Utilising primary care electronic health records to deliver the ALABAMA randomised controlled trial of penicillin allergy assessment.

BACKGROUND: Use of electronic health records (EHR) to provide real-world data for research is established, but using EHR to deliver randomised controlled trials (RCTs) more efficiently is less developed. The Allergy AntiBiotics And Microbial resistAnce (ALABAMA) RCT evaluated a penicillin allergy assessment pathway versus usual clinical care in a UK primary care setting. The aim of this paper is to describe how EHRs were used to facilitate efficient delivery of a large-scale randomised trial of a complex intervention embracing efficient participant identification, supporting minimising GP workload, providing accurate post-intervention EHR updates of allergy status, and facilitating participant follow up and outcome data collection. The generalisability of the EHR approach and health economic implications of EHR in clinical trials will be reported in the main ALABAMA trial cost-effectiveness analysis. METHODS: A descriptive account of the adaptation of functionality within SystmOne used to deliver/facilitate multiple trial processes from participant identification to outcome data collection. RESULTS: An ALABAMA organisation group within SystmOne was established which allowed sharing of trial functions/materials developed centrally by the research team. The 'ALABAMA unit' within SystmOne was also created and provided a secure efficient environment to access participants' EHR data. Processes of referring consented participants, allocating them to a trial arm, and assigning specific functions to the intervention arm were developed by adapting tools such as templates, reports, and protocols which were already available in SystmOne as well as pathways to facilitate allergy de-labelling processes and data retrieval for trial outcome analysis. CONCLUSIONS: ALABAMA is one of the first RCTs to utilise SystmOne EHR functionality and data across the RCT delivery, demonstrating feasibility and applicability to other primary care RCTs. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04108637, registered 05/03/2019. ISRCTN: ISRCTN20579216.

Rash decisions: Unmasking a risk phenotype in adults with persistent delayed penicillin allergy sensitized during historic infection with Epstein-Barr virus.

Background: Penicillin-associated exanthems in the setting of infectious mononucleosis caused by Epstein-Barr virus (EBV) are often viewed as a transient event, not a true allergy. Recent evidence challenges this and suggests that a notable subset of patients retain penicillin hypersensitivity. Objective: We investigated the occurrence and predictors of persistent adulthood hypersensitivity in those with penicillin-associated rash occurring in the setting of EBV infection. Methods: Retrospective analysis of data of patients referred for penicillin allergy testing to an Australian tertiary-care hospital captured from 2015 to 2023 was carried out. Results: Of 2066 patients, 23 (1%) had penicillin-associated rash during an historic EBV infection; 16 (70%) were female; and median (interquartile range) age was 18 (16-20) years at index reaction and 38 (33.5-57) years at allergy testing. Skin prick testing and delayed intradermal testing to a penicillin panel were performed, followed by oral provocation challenge in those testing negative. Persistent sensitization was shown in 6 (26%) of 23; 4 (67%) of 6 positive delayed intradermal testing; and 3 (50%) of 6 had positive oral challenge test. Notably, 5 (83%) of 6 had a severe maculopapular exanthem with facial swelling, including 2 (33%) of 6 with probable drug reaction with eosinophilia and systemic symptoms (aka DRESS) during the index reaction, compared to 0 of 17 in patients tolerating penicillin on reexposure. Conclusion: This study highlights the requirement of allergy testing in adult patients reporting a penicillin-associated severe maculopapular exanthem in the setting of EBV, even if it occurred during childhood or adolescence.

Penicillin allergy delabeling has a significant impact on subsequent antibiotic use in primary care.

Efforts to delabel penicillin allergic patients are important as the majority of suspected penicillin allergy can be ruled out by relevant allergy testing. The aim is to change the antibiotic pattern in delabeled patients to minimize use of unnecessary broad-spectrum antibiotics, reducing the risk of antimicrobial resistance and making treatment more cost effective. However, published information on subsequent antibiotic use is scarce. To evaluate the effect of delabeling on subsequent antibiotic use in primary care, a cohort of 2911 patients tested for penicillin allergy was compared to a matched control group of 14,522 individuals from the background population. In total 86.4% of the tested patients were delabeled. For delabeled patients, penicillin use increased from 0.07 prescriptions per patient year before allergy investigation, to 0.53 prescriptions per patient year post investigation (p < 0.001). The use of fluoroquinolones and macrolides was reduced and reached a level comparable to the background population. This study shows that penicillin allergy delabeling has significant positive impact on subsequent antibiotic use in primary care, and that penicillin use increases to levels similar to the background population. Penicillin allergy delabeling should be prioritized as an important and efficient element in antimicrobial stewardship initiatives.

