Promoting penicillin allergy de-labeling for children attending a hematology clinic.

BACKGROUND: Up to 10% of children are reported to be allergic to penicillin, but many allergy labels are unverified and may require formal testing. Inaccurate drug allergy labels are associated with a range of adverse clinical outcomes. Patients with hematological disorders may experience frequent and severe infections; those who have been incorrectly labeled penicillin allergic may benefit from allergy de-labeling (ADL) efforts to facilitate access to beta-lactam antibiotics. We developed a multidisciplinary, pharmacist-driven process that enabled non-allergist trained providers to assess and de-label penicillin allergies in a pediatric hematology center. METHODS: Volunteers, including physicians, advanced practice providers, nurses, and pharmacists, were trained in skin testing and oral challenge procedures. Patients were identified by review of electronic medical records for penicillin or penicillin-derivative allergy. Patient and family interviews were conducted in cases where a true penicillin allergy was deemed uncertain based on chart review. If allergy could not be de-labeled by chart review or interview alone, patients were offered skin and/or oral challenge testing. RESULTS: Fifty-nine patients were initially labeled as penicillin allergic. Allergy labels of 11 (19%) were removed by chart review only, and 15 (25%) after conducting interviews. A total of two (3%) patients were ineligible due to contraindications, and five (9%) declined participation. Twenty-six patients (44%) underwent allergy testing (50% skin testing, 50% oral challenge) of which 23 (88%) were negative. CONCLUSIONS: ADL was possible in most patients previously identified as penicillin allergic. Testing was well tolerated with no serious adverse effects.

A multicentre observational study to investigate feasibility of a direct oral penicillin challenge in de-labelling 'low risk' patients with penicillin allergy by non-allergy healthcare professionals (SPACE study): Implications for healthcare systems.

OBJECTIVE: The huge burden of inaccurate penicillin allergy labels (PALs) is an important driver of antimicrobial resistance. This is magnified by insufficient allergy specialists and lack of 'point-of-care' tests. We investigated the feasibility of non-allergy healthcare professionals (HCPs) delivering direct oral penicillin challenges (DPCs) for penicillin allergy de-labelling. METHODS: This prospective observational study was conducted in three hospitals in England across three settings (acute medical, pre-surgical and haematology-oncology). Patients with a PAL were screened and stratified as low risk/high risk. Low risk patients (non-immune mediated symptoms, benign rash, tolerated amoxicillin since and family history) underwent a DPC. RESULTS: N = 2257 PALs were screened, 1054 were eligible; 643 were approached, 373 declined, 270 consented and 259 risk stratified (low risk = 155; high risk = 104). One hundred and twenty-six low risk patients underwent DPC, 122 (96.8%) were de-labelled with no serious allergic reactions. Conversion rate from screening-to-consent was 12% [3.3% and 17.9% in acute and elective settings respectively; odds ratios for consent were 3.42 (p < 0.001) and 5.53 (p < 0.001) in haematology-oncology and pre-surgical setting respectively. Common reasons for failure to progress in the study included difficulty in reaching patients, clinical instability/medical reasons, lacking capacity to consent and psychological factors. INTERPRETATION: DPCs can be delivered by non-allergy HCPs. A high proportion of patients with PALs did not progress in the study pathway. Strategies to deliver DPC at optimal points of the care pathway are needed to enhance uptake. Elective settings offer greater opportunities than acute settings for DPC. The safety and simplicity of DPCs lends itself to adoption by healthcare systems beyond the UK, including in resource-limited settings.

Examining cefazolin utilization and perioperative anaphylaxis in patients with and without a penicillin allergy label: A cross-sectional study.

