Delabeling of allergy to beta-lactam antibiotics in hospitalized patients: a prospective study evaluating cost savings.

BACKGROUND: Patients with a penicillin allergy label are at risk of an associated increase in adverse antibiotic events and hospitalization costs. AIM: We aimed to study the economic savings derived from the correct diagnosis and delabeling inpatients with suspected beta-lactam allergy, considering the acquisition cost of antimicrobials prescribed during a patient's hospital stay. METHOD: We prospectively evaluated patients admitted to the University Hospital of Salamanca who had been labeled as allergic to beta-lactams and performed a delabeling study. Subsequently, cost differences between antibiotics administered before and after the allergy study and those derived from those patients who received alternative antibiotics during admission and those who switched to beta-lactams after the allergy study were calculated. RESULTS: One hundred seventy-seven inpatients labeled as allergic to beta-lactams underwent a delabeling study; 34 (19.2%) were confirmed to have allergy to beta-lactams. Of the total number of patients, 136 (76.8%) received antibiotics during their hospitalization, involving a mean (SD) cost of €203.07 (318.42) and a median (IQR) cost of €88.97 (48.86-233.56). After delabeling in 85 (62.5%) patients, the antibiotic treatment was changed to beta-lactams. In this group of patients, the mean cost (SD) decreased from €188.91 (351.09) before the change to 91.31 (136.07) afterward, and the median cost (IQR) decreased from €72.92 (45.82-211.99) to €19.24 (11.66-168). The reduction was significant compared to the median cost of patients whose treatment was not changed to beta-lactams (p<0.001). CONCLUSION: Delabeling hospitalized patients represents a cost-saving measure for treating patients labeled as allergic to beta-lactams.

Report of two sisters with Netherton syndrome successfully treated with dupilumab and review of the literature.

Different monoclonal antibodies have been used for the treatment of Netherton's syndrome (NS); secukinumab (anti-IL17A), infliximab (anti-TNF-α), ustekinumab (anti p40 subunit of IL-12 and IL-23), omalizumab (anti-IgE), and dupilumab (anti-IL4 and IL13). We report two sisters with severe NS who were treated with omalizumab in one and with secukinumab in the other. In view of the therapeutic failure, treatment with dupilumab was started in both sisters. The data were analyzed 16 weeks after starting treatment with dupilumab. Treatment response was assessed using the Severity Scoring Atopic Dermatitis (SCORAD); Eczema Area and Severity Index (EASI); Pruritus Numeric Rating Scale (NSR); Netherton Area Severity Assessment (NASA) and Dermatology Life Quality Index Ichthyosis. All scores were reduced after 16 weeks of treatment with dupilumab in both patients. She maintains improvement after 18 months and 12 months of treatment, respectively. No severe adverse events were reported. Treatment with dupilumab in two sisters with NS and atopic diseases produced a marked cutaneous improvement after a failed attempt with omalizumab and secukinumab. Further studies are needed to determine which biologic therapy is the most effective in NS.

Changes in Sensitization Patterns in the Last 25 Years in 619 Patients with Confirmed Diagnoses of Immediate Hypersensitivity Reactions to Beta-Lactams.

Beta-lactam (BL) drugs are the antibiotics most prescribed worldwide due to their broad spectrum of action. They are also the most frequently implied in hypersensitivity reactions with a known specific immunological mechanism. Since the commercialization of benzylpenicillin, allergic reactions have been described; over the years, other new BL drugs provided alternative treatments to penicillin, and amoxicillin is now the most prescribed BL in Europe. Diagnosis of BL allergy is mainly based on skin tests and drug provocation tests, defining different sensitization patterns or phenotypes. In this study, we evaluated 619 patients with a confirmed diagnosis of BL-immediate allergy during the last 25 years, using the same diagnostic procedures with minor adaptations to the successive guidelines. The initial eliciting drug was benzylpenicillin, which changed to amoxicillin with or without clavulanic acid and cephalosporins in recent years. In skin tests, we found a decrease in sensitivity to major and minor penicillin determinants and an increase in sensitivity to amoxicillin and others; this might reflect that the changes in prescription could have influenced the sensitization patterns, thus increasing the incidence of specific reactions to side-chain selective reactions.

Hypersensitivity to Gadolinium-Based Contrast Media.

Gadolinium-based contrast agents (GBCAs) are frequently used in magnetic resonance imaging (MRI) examinations to increase sensitivity in diagnoses. Recently, an increase in the description of hypersensitivity reactions to GBCAs has been detected. We performed research in PubMed, PubMed, SCOPUS, and EMBASE until September 2021, searching for studies regarding immediate and delayed hypersensitivity reactions to gadolinium-based contrast agents in which an allergy study was performed. The initial research identified 149 articles written in English. After excluding articles duplicated and articles that had irrelevant designs, 26 articles were included. Finally, 17 studies concerning immediate reactions, six studies concerning non-immediate reactions, and three concerning both that performed allergy evaluations were selected. In the review, we analyzed the characteristics of immediate and delayed reactions and the results of the allergy study and cross-reactivity. Skin tests seem to have acceptable accuracy, but drug provocation tests are still needed when skin tests are negative o to find alternative agents. Although cross-reactivity patterns are not well established, cross-reactivity seems to exist among macrocyclic agents. Notwithstanding, the number of patients analyzed is low and further studies are required. A management algorithm is suggested.