Management of Tubo-Ovarian Abscess in a Patient With Factor V Leiden Deficiency and High Body Mass Index (BMI).

This case report details the clinical course, diagnostic challenges, and management of a 53-year-old female patient with a history of factor V Leiden deficiency, hypertension, and high body mass index (BMI), presenting with an acute tubo-ovarian abscess (TOA). The patient's medical history also included penicillin allergy, premenopausal bleeding, and two previous cesarean sections, adding complexity to her management. Upon presentation, the patient exhibited symptoms of TOA, a severe complication of pelvic inflammatory disease (PID). Given her high BMI and surgical history, the risks associated with surgical intervention were significant. Consequently, a conservative approach with prolonged antibiotic therapy was chosen. The diagnosis was supported by initial and follow-up CT scans, which revealed multiple fluid collections indicative of infection but did not suggest a safe access route for percutaneous drainage. The patient's penicillin allergy required a careful selection of antibiotics to ensure efficacy and avoid adverse reactions. A multidisciplinary team comprising specialists from gynecology, microbiology, and radiology collaborated to devise and implement an effective treatment plan. This approach allowed for regular reassessment and adjustments to the therapeutic regimen. The patient received broad-spectrum antibiotics tailored to her specific needs, with the regimen prolonged due to the infection's severity and the high risk of surgical complications. The patient's inflammatory markers, including C-reactive protein (CRP) levels, were closely monitored, guiding treatment adjustments. Over time, significant clinical improvement was observed, with a gradual decrease in CRP levels and symptom resolution. This case underscores the importance of a tailored, patient-specific approach in managing complex TOA cases. It highlights the potential for conservative management with antibiotics in high-risk patients where surgical intervention poses significant risks. The successful outcome emphasizes the value of a multidisciplinary approach and individualized care in achieving favorable outcomes in TOA management.

Antepartum versus postpartum amoxicillin oral challenge in pregnant patients with a reported penicillin allergy: A two-center prospective cohort study.

INTRODUCTION: While 10% of pregnant individuals report a penicillin allergy, there is no established best practice for penicillin allergy delabeling in pregnancy. To better understand options for penicillin delabeling, we aimed to evaluate two penicillin allergy delabeling protocols in pregnancy regarding efficacy, adverse events, and patient satisfaction. MATERIAL AND METHODS: From July 2019 to December 2022, we completed a two-center prospective cohort study, where each site recruited pregnant patients over 24 weeks gestational age with a reported penicillin allergy. One center offered antepartum amoxicillin oral challenges, either directly or after negative skin testing (i.e., antepartum oral challenge site). Our other centers completed a two-step approach with antepartum penicillin skin testing only and deferred oral challenges to the postpartum period (i.e., postpartum oral challenge site). Our primary outcome was the rate of penicillin allergy delabeling, defined as tolerating an antibiotic challenge with penicillin or amoxicillin. Univariate analyses were completed using chi-squared, Fisher's exact, and Wilcoxon rank tests. RESULTS: During the study period, 276 pregnant patients were assessed, with 207 in the antepartum oral challenge site and 69 in the postpartum oral challenge site. Among the 204 patients who completed antepartum oral challenges, 201 (98%) passed without reactions. Deferring oral challenges to the postpartum period led to a loss of follow-up for 37/53 (70%) of eligible individuals. Overall, 97% (201/207) of patients at the antepartum oral challenge site were delabeled from their penicillin allergy-compared to 38% (26/69) of patients referred to the postpartum oral challenge site (p < 0.0001). Three antepartum oral challenge reactions were noted, including two mild cutaneous reactions and a case of transient abdominal discomfort. CONCLUSIONS: Antepartum amoxicillin oral challenge is a more effective method to delabel pregnant patients from their penicillin allergy. Deferral of oral challenges to the postpartum period introduces a significant barrier for penicillin allergy delabeling.

