[Supposed allergy to beta-lactam antibiotics: is it time for reflections and actions?] / Presunta allergia agli antibiotici beta-lattamici: è tempo di riflessioni e azioni?

The excessive, often unconfirmed suspicions of beta-lactam allergy affect up to 10% of the general population, improperly denying a significant percentage of individuals the opportunity to be treated with first-line antibiotics, forcing clinicians to resort to second-line choices that are not always equally effective, safe, and contribute to the increase in antibiotic resistance. Pediatricians and general practitioners can play a crucial role in recognizing and addressing weak suspicions of beta-lactam allergy, actively participating in removing the "label" of being allergic. The article, based on Who AWaRe Manual recommendations, presents current evidence on the issue with practical guidance to promote accurate interpretation and management of an overestimated problem that does not encourage a culture of optimal and prudent antibiotic use.

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.

Safety of direct oral provocation test to delabel reported mild beta-lactam allergy in infants.

BACKGROUND: Around 10% of people report a drug allergy and avoid some medications because of fear of allergic reactions. However, only after a proper diagnostic workup can some of these reactions be confirmed as allergic or nonallergic hypersensitivities. Beta-lactams (BLs) are the most common medication suspected of being involved in drug hypersensivity reactions (DHRs) in children. Recently, direct oral provocation tests (DPT) with BLs gained popularity within pediatric populations as a tool for delabeling children with suspected BL allergies. This study aimed to evaluate the safety of direct provocation tests in infants with mild cutaneous non-immediate reactions to BLs. METHODS: The authors retrospectively analyzed the data of 151 infants between 2015 and 2022, referred for evaluating a suspected allergy to BLs that occurred before age 24 months. RESULTS: The mean age of the children, including 55% male kids, at the suspected reaction was 15.9 months and the mean age at the time of the DPT was 39.6 months. In most cases, antibiotics were prescribed to treat common upper respiratory infections, such as acute otitis (54.3%) and acute tonsillitis (27.2%). Amoxicillin was considered the culprit drug in 62.9% of the cases, and the combination of amoxicillin-clavulanic acid in the case of 33.8% of children. The most frequent associated cutaneous clinical manifestations were maculopapular exanthema in 74.8% and delayed urticaria/angioedema in 25.2%. Of the 151 infants evaluated, parents of 149 infants agreed for a direct DPT, and only three had a positive test (2%). Symptoms resulting from the DPT were mild and easily treatable. CONCLUSIONS: A direct DPT without prior tests is a safe and effective procedure to delabel BL allergy, even in infants. The authors wish to emphasize the importance of properly validating BL allergy suspicions by promoting appropriate diagnostic procedures in infants as, in most cases, DHRs can be excluded and there is no need for further therapeutic restrictions.

Comparison of Empiric Antibiotic Treatment Regimens for Hospitalized, Non-severe Community-acquired Pneumonia: A Retrospective, Multicenter Cohort Study.

PURPOSE: Consensus guidelines for hospitalized, non-severe community-acquired pneumonia (CAP) recommend empiric macrolide + ß-lactam or respiratory fluoroquinolone monotherapy in patients with no risk factors for resistant organisms. In patients with allergies or contraindications, doxycycline + ß-lactam is a recommended alternative. The purpose of this study was to compare differences in outcomes among guideline-recommended regimens in this population. METHODS: This retrospective, multicenter cohort study included patients ≥18 years of age with CAP who received respiratory fluoroquinolone monotherapy, empiric macrolide + ß-lactam, or doxycycline + ß-lactam. Major exclusion criteria included patients with immunocompromising conditions, requiring vasopressors or invasive mechanical ventilation within 48 hours of admission, and receiving less than 2 days of total antibiotic therapy. The primary outcome was in-hospital mortality. Secondary outcomes included clinical failure, 14- and 30-day hospital readmission, and hospital length of stay. Safety outcomes included incidence of new Clostridioides difficile infection and aortic aneurysm ruptures. FINDINGS: Of 4685 included patients, 1722 patients received empiric respiratory fluoroquinolone monotherapy, 159 received empiric doxycycline + ß-lactam, and 2804 received empiric macrolide + ß-lactam. Incidence of in-hospital mortality was not observed to be significantly different among empiric regimens (doxycycline + ß-lactam group: 1.9% vs macrolide + ß-lactam: 1.9% vs respiratory fluoroquinolone monotherapy: 1.5%, P = 0.588). No secondary outcomes were observed to differ significantly among groups. IMPLICATIONS: We observed no differences in clinical or safety outcomes among three guideline-recommended empiric CAP regimens. Empiric doxycycline + ß-lactam may be a safe empiric regimen for hospitalized CAP patients with non-severe CAP, although additional research is needed to corroborate these observations with larger samples.