STUDY OBJECTIVE: To compare the occurrence of cefazolin perioperative anaphylaxis (POA) in patients with and without a penicillin allergy label (PAL) to determine whether the prevalence of cefazolin POA differs based on the presence of a PAL. DESIGN: Cross-sectional study. SETTING: A large U.S. healthcare system in the Baltimore-D.C. region, July 2017 to July 2020. PATIENTS: 112,817 surgical encounters across inpatient and outpatient settings in various specialties, involving 90,089 patients. Of these, 4876 (4.3%) encounters had a PAL. INTERVENTIONS: Perioperative cefazolin administration within 4 h before surgery to 4 h after the procedure began. MEASUREMENTS: The primary outcome was cefazolin POA in patients with and without PALs. Potential POA cases were identified based on tryptase orders or diphenhydramine administrations within the initial cefazolin administration to 6 h postoperatively. Verification included two validation steps. The first checked for hypersensitivity reaction (HSR) documentation, and the second, led by Allergy specialists, identified POA and the probable culprit. The secondary outcome looked at cefazolin use trends in patients with a PAL, stratified by setting and specialty. MAIN RESULTS: Of 112,817 encounters, 1421 (1.3%) had possible cefazolin HSRs. Of these, 22 (1.5%) had POA, resulting in a 0.02% prevalence. Of these, 13 (59.1%) were linked to cefazolin and 9 (40.9%) attributed to other drugs. Only one cefazolin POA case had a PAL, indicating no significant difference in cefazolin POA prevalence between patients with and without PALs (p = 0.437). Perioperative cefazolin use in patients with PALs steadily increased from 2.6% to 6.0% between 2017 and 2020, specifically in academic settings. CONCLUSIONS: The prevalence of cefazolin POA does not exhibit significant differences between patients with and without PALs, and notably, the incidence remains remarkably low. Based on these findings, it is advisable to view cefazolin as an acceptable choice for prophylaxis in patients carrying a PAL.

Postoperative infections after sinus lifts and onlay grafts in penicillin allergic patients.

INTRODUCTION: The primary objective of this retrospective study was to determine whether patients treated with clindamycin due to a reported allergy to penicillin have an increased risk of postsurgical infections after sinus lifts and onlay grafts. MATERIAL AND METHODS: A retrospective cohort study was performed on patients who underwent bone reconstruction procedures between October 2018 and December 2020. Data from all patients operated at the Pitié Salpêtrière University Hospital for sinus lifts or onlay grafts were collected. All surgical procedures studied were performed under preoperative and postoperative antibiotic prophylaxis with either amoxicillin (+/- clavulanic acid) or clindamycin for patients with reported penicillin allergy. Bone graft-associated infections as well as graft failures were recorded. RESULTS: In this study, 111 patients received bone reconstructions (89 sinus lifts and 148 onlay grafts). In the sinus lifts group, infections occurred in 5 of 89 sites (5.6 %). The infection rate was 28.5 % (7 graft sites) and only 3.9 % (82 graft sites) for clindamycin and for amoxicillin, respectively. In the onlay graft group, infections occurred in 25 of 148 sites (16.8 %). The infection rate was 56 % and only 12 % for clindamycin (18 graft sites) and for amoxicillin, respectively (130 graft sites). Non-Penicillin treated patients had a higher risk of infection with an odd ratio of 7.8 (95 % CI 1.1-54.8, P = 0.04) and 4.8 (95 % CI 1.9-12.3, P = 0.001) compared with patients receiving amoxicillin for onlay grafts and sinus lifts. CONCLUSION: Penicillin allergy and clindamycin use after sinus lift and onlay graft procedures were associated with a higher rate of infection and may be a risk factor for complications related to bone reconstruction surgery.

A Process Improvement Project to Increase Compliance With Cephalosporin-based Surgical Antimicrobial Prophylaxis in Children With Non-severe Penicillin Allergies.

BACKGROUND/PURPOSE: Cephalosporins are considered safe and first-line prophylaxis in children with non-severe penicillin allergies. However, use of second-line agents is common and is primarily driven by poor allergic response documentation and misunderstanding of cross-reactivity risk. The goal of this project was to improve compliance with cephalosporin prophylaxis through improved documentation and targeted educational efforts. METHODS: A multidisciplinary working group including representatives from allergy, surgery, infectious disease, and pharmacy developed staged interventions to facilitate compliance with cephalosporin prophylaxis. These included: (1) caregiver outreach to clarify incomplete allergy documentation, (2) a decision-support algorithm for prophylaxis use in penicillin-allergic patients, (3) standardized educational resources for surgical faculty and rotating trainees, (4) email reminders with prophylaxis recommendations sent out prior to scheduled cases, and (5) EMR-based decision support during antibiotic ordering. Rates of complete allergy documentation and cephalosporin utilization were compared for general surgery procedures between a 12-month pre-intervention and 14-month post-intervention period. RESULTS: 578 patients with penicillin allergies recorded in the EMR were included (301 pre-intervention and 277 post-intervention), 54.0% of which received prophylaxis. Compared to the pre-intervention period, complete documentation of allergic reactions increased from 57.1% to 84.2% (p < 0.001) following implementation of all interventions. Appropriate prophylaxis utilization increased from 34.5% to 88.5% following implementation of all interventions (p < 0.001), and evidence of a stepwise increase in appropriate utilization was evident with each intervention stage. Persistent compliance failures during the post-implementation period were most commonly associated with urgent and emergent add-on cases. No adverse events or allergic responses were reported before or after project implementation. CONCLUSIONS: Compliance with cephalosporin prophylaxis significantly improved following a multidisciplinary effort targeting education, allergy documentation, and clinical support at the point of care. Ongoing efforts include postoperative audits within 24 h for noncompliant cases in order to identify barriers and improve compliance for urgent and emergent add-on cases. LEVEL OF EVIDENCE: III. TYPE OF STUDY: Prospective.