"What if the patient has a severe reaction, and it is my fault?" A qualitative study exploring factors for sustainable implementation of penicillin allergy delabelling.

BACKGROUND: Penicillin allergy delabelling (PAD), the process of evaluating penicillin allergy labels, is a key target in antibiotic stewardship, but uptake of the procedure outside clinical studies is limited. We aimed to explore factors that need to be addressed to sustainably implement a clinical pathway for PAD. METHODS: We conducted a qualitative study based on semi-structured interviews with focus groups consisting of a purposive sample of twenty-five nurses and physicians working in four different hospitals in Western Norway. Systematic text condensation was applied for analysis. RESULTS: Psychological safety was reported as crucial for clinicians to perform PAD. A narrative of uncertainty and anticipated negative outcomes were negatively associated with PAD performance. Education, guidelines, and colleague- and leadership support could together create psychological safety and empower health personnel to perform PAD. Key factors for sustainable implementation of PAD were facilitating the informant's profound motivation for providing optimal health care and for reducing antimicrobial resistance. Informants were motivated by the prospect of a simplified PAD procedure. We identified three main needs for implementation of PAD: (1) creating psychological safety; (2) utilising clinicians' inherent motivation and (3) optimal organisational structures. CONCLUSION: A planned implementation of PAD must acknowledge clinicians' need for psychological safety and aid reassurance through training, leadership, and guidelines. To implement PAD as an everyday practice it must be minimally disruptive and provide a contextually adaptive logistic chain. Also, the clinician's motivation for providing the best possible healthcare should be utilised to aid implementation. The results of this study will aid sustainable implementation of PAD in Norway. ETHICS: The study was approved by the Western Norway Regional Committee for Medical Research Ethics (Study No:199210).

Preadmission Penicillin Allergy Evaluation Before Hematopoietic Stem Cell Transplantation Optimizes Febrile Neutropenia Treatment and Inpatient Resource Utilization.

Febrile neutropenia is a common complication of conditioning chemotherapy for hematopoietic stem cell transplant (HSCT), but a major barrier for optimal treatment of febrile neutropenia is historical penicillin allergies. Our group recently published a development of a clinical pipeline for delabeling penicillin allergies in adult patients planned to undergo hematopoietic stem cell transplant (HSCT). In this retrospective cohort study, we followed patients to evaluate their outcomes during inpatient admission for HSCT. We hypothesized that, among patients planned for HSCT with a self-reported penicillin allergy, completing penicillin allergy testing (amoxicillin ingestion challenge with or without concomitant penicillin skin testing) prior to HSCT admission would be associated with differences in inpatient treatment for febrile neutropenia (including antibiotic selection and timing of antibiotic administration) and improved inpatient resource utilization (including nursing and inpatient physician consults). We identified patients with a self-reported penicillin allergy who answered a penicillin allergy questionnaire and were subsequently admitted to our institution for HSCT. We divided the cohort into 2 groups: patients whose penicillin allergy was evaluated prior to admission (EPTA) and patients whose penicillin allergy was not evaluated prior to admission (NEPTA). We then performed comparison between the 2 groups for general clinical outcomes of HSCT admission (duration of admission, need for ICU transfer, readmission rate, etc.), febrile neutropenia treatment, and inpatient resource utilization. Statistics were calculated using the nonparametric 2-tailed Fisher exact test for categorical outcomes and the nonparametric 2-tailed Mann-Whitney U test for numerical outcomes. Within our cohort, 35 patients completed penicillin allergy testing prior to HSCT admission (EPTA) and 44 patients did not (NEPTA). Demographics were similar between these groups, and there was no significant difference in the rate of febrile neutropenia during HSCT admission (EPTA 64% versus NEPTA 66%, P = 1.00). EPTA patients were significantly more likely to receive standard first-line antibiotics (cefepime or ceftazidime) for febrile neutropenia (EPTA 95% versus NEPTA 65%, P = .015) and time between febrile neutropenia onset and antibiotic administration was shorter (EPTA mean 66 mins versus NEPTA mean 121 mins, P = .0058). No patients in the EPTA group experienced an immediate hypersensitivity reaction (hives, anaphylaxis, etc.) or severe cutaneous adverse reaction (SCAR) during HSCT admission. EPTA patients were also significantly less likely to require 1:1 nursing for antibiotic test doses, challenges, and desensitizations (EPTA 0% versus NEPTA 49%, P < .0001); less likely to require inpatient allergy consult (EPTA 0% versus NEPTA 12%, P = .031); and less likely to require inpatient antimicrobial stewardship consult (EPTA 0% versus NEPTA 13%, P = .013) during their HSCT admission. In summary, patients who completed penicillin allergy testing prior to HSCT admission were more likely to receive first-line antibiotics and received antibiotics more rapidly for treatment of febrile neutropenia. Furthermore, patients who completed penicillin allergy testing prior to HSCT admission were less likely to require 1:1 nursing, inpatient allergy consults, and inpatient antimicrobial stewardship consults during HSCT admission.

