. Methods: Tufts Medical Center is a teaching medical center in Boston, Massachusetts. This study cohort contains all patients seen in 2019 by clinicians at Primary Care Boston, the main primary care practice at Tufts Medical Center. Demographic data, documented allergies, and referral history were collected from the electronic medical record. We performed univariate and multivariable analyses using logistic regression models. Covariates found to be statistically significant (P &lt; .05) in the univariate analyses were included in the multivariable model. Results:In total, 2,391 (11%) patients reported a penicillin allergy, but only 249 (10%) were referred to an allergist (Table 1). Black patients and Asian patients were less likely to report a penicillin allergy than White patients. We detected no differences related to Hispanic ethnicity. Black patients with penicillin allergy were more likely to be referred to an allergist. Conclusions: There were low rates of allergist referral for penicillin allergy delabeling in this cohort. We identified racial differences in both penicillin allergy reporting and allergist referral. Allergist consultation is an important opportunity to combat AMR and should be considered for all patients reporting a penicillin allergy. Future work should evaluate equitable access to allergy delabeling resources.Funding: NoneDisclosures: None

Penicillin allergy reinstatement in a cohort of patients previously delabeled following formal allergy assessment

Background: Penicillin allergies are frequently reported and are associated with adverse clinical and antimicrobial stewardship outcomes. Allergy delabeling, either by patient history or skin testing and oral challenge can facilitate removal of penicillin allergy label. However, penicillinallergies are often reinstated in the medical record and data is limited about how and why this occurs. In our center, the departments of allergy and infectious diseases utilize an allergist nurse practitioner for penicillin allergy delabeling. We investigated the prevalence of penicillin allergy reinstatement following removal and associated factors thereof. Methods: We performed a retrospective observational study of patients who previously had penicillin allergy removed by the allergist nurse practitioner between August 2020 and May 2021 (250 days). Patients were followed for a minimum of 8 months and up to 16 months after penicillin allergy removal. We then assessed whether the allergy was reinstated. Clinical characteristics were compared between patients with penicillin allergy reinstated and not reinstated using the χ2 and Mann-Whitney U test. The primary end point was prevalence of penicillin allergy reinstatement following removal. Results: During the study period, 81 patients had penicillin allergy removed, but it was later reinstated in 19 patients (23%) (Fig 1). Median time to reinstatement was 94 days. Allergies were reinstated most frequently by nurses (53%) and medical assistants (37%). Reinstatement occurred in both outpatient (53%) and inpatient (47%) settings. In 18 of 19 cases, there was no acknowledgment that a prior assessment had determined the patient was not allergic to penicillin. Only 1 patient experienced a reaction prompting reinstatement of penicillin allergy. Once the allergy was redocumented, it was subsequently mentioned in a median of 17 notes per patient. Comorbidities did not differ between patients with allergy reinstated versus those without (Table 1). Patients with penicillin allergy reinstated were more often originally delabeled via history rather than skin test followed by oral challenge and were more likely to have been readmitted subsequently. Conclusions: Penicillin allergies were redocumented in almost one-quarter of patients, most frequently by a nonphysician team member and without acknowledgement of prior removal. Patients who undergo skin testing may be less likely to continue to report a penicillin allergy to medical staff compared to those whose allergy is removed based on history. Increased interactions with the healthcare system may have contributed to having the allergy reinstated.Funding: NoneDisclosures: None

Addressing beta‐lactam allergy: A time for action

Addressing beta‐lactam allergy: A time for action

Antibiotic allergy labels and optimal antimicrobial stewardship.

