Single-step direct drug provocation testing is safe for delabelling selected non-low-risk penicillin allergy labels.

BACKGROUND: Penicillin allergy labels are prevalent, and removal of incorrect labels improves patient outcomes and health economics. Labels may be classified as "low-risk" or "non-low-risk," of which the symptoms of the latter chiefly suggest immunoglobulin E-mediated etiology. Traditionally, "non-low-risk" allergy labels are evaluated by penicillin skin testing followed by graded multistep penicillin drug provocation testing (DPT). OBJECTIVE: To evaluate the safety of assessing "non-low-risk" labels with single-step direct DPT. METHODS: We consecutively enrolled inpatients and outpatients of a teaching hospital in Sydney, Australia, with penicillin allergy labels requiring penicillin for first-line treatment. Patients were classified as "low-risk" or "non-low-risk" based on the allergy labels. All patients proceeded directly to amoxicillin DPT, unless there was a history of anaphylaxis within 10 years of assessment to a beta-lactam (except for cefazolin) or Gell and Coombs type 2, type 3, or severe type 4 reaction. This was followed by a course of amoxicillin. RESULTS: A total of 149 patients (41 inpatients, 108 outpatients) were enrolled. No patient was excluded from the study. No patient experienced life-threatening reactions to the protocol. There were 85 patients who reported "non-low-risk" allergy labels. One patient developed generalized pruritus and rash that resolved with standard-dose antihistamines, 2 developed delayed benign maculopapular exanthem, and 3 experienced diarrhea during the course of amoxicillin. CONCLUSION: In our cohort, direct single-step DPT was safe, with only 6 patients with "non-low-risk" allergy experiencing benign reactions. We hope that further studies can be performed into single-step direct DPT to evaluate "non-low-risk" penicillin allergy labels. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: LNR/16/HAWKE/452.

Enabling antibiotic allergy evaluations and reintroduction of first-line antibiotics for patients with cystic fibrosis.

BACKGROUND: Patients with cystic fibrosis (CF) often have a history of antibiotic adverse drug reactions (ADRs) that pose a barrier to receiving recommended first-line treatment. Targeted antibiotic allergy evaluations are increasingly recognized as an important strategy for optimization of antimicrobial stewardship. OBJECTIVE: To improve first-line antibiotic use in patients with CF with antibiotic ADRs by streamlining access to antibiotic allergy evaluations and standardizing documentation of plans for antibiotic reintroduction. METHODS: We incorporated allergy evaluations into a multidisciplinary CF clinic and used telemedicine when allergy evaluations could not be performed during CF clinic. Standard documentation of antibiotic allergy plans was used to enable safe reintroduction of first-line antibiotics by CF providers. RESULTS: Strategies used in this study allowed 81.3% (26 of 32) of patients with CF to receive allergy evaluations and antibiotic allergy plans for prioritized antibiotics (penicillin, cephalosporin, sulfonamide), with removal of 41.0% (16 of 39) of prioritized antibiotic ADRs. Only 5.1% (2 of 39) of prioritized antibiotic ADRs evaluated required strict avoidance after evaluation. There were 9 patients who received at least 1 prioritized antibiotic, with 66.6% (6 of 9) of these patients given the antibiotic after only 1 allergy evaluation visit. Furthermore, these strategies allowed allergy evaluations of 23 nonprioritized antibiotics to occur, with removal of the ADR in 39.1% (9 of 23) and use of 77.8% (7 of 9) of nonprioritized antibiotics after removal. CONCLUSION: Incorporating allergy evaluations into a multidisciplinary CF clinic can liberalize first-line antibiotic use in patients with CF. Standard documentation of antibiotic allergy plans allowed antibiotic reintroduction to occur even before complete removal of documented antibiotic ADRs.

Covalent Heterobivalent Inhibitor Design for Inhibition of IgE-Dependent Penicillin Allergy in a Murine Model.