A call to address penicillin allergy labels in patients with hematopoietic stem cell transplants: How to avoid rash decisions.

Among patients with hematopoietic stem cell transplants, infections, particularly multidrug-resistant infections, pose a grave threat. In this setting, penicillin allergy labels are both common and harmful. Though the majority of patients who report penicillin allergy can actually tolerate penicillin, penicillin allergy labels are associated with use of alternative antibiotics, which are often more broad spectrum, less effective, and more toxic. In turn, they are associated with more severe infections, multidrug-resistant infections, Clostridium difficile, and increased mortality. Evaluating penicillin allergy labels can immediately expand access to preferred therapeutic options, which are critical to care in patients with recent hematopoietic stem cell transplants. Point-of-care assessment and clinical decision tools now exist to aid the nonallergist in assessment of penicillin allergy. This can aid in expanding use of other beta-lactam antibiotics and assist in risk-stratifying patients to determine a testing strategy. In patients with low-risk reaction histories, direct oral challenges can be employed to efficiently delabel patients across clinical care settings. We advocate for multidisciplinary efforts to evaluate patients with penicillin allergy labels prior to transplantation.

Patient Perceptions of Penicillin Allergy Testing in a Public Health System.

BACKGROUND: Documented penicillin allergies are associated with increased morbidity, increased hospital stay, and an increase in resistant infections. Penicillin allergy evaluations using a direct oral challenge with or without skin testing has been recommended as a delabeling strategy for patients with penicillin reaction histories. Barriers for achieving equitable access, however, exist. Understanding patient perceptions regarding their penicillin allergy across diverse populations is crucial to mitigate potential obstacles to penicillin allergy testing (PAT) and the use of penicillin-like antibiotics after delabeling. OBJECTIVE: The objective of this study was to gather perceptions of patients delabeled of their penicillin allergy after testing through a PAT program. METHODS: Patients who underwent PAT and had a subsequent allergy removal due to a negative result were interviewed using closed and open-ended questions. RESULTS: A total of 100 patient interviews were completed. Awareness of the risks associated with unnecessary penicillin avoidance and PAT was low. Initial concerns regarding PAT were common but were frequently alleviated with targeted education. Most patients undergoing testing reported a positive experience and would recommend PAT to others. A minority of patients continued to have discordant perceptions regarding their penicillin allergy label with mistrust in the negative result being a critical theme identified. CONCLUSIONS: Future interventions increasing the awareness of penicillin allergy labels and the risks and benefits of PAT in the general population are needed and must consider health literacy levels, languages, and cultural contexts. Measures to offer PAT within a clinical setting that has built high levels of patient trust will likely achieve the greatest long-term success.

Rising to the Challenge: An ID Provider-Led Initiative to Address Penicillin Allergy Labels at a Large Veterans Affairs Medical Center.

