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BMJ Open Sep 2023Incorrect penicillin allergy records are recognised as an important barrier to the safe treatment of infection and affect an estimated 2.7 million people in England....
Penicillin allergy status and its effect on antibiotic prescribing, patient outcomes and antimicrobial resistance (ALABAMA): protocol for a multicentre, parallel-arm, open-label, randomised pragmatic trial.
INTRODUCTION
Incorrect penicillin allergy records are recognised as an important barrier to the safe treatment of infection and affect an estimated 2.7 million people in England. Penicillin allergy records are associated with worse health outcome and antimicrobial resistance. The ALlergy AntiBiotics And Microbial resistAnce (ALABAMA) trial aims to determine if an intervention package, centred around a penicillin allergy assessment pathway (PAAP) initiated in primary care, is safe and effective in improving patient health outcomes and antibiotic prescribing.
METHODS AND ANALYSIS
The ALABAMA trial is a multicentre, parallel-arm, open-label, randomised pragmatic trial with a nested pilot study. Adults (≥18 years) with a penicillin allergy record and who have received antibiotics in the previous 24 months will be eligible for participation. Between 1592 and 2090 participants will be recruited from participating National Health Service general practices in England. Participants will be randomised to either usual care or intervention to undergo a pre-emptive PAAP using a 1:1 allocation ratio. The primary outcome measure is the percentage of treatment response failures within 28 days of an index prescription. 2090 and 1592 participants are estimated to provide 90% and 80% power, respectively, to detect a clinically important absolute difference of 7.9% in primary outcome at 1 year between groups. The trial includes a mixed-methods process evaluation and cost-effectiveness evaluation.
ETHICS AND DISSEMINATION
This trial has been approved by London Bridge Research Ethics Committee (ref: 19/LO/0176). It will be conducted in compliance with Good Clinical Practice guidelines according to the Declaration of Helsinki. Informed consent will be obtained from all subjects involved in the study. The primary trial results will be submitted for publication to an international, peer-reviewed journal.
TRIAL REGISTRATION
ISRCTN20579216.
Topics: Adult; Humans; Alabama; Anti-Bacterial Agents; Drug Hypersensitivity; Drug Resistance, Bacterial; Hypersensitivity; Multicenter Studies as Topic; Penicillins; Pilot Projects; Randomized Controlled Trials as Topic; State Medicine; Pragmatic Clinical Trials as Topic
PubMed: 37666558
DOI: 10.1136/bmjopen-2023-072253 -
Journal of Medical Ethics Dec 2023Antibiotic allergies are commonly reported among patients, but most do not experience reactions on rechallenge with the same agents. These reported allergies complicate...
Antibiotic allergies are commonly reported among patients, but most do not experience reactions on rechallenge with the same agents. These reported allergies complicate management of infections in patients labelled as having penicillin allergy, including serious infections where penicillin-based antibiotics are the first-line (most effective and least toxic) treatment option. Allergy labels are rarely questioned in clinical practice, with many clinicians opting for inferior second-line antibiotics to avoid a perceived risk of allergy. Reported allergies thereby can have significant impacts on patients and public health, and present major ethical challenges. Antibiotic allergy testing has been described as a strategy to circumvent this dilemma, but it carries limitations that often make it less feasible in patients with acute infections or in community settings that lack access to allergy testing. This article provides an empirically informed ethical analysis of key considerations in this clinical dilemma, using bacteraemia in patients with penicillin allergies as a case study. We argue that prescribing first-line penicillin-based antibiotics to patients with reported allergies may often present a more favourable ratio of benefits to risks, and may therefore be more ethically appropriate than using second-line drugs. We recommend changes to policy-making, clinical research and medical education, in order to promote more ethically acceptable responses to antibiotic allergies than the status quo.