El farmacéutico clínico en el abordaje del paciente con sospecha de alergia a beta-lactámicos: una revisión sistemática / The role of clinical pharmacists in patients with suspected allergy to B-lactams: A systematic review

Objetivo analizar el papel desempeñado por el farmacéutico clínico y su impacto en el ámbito de los programas de optimización de antimicrobianos ante la sospecha de alergia a antibióticos beta-lactámicos.Método se realizaron 2 búsquedas bibliográficas independientes. Se encontraron un total de 35 artículos incluyéndose 12. Se analizaron los artículos incluidos y se recogieron variables de eficacia, seguridad y aplicabilidad de herramientas de evaluación a pacientes con sospecha de alergia a beta-lactámicos. Además, se analizó la variación en el consumo y en el perfil de prescripción de antibióticos alternativos. Resultados los estudios seleccionados analizaron cuestionarios, desetiquetado, test intradérmicos y pruebas de provocación oral realizados por farmacéuticos. Se hallaron diferencias significativas en la variable principal de eficacia en 4 estudios incluidos a favor de la intervención farmacéutica. En un estudio cuasi experimental, la utilización de cefazolina aumentó tras la intervención farmacéutica (65 vs. 28%; p < 0,01). En otro estudio cuasi experimental, la dosis diaria definida media de aztreonam y la media de días de terapéutica por 1.000 pacientes/día disminuyeron (21,23 vs. 9,05; p < 0,01) y (8,79–4,24; p = 0,016), pre y postintervención, respectivamente, aumentando las desescaladas antibióticas (p ≤ 0,01). En otro estudio, disminuyó la prescripción de antibióticos de uso restringido (42,5 vs. 17,9%; p < 0,01) y en otro, la utilización de antibióticos profilácticos prequirúrgicos alternativos a cefazolina (81,9 vs. 55,9%; p < 0,01). En otro estudio, el tiempo medio por entrevista fue de 5,2 minutos por paciente. No se reportaron eventos adversos en ningún estudio. Conclusiones la intervención del farmacéutico en la evaluación del paciente con sospecha de alergia a beta-lactámicos resulta eficaz, segura y aplicable a la práctica clínica (AU)

Objective To analyze the role played by the clinical pharmacist and its impact in antibiotic stewardship facing suspected allergy to beta-lactam antibiotics. Method We performed two different independent bibliographic searches. A total of 35 articles were found, and the final number included in the study was 12. We analysed the articles and collected variables of efficacy, safety and applicability of evaluation tools applied to patients with suspected allergy to beta-lactams. Also, the variation in the consumption and prescription profile of alternative antibiotics was analyzed. Results The selected studies analysed questionnaires, allergy delabeling, intradermal tests and oral challenge tests performed by pharmacists. Significant differences in the efficacy endpoint were found in 4 studies in favour of pharmaceutical intervention. In the study of Kwiatkowski et al, cefazolin use increased in surgical patients after pharmacist intervention (65 vs. 28%; p < 0.01). In a quasi-experimental study, the mean defined daily dose of aztreonam and the mean days of therapy per 1000 patients/day decreased (21.23 vs 9.05, p <0.01) and (8.79–4.24, p = 0.016), pre and post-intervention, respectively, increasing antibiotic de-escalations (p ≤ 0.01). In another quasi-experimental study, the prescription of restricted-use antibiotics decreased (42.5% vs. 17.9%, p < 0.01) and the use of pre-surgical prophylactic antibiotics alternative to cefazolin (81.9% vs 55.9%, p<0.01) in another study. Other study showed that the mean time per interview was 5.2 minutes per patient. No adverse events were reported in any study. Conclusion The pharmacist intervention in the evaluation of the patient with suspected allergy to beta-lactams is effective, safe and feasible to implement on daily clinical practice (AU)

Efficacy and safety of a structured de-escalation from antipseudomonal ß-lactams in bloodstream infections due to Enterobacterales (SIMPLIFY): an open-label, multicentre, randomised trial.