Drug allergies occur when hapten-like drug metabolites conjugated to serum proteins, through their interactions with specific IgE, trigger allergic reactions that can be life threatening. A molecule termed covalent heterobivalent inhibitor (cHBI) was designed to specifically target drug hapten-specific IgE to prevent it from binding drug-haptenated serum proteins. cHBI binds the two independent sites on a drug hapten-specific Ab and covalently conjugates only to the specific IgE, permanently inhibiting it. The cHBI design was evaluated via ELISA to measure cHBI-IgE binding, degranulation assays of rat basophil leukemia cells for in vitro efficacy, and mouse models of ear swelling and systemic anaphylaxis responses for in vivo efficacy. The cHBI design was evaluated using two separate models: one specific to inhibit penicillin G-reactive IgE and another to inhibit IgE specific to a model compound, dansyl. We show that cHBI conjugated specifically to its target Ab and inhibited degranulation in cellular degranulation assays using rat basophil leukemia cells. Furthermore, cHBIs demonstrated in vivo inhibition of allergic responses in both murine models. We establish the cHBI design to be a versatile platform for inhibiting hapten/IgE interactions, which can potentially be applied to inhibit IgE-mediated allergic reactions to any drug/small-molecule allergy.

Safety and efficacy of direct two-step penicillin challenges with an inpatient pharmacist-driven allergy evaluation.

Background: Penicillin allergy is commonly reported and has clinical and financial consequences for patients and hospitals. A penicillin evaluation program can safely delabel patients and optimize antibiotic therapy. Pharmacists who perform this task have focused on a detailed interview or penicillin skin testing (PST). Antibiotic graded challenge after PST requires more resources and is more costly than going directly to a two-step challenge. Objective: To determine whether a pharmacist-driven penicillin allergy evaluation and a testing protocol that primarily uses direct oral challenges can safely delabel patients. Methods: Adult patients (ages >18 years) with a penicillin allergy in their electronic medical record (EMR) who were admitted between September 2019 and June 2020 were eligible. Although all patients with penicillin allergy were eligible, priority was given to patients who required antibiotics. Patients were interviewed, and, if indicated, based on an institutional protocol, were tested by using PST and/or two-step oral challenge. If the patient passed the challenge, then the penicillin allergy label was removed in the EMR and the patient counseled. Demographic information, allergy questionnaire results, testing results, and changes in antimicrobial therapy were collected. Results: Fifty patients were evaluated from September 2019 to June 2020. Ninety-six percent of the patients were delabeled, and antibiotic therapy changed for 54%. Twenty patients were delabeled with an interview alone, and 30 patients underwent oral two-step challenge. Only one patient required PST. Conclusion: A pharmacist-driven penicillin allergy evaluation program focused on direct oral graded challenges and bypassing PST can effectively delabel admitted patients. However, more safety data are needed before implementation of similar programs to optimize antibiotic treatment.

Update on penicillin allergy delabeling.

PURPOSE OF REVIEW: To review phenotyping and risk classification of penicillin allergy and provide an update on penicillin allergy delabeling strategies for primary care. RECENT FINDINGS: Beta-lactams are considered the treatment of choice for a wide range of bacterial pathogens; however, many patients receive second-line agents due to being labeled as having an allergy to penicillin. This approach can lead to antibiotic resistance and inferior health outcomes. While 10% of the population is labeled as penicillin allergic, penicillin anaphylaxis occurs in less than 1% of patients. For patients with delayed benign skin rashes (e.g., urticaria or maculopapular exanthem >1 h after administration) attributable to beta-lactam administration occurring more than 12 months ago, direct oral challenge (rechallenge with antibiotic in the clinical setting) can be a safe and effective strategy, with immediate reactions occurring in less than 5% of such low-risk patients and delayed reactions appearing infrequently. In patients with penicillin-associated immediate urticaria, other IgE-mediated features, or anaphylaxis, further allergy evaluation and penicillin skin testing is warranted. Any severe idiosyncratic cutaneous adverse reaction is rare, but can be dangerous so prompt removal of the inciting agent is required. SUMMARY: Penicillin allergy delabeling is a high-value service that can be effectively delivered through a multidisciplinary collaborative approach.

Skin testing and oral amoxicillin challenge in the outpatient allergy and clinical immunology clinic in pregnant women with penicillin allergy.