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.

Does thePenicillin Allergy Label Affect Outcomes of Complicated Odontogenic Infections?

PURPOSE: Penicillins are a potent antibiotic in managing odontogenic infections, but 10% of the population is labelled as allergic to these drugs. This has limited their use and resulted in increased utilization of health care resources as well as complications associated with alternative antibiotics. The purpose of the study was to measure the association between patients labeled as penicillin allergic and treatment outcomes in a sample of patients treated for complicated odontogenic infections. Additionally, we sought to investigate antibiotic resistance patterns in these patients. MATERIALS AND METHODS: A retrospective cohort study was performed at the Michigan Medicine health care system to include patients who were treated for complicated odontogenic infections by oral and maxillofacial surgery between 2016 and 2020. Complicated odontogenic infection was defined as any odontogenic infection requiring admission and surgical management in the operating room. The primary predictor variable was the penicillin allergy label, which was determined by chart review and not confirmed with formal testing. Outcomes were measures of disease severity. The primary outcome variable was hospital length of stay. Secondary outcome variables were ICU admission (yes/no), repeat computed tomography scan(s), repeat surgery (yes/no), and re-admission (yes/no). Co-variates included were age, sex (male/female), tobacco use status, diabetes, immunocompromised state, number of spaces involved, white blood cell count upon admission and insurance status. For our secondary aim, the primary predictor variable was again penicillin allergy and outcome variable was antibiotic resistance as determined by wound culture results following surgical intervention. Negative binomial regression and logistic regression analyses were performed. P < .05 was considered significant. RESULTS: A total of 150 patients met the inclusion criteria and of those 17.3% reported as penicillin allergic. Patients labelled as penicillin allergic did not differ significantly from patients without penicillin allergy label in terms of treatment outcomes. Age, diabetes, and immunosuppression were associated with an increased length of stay. Patients labelled as penicillin allergic were at significantly higher risk for antibiotic resistance (relative risk = 2.34; 95% confidence interval, 1.66 to 3.32; P < .001), specifically clindamycin resistance (relative risk = 3.17; 95% confidence interval, 1.93 to 5.18; P < .001). CONCLUSIONS: Penicillin allergy was significantly associated with clindamycin resistance. There were similar outcomes amongst patients with and without a penicillin allergy label despite antibiotic differences. Delabeling efforts for patients with a reported penicillin allergy must be considered and local nomograms for antibiotic selection should be used by providers when seeking alternative antibiotics.

Should Penicillin Allergy Testing Be Included as Part of Preoperative Testing?

INTRODUCTION: Penicillin allergy is the most commonly reported drug allergy in the United States. Patients labeled with penicillin allergy are at risk of receiving broad-spectrum antibiotics for surgical site infection prophylaxis, which can lead to increased antibiotic resistance, higher morbidity, suboptimal antibiotic therapy, and higher medical costs. This study aimed to determine the true prevalence of penicillin allergy among surgical patients and to decrease the unnecessary use of broad-spectrum antibiotics. METHODS: A retrospective chart review was performed of patients who underwent urogynecologic surgery in 2017. In 2018, a quality initiative was started, and all patients reporting penicillin allergies were offered antibiotic allergy testing as part of their preoperative testing. RESULTS: In 2017, 15% of patients reported penicillin allergy and 52% of them received surgical prophylaxis with broad-spectrum antibiotics. In 2018, 463 patients underwent surgery, 55 of whom reported penicillin allergy and were offered penicillin allergy testing. 35 (64%) agreed to proceed with testing, and of those tested, 33 (94%) tested negative for penicillin allergy. CONCLUSIONS: 94% of patients with stated penicillin allergy who consented to allergy testing proved to have negative test. Penicillin allergy testing should be considered as part of preoperative management.

A pharmacist-led penicillin allergy de-labelling project within a preoperative assessment clinic: the low-hanging fruit is within reach.