BACKGROUND: De-escalation from broad-spectrum to narrow-spectrum antibiotics is considered an important measure to reduce the selective pressure of antibiotics, but a scarcity of adequate evidence is a barrier to its implementation. We aimed to determine whether de-escalation from an antipseudomonal ß-lactam to a narrower-spectrum drug was non-inferior to continuing the antipseudomonal drug in patients with Enterobacterales bacteraemia. METHODS: An open-label, pragmatic, randomised trial was performed in 21 Spanish hospitals. Patients with bacteraemia caused by Enterobacterales susceptible to one of the de-escalation options and treated empirically with an antipseudomonal ß-lactam were eligible. Patients were randomly assigned (1:1; stratified by urinary source) to de-escalate to ampicillin, trimethoprim-sulfamethoxazole (urinary tract infections only), cefuroxime, cefotaxime or ceftriaxone, amoxicillin-clavulanic acid, ciprofloxacin, or ertapenem in that order according to susceptibility (de-escalation group), or to continue with the empiric antipseudomonal ß-lactam (control group). Oral switching was allowed in both groups. The primary outcome was clinical cure 3-5 days after end of treatment in the modified intention-to-treat (mITT) population, formed of patients who received at least one dose of study drug. Safety was assessed in all participants. Non-inferiority was declared when the lower bound of the 95% CI of the absolute difference in cure rate was above the -10% non-inferiority margin. This trial is registered with EudraCT (2015-004219-19) and ClinicalTrials.gov (NCT02795949) and is complete. FINDINGS: 2030 patients were screened between Oct 5, 2016, and Jan 23, 2020, of whom 171 were randomly assigned to the de-escalation group and 173 to the control group. 164 (50%) patients in the de-escalation group and 167 (50%) in the control group were included in the mITT population. 148 (90%) patients in the de-escalation group and 148 (89%) in the control group had clinical cure (risk difference 1·6 percentage points, 95% CI -5·0 to 8·2). The number of adverse events reported was 219 in the de-escalation group and 175 in the control group, of these, 53 (24%) in the de-escalation group and 56 (32%) in the control group were considered severe. Seven (5%) of 164 patients in the de-escalation group and nine (6%) of 167 patients in the control group died during the 60-day follow-up. There were no treatment-related deaths. INTERPRETATION: De-escalation from an antipseudomonal ß-lactam in Enterobacterales bacteraemia following a predefined rule was non-inferior to continuing the empiric antipseudomonal drug. These results support de-escalation in this setting. FUNDING: Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases; Spanish Clinical Research and Clinical Trials Platform, co-financed by the EU; European Development Regional Fund "A way to achieve Europe", Operative Program Intelligence Growth 2014-2020.

DNA methylation profiling reveals potential biomarkers of ß-lactams induced fatal anaphylactic shock.

Anaphylaxis is a serious reaction of systemic hypersensitivity with that rapid onset and sudden death. Drug hypersensitivity, particularly induced by ß-lactams, is one of the most frequent causes of anaphylaxis in adults. But identification of anaphylactic shock, in forensic sciences recently, is difficult, because it mainly depends on nonspecific characteristic morphological changes, as well as exclusion and circumstantial evidence. Here, we detected DNA methylation signatures of ß-lactams-induced fatal anaphylactic shock with the Illumina Infinium Human Methylation EPIC BeadChip, to screen potential forensic biomarkers and reveal the molecular mechanisms of drug-induced anaphylaxis with fatal shock and sudden death. Our results indicated that DNA methylation was associated with ß-lactams-induced fatal anaphylactic shock, in which the hypomethylation played a vital role. We found that 1459 differentially methylated positions (DMPs) were mainly involved in ß-lactams-induced fatal anaphylactic shock by regulating MAPK and other signaling pathways. 18 DNA methylation signatures that could separate ß-lactams-induced anaphylactic shock from healthy individuals were identified. The altered methylation of DMPs can affect the transcription of corresponding genes and promote ß-lactams-induced fatal anaphylactic shock. The results suggest that DNA methylation can detect forensic identification markers of drug-induced anaphylaxis with fatal shock and sudden death, and it is an effective method for the forensic diagnosis.