Background: Given the negative consequences associated with a penicillin allergy label, broader penicillin allergy delabeling initiatives are highly desirable but hindered by the shortage of allergists in the United States. To address this problem at our facility, the infectious diseases section introduced a quality improvement initiative to evaluate and remove allergy labels among inpatient veterans. Methods: Between 15 November 2022 and 15 December 2023, we identified inpatients with a penicillin allergy label. We subsequently interviewed eligible candidates to stratify penicillin allergy risk and attempt to remove the allergy label directly via chart review, following inpatient oral amoxicillin challenge or outpatient community care allergy referral. Delabeling outcomes, subsequent penicillin-class prescriptions, and relabeling were tracked after successful allergy label removal. Results: We screened 272 veterans, of whom 154 were interviewed for this intervention. A total of 53 patients were delabeled: 26 directly, 23 following oral amoxicillin challenge, and 4 following outpatient allergy referrals. Of the patients who were delabeled, 25 received subsequent penicillin-class prescriptions. No adverse reactions occurred following inpatient oral amoxicillin challenges. Patients with a low-risk penicillin allergy history were more likely to undergo a challenge if admitted with an infectious diseases-related condition. Only 1 inappropriate relabeling event occurred during the study period, which was subsequently corrected. Conclusions: An infectious diseases provider-led initiative resulted in penicillin allergy label removal in more than one third of inpatients evaluated using direct removal or oral amoxicillin challenge. Efforts focused on patients who had been admitted for infections were particularly successful.

Evaluation of indications and efficacy of doxycycline for surgical antibiotic prophylaxis.

Given medical advancements in global healthcare systems over the past decade, it may be reasonable to assume that the incidence of surgical site infections would have decreased; however, surveillance data indicate that these rates have held constant. Surgical prophylaxis guidelines from the United States and United Kingdom recommend cefazolin, vancomycin and clindamycin in most surgeries for no longer than 24 hours. As a result of medication shortages impacting the global supply chain, surgeons have needed to evaluate alternative perioperative antibiotics, such as doxycycline; however, research into using doxycycline for preventing surgical site infections is limited. The goal of this study is to retrospectively assess doxycycline's efficacy, safety and role in preventing surgical site infections.

Comparative Performance of 4 Penicillin-Allergy Prediction Strategies in a Large Cohort.

BACKGROUND: A safe and pragmatic guide for labelling and delabelling patients with suspected penicillin allergy is mandatory. OBJECTIVE: To compare the performance of 4 penicillin-allergy prediction strategies in a large independent cohort. METHODS: We conducted a retrospective study for subjects presenting between January 2014 and December 2021 at the University Hospital of Montpellier, with a history of hypersensitivity to penicillins. The outcome targeted by the study was a positive penicillin-allergy test. RESULTS: Of the 1,884 participants included, 382 (20.3%) had positive penicillin-allergy tests. The ENDA (European Network on Drug Allergy) and Blumenthal strategies yielded relatively high sensitivities and low specificities and, by design, did not misclassify any positive subjects with severe index reactions. The PEN-FAST <3 score had a negative predictive value of 90% (95% confidence interval [95% CI] 88%-91%), with a sensitivity of 66% (95% CI 62%-71%) and a specificity of 73% (95% CI 71%-75%), and incorrectly delabelled 18 subjects with anaphylaxis and 15 with other severe nonimmediate reactions. For the adapted Chiriac score, the specificity corresponding to 66% sensitivity was 73% (95% CI 70%-75%). Conversely, at a 73% specificity threshold, the sensitivity was 65% (95% CI, 61%-70%). Attempts to improve these prediction algorithms did not substantially enhance performance. CONCLUSIONS: The ENDA and Blumenthal strategies are safe for high-risk subjects, but their delabelling effectiveness is limited, leading to unnecessary avoidance. Conversely, the PEN-FAST and Chiriac scores are performant in delabelling, but more frequently misclassify high-risk subjects with positive penicillin-allergy tests. Selection of the most appropriate tool requires careful consideration of the target population and the desired goal.

Safe Penicillin Allergy Delabeling in Primary Care: A Systematic Review and Meta-Analysis.