BACKGROUND: Having a false penicillin-allergy label is linked to longer hospital stays and to an increased risk of Clostridioides difficile and meticillin-resistant Staphylococcus aureus infection. AIM: To assess a penicillin-allergy de-labelling tool designed for use by the non-allergist. METHODS: Patients attending the surgical preoperative assessment clinic (POAC) at a large UK teaching hospital, who reported a penicillin allergy, were directly de-labelled by nursing or pharmacy staff, where appropriate. A penicillin-allergy de-labelling tool designed for use by the non-allergist was adapted and applied; nursing staff were provided with supporting information and education to enable removal of spurious labels. Antimicrobial pharmacists (AMPs) provided follow-up, cross-checked prophylactic antibiotics administered, interrogated clinical notes, and telephoned patients following their surgery, for details of any adverse reactions suffered. FINDINGS: A total of 163 patients reporting a penicillin allergy were identified for intervention. Twenty-nine (17.8%) patients reported a penicillin-allergy history appropriate for direct de-labelling, of whom eight (27.6%) declined to consent. The remaining 21 patients (12.8%) were directly de-labelled, with 12 (7.4%) patients consenting during their POAC appointment; the remaining nine (5.5%) patients were consented and de-labelled after their surgery by an AMP. CONCLUSION: The POAC was identified as an appropriate location and time-point in the patient pathway to enable the direct removal of spurious penicillin-allergy labels prior to surgery. Results suggest that this could be undertaken by nursing staff, although support from AMPs enabled a greater number of patients to be de-labelled.

Debilitating Gentamicin Ototoxicity: Case Report and Recommendations Against Routine Use in Surgical Prophylaxis.

INTRODUCTION: Aminoglycoside antibiotics such as gentamicin are bactericidal and effective against gram negative organisms and act synergistically against gram positive organisms, including Staphylococcus aureus. However, they have serious adverse effects such as nephrotoxicity and ototoxicity. Gentamicin ototoxicity may occur after a single dose and results in decreased vestibular function, which is frequently debilitating and often permanent. OBJECTIVE: To emphasize the risk of gentamicin ototoxicity and suggest alternative antibiotics in penicillin-allergic patients undergoing surgery. CASE SUMMARY: We present a case of a woman with preexisting Meniere's Disease who received gentamicin 400 mg perioperatively for a sigmoidectomy due to a penicillin allergy listed in the patient's medical record. The patient developed severe ototoxicity preventing her from working or driving. Physical examination was remarkable for a broad-based gait requiring assistance to walk and bilateral corrective saccades. Vestibular testing revealed high-grade bilateral vestibular loss associated with all semicircular canals, a considerable decline compared to her function 3 years prior. DISCUSSION: Gentamicin is indicated for surgical prophylaxis when a patient has a true allergy to penicillins and cannot receive cephalosporins, though alternatives exist. True allergies include IgE-mediated illness (anaphylaxis, bronchospasm, or urticaria 30-60 minutes after administration) or exfoliative reactions (Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis). The authors encourage more prudent use of gentamicin, especially in patients susceptible for debilitating otologic insults, and offer recommendations for alternative agents prior to using gentamicin.

The association between penicillin allergy and surgical site infection after orthopedic surgeries: a retrospective cohort study.

Background: Cephalosporins are used as first-line antimicrobial prophylaxis for orthopedics surgeries. However, alternative antibiotics are usually used in the presence of penicillin allergy (PA), which might increase the risk of surgical site infection (SSI). This study aimed to analyze the relationship between SSI after orthopedic surgeries and PA among surgical candidates and related alternative antibiotic use. Methods: In this single-center retrospective cohort study, we compared inpatients with and without PA from January 2015 to December 2021. The primary outcome was SSI, and the secondary outcomes were SSI sites and perioperative antibiotic use. Moreover, pathogen characteristics of all SSIs were also compared between the two cohorts. Results: Among the 20,022 inpatient records, 1704 (8.51%) were identified with PA, and a total of 111 (0.55%) SSI incidents were reported. Compared to patients without PA, patients with PA had higher postoperative SSI risk (1.06%, 18/1704 vs. 0.51%, 93/18318), shown both in multivariable regression analysis (odds ratio [OR] 2.11; 95% confidence interval [CI], 1.26-3.50; p= 0.004) and propensity score matching (OR 1.84; 95% CI, 1.05-3.23; p= 0.034). PA was related to elevated deep SSI risk (OR 2.79; 95% CI, 1.47-5.30; p= 0.002) and had no significant impact on superficial SSI (OR 1.39; 95% CI, 0.59-3.29; p= 0.449). The PA group used significantly more alternative antibiotics. Complete mediation effect of alternative antibiotics on SSI among these patients was found in mediation analysis. Pathogen analysis revealed gram-positive cocci as the most common pathogen for SSI in our study cohort, while patients with PA had higher infection rate from gram-positive rods and gram-negative rods than non-PA group. Conclusion: Compared to patients without PA, patients with PA developed more SSI after orthopedic surgeries, especially deep SSI. The elevated infection rate could be secondary to the use of alternative prophylactic antibiotics.