IFN-γ ELISpot-enabled machine learning for culprit drug identification in nonimmediate drug hypersensitivity.

BACKGROUND: Diagnosing drug-induced allergy, especially nonimmediate phenotypes, is challenging. Incorrect classifications have unwanted consequences. OBJECTIVE: We sought to evaluate the diagnostic utility of IFN-γ ELISpot and clinical parameters in predicting drug-induced nonimmediate hypersensitivity using machine learning. METHODS: The study recruited 393 patients. A positive patch test or drug provocation test (DPT) was used to define positive drug hypersensitivity. Various clinical factors were considered in developing random forest (RF) and logistic regression (LR) models. Performances were compared against the IFN-γ ELISpot-only model. RESULTS: Among the 102 patients who had 164 DPTs, most patients had severe cutaneous adverse reactions (35/102, 34.3%) and maculopapular exanthems (33/102, 32.4%). Common suspected drugs were antituberculosis drugs (46/164, 28.1%) and ß-lactams (42/164, 25.6%). Mean (SD) age of patients with DPT was 52.7 (20.8) years. IFN-γ ELISpot, fixed drug eruption, Naranjo categories, and nonsteroidal anti-inflammatory drugs were the most important features in all developed models. The RF and LR models had higher discriminating abilities. An IFN-γ ELISpot cutoff value of 16.0 spot-forming cells/106 PBMCs achieved 94.8% specificity and 57.1% sensitivity. Depending on clinical needs, optimal cutoff values for RF and LR models can be chosen to achieve either high specificity (0.41 for 96.1% specificity and 0.52 for 97.4% specificity, respectively) or high sensitivity (0.26 for 78.6% sensitivity and 0.37 for 71.4% sensitivity, respectively). CONCLUSIONS: IFN-γ ELISpot assay was valuable in identifying culprit drugs, whether used individually or incorporated in a prediction model. Performances of RF and LR models were comparable. Additional test datasets with DPT would be helpful to validate the model further.

The role of clinical pharmacists in patients with suspected allergy to ß-lactams: A systematic review. / El farmacéutico clínico en el abordaje del paciente con sospecha de alergia a beta-lactámicos: una revisión sistemática.

OBJECTIVE: To analyze the role played by the clinical pharmacist and its impact in antibiotic stewardship facing suspected allergy to beta-lactam antibiotics. METHOD: We performed two different independent bibliographic searches. A total of 35 articles were found, and the final number included in the study was 12. We analysed the articles and collected variables of efficacy, safety and applicability of evaluation tools applied to patients with suspected allergy to beta-lactams. Also, the variation in the consumption and prescription profile of alternative antibiotics was analyzed. RESULTS: The selected studies analysed questionnaires, allergy delabeling, intradermal tests and oral challenge tests performed by pharmacists. Significant differences in the efficacy endpoint were found in 4 studies in favour of pharmaceutical intervention. In the study of Kwiatkowski et al, cefazolin use increased in surgical patients after pharmacist intervention (65 vs. 28%; p < 0.01). In a quasi-experimental study, the mean defined daily dose of aztreonam and the mean days of therapy per 1000 patients/day decreased (21.23 vs 9.05, p <0.01) and (8.79-4.24, p = 0.016), pre and post-intervention, respectively, increasing antibiotic de-escalations (p ≤ 0.01). In another quasi-experimental study, the prescription of restricted-use antibiotics decreased (42.5% vs. 17.9%, p < 0.01) and the use of pre-surgical prophylactic antibiotics alternative to cefazolin (81.9% vs 55.9%, p<0.01) in another study. Other study showed that the mean time per interview was 5.2 minutes per patient. No adverse events were reported in any study. CONCLUSION: The pharmacist intervention in the evaluation of the patient with suspected allergy to beta-lactams is effective, safe and feasible to implement on daily clinical practice. The standardization of protocols to clarify the history of allergies and development of evaluation tools represent simple screenings to perform delabelling or refer to the Immunoallergology service, improving penicilins use and reducing the need for second line antibiotics. More studies are needed to standardize the desensitization tests made by pharmacists. However, despite these results, the involvement and leadership of the pharmacist in this area is limited and constitutes a future challenge for the profession.