BACKGROUND: Penicillin allergy is frequently reported. In pregnant women, reported penicillin allergy is associated with negative health outcomes and suboptimal group B streptococcal prophylaxis. For individuals having penicillin allergy, skin testing followed by an observed oral challenge is recommended. Previous data indicate a low risk of adverse reaction with skin testing in pregnant women, but the subsequent oral challenge was not routinely pursued. OBJECTIVE: To determine whether skin testing followed by the outpatient oral challenge is tolerated by pregnant women. METHODS: We conducted a retrospective review of all pregnant women who underwent penicillin allergy evaluation at an outpatient allergy and clinical immunology clinic. The patients underwent oral amoxicillin challenges based on the discretion of the allergy provider. We evaluated the index reaction history, skin test results, oral challenge results, and subsequent antibiotic exposure. RESULTS: A total of 46 pregnant women underwent skin testing without adverse reactions, of whom 44 patients (95.6%) received negative results. A total of 18 women (39%) completed an oral challenge without adverse reactions. Patients challenged vs not challenged did not differ in patient age, gestational age, latency since index reaction, or reaction history risk level. Notably, 28 women received intrapartum antibiotics. There was no difference in intrapartum antibiotic administration between those who did or who did not complete an in-office oral challenge (P = .90). CONCLUSION: Penicillin skin testing and oral challenge in pregnant women can safely be performed in the outpatient setting. There was no difference in the intrapartum antibiotic use between women who were and those who were not challenged. Further research is needed to determine the utility of oral challenge in pregnant patients.

Hypersensitivity to antibiotics in drug reaction with eosinophilia and systemic symptoms (DRESS) from other culprits.

BACKGROUND: Antibiotics have been implicated in the reactivation of exanthema and systemic involvement in drug reaction with eosinophilia and systemic symptoms (DRESS); however, it is not clear whether these patients become sensitized to the antibiotic. OBJECTIVE: To evaluate if, after DRESS, patients become sensitized to antibiotics. METHODS: We retrospectively reviewed the patch test (PT) data and clinical files of DRESS patients who were administered antibiotics during DRESS from other culprits. RESULTS: Nine patients out of 17 (53%) were positive to antibiotics in PT: six to the penicillin group and three to cephalosporins (including one patient with additional positivity to vancomycin). Considering the eight patients who were negative to antibiotics in PT, seven were exposed to a fluoroquinolone. Four cases were patch tested again and three remained positive to antibiotics 2 to 5 years thereafter. Two patients with positive PT results had an accidental re-exposure to antibiotics and developed a maculopapular exanthema without systemic symptoms. CONCLUSION: Exposure to antibiotics during DRESS or its prodromal phase could enhance sensitization to antibiotics, as confirmed by a positive PT. Reproducibility of positive PTs to antibiotics after several years and reactivation after re-exposure support that T-cell-mediated hypersensitivity to antibiotics in the setting of DRESS is a specific reaction.

Diagnostic value and safety of penicillin skin tests in children with immediate penicillin allergy.

Background: The first-line method in the diagnosis of patients who describe an immediate reaction after penicillin intake is a skin test (ST) with penicillin reagents. Objectives: We aimed to determine the safety and diagnostic value of penicillin STs in the diagnosis of immediate reactions to penicillins in pediatric patients. Methods: The study included pediatric patients with suspected immediate reaction to penicillin who were subjected to STs by using a standard penicillin test kit as well as suspected penicillin and the drug provocation tests (DPT) with the suspected penicillin at our clinic. Results: A total of 191 patients (53.9% boys) with a median age of 6.83 years (interquartile range, 4.2-12 years) were included in the study. The time from drug intake to the onset of reaction was ≤1 hour in 138 patients (72.3%) and 1 to 6 hours in 53 patients (27.7%). Penicillin allergy (PA) was confirmed by diagnostic tests in 36 of the 191 patients (18.8%). In multivariate logistic regression analysis, the history of both urticaria and angioedema (odds ratio [OR] 27.683 [95% confidence interval {CI}, 3.143-243.837]; p = 0.003) and anaphylaxis (OR 56.246 [95% CI, 6.598-479.489]; p < 0.001) were the main predictors of a PA diagnosis. Although ST results were positive in 23 patients (63.8%), 13 patients (26.2%) had positive DPT results despite negative ST results. The negative predictive value (NPV) of STs was calculated 92.2% (155/168). None of our patients experienced immediate or delayed systemic and/or local reactions in relation to the STs. Conclusion: A history of urticaria with angioedema and anaphylaxis were the main predictors of true PA in children with suspected immediate reactions. STs with penicillin reagents are safe for use in children. Although STs have a high NPV, DPT is the gold standard for diagnosis. DPTs should be performed as the final step of the diagnostic evaluation of PA in patients with negative ST results.

Minimal agreement between basophil activation test and immunoassay in diagnosis of penicillin allergy.