A case of persistent IgE sensitisation almost two decades following ampicillin anaphylaxis.

BACKGROUND: Although most immunoglobulin E (IgE)-mediated penicillin allergy wanes with time, sensitisation may occasionally persist for many years. Previous reports on the loss of penicillin-specific IgE sensitisation were based on non-anaphylaxis cases and, although uncommon, persistent sensitisation may still be possible in the minority of cases. OBJECTIVE: This case highlights that irrespective of the elapsed duration since the index reaction, it is important to remain vigilant when approaching patients with a history of severe reactions. MATERIAL AND METHODS: We described a case of persistent IgE sensitisation almost two decades following ampicillin anaphylaxis. RESULTS: A 78-year-old male with a history of perioperative penicillin anaphylaxis in 2003 was referred for allergy workup in 2022 before his knee joint replacement surgery. The patient had strictly avoided all beta-lactams since the index reaction. However, his penicillin-specific sensitisation persisted, evidenced by positive skin tests (with generalised urticaria after intradermal testing) and basophil activation tests. CONCLUSION: To our knowledge, this was the first case of positive BAT tested around two decades following the index reaction. This case illustrates that a cautious approach may still be warranted in patients with a history of severe reaction to penicillin regardless of the duration since the reported index reaction.

Outcome of preoperative cefazolin use for infection prophylaxis in patients with self-reported penicillin allergy.

BACKGROUND: Cephalosporins are the preferred antibiotics for prophylaxis against surgical site infections. Most studies give a rate of combined IgE and non-IgE penicillin allergy yet it is recommended that cephalosporins be avoided in patients having the former but can be used in those with the latter. Some studies use penicillin allergy while others penicillin family allergy rates. The primary goal of this study was to determine the rates of IgE and non-IgE allergy as well as cross reactions to both penicillin and the penicillin family. Secondary goals were to determine the surgical services giving preoperative cefazolin and the types of self reported reactions that patients' had to penicillin prompting their allergy status. METHODS: All patients undergoing elective and emergency surgery at a University Health Sciences Centre were retrospectively studied. The hospital electronic medical record was used for data collection. RESULTS: 8.9% of our patients reported non-IgE reactions to penicillin with a cross reactivity rate of 0.9% with cefazolin. 4.0% of our patients reported IgE reactions to penicillin with a cross reactivity rate of 4.0% with cefazolin. 10.5% of our patients reported non-IgE reactions to the penicillin family with a cross reactivity rate of 0.8% with cefazolin. 4.3% of our patients reported IgE reactions to the penicillin family with a cross reactivity rate of 4.0% with cefazolin. CONCLUSIONS: Our rate of combined IgE and non-IgE reactions for both penicillin and penicillin family allergy was within the range reported in the literature. Our rate of cross reactivity between cefazolin and combined IgE and non-IgE allergy both to penicillin and the penicillin family were lower than reported in the old literature but within the range of the newer literature. We found a lower rate of allergic reaction to a cephalosporin than reported in the literature. We documented a wide range of IgE and non-IgE reactions. We also demonstrated that cefazolin is frequently the preferred antibiotics for prophylaxis against surgical site infections by many surgical services and that de-labelling patients with penicillin allergy is unnecessary.

In-utero exposure to antibiotics and risk of colorectal cancer in a prospective cohort of 18 000 adult offspring.