Topics: Humans; Bacteremia; Staphylococcal Infections; Staphylococcus aureus; Anti-Bacterial Agents; Penicillins; Drug Hypersensitivity; Hypersensitivity
PubMed: 37286334
DOI: 10.1136/jme-2022-108648 -
Annals of Allergy, Asthma & Immunology... Nov 2023Older adults have an increased risk of adverse drug reactions and negative effects associated with alternative antibiotic use. Although the number of antibiotic...
BACKGROUND
Older adults have an increased risk of adverse drug reactions and negative effects associated with alternative antibiotic use. Although the number of antibiotic allergies reported increases with age, the characteristics and outcomes of older adults receiving drug allergy assessment are unknown.
OBJECTIVE
To assess the characteristics and outcomes of drug allergy evaluations in older adults.
METHODS
We considered patients aged above or equal to 65 years enrolled in the United States Drug Allergy Registry (USDAR), a US multisite prospective cohort (January 16, 2019 to February 28, 2022). Data were summarized using descriptive statistics.
RESULTS
Of 1678 USDAR participants from 5 sites, 406 older adults aged above or equal to 65 years (37% 65-69 years, 37% 70-74 years, 16% 75-79 years, and 10% ≥80 years) received 501 drug allergy assessments. USDAR older adults were primarily of female sex (69%), White (94%), and non-Hispanic (98%). Most USDAR older adults reported less than or equal to 1 infections per year (64%) and rated their general health as good, very good, or excellent (80%). Of 296 (59%) penicillin allergy assessments in USDAR older adults, 286 (97%) were disproved. Other drug allergy assessments included sulfonamide (n = 41, 88% disproved) and cephalosporin (n = 20, 95% disproved) antibiotics. All 41 drug allergy labels in USDAR participants aged above or equal to 80 years and all 80 penicillin allergy labels in USDAR men aged above or equal to 65 years were disproved.
CONCLUSION
Older adults represented a quarter of USDAR participants but were neither racially nor ethnically diverse and were generally healthy without considerable antibiotic need. Most older adults presented for antibiotic allergy assessments, the vast majority of which were disproved. Drug allergy assessments may be underutilized in the older adults who are most vulnerable to the harms of unconfirmed antibiotic allergy labels.
Topics: Male; Humans; Female; United States; Aged; Prospective Studies; Penicillins; Anti-Bacterial Agents; Drug Hypersensitivity; Hypersensitivity
PubMed: 37557950
DOI: 10.1016/j.anai.2023.07.024 -
The Journal of Bone and Joint Surgery.... Nov 2023
Topics: Humans; Orthopedics; Iodine; Drug Hypersensitivity; Hypersensitivity; Contrast Media
PubMed: 37262181
DOI: 10.2106/JBJS.22.01389 -
Transgenic murine models for the study of drug hypersensitivity reactions linked to HLA-I molecules.Current Opinion in Allergy and Clinical... Aug 2023Immune-mediated drug hypersensitivity reactions (DHRs) can be life-threatening and an impediment to drug development. Mechanism of disease studies are difficult to... (Review)
Review
PURPOSE OF REVIEW
Immune-mediated drug hypersensitivity reactions (DHRs) can be life-threatening and an impediment to drug development. Mechanism of disease studies are difficult to perform in humans. Here we review human leukocyte antigens class I (HLA-I) transgenic murine models and highlight how these systems have helped to elucidate drug-specific and host immune factors that initiate, propagate and control severe drug toxicities to skin and liver.
RECENT FINDINGS
HLA transgenic mice have been developed and used to study immune-mediated drug reactions in vitro and in vivo . CD8+ T cells from HLA-B∗57:01-expressing mice respond strongly to abacavir (ABC) in vitro but have self-limited responses to drug exposure in vivo . Immune tolerance can be overcome by depleting regulatory T cells (Treg) allowing antigen-presenting dendritic cells to express CD80/86 costimulatory molecules and signal through CD28 on the CD8+ T cell. Depletion of Treg also removes competition for interleukin 2 (IL-2) to allow T cell expansion and differentiation. Fine tuning of responses depends on inhibitory checkpoint molecules such as PD-1. Improved mouse models express only HLA in the absence of PD-1. These models show enhanced liver injury to flucloxacillin (FLX) which depends on drug priming, CD4+ T cell depletion, and lack of PD-1 expression. Drug-specific HLA-restricted cytotoxic CD8+ T cells can infiltrate the liver but are suppressed by Kupffer and liver sinusoidal endothelial cells.