INTRODUCTION: Basophil activation test (BAT) and immunoassays are the most widely used in vitro tests to diagnose IgE-mediated allergic reactions to penicillin. However, studies to determine if one test is interdependent from another are limited. OBJECTIVE: The present study aimed to measure the agreement between BAT and immunoassay in diagnosis of penicillin allergy. METHOD: BAT was performed using penicillin G (Pen G), penicillin V (Pen V), penicilloyl-polylysine (PPL), minor determinant mix (MDM), amoxicillin (Amx) and ampicillin (Amp) in 25 patients. Immunoassay of total IgE (tIgE) and specific IgE (sIgE) antibodies to Pen G, Pen V, Amx and Amp were quantified. Skin prick test (SPT) using PPL-MDM, Amx, Amp and Clavulanic acid were also performed. RESULTS: Minimal agreement was observed between BAT and immunoassay (k=0.25). Of two BAT-positive patients, one patient is positive to Amx (59.27%, SI=59) and Amp (82.32%, SI=82) but sIgE-negative to all drug tested. This patient is also SPT-positive to both drugs. Another patient is BAT-positive to Pen G (10.18%, SI=40), Pen V (25.07%, SI=100) and Amp (19.52%, SI=79). In sIgE immunoassay, four patients were sIgE-positive to at least one of the drugs tested. The sIgE level of three patients was between low and moderate and they were BAT-negative. One BAT-positive patient had a high level of sIgE antibodies (3.50-17.5kU/L) along with relatively high specific to total IgE ratio ≥0.002 (0.004-0.007). CONCLUSIONS: The agreement between BAT and immunoassay is minimal. Performing both tests provides little increase in the sensitivity of allergy diagnosis work-up for immediate reactions to penicillin.

Drug allergy is associated with the development of extraintestinal manifestations in patients with ulcerative colitis.

Summary: Drug allergies are developed by antibody or cell-mediated reactions as immunologic mechanisms. It has been demonstrated that hypersensitivity reaction to certain allergens may play a role in the pathogenesis of inflammatory bowel disease (IBD) focused on food allergies. A total of 256 patients with UC were divided in two groups: 203 patients with active UC and 53 in remission UC were included in the present study. In the present study we found that 11.7% had allergy to at least one drug distributed. The most frequent drug-allergies were sulfonamides in 2.8% and penicillin in 3.1%. Sulfonamide allergy was associated with several extraintestinal manifestations such as: peripheral arthritis/arthralgia (OR = 9.06, 95% CI 1.71 - 48.00, p = 0.002); pyoderma gangrenosum (OR = 24.10, 95% CI 3.55 - 163.48, p minor 0.0001) and uveitis (OR = 15.93, 95% CI 2.55 - 99.23, p minor 0.0001). The frequency of drug allergy was 11.7% in Mexican UC patients, most frequently to sulfonamides and penicillin drugs. The presence of sulfonamide allergy was associated with the presence of several extra-intestinal manifestations.

Evaluation and Management of Penicillin Allergy: A Review.

IMPORTANCE: ß-Lactam antibiotics are among the safest and most effective antibiotics. Many patients report allergies to these drugs that limit their use, resulting in the use of broad-spectrum antibiotics that increase the risk for antimicrobial resistance and adverse events. OBSERVATIONS: Approximately 10% of the US population has reported allergies to the ß-lactam agent penicillin, with higher rates reported by older and hospitalized patients. Although many patients report that they are allergic to penicillin, clinically significant IgE-mediated or T lymphocyte-mediated penicillin hypersensitivity is uncommon (<5%). Currently, the rate of IgE-mediated penicillin allergies is decreasing, potentially due to a decreased use of parenteral penicillins, and because severe anaphylactic reactions to oral amoxicillin are rare. IgE-mediated penicillin allergy wanes over time, with 80% of patients becoming tolerant after a decade. Cross-reactivity between penicillin and cephalosporin drugs occurs in about 2% of cases, less than the 8% reported previously. Some patients have a medical history that suggests they are at a low risk for developing an allergic reaction to penicillin. Low-risk histories include patients having isolated nonallergic symptoms, such as gastrointestinal symptoms, or patients solely with a family history of a penicillin allergy, symptoms of pruritus without rash, or remote (>10 years) unknown reactions without features suggestive of an IgE-mediated reaction. A moderate-risk history includes urticaria or other pruritic rashes and reactions with features of IgE-mediated reactions. A high-risk history includes patients who have had anaphylaxis, positive penicillin skin testing, recurrent penicillin reactions, or hypersensitivities to multiple ß-lactam antibiotics. The goals of antimicrobial stewardship are undermined when reported allergy to penicillin leads to the use of broad-spectrum antibiotics that increase the risk for antimicrobial resistance, including increased risk of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus. Broad-spectrum antimicrobial agents also increase the risk of developing Clostridium difficile (also known as Clostridioides difficile) infection. Direct amoxicillin challenge is appropriate for patients with low-risk allergy histories. Moderate-risk patients can be evaluated with penicillin skin testing, which carries a negative predictive value that exceeds 95% and approaches 100% when combined with amoxicillin challenge. Clinicians performing penicillin allergy evaluation need to identify what methods are supported by their available resources. CONCLUSIONS AND RELEVANCE: Many patients report they are allergic to penicillin but few have clinically significant reactions. Evaluation of penicillin allergy before deciding not to use penicillin or other ß-lactam antibiotics is an important tool for antimicrobial stewardship.