BACKGROUND: Ten percent of the population is labeled as allergic to penicillin(s), when in fact 90% of these labels are inappropriate. Recent studies have shown that inpatient delabeling by a direct drug challenge (dDC) is safe in low-risk patients. However, there is a need for outpatient and nonallergist delabeling. OBJECTIVE: To assess the safety of delabeling low-risk adults by means of dDC in primary care. METHODS: We searched the MEDLINE, Embase, and Cochrane Library databases from inception to March 15, 2022 (updated June 5, 2023) for studies performing dDC in adults in primary care or other outpatient settings. Two researchers independently screened studies for eligibility. The data extraction and critical appraisal were performed by 1 reviewer, and we pooled the results in a meta-analysis. RESULTS: Of 2138 results, 12 studies (1070 participants) were eligible for inclusion. Three studies evaluated delabeling in primary care and 9 studies in an outpatient hospital setting. There were no critical adverse events during dDC. No reaction occurred in 97.13% of the 1070 patients, who previously labeled as penicillin-allergic, and were safely delabeled. Ten patients (<1%) developed an immediate reaction: 3 had self-limiting reactions and 7 needed antihistaminics, steroids, epinephrine, and/or salbutamol. CONCLUSIONS: No serious allergic reactions are observed during direct amoxicillin challenge in adults in an outpatient setting. However, with the exception of 1 recent report, these studies are of low to moderate quality. Nonspecialist delabeling is promising, but further research is required on correct risk stratification and safety assessment in large cohort studies evaluating dDC in primary care.

The Safety of Aztreonam Versus Ceftazidime in Patients Labeled With Penicillin Allergy: A Cohort Study.

PURPOSE: Penicillin allergy is the most common drug allergy among hospitalized patients. Traditionally, aztreonam is recommended for patients labeled with penicillin allergy (PLWPA) in our institutional empirical antibiotic guidelines. Due to a global aztreonam shortage in December 2022, the antimicrobial stewardship unit recommended ceftazidime as a substitute. There is a paucity of real-world data on the safety profile of ceftazidime in PLWPA. Hence, we evaluated tolerability outcomes of ceftazidime use in PLWPA. METHODS: This retrospective cohort study compared PLWPA in Singapore General Hospital who received aztreonam (October 2022-December 2022) or ceftazidime (December 2022-February 2023). Patients were stratified according to their risk of allergic reaction (AR) based on history of penicillin allergy. The severity of AR was based on the Delphi study grading system. The primary outcome was development of AR after initiation of aztreonam or ceftazidime. The secondary tolerability outcomes include hepatotoxicity and neurotoxicity. FINDINGS: There were 168 patients in the study; 69 were men (41.1%) and the median age was 69 years (interquartile range: 59-76 years). Incidence of AR was statistically similar in both arms: 1 of 102 patients (0.98%) in the aztreonam arm vs 2 of 66 patients (3.03%) in the ceftazidime arm (P = 0.33). The patient in the aztreonam arm was deemed at medium risk of having an AR and developed localized rashes (grade 1). Both patients in the ceftazidime arm were deemed at high risk of AR and developed localized skin reaction (grade 1). Hepatotoxicity was observed in 1 patient prescribed aztreonam. No patients in the ceftazidime arm developed adverse events. IMPLICATIONS: Ceftazidime appears to be better tolerated and cheaper compared with aztreonam in PLWPA, and serves as an antimicrobial stewardship strategy to conserve broader-spectrum antibiotics use.

The appropriateness of penicillin allergy de-labelling by non-allergist clinical ward teams.

OBJECTIVES: We aimed to assess the appropriateness of penicillin allergy (PenA) assessment conducted by clinical teams and to review the safety of subsequent exposure of these patients to penicillin. METHODS: Opportunistic, prospective observational study of usual clinical care, between 16 May 2023 and 14 August 2023, of inpatients with a PenA and requiring antibiotics, in a 750-bed hospital in England. To assess the appropriateness of management, PenA patients prescribed penicillins were grouped into risk categories using a validated antibiotic allergy assessment tool: eligible for de-label on history alone (direct de-label; DDL), eligible for direct oral challenge (DOC), high risk or unable to obtain history. RESULTS: Of the 123 patients admitted with a PenA (or sensitivity record) and exposed to a penicillin, data were collected for 50. Their PenA records were grouped follows: eligible for DDL 34 (68%), eligible for DOC 11 (22%), high risk 4 (8%) and unable to obtain history 1 (2%). In 14/50 (28%) patients there was no evidence of a current PenA assessment in the medical notes. CONCLUSIONS: Using the allergy risk tool, most patients with PenA records were exposed to penicillin appropriately. However, patients meeting high-risk criteria were also exposed to penicillin when the tool excluded them. PenA assessment needs to be carried out with appropriate training and governance structures in place.