Although common, antimicrobial allergy labels (AAL) rarely reflect immunologically-mediated hypersensitivity and can lead to poorer outcomes from alternative antimicrobial agents. Antimicrobial stewardship programs are ideally placed to assess AAL early as a means of improving antimicrobial use. To quantify the prevalence of AAL in patients referred for antimicrobial stewardship review and assess their impact on antibiotic prescribing, patient mortality, hospital length of stay, readmission and rates of multidrug-resistant infections. We conducted a retrospective analysis of adult patients referred for inpatient antimicrobial prospective audit and feedback rounds (PAFR) through an electronic referral system (eReferrals) over a 12-month period in 2015. Outcome data were collected for a period of 36 months following the initial review. Of the 639 patient records reviewed, 630 met inclusion criteria; 103 (16%) had an AAL, of which 82 (13%) had reported allergies to β-lactam antibiotics. Those with AAL were significantly less likely to be receiving guideline-recommended antimicrobial therapy (50% vs 64%, P=0.0311); however, there were no significant difference in mortality, hospital length of stay, readmission or increased incidence of multidrug-resistant infections. Our cohort demonstrated that AAL was associated with reduced adherence to antibiotic guidelines. The lack of association with adverse outcomes may reflect limitations within the study including retrospective cohort study numbers and observational nature, further skewed by high rates of poor documentation. A clear opportunity exists for antimicrobial stewardship programs to incorporate allergy assessment, de-labelling, challenge and referral into these rounds.

Drug allergy desensitization is not a unique recipe.

Drug desensitization is the only therapeutic option for patients with drug allergies who need to receive the drugs they are allergic to, and it is especially critical in patients with an urgent need for chemotherapy, biologics, or antibiotics, where equally effective alternatives might not be available. However, drug desensitization is not a cookbook where anyone with no experience or specific training can find a general recipe. This review article will approach the singularities that make personalized and highly specialized care essential in this field. Drug desensitization needs to be personalized for each individual patient bearing in mind countless factors. Recent articles have tried to define the optimal resources and the most important factors to account for in personalization. However, drug desensitization is only a tool within the wider management pathway, and we will discuss recent findings in allergy delabelling in chemotherapy, biologics, and antibiotics. Risk-assessment, delabelling, and desensitization protocols, as a part of wider management pathways, can be adapted locally along with comprehensive and multifactorial risk-management strategies. These high-complexity and high-risk procedures, such as drug desensitization, need to be managed by expert allergists who can provide personalization, innovation, continuous improvement, research, and teaching in expert centres.

Promoting β-lactam utilization through suppression of electronic medical record cross-allergy alerts.

Current literature surrounding management of patients with reported β-lactam allergies focuses on allergy delabeling. Standard clinical decision support tools have not been optimized to be compatible with the currently accepted cross-reaction rate of 1% to 2%. This potentially promotes use of non-β-lactam antibiotics, which are often not first-line therapy and may carry increased risks. The impact of electronic medical record (EMR) clinical decision support tool optimization on utilization of β-lactam antibiotics in β-lactam-allergic patients was evaluated. A retrospective pre-post β-lactam cross-allergy EMR alert suppression quality improvement intervention cohort study of β-lactam-allergic adult inpatients prescribed antibiotics was conducted. Preintervention baseline data were collected for an initial cohort admitted during September 2018. The intervention, in which clinical decision support rules were updated to display β-lactam cross-sensitivity allergy alerts only for β-lactam-allergic patients with documentation of organization-defined high-severity reactions of anaphylaxis, hives, and shortness of breath, was implemented August 20, 2019. The postintervention cohort included patients admitted during September 2019. A 91% increase in the percentage of β-lactam-allergic patients who received a β-lactam agent at any time during their admission was noted after the intervention (26.6% vs 51%, P < 0.001). Statistically significant decreases in prescribing of alternative antibiotic classes were seen for fluoroquinolones (decrease from 45.3% to 26%, P < 0.001), aminoglycosides (decrease from 9.4% to 2.9%, P = 0.002), and aztreonam (decrease from 30% to 16.7%, P < 0.001). EMR β-lactam cross-allergy alert optimization consistent with current literature significantly improved the utilization of alternative β-lactam subclasses, mostly through β-lactam prescribing as initial therapy in β-lactam-allergic patients.

Implementing Outpatient Penicillin Allergy Assessments by Non-Allergy Providers

Penicillin (PCN) allergy evaluation/testing is underutilized in outpatient settings directly impacting antibiotic use. We initiated an outpatient PCN allergy assessment program allowing initial risk stratification and/or PCN allergy delabeling in non-allergy clinics at University of North Carolina.

A Qualitative Analysis of Antibiotic Allergy Assessment by Pharmacy and Antimicrobial Stewardship Team Members at a Veterans Hospital

Penicillin allergy de-labeling is a high impact intervention requiring a multidisciplinary team to improve antimicrobial stewarsdhip (AMS) and the judicious use of antibiotics. Using a qualitative approach, we studied the perception of antibiotic allergy review and the workflow of the inpatient pharmacy and AMS teams in a single site Veterans Hospital to identify workflow process gaps and opportunities for future interventions.