Das Kreuz mit der Kreuzallergie: Betalaktamantibiotika-Allergie.

Hypersensitivity reactions to betalactam antibiotics are the most commonly mentioned drug allergies. Up to 10 percent of patients report to suffer from a penicillin allergy. However, classical side effects of antibiotics are often misdiagnosed as an allergy. Many of these patients with suspected betalactam allergy tolerate betalactam antibiotics well. Therefore, a thorough allergy workup is essential to confirm a suspected allergy or to enable again a treatment with betalactam antibiotics. Most important is a good documentation as skin- and in-vitro tests have a reduced sensitivity. Gold standard is the provocation test to help exclude a supposed allergy or to test alternative, potential cross reactive betalactam antibiotics. Cross-reactions between penicillins and cephalosporins, especially cephalosporins of the third and fourth generation are unusual. Cross reactions to carbapenem antibiotics are rare.

Penicillin minor determinants: History and relevance for current diagnosis.

OBJECTIVE: To review the history of the penicillin minor determinants and evaluate their relevance for current diagnosis. DATA SOURCES: Skin testing to detect immunoglobulin E (IgE) sensitivity to penicillins in patients with a history of penicillin allergy has been the subject of more than 55 years of published research involving tens of thousands of patients. STUDY SELECTIONS: Selection of data was based on its relevance to the objective of this article. RESULTS: It was established early on that testing with the major penicilloyl determinant using the polyvalent penicilloyl-polylysine (PPL) is negative in a substantial portion (10% to 64%, including recent increases) of those at risk for immediate hypersensitivity reactions. A variety of minor penicillin determinants are clinically significant in that their use in skin testing is essential to detect all those at risk. In particular, a minor determinant mixture of benzylpenicillin, benzylpenicilloate, and benzylpenilloate, used in conjunction with PPL, has been shown in numerous studies to achieve an average negative predictive value (NPV) of 97.9% in history-positive patients. Benzylpenicillin alone, as the sole minor determinant, leaves many skin test-positive patients undiscovered. Use of amoxicillin as an additional minor determinant reagent appears to identify another 2% to 8% of skin test-positive patients in some populations. CONCLUSION: IgE skin testing, using both the major and appropriate minor determinants of penicillin, can identify, with a high degree of reliability (NPV ∼97%), penicillin allergy history-positive patients who can receive beta-lactam antibiotics without concern for serious acute allergy, including anaphylaxis. The few false-negative skin tests reported globally are largely confined to minor, self-limited cutaneous reactions.

Clinical and economic burden of hospitalizations with registration of penicillin allergy.

BACKGROUND: Penicillin allergy is commonly reported, but only a minority of claimants has a confirmed diagnosis. Nevertheless, patients labeled as having penicillin allergy are treated with second-line antibiotics, which are more expensive and less effective, possibly increasing the risk of drug-resistant infections. OBJECTIVE: To compare hospitalizations with and without registration of penicillin allergy concerning their morbidity and hospital resource use. METHODS: We analyzed a national administrative database containing a registration of all Portuguese hospitalizations from 2000 to 2014. All episodes occurring in adults with a penicillin allergy registration were compared with an equal number of hospitalizations without such registration and matched for inpatients' age, sex, and main diagnosis. We compared those episodes concerning their length of stay, hospital price charges, comorbidities, and frequency of drug-resistant infections. Differences between medical and surgical hospitalizations were explored. RESULTS: Hospitalizations with registration of penicillin allergy (n = 102,872) had a longer average length of stay than the remainder episodes (8 vs 7 days; P < .001) and higher hospital charges (3,809.0 vs 3,490.0 USD; P < .001). Inpatients with penicillin allergy registration also had a higher mean Charlson Comorbidity Index (0.91 vs 0.76; P < .001) and a significantly higher frequency of infections by several agents, including methicillin-resistant Staphylococcus aureus, Enterococcus species, and Escherichia coli. Among surgical episodes, septicemia was 1.2-fold more frequent among penicillin allergy cases. CONCLUSION: Hospitalizations with registration of penicillin allergy are associated with increased economic costs and frequency of infections by drug-resistant agents, reinforcing the need to establish a correct diagnosis of penicillin allergy.