Management and Implications of Beta-Lactam Allergies.

Beta-lactam antibiotics are essential components in the current antimicrobial treatment strategy, playing a crucial role in ambulatory patients and hospitalized patients. Despite their prominent therapeutic index, the use of beta-lactam can lead to adverse effects, with allergic reactions being the most concerning because of their severity. Additionally, the phenomenon of cross-reactivity may occur among various beta-lactam families, with side chains significantly contributing to immunological recognition, making these structures often responsible for the cross-allergic reactivity of beta-lactams. Tools to assess beta-lactam allergy include taking a patient's medical history, performing skin tests, and conducting provocation tests. This research aims to analyze the relevant aspects related to the safe administration of beta-lactam antibiotics in hospitalized patients as well as provide knowledge on the proper management of patients with such hypersensitivity, by doing systemic research. This research was made using Google Scholar and keywords such as "Beta-lactam allergy," "Hypersensitivity," "Cross-reactivity," "Desensitization," and "Beta-lactam allergy management." In conclusion, substituting a beta-lactam antibiotic with an alternative antibiotic may not always be the best management option for these patients, as it may lead to more adverse effects, be less effective, and prolong hospitalization time. It may also result in higher rates of antibiotic-resistant infections and increased medical costs, as these alternatives are often more expensive. However, an alternative within the beta-lactam family can be sought by conducting the appropriate analyses. Although cross-reactivity does not always occur among all beta-lactams, potential cross-reactivity should always be considered.

After primary shoulder arthroplasty appropriate vancomycin antibiotic prophylaxis does not lead to increased infectious complications when compared to cefazolin.

BACKGROUND: In primary shoulder arthroplasty (SA), intravenous (IV) cefazolin has demonstrated lower rates of infectious complications when compared to IV vancomycin. However, previous analyses included SA cohorts with both complete and incomplete vancomycin administration. Therefore, it is currently unclear whether cefazolin still maintains a prophylactic advantage to vancomycin when it is appropriately indicated and sufficiently administered at the time of surgical incision. This study evaluated the comparative efficacy of cefazolin and complete vancomycin administration for surgical prophylaxis in primary shoulder arthroplasty with respect to infectious complications. METHODS: A retrospective cohort study was conducted utilizing a single institution total joint registry database, where all primary SA types (hemiarthroplasty, anatomic total shoulder arthroplasty, and reverse shoulder arthroplasty) performed between 2000 to 2019 for elective and trauma indications using IV cefazolin or complete vancomycin administration as the primary antibiotic prophylaxis were identified. Vancomycin was primarily indicated for patients with a severe self-reported penicillin or cephalosporin allergy and/or MRSA colonization. Complete administration was defined as at least 30 minutes of antibiotic infusion prior to incision. All included SA had at least 2 years of clinical follow-up. Multivariable Cox proportional hazard regression was used to evaluate all-cause infectious complications including survival free of prosthetic joint infection (PJI). RESULTS: The final cohort included 7177 primary SA, 6879 (95.8%) received IV cefazolin and 298 (4.2%) received complete vancomycin administration. Infectious complications occurred in 120 (1.7%) SA leading to 81 (1.1%) infectious reoperations. Of the infectious complications, 41 (0.6%) were superficial infections and 79 were (1.1%) PJIs. When categorized by administered antibiotics, there were no differences in rates of all infectious complications (1.6% vs. 2.3%; P = .352), superficial complications (0.5% vs. 1.3%; P = .071), PJI (1.1% vs. 1.0%; P = .874), or infectious reoperations (1.1% vs. 1.0%; P = .839). On multivariable analyses, complete vancomycin infusion demonstrated no difference in rates of infectious complications compared to cefazolin administration (hazard ratio [HR], 1.50 [95% confidence interval (CI), 0.70 to 3.25]; P = .297), even when other independent predictors of PJI (male sex, prior surgery, and Methicillin-resistant Staphylococcus aureus colonization) were considered. CONCLUSIONS: In comparison to cefazolin, complete administration of vancomycin (infusion to incision time greater than 30 minutes) as the primary prophylactic agent does not adversely increase the rates of infectious complications and PJI. Prophylaxis protocols should promote appropriate indications for the use of cefazolin or vancomycin, and when necessary, ensure complete administration of vancomycin to mitigate additional infectious risks after primary SA.