[Translated article] The role of clinical pharmacists in patients with suspected allergy to ß-lactams: A systematic review.

OBJECTIVE: To analyze the role played by the clinical pharmacist and its impact in antibiotic stewardship facing suspected allergy to beta-lactam antibiotics. METHOD: We performed 2 different independent bibliographic searches. A total of 35 articles were found, and the final number included in the study was 12. We analyzed the articles and collected variables of efficacy, safety, and applicability of evaluation tools applied to patients with suspected allergy to beta-lactams. Also, the variation in the consumption and prescription profile of alternative antibiotics was analyzed. RESULTS: The selected studies analyzed questionnaires, allergy delabeling, intradermal tests, and oral challenge tests performed by pharmacists. Significant differences in the efficacy endpoint were found in 4 studies in favor of pharmaceutical intervention. In the study of Kwiatkowski et al., cefazolin use increased in surgical patients after pharmacist intervention (65% vs 28%; P < .01). In a quasi-experimental study, the mean defined daily dose of aztreonam and the mean days of therapy per 1000 patients/day decreased (21.23 vs 9.05, P <.01) and (8.79-4.24, P = .016), pre- and post-intervention, respectively, increasing antibiotic de-escalations (P = < .01). In another quasi-experimental study, the prescription of restricted use antibiotics decreased (42.5% vs 17.9%, P < .01)and the use of pre-surgical prophylactic antibiotics alternative to cefazolin (81.9% vs 55.9%, P < .01)in another study. Other study showed that the mean time per interview was 5.2 min per patient. No adverse events were reported in any study. CONCLUSION: The pharmacist intervention in the evaluation of the patient with suspected allergy to beta-lactams is effective, safe, and feasible to implement on daily clinical practice. The standardization of protocols to clarify the history of allergies and development of evaluation tools represent simple screenings to perform delabeling or refer to the Immunoallergology service, improving penicilins use and reducing the need for second-line antibiotics. More studies are needed to standardize the desensitization tests made by pharmacists. However, despite these results, the involvement and leadership of the pharmacist in this area is limited and constitutes a future challenge for the profession.

Is a Prolonged Drug Provocation Test Better Than a Single-Day Drug Provocation Test? A Systematic Review and Meta-Analysis.

BACKGROUND: There is currently no standardized duration of drug provocation test (DPT) for confirming/delabeling beta-lactam hypersensitivity reaction (BL-HSR). OBJECTIVES: This meta-analysis and systematic review aimed to investigate the added diagnostic value of extended-day over single-day DPT for confirming/delabeling BL-HSR in adults and children. METHODS: The MEDLINE, EMBASE, Web of Science, and CINAHL online databases were searched from inception to March 15, 2023, for studies that performed extended-day DPT to confirm/delabel BL-HSR. Risk difference and risk ratio were used to compare the proportions of patients with confirmed BL-HSR by single-day or extended-day DPT. RESULTS: A total of 10,371 DPTs from 42 studies were included. Extended-day DPTs ranged from 2 to 7 days, or as long as index reactions were reported (maximum 10 days). The overall prevalence of confirmed BL-HSR was 6.96% (3.31% during the first-day DPT, and 3.65% during extended-day DPT). Approximately half of the positive reactions during extended-day DPT occurred during the second/third day. The increased detected pool prevalence of confirmed BL-HSR yielded by extended-day DPT was 0.03 (95% CI, 0.02%-0.04%; I2 = 57.69%; P < .001), and the risk ratio of positive reactions between extended-day and single-day DPT was 1.94 (95% CI, 1.62-2.33; I2 = 36.26%; P < .001). The risk difference increased per 1% increase in prevalence of BL-HSR by 0.6% (95% CI, 0.4%-0.7%; P < .001). Twenty-three severe reactions occurred during DPT, and only 2 severe reactions (0.02%) occurred during extended-day DPT. An additional 28 extended-day DPTs were needed to identify 1 mild reaction. CONCLUSIONS: The increased prevalence of confirmed BL-HSR observed during extended-day DPT could be attributed to the first-day DPT. As a result, our findings do not conclusively support the use of extended-day DPT over single-day DPT. Further studies, incorporating a washout period, are required to comprehensively compare these 2 approaches.