Misconceptions Surrounding Penicillin Allergy: Implications for Anesthesiologists.

Administration of preoperative antimicrobial prophylaxis, often with a cephalosporin, is the mainstay of surgical site infection prevention guidelines. Unfortunately, due to prevalent misconceptions, patients labeled as having a penicillin allergy often receive alternate and less-effective antibiotics, placing them at risk of a variety of adverse effects including increased morbidity and higher risk of surgical site infection. The perioperative physician should ascertain the nature of previous reactions to aid in determining the probability of the prevalence of a true allergy. Penicillin allergy testing may be performed but may not be feasible in the perioperative setting. Current evidence on the structural determinants of penicillin and cephalosporin allergies refutes the misconception of cross-reactivity between penicillins and cefazolin, and there is no clear evidence of an increased risk of anaphylaxis in cefazolin-naive, penicillin-allergic patients. A clinical practice algorithm for the perioperative evaluation and management of patients reporting a history of penicillin allergy is presented, concluding that cephalosporins can be safely administered to a majority of such patients.

Successful desensitization to cloxacillin in a patient with sepsis, with infective endocarditis and clinical suspicion of hypersensitivity to penicillins, a case report.

WHAT IS KNOWN AND OBJECTIVE: Beta-lactam antibiotic (BLA) therapy is frequently needed to treat infective endocarditis (IE). Hypersensitive reactions to BLA restrict BLA therapy in allergic patients. In the current case, we aim to describe the utility of desensitization (DS) in this context. Although the evidence is limited, DS is recommended. CASE DESCRIPTION: This case report deals with a 79-year-old woman with a clinical suspicion of allergy to BLA and a methicillin-sensitive Staphylococcus aureus (MSSA) IE. A cloxacillin DS protocol was developed to enable treatment with cloxacillin. WHAT IS NEW AND CONCLUSION: Alternative antibiotic treatments may be less effective or not available in MSSA IE. In this case report, DS allowed optimal cloxacillin treatment.

Utilization and timeliness of an inpatient penicillin allergy evaluation.

BACKGROUND: A history of penicillin allergy is associated with an increased risk of nosocomial infections because patients are exposed to non-beta lactam antibiotics. Ruling out inaccurate penicillin allergy during hospitalization decreases prescription of beta lactam antibiotics. However, the utilization of penicillin allergy testing and timeliness in relation to initiation of antibiotics is not known. OBJECTIVE: Our aim was to describe the proportion and characteristics of patients who underwent inpatient penicillin allergy testing in a hospital without a guideline or infrastructure for inpatient penicillin allergy testing. METHODS: We performed a retrospective chart review of patients admitted to our institution between January 1, 2008, and December 31, 2015, who underwent penicillin allergy testing. RESULTS: Forty-nine patients were identified; 27 (55.1%) were women. The median age was 61.5 years (interquartile range [IQR], 48.5-71 years). The median Charlson-Comorbidity index score was 4 (IQR, 2-5.5). Of these patients, 42.86% (21) were admitted to the intensive care unit, 79.6% of allergy consults were requested by infectious disease physicians, and 87.8% of patients were receiving non-beta lactam antibiotics at the time of testing. The patients received a median of 5 days of antibiotics before testing (range, 0-16 days; IQR, 3-7 days). Antimicrobial therapy was changed in 78.0% of the patients (32), of whom 68.3% (21/32) was attributable to penicillin allergy testing. CONCLUSION: Inpatient penicillin allergy testing is a critical component of antibiotic stewardship; however, an adequate infrastructure is essential for timely evaluation. Inpatient penicillin allergy evaluation requires a multidisciplinary approach focused on patient selection; risk stratification; and optimization of a timely, safe, and cost-effective approach to optimize patient outcomes.