Polymorphisms of HLA genes and hypersensitivity to penicillin among patients in a Taiwanese population.

Penicillin allergy is a potentially life-threatening condition that is common among patients. However, the genetic associations with penicillin allergy are not yet recognized for prevention or diagnosis, particularly in East Asian populations. We conducted a retrospective case-control study using data from the Taiwan Precision Medicine Initiative and analysing DNA samples to identify eight major MHC Class I and Class II loci. We employed imputation methods for accurate HLA typing and enrolled 17,827 individuals who received penicillin. Logistic regression analyses were utilized to explore associations between HLA genotypes, comorbidities and allergy risk, while simultaneously conducting a subgroup analysis to explore the association between HLA genotypes, comorbidities and the severity of allergic reactions. Our study assigned 496 cases to the penicillin allergy group and 4960 controls to a matched group. The risk of penicillin allergy was significantly higher with HLA-DPB1*05:01 (OR = 1.36, p = .004) and HLA-DQB1*05:01 (OR = 1.54, p = .03), with adjusted p-values of .032 and .24, respectively. Urticaria was identified as a separate risk factor (OR = 1.73, p < .001). However, neither the HLA alleles nor the comorbidities had a significant relationship with the risk of severe penicillin-induced allergy. HLA-DPB1*05:01 was found to be significantly associated with penicillin allergy reactions among the Taiwanese population.

ß-Lactam allergy delabeling is safe and saves costs in Primary Care.

OBJECTIVE: To determine whether the ß-lactam allergy delabeling was safe and cost-saving in Primary Care (PC) patients. DESIGN: We have conducted a retrospective chart review of PC patients with ß-lactam allergy label evaluated in our Allergy Unit between 2017 and 2022. SITE: Allergy Department. Hospital Virgen del Rocio (Sevilla). PARTICIPANTS: A total of 391 patients labeled for ß-lactam allergy in PC were studied. MAIN MEASUREMENTS: (a) Outcome evaluation of a ß-lactam allergy delabeling procedure. (b) A ratio between the total e-prescribed antibiotic cost and the number of treatment days (the experimental daily antibiotic cost or EDAC) before and after delabeling was analyzed in delabeled and truly allergic patients. RESULTS: The results of skin testing were positive in 9.2% of the reported cases (36 of 391 patients). The reactions to oral provocation challenge (OPC) occurred in 2.14% of the patients who underwent negative skin testing to offending ß-lactam (in 15 of 699 OPC). A total of 307 patients (78.5%) were delabeled; 70 (17.9%) had a ß-lactam selective response and 14 (3.59%) reacted to both penicillin and cephalosporin. The EDAC before and after the procedure in delabeled patients was significantly lower (0.88 € vs 0.62 €, p<10-3), than that observed in truly allergic group (0.87 € vs. 0.76 €, p=not significant). CONCLUSION: To delabel ß-lactam allergy in Primary Care patients is safe in most patients, cost-saving in antibioticotherapy, and allows identify the main clinical ß-lactam allergy phenotypes that benefit from this procedure.

Penicillin Allergy: Mechanisms, Diagnosis, and Management.

Allergy to penicillin can occur via any of the 4 types of Gel-Coombs hypersensitivity reactions, producing distinct clinical histories and physical examination findings. Treatments include penicillin discontinuation, and depending on the type of reaction, epinephrine, antihistamines, and/or glucocorticoids. Most beta-lactams may be safely used in penicillin-allergic patients, with the possible exception of first-generation and second-generation cephalosporins. Penicillin testing includes skin testing, patch testing, and graded challenge. The selection of the type of testing depends on the clinical setting, equipment availability, and type of hypersensitivity reaction. Desensitization may be used in some cases where treatment with penicillins is essential.