A novel 2-step process for the management of inpatient beta-lactam allergy labels.

BACKGROUND: Inpatient beta-lactam allergy labels may increase the unnecessary use of aztreonam and non-beta-lactam antibiotics, which can then lead to more adverse events and increased health care costs, OBJECTIVE: To assess the impact of a novel 2-step process (medication history review followed by risk stratification) on rates of beta-lactam delabeling, aztreonam use, and desensitizations on pediatric, adult, and obstetrics inpatients at a tertiary academic center. METHODS: We prospectively collected data on 700 patients who received inpatient consultation from the Beta-Lactam Allergy Evaluation Service between August 2021 and July 2022. Patients were delabeled either by medication review alone, drug challenge alone if with a low-risk history, or penicillin skin test followed by drug challenge if with a high-risk history. Generalized linear regression modeling was used to compare aztreonam days of therapy in the intervention year with the 2 prior years. Drug desensitizations were assessed by electronic chart review. RESULTS: Most of the patients (n = 656 of 700, 94%) had more than or equal to 1 beta-lactam allergy label removed, clarified, or both; 77.9% of these patients (n = 511 of 656) had 587 beta-lactam allergy labels removed. Nearly one-third (n = 149, 27.6%) had 162 allergy labels removed solely by medication history review. All 114 penicillin skin tests performed had negative results, and 98% (8 of 381) of the patients who underwent any drug challenge passed. Only 5.7% of the delabeled patients were relabeled. There was a 27% reduction in aztreonam use (P = .007). Beta-lactam desensitizations were reduced by 80%. CONCLUSION: A full-time inpatient beta-lactam allergy service using medication history review and risk stratification can safely and effectively remove inpatient beta-lactam allergy labels, reduce aztreonam use, and decrease beta-lactam desensitizations.

Development of a Pipeline for Removing Allergy Labels in Patients Undergoing Hematopoietic Stem Cell Transplantation.

Penicillin allergy is reported by 10% to 20 % of patients, but when evaluated only 1% to 2% may have a true allergy. Patients undergoing hematopoietic stem cell transplantation (HSCT) have a high likelihood of requiring beta-lactam antibiotics due to increased infection risk, which can be limited by a penicillin allergy label. When a penicillin allergy is recorded, alternatives are needed, including more expensive broader-spectrum antibiotics, with increases in drug-resistant bacteria, longer hospital stays, higher expenditures, and increases in nosocomial infections, such as Clostridium difficile colitis. This group of patients already undergoes extensive pretreatment testing and would especially benefit from allergy delabeling. This study aimed to develop a self-sustaining, low-cost pipeline between an HSCT clinic and an allergy clinic to identify and successfully delabel low-risk patients who endorse an allergy to penicillin, amoxicillin, amoxicillin-clavulanate, piperacillin-tazobactam, or ampicillin before admission to the hospital. We developed a survey to triage allergy risk, identified key stakeholders in building the pipeline, and underwent 4 plan, do, study, act (PDSA) cycles. Changes were made in each of the PDSA cycles to minimize cost and uncompensated provider time, as well as to increase patient retention throughout the pipeline by increasing appointment availability and decreasing reliance on patients to independently progress through the pathway. Of the 410 patients with planned HSCT who were screened over 11 months, 89 (21.7%) were listed as having a penicillin and/or beta lactam allergy. All but 1 (66 of 67; 98.5%) of the participants completed the survey accurately when confirmed by an allergist, and the survey was 100% accurate in predicting delabeling success in low-risk patients. Of eligible patients, 43.8% (n = 39) were successfully delabeled before their transplant date, and 97.4% of these (n = 38) have undergone HSCT to date. This pipeline is maintained by approximately 5 hours of work per week (1 hour of allergy physician time, 4 hours of nurse and/or clinical coordinator time), with no other direct costs. There is an estimated direct savings of at least $1914.93 per patient delabeled. We successfully designed and implemented a pipeline between the HSCT clinic and the allergy clinic as a quality improvement initiative to identify and address high rates of reported beta-lactam allergies. We identified and addressed patient-based factors, logistical, temporal, and financial barriers that impacted patient retention and sustainability. This model is expected to yield significant and sustained cost savings for the healthcare system as well as to improve patient outcomes, and this hypothesis is currently undergoing formal analysis. We anticipate that this model can be used to create a similar pipeline in other healthcare systems for HSCT recipients, as well as patients in other clinical settings, such as oncology and chimeric antigen receptor T cell therapy.