Penicillin allergy de-labeling by primary care physicians

Inaccurate penicillin allergy (PCN-A) labels pose a major public health challenge. De-labeling in primary care is crucial but underutilized. We demonstrate an effective model for PCN-A evaluation and de-labeling by primary care physicians (PCPs) in an adult primary care clinic.

Drug Allergy Delabeling Programs: Recent Strategies and Targeted Populations

Drug allergy delabeling programs have become an essential element of antibiotic stewardship. Development of delabeling programs involves careful selection of target patient population, thoughtful design of delabeling approach, stakeholder engagement, assembly of key team members, implementation, and evaluation of clinical and safety outcomes. Recent programs have targeted patients thought to be most likely to benefit from removal of inaccurate antibiotic allergy labels, those with β-lactam antibiotic allergies and high-risk populations likely to need β-lactam antibiotics as first-line treatment. This review provides an overview of current risk stratification methods and β-lactam cross-reactivity data and summarizes how different inpatient and outpatient delabeling programs have used these concepts in delabeling algorithms. β-Lactam delabeling programs for inpatients, pediatric patients, and programs utilizing telehealth have been implemented with good outcomes. This review also focuses on delabeling programs for high-risk populations likely to benefit from first-line β-lactam antibiotics. These populations include perioperative, prenatal, and immunocompromised patients. Delabeling programs have been successful in the inpatient and outpatient settings at enabling appropriate antibiotic use. This article reviews delabeling strategies utilized by these programs with a focus on highlighting elements key to their success and future areas for innovation.

Impact of an inpatient nurse-initiated penicillin allergy delabeling questionnaire.

Penicillin allergy delabeling is an important component of antimicrobial stewardship and improves patient outcomes. We demonstrated the successful use of a nurse-initiated questionnaire to remove inappropriate penicillin allergy labels in inpatients. Nurses can play a key role in improving antibiotic allergy assessment and more broadly in interprofessional antimicrobial stewardship.

60. Penicillin Allergy Delabeling Program in the Post-acute Care Setting

BackgroundA significant proportion of inpatients labeled with penicillin allergies do not have a true IgE-mediated hypersensitivity, which may unnecessarily limit options for treatment of infection and lead to suboptimal antibiotic selection. Post-acute care settings may provide a unique opportunity to capture patients at risk for adverse outcomes related to penicillin allergy labels. The objective of the study was to assess the feasibility and impact of a penicillin delabeling program in an inpatient rehab setting.MethodsWe conducted a prospective observational study. Inpatients with penicillin allergies were identified weekly by manual review of electronic medical records. A clinical pharmacist reviewed each patient’s chart and identified patients for inclusion. Patients were excluded if they had a history of IgE-mediated hypersensitivity to penicillin within last 5 years, a history of a non-IgE mediated hypersensitivity, were severely immunocompromised, or were prescribed a contraindicated medication.ResultsA total of 72 charts were reviewed over nine months, and 37 (51.4%) had their penicillin allergy updated to reflect prior beta-lactam tolerance. Of the 72 patient that were evaluated, 28 (38.9%) were eligible for potential penicillin allergy delabeling, and 44 (61.1%) were ineligible. 59 (81.9%) of the patients had a moderate-high risk allergy, 12 (16.6%) had a low risk allergy, and 1 (1.4%) had an intolerance. Of the 28 eligible patients, 11 (39.3%) had their allergy removed, 13 (46.4%) deferred testing, and 4 (14.2%) could not be tested due to staffing. Of the 28 patients that had their allergy delabeled, 7 (21.4%) had their allergy removed by MAR review, 2 (7.2%) had a skin test with a negative result, and 2 (7.2%) had a direct oral challenge with a negative result.ConclusionA penicillin allergy delabeling program using a collaborative physician-pharmacist team model efficiently removed reported allergies in post-acute care patients. The post-acute care setting is an opportune environment to conduct a penicillin allergy delabeling program for patients not currently needing acute medical treatment.Disclosures All Authors: No reported disclosures