Angioedema Due to Acquired Deficiency of C1-Inhibitor: A Cohort Study in Spain and a Comparison With Other Series.

BACKGROUND: Data on acquired angioedema due to C1-inhibitor deficiency (C1-INH-AAE) from 4 European countries (France, Italy, Germany, and Hungary) were recently published. OBJECTIVE: To report data from a group of 50 patients with acquired C1-INH deficiency from Spain, of whom 46 had angioedema, and compare them with other European series. METHODS: We performed a retrospective observational study of 46 patients with C1-INH-AAE and 4 asymptomatic patients. Clinical and biological characteristics and associated diseases were assessed and compared with other European series. RESULTS: Women accounted for 73.9% of cases. The prevalence of C1-INH-AAE related to hereditary forms was 1/10.1. Overall, 8.7% patients were aged <40 years. Diagnostic delay was 1.1 years. Angioedema mainly affected the face (91.3%), followed by the oropharynx (63%), extremities (50%), and abdomen (37%). Only 1 patient underwent orotracheal intubation. Erythema marginatum was present in 1 patient. A hematologic disorder was recorded in 50% of patients. Angioedema preceded all benign conditions, mostly monoclonal gammopathy of undetermined significance, but appeared very close to or after malignant hematologic diseases (median, 2.2 and 0.29 years). Autoimmune diseases were associated in 50% (autoimmune thyroiditis, 21.5%; systemic lupus erythematosus, 10.9%). Half of them coexisted with hematologic disorders. Anti-C1-INH antibodies were found in 67% of tested patients and were not related to the associated disease. Long-term prophylaxis was necessary in 52.2%, most of whom responded to tranexamic acid. CONCLUSIONS: This study emphasizes the possibility of C1-INH-AAE in patients younger than 40 and in autoimmune diseases other than systemic lupus erythematosus such as autoimmune thyroiditis.

Usefulness of an Artificial Neural Network in the Prediction of ß-Lactam Allergy.

BACKGROUND: An accurate diagnosis of ß-lactam (BL) allergy improves the use of antibiotics, increases patients' safety, and reduces costs to health systems. Nevertheless, it requires skin and drug provocation tests, which are time-consuming and put the patient at risk. Furthermore, allergy testing is not available in circumstances such as the urgent need for antibiotic therapy. OBJECTIVE: To evaluate the usefulness of an artificial neural network (ANN) in the prediction of hypersensitivity to BLs, and compare it with logistic regression (LR) analysis. METHODS: In a single-center study, 656 patients evaluated for BL allergy between 1994 and 2000 were retrospectively analyzed, and the data were used to construct an ANN. The ANN predictive capabilities were compared with LR and then prospectively evaluated in 615 patients who underwent BL evaluation between 2011 and 2017. RESULTS: A total of 1271 patients were evaluated. All patients had a definite diagnosis as allergic or nonallergic to BL. The prospective sample showed a lower percentage of patients with allergy than the retrospective sample (20.7% vs 25.8%; P = .018). In the retrospective and prospective series, the ANN reached a sensitivity of 89.5% and 81.1%, a specificity of 86.1% and 97.9%, a positive predictive value of 82.1% and 91.1%, and a negative predictive value of 92.1% and 95.2%, respectively. The ANN's performance was far superior to that of the LR, whose best performance reached a sensitivity of 31.9% and a specificity of 98.8%. CONCLUSIONS: This ANN demonstrated a superior performance than the LR in predicting BL hypersensitivity without misdiagnosing severe allergic reactions. The ANN could be a helpful tool to classify the reaction risk, particularly in the identification of low-risk patients, in which an open challenge could be done to delabel patients.

A Prospective Study of Costs Associated with the Evaluation of ß-Lactam Allergy in Children.

OBJECTIVE: To evaluate the costs associated with evaluation of ß-lactam allergy in children labeled as allergic. STUDY DESIGN: We performed a prospective year-long real life observational study designed to evaluate all pediatric patients with suspected ß-lactam allergy who consulted for allergy evaluation. Direct and indirect costs were systematically recorded. Direct healthcare costs were calculated by taking into account the number of visits and all complementary and diagnostic tests performed. Direct nonhealthcare costs were calculated by considering the number of visits and the kilometers from their homes to the clinic. Finally, indirect costs were evaluated by considering the absenteeism of parents or other companions who took the children to the clinic. RESULTS: A total of 40 children with suspected allergy to ß-lactams were evaluated in our outpatient clinic from June 1, 2017 to May 31, 2018. Total direct healthcare costs were $5038.03, with an average cost per patient of $125.95. Direct nonhealthcare costs reached $901.87 ($22.55 per patient) and indirect nonhealthcare costs reached $6384.35 ($159.61 per patient). The total cost was $12 324.25, a cost of $308.11 per patient. CONCLUSIONS: Elective evaluation of ß-lactam allergy and delabeling children who are not allergic is not expensive. In addition, it could save future expenses because of an unnecessary lifelong use of alternative antibiotics that are usually more expensive, less effective, and more frequently associated with antimicrobial resistance and different side effects.