BACKGROUND: Incidence rates of colorectal cancer (CRC) are increasing among younger adults and in mid-life, implicating exposures in early life as risk factors. We examined the association between in-utero exposure to antibiotics and risk of CRC in adult offspring. METHODS: The Child Health and Development Studies is a prospective cohort of women receiving prenatal care between 1959 and 1966 in Oakland, California, with deliveries through June 1967. Diagnosed conditions and all prescribed medications were abstracted from mothers' medical records beginning 6 months prior to pregnancy through delivery. We identified mothers who received antibiotics in pregnancy, including penicillins, tetracyclines, short-acting sulfonamides and long-acting sulfonamides. Diagnoses of CRC in adult (age ≥18 years) offspring were ascertained through 2021 by linkage with the California Cancer Registry. Cox proportional models were used to estimate adjusted hazard ratios (aHR), with follow-up accrued from birth through cancer diagnosis, death or last contact. RESULTS: Of 18 751 liveborn offspring, about 15% (n = 2635) were exposed in utero to antibiotics: 5.4% (n = 1016) to tetracyclines, 4.9% (n = 918) to penicillins, 4.2% (n = 785) to short-acting sulfonamides and 1.5% (n = 273) to long-acting sulfonamides. Compared with offspring not exposed, associations between in-utero exposure and CRC in adult offspring were: aHR 1.03 (95% CI 0.32, 3.31) for tetracyclines; aHR 1.12 (95% CI 0.35, 3.58) for penicillins; aHR 0.83 (95% CI 0.20, 3.42) for short-acting sulfonamides; and aHR 4.40 (95% CI 1.63, 11.88) for long-acting sulfonamides. CONCLUSION: Our findings support an association between in-utero exposure to long-acting sulfonamides and CRC in adulthood.

Beta-lactam hypersensitivity diagnosis in ambulatory and hospitalized settings require different approaches.

BACKGROUND: Data on beta-lactam hypersensitivity (BLH) are mainly focused on immediate or mild nonimmediate reactions in the ambulatory setting, but limited in patients with concurrent illness and moderate-to-severe nonimmediate reactions in the hospitalized setting. OBJECTIVE: To investigate the entire spectrum of BLH in Thai tertiary hospital. METHODS: Clinical characteristics of 357 patients with suspected BLH were evaluated in a 7-year period. Culprit drug identification was performed in 335 patients by combined skin testing, in vitro testing, or drug provocation tests. RESULTS: The predominant BLH presentations were non-immunoglobulin (Ig)E-mediated reactions with severe cutaneous adverse reactions of 18.9%, and BLH status was definitively confirmed in 18.1%. The most common verified culprits were cephalosporins (34.8%), particularly in hypersensitivity type IV reactions. Natural penicillins were the main implicated drugs in 48.5% of ambulatory patients. In contrast, cephalosporins and carbapenems were the main implicated drugs in hospitalized patients. Non-IgE-mediated anaphylaxis and serum sickness-like reaction remained diagnostically challenged. New generations of beta-lactams, hospitalized patients, recent allergic history, and underlying malignancies or autoimmune diseases were associated with increased BLH risk. CONCLUSION: At present, cephalosporins are the leading causes of BLH, particularly in non-IgE-mediated reactions. More research on the verification of non-IgE hypersensitivity reactions from new generations of beta-lactams should be better emphasized. CLINICAL TRIAL REGISTRATION: The registry was approved by the Ethics and Research Committee of the Faculty of Medicine, Chulalongkorn University, and listed on ClinicalTrials.gov (Identifier: NCT01667055; https://www. CLINICALTRIALS: gov/ct2/show/NCT01667055).

Preoperative allergy testing for patients reporting penicillin and cephalosporin allergies is economically justified in preventing infection after total shoulder arthroplasty.

BACKGROUND: The use of alternative antibiotics to cefazolin has been associated with increased risk of infection after shoulder arthroplasty. Routine preoperative allergy testing in patients reporting penicillin and cephalosporin allergies increases the number able to receive cefazolin and may reduce the occurrence of infection after shoulder arthroplasty, but the financial viability of this practice is unclear. We used break-even modeling to determine the economic viability of routine preoperative allergy testing for infection prevention in total shoulder arthroplasty patients reporting penicillin and cephalosporin allergies. METHODS: Allergy testing cost ($248.24), infection rates after shoulder arthroplasty following use of noncefazolin antibiotics (3.09%), and infection-related care costs ($55,243) were derived from the literature. A break-even equation using these variables was developed to determine the absolute risk reduction (ARR) in the infection rate that would economically justify the routine implementation of preoperative allergy testing. The number needed to treat was calculated from the ARR. RESULTS: Preoperative allergy testing is considered economically justified if it prevents at least 1 infection out of 223 shoulder arthroplasties (ARR = 0.45%). These protocols remained economically viable at varying allergy testing costs, initial infection rates, and infection-related care costs. CONCLUSIONS: Routine preoperative penicillin allergy testing is an economically justified infection prevention strategy among patients reporting penicillin and cephalosporin allergies in the setting of elective shoulder arthroplasty. Widespread implementation of this practice may considerably reduce the economic and societal burden associated with prosthetic infections.

Pharmacist adjustment of preoperative antibiotic orders to the preferred preoperative antibiotic cefazolin for patients with penicillin allergy labeling.