SUMMARY
HLA-I transgenic mouse models are now available to study ABC, FLX and carbamazepine-induced adverse reactions. In vivo studies range from characterizing drug-antigen presentation, T cell activation, immune-regulatory molecules and cell-cell interaction pathways that are specifically involved in causing or controlling unwanted DHRs.
Topics: Mice; Humans; Animals; Disease Models, Animal; Programmed Cell Death 1 Receptor; Endothelial Cells; Drug Hypersensitivity; Mice, Transgenic; CD8-Positive T-Lymphocytes; Drug-Related Side Effects and Adverse Reactions
PubMed: 37284777
DOI: 10.1097/ACI.0000000000000913 -
The Journal of Allergy and Clinical... Sep 2023
Topics: Humans; Drug Hypersensitivity Syndrome; Eosinophilia
PubMed: 37236348
DOI: 10.1016/j.jaip.2023.05.017 -
International Journal of Occupational... Nov 2023On 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...
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 Łódź, 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 β-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.
Topics: Child; Humans; Drug Hypersensitivity; Hypersensitivity; Skin Tests; beta-Lactams; Risk Factors; Anti-Bacterial Agents
PubMed: 37750429
DOI: 10.13075/ijomeh.1896.02227 -
The Journal of Allergy and Clinical... Dec 2023Penicillin allergy is the most common drug allergy in the US population. A penicillin allergy label is associated with poor patient outcomes including increased hospital...
Penicillin allergy is the most common drug allergy in the US population. A penicillin allergy label is associated with poor patient outcomes including increased hospital length of stay, increased perioperative infections, and overall increased mortality. A penicillin allergy evaluation accurately identifies approximately 9 of 10 patients who, despite reporting a history of penicillin allergy, can receive penicillins safely. Penicillin allergy evaluations should be offered proactively to healthy patients during routine visits, including children and pregnant women, in advance of antibiotic need.
Topics: Child; Humans; Female; Pregnancy; Penicillins; Anti-Bacterial Agents; Drug Hypersensitivity; Hospitals; Hypersensitivity; Skin Tests
PubMed: 37838278
DOI: 10.1016/j.jaip.2023.09.045 -
Current Opinion in Allergy and Clinical... Aug 2024To understand the current global scale of drug hypersensitivity (DH) and drug allergy (DA), and to identify possible strategies to increase the accuracy of... (Review)
Review
PURPOSE OF REVIEW
To understand the current global scale of drug hypersensitivity (DH) and drug allergy (DA), and to identify possible strategies to increase the accuracy of epidemiological data.
RECENT FINDINGS
Global patterns of DH/DA seem to be changing and increasing worldwide, but there are still great challenges in capturing quality DH/DA mortality and morbidity statistics (MMS). DH/DA MMS may gain new perspectives with the global implementation of the International Classification of Diseases (ICD)-11. Improving the quality of epidemiological data related to DH/DA should clarify areas of uncertainty, which would lead to better strategies to reduce the burden of these conditions.
SUMMARY
DH/DA remains a complex and unaddressed problem globally that often deprives patients of optimal medication choices and places them at risk for life-threatening reactions. DH/DA labels should contribute to people well being, by protecting true allergic individuals from being re-exposed to their allergic drugs and providing needed medications to individuals wrongly labeled as allergic or who have lost allergic sensitivity. The true rate of DH/DA is in fact unknown due to a number of factors, such as misdiagnosis, miscoding and under- and over-notification, among others. Moreover, there is lack of data about DH/DA epidemiology in many countries. Difficulties on collecting accurate and comparable data should be acknowledged, with great impact