Analysis of the Costs Associated With the Elective Evaluation of Patients Labelled as Allergic to Beta-Lactams or Nonsteroidal Antiinflamatory Agents.

Introduction: Being labelled as allergic to different drugs results in patients receiving other treatments, which are more toxic, less effective and more expensive. We aimed to analyze different studies of the costs of drug hypersensitivity assessment. Methods: A bibliographic search on studies regarding this issue was performed, including the available scientific evidence up to June 2020. We searched three databases with terms related to costs and allergy testing in drug hypersensitivity reactions. Results: Our search revealed 1,430 publications, of which 20 met the inclusion criteria. In the manuscript, prospective studies evaluating the costs of the evaluation of patients with suspected allergy to beta-lactams or non-steroidal anti-inflammatory drugs are analyzed. Also, comment is made on the costs associated with incorrect labeling as non-steroidal anti-inflammatory drug or penicillin hypersensitivity. Conclusions: Taking all costs into account, the study of drug hypersensitivity is not expensive, particularly considering the economic and clinical consequences of labeling a patient with hypersensitivity to drugs.

Cluster Analysis Identifies 3 Phenotypes within Allergic Asthma.

BACKGROUND: Asthma is a heterogeneous chronic disease with different clinical expressions and responses to treatment. In recent years, several unbiased approaches based on clinical, physiological, and molecular features have described several phenotypes of asthma. Some phenotypes are allergic, but little is known about whether these phenotypes can be further subdivided. OBJECTIVE: We aimed to phenotype patients with allergic asthma using an unbiased approach based on multivariate classification techniques (unsupervised hierarchical cluster analysis). METHODS: From a total of 54 variables of 225 patients with well-characterized allergic asthma diagnosed following American Thoracic Society (ATS) recommendation, positive skin prick test to aeroallergens, and concordant symptoms, we finally selected 19 variables by multiple correspondence analyses. Then a cluster analysis was performed. RESULTS: Three groups were identified. Cluster 1 was constituted by patients with intermittent or mild persistent asthma, without family antecedents of atopy, asthma, or rhinitis. This group showed the lowest total IgE levels. Cluster 2 was constituted by patients with mild asthma with a family history of atopy, asthma, or rhinitis. Total IgE levels were intermediate. Cluster 3 included patients with moderate or severe persistent asthma that needed treatment with corticosteroids and long-acting ß-agonists. This group showed the highest total IgE levels. CONCLUSIONS: We identified 3 phenotypes of allergic asthma in our population. Furthermore, we described 2 phenotypes of mild atopic asthma mainly differentiated by a family history of allergy.

Satisfaction and quality of life of allergic patients following sublingual five-grass pollen tablet immunotherapy in Spain.

BACKGROUND: Five-grass pollen tablet is an effective and well-tolerated therapy for patients with allergic rhinoconjunctivitis (ARC). This trial sought to determine the satisfaction and health-related quality of life (HRQoL) of patients undergoing this treatment. METHODS: This was a cross-sectional, multicentre, observational, naturalistic study, following a discontinuous pre- and co-seasonal five-grass pollen regimen over two seasons in Spain (2012, 2013). The HRQoL of the patients was measured with the specific Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) for adults, adolescent (AdolRQLQ), or paediatric (PRQLQ) patients. Treatment satisfaction was assessed by the Satisfaction Scale for Patients Receiving Allergen Immunotherapy (ESPIA) questionnaire. Patients/investigators were surveyed on beliefs and attitudes towards the five-grass pollen tablet. ARC evolution according to allergic rhinitis and its impact on asthma (ARIA) criteria and treatment adherence were evaluated. RESULTS: Among the 591 ARC patients included, the mean (SD) HRQoL scores were 1.40 (1.1) in adults, 1.33 (1.1) in adolescents, and 1.15 (1.1) in children, indicating low levels of impairment (scale 0-6). ESPIA answers showed high levels of satisfaction, with an average score of 69.2 (scale 0-100). According to ARIA criteria, 88.2% of patients reported improvement of ARC. Moreover, this was accompanied by a reduced use of symptomatic medication. Adherence to treatment was estimated at 96.8%. In general, both patients and specialists exhibited a positive attitude towards five-grass pollen tablet treatment. CONCLUSION: ARC patients treated with five-grass pollen tablet showed favourable levels of HRQoL and treatment satisfaction, with concomitant improvements in ARC and symptomatic medication use, which translated into high levels of treatment adherence and a positive attitude towards five-grass pollen tablet.