[Antibiotic allergies: targeted approach in suspected ß­lactam allergy]. / Antibiotikaallergien ­ gezieltes Vorgehen bei vermeintlicher ß­Laktam-Allergie.

Allergic reactions to antibiotics belong to hypersensitivity drug reactions and can trigger both immunoglobulin E-mediated symptoms and T cell-mediated symptoms. Skin manifestations are the most common symptoms. Although reporting a penicillin allergy results in considerable restrictions in the treatment of acute infections, which may be associated with poor treatment outcomes, in most cases the label 'penicillin allergy' is not called into question or critically reviewed. However, in 85-90% of patients, 'penicillin allergy' constitutes a mislabeling of a non-specific intolerance reaction that does not pose a risk to the patient when re-exposed to penicillins. Careful history taking, an evaluation of manifestations in the past, and easy-to-perform initial diagnostic steps are crucial in differentiating non-specific intolerance reactions from penicillin allergy sensu stricto. Thus, a penicillin de-labeling strategy allows for optimized antibiotic therapy in the event of a future infection. Although allergic cross-reactivity between different ß­lactam antibiotics can occur, the risk for a severe cross-reactivity is dependent on chemical properties of the specific ß­lactam. Published cross-reactivity tables can help in risk stratification and choice of alternative ß­lactam agents.

Drug reintroduction testing and beta-lactam hypersensitivity in children: Protocols and results, a 12-year experience.

Introduction: Oral provocation test (OPT) to beta-lactam antibiotics (BL) is a gold standard in allergology investigation. We aimed to demonstrate the contribution of OPT in BL hypersensitivity (HS) indicated as a first step in diagnosis. Methods: We conducted a retrospective study from 2007 to 2019, in a single Tunisian tertiary care academic center. It concerned children with presumed non-severe allergic manifestations to BL, with a reaction that has occurred at least 6 months before the OPT. Results: We identified 35 children for inclusion. After the first OPT, a second OPT with a different BL was performed in case of a positive result of the first one. In 12 cases (34.2%), the OPT elicited a reaction. In eight cases the allergy was to penicillin and in two cases to cephalosporins (cefixim). Cross-reactivity was noted in two cases. Conclusion: An OPT to BL indicated in the first instance in non-severe reaction in children will allow a rapid diagnosis in case of suspicion of HS to BL.

Don't we overestimate drug allergies in children?

OBJECTIVES: On average about 10% of parents report hypersensitivity to at least 1 drug in their children. After diagnosis process a few of these reactions are being confirmed as drug hypersensitivity reactions. The aim of the study was to assess the real-life prevalence of drug hypersensitivity in children based on drug provocation tests. MATERIAL AND METHODS: The authors included 113 children, aged 4-18 years, referred to Pediatrics and Allergy Clinic in Lódz, Poland, due to incidence of adverse reaction during treatment. Medical history regarding allergies to drugs was taken in accordance to the form developed by the United States Food and Drug Administration Adverse Event Reporting System. Skin prick tests, intradermal test and drug provocation test were performed in all patients. RESULTS: In all 113 patients suspected of drug allergy, after all diagnostic procedures, the authors proved IgE-mediated allergy to ß-lactams, nonsteroid anti-inflammatory drugs, local anesthetics in 19 patients (16.8%). Previous history of allergy was a risk factor for drug allergy in studied patients (p = 0.001). The most frequent symptoms of allergy were urticaria and erythematous papular rash. CONCLUSIONS: Drug allergy is a difficult problem in the practice of a doctor and is difficult to diagnose, especially in the pediatric population. It seems that too often isolated symptoms reported during infection or disease are taken as a symptom of drug allergy, and not as a symptom resulting from the course of the disease. Int J Occup Med Environ Health. 2023;36(5):632-42.