PURPOSE: Emerging literature has detailed the safe use of cefazolin in patients with immunoglobulin E-mediated penicillin allergy labeling (PAL) such as hives and anaphylaxis. The purpose of this article is to detail efforts led by an antimicrobial stewardship pharmacist working with an interdisciplinary team to optimize preoperative antimicrobials in patients with PAL. METHODS: A pharmacist-led, interdisciplinary collaborative practice agreement (CPA) was activated in January 2020 to permit pharmacists to independently optimize preoperative antibiotics to the preferred cefazolin in patients with PAL if nonsevere or severe reactions had been reported. A patient registry was established covering the timeframe between January 8, 2020, and January 6, 2022. Reaction during surgery was assessed via 2-provider documentation, which included surgeon and anesthesiology staff documentation of any complications during the procedure related to a suspected allergic safety event. Utilization of cefazolin, clindamycin, and vancomycin for preoperative prophylaxis was monitored before and after implementation of the CPA. RESULTS: During the stated timeframe, 10,182 procedures and/or surgeries were completed on 1,572 (15.4%) patients with PAL and 659 (41.9%) patients previously reporting at least one reaction categorized as a severe reaction, which was hives for 71.2% of these patients. Of the 659 patients with PAL reporting a severe reaction, 356 received a preoperative cephalosporin (cefazolin, 98.8%; ceftriaxone, 1.2%) and tolerated it without a reported safety event, including 52 patients with PAL previously reporting anaphylaxis. An increase in preferred preoperative antimicrobial prophylaxis utilization was noted (cefazolin: 86% to 96.3%, P < 0.001; 2019 to 2021) with reductions noted in the use of nonpreferred preoperative antibiotics (clindamycin: 2.1% to 0.2%, P < 0.001; vancomycin: 3.2% to 0.4%, P < 0.001; 2019 to 2021). CONCLUSION: A pharmacist-led, interdisciplinary CPA increased preferred preoperative antimicrobial use in patients with PAL reporting severe allergic reactions, including hives and anaphylaxis, without reported safety events.

Economic Viability of Penicillin Allergy Testing to Avoid Improper Clindamycin Surgical Prophylaxis.

OBJECTIVE: Patients mislabeled with a penicillin allergy are often unnecessarily given prophylactic clindamycin. Thus, otolaryngologists may cause harm due to clindamycin's associated risk of Clostridioides difficile infections (CDI) and surgical site infections (SSI). The objective of this study was to determine the economic feasibility of penicillin allergy testing in preventing unnecessary clindamycin use among patients with an unconfirmed penicillin allergy prior to otolaryngologic surgery. METHODS: A break-even analysis was performed using the average cost of penicillin allergy testing and a CDI/SSI to calculate the absolute risk reduction (ARR) in baseline CDI/SSI rate due to clindamycin required for penicillin testing to be economically sustainable. The binomial distribution was used to calculate the probability that current penicillin testing can achieve this study's ARR. RESULTS: Preoperative penicillin testing was found to be economically sustainable if it could decrease the baseline CDI rate by an ARR of 1.06% or decrease the baseline SSI rate by an ARR of 1.34%. The probability of penicillin testing achieving these ARRs depended on the baseline CDI and SSI rates. When the CDI rate was at least 5% or the SSI rate was at least 7%, penicillin allergy testing was guaranteed to achieve economic sustainability. CONCLUSION: In patients mislabeled with a penicillin allergy, preoperative penicillin allergy testing may be an economically sustainable option to prevent the unnecessary use of prophylactic clindamycin during otolaryngologic surgery. Current practice guidelines should be modified to recommend penicillin allergy testing in patients with an unconfirmed allergy prior to surgery. LEVEL OF EVIDENCE: NA Laryngoscope, 133:1086-1091, 2023.

The antiinflammatory and electrophysiological effects of fingolimod on penicillin-induced rats.

BACKGROUND: The fact that inflammation triggers epileptic seizures brings to mind the antiepileptic properties of anti-inflammatory drugs. OBJECTIVE: To investigate the electrophysiological and anti-inflammatory effects of fingolimod on an experimental penicillin-induced acute epileptic seizure model in rats. METHODS: Thirty-two male Wistar rats were divided into four groups: control (penicillin), positive control (penicillin + diazepam [5 mg/kg]), drug (penicillin + fingolimod [0.3 mg/kg]) and synergy group (penicillin + diazepam + fingolimod). The animals were anesthetized with urethane, and epileptiform activity was induced by intracortical injection of penicillin (500,000 IU). After electrophysiological recording for 125 minutes, IL-1ß, TNF-α, and IL-6 were evaluated by ELISA in the serum of sacrificed animals. RESULTS: During the experiment, animal deaths occurred in the synergy group due to the synergistic negative chronotropic effect of diazepam and fingolimod. Although not statistically significant, fingolimod caused a slight decrease in spike-wave activity and spike amplitudes in the acute seizure model induced by penicillin (p > 0.05). Fingolimod decreased serum IL-1ß (p < 0.05); fingolimod and diazepam together reduced IL-6 (p < 0.05), but no change was observed in serum TNF-α values. CONCLUSION: Even in acute use, the spike-wave and amplitude values of fingolimod decrease with diazepam, anticonvulsant and anti-inflammatory effects of fingolimod will be more prominent in chronic applications and central tissue evaluations. In addition, concomitant use of fingolimod and diazepam is considered to be contraindicated due to the synergistic negative inotropic effect.

ANTECEDENTES: O fato de a inflamação desencadear crises epilépticas traz à mente as propriedades antiepilépticas dos anti-inflamatórios. OBJETIVO: Investigar os efeitos eletrofisiológicos e anti-inflamatórios do fingolimode em um modelo experimental de crise epiléptica aguda induzida por penicilina em ratos. MéTODOS: Trinta e dois ratos Wistar machos foram divididos em quatro grupos: controle (penicilina), controle positivo (penicilina + diazepam [5 mg/kg]), droga (penicilina + fingolimode [0,3 mg/kg]) e grupo sinergia (penicilina + diazepam + fingolimode). Os animais foram anestesiados com uretano, e a atividade epileptiforme foi induzida por injeção intracortical de penicilina (500.000 UI). Após registro eletrofisiológico por 125 minutos, IL-1ß, TNF-α e IL-6 foram avaliados por ELISA no soro dos animais sacrificados. RESULTADOS: Durante o experimento, ocorreram mortes de animais no grupo sinérgico devido ao efeito cronotrópico negativo sinérgico do diazepam e do fingolimode. Embora não seja estatisticamente significativo, o fingolimode causou uma ligeira diminuição na atividade pico-onda e nas amplitudes pico no modelo de convulsão aguda induzida pela penicilina (p > 0,05). O fingolimode diminuiu a IL-1ß sérica (p < 0,05); fingolimode e diazepam juntos reduziram a IL-6 (p < 0,05), mas não foi observada alteração nos valores séricos de TNF-α. CONCLUSãO: Pensa-se que o efeito anticonvulsivante leve de uma dose única de fingolimode será mais proeminente em aplicações crônicas e em avaliações de tecidos centrais. Além disso, o uso concomitante de fingolimode e diazepam é considerado contraindicado devido ao efeito inotrópico negativo sinérgico.

Detection of Serum-Specific IgE by Fluoro-Enzyme Immunoassay for Diagnosing Type I Hypersensitivity Reactions to Penicillins.

Diagnosis of type I hypersensitivity reactions (IgE-mediated reactions) to penicillins is based on clinical history, skin tests (STs), and drug provocation tests (DPTs). Among in vitro complementary tests, the fluoro-enzyme immunoassay (FEIA) ImmunoCAP® (Thermo-Fisher, Waltham, MA, USA) is the most widely used commercial method for detecting drug-specific IgE (sIgE). In this study, we aimed to analyze the utility of ImmunoCAP® for detecting sIgE to penicillin G (PG) and amoxicillin (AX) in patients with confirmed penicillin allergy. The study includes 139 and 250 patients evaluated in Spain and Italy, respectively. All had experienced type I hypersensitivity reactions to penicillins confirmed by positive STs. Additionally, selective or cross-reactive reactions were confirmed by DPTs in a subgroup of patients for further analysis. Positive ImmunoCAP® results were 39.6% for PG and/or AX in Spanish subjects and 52.4% in Italian subjects. When only PG or AX sIgE where analyzed, the percentages were 15.1% and 30.4%, respectively, in Spanish patients; and 38.9% and 46% in Italian ones. The analysis of positive STs showed a statistically significant higher percentage of positive STs to PG determinants in Italian patients. False-positive results to PG (16%) were detected in selective AX patients with confirmed PG tolerance. Low and variable sensitivity values observed in a well-defined population with confirmed allergy diagnosis, as well as false-positive results to PG, suggest that ImmunoCAP® is a diagnostic tool with relevant limitations in the evaluation of subjects with type I hypersensitivity reactions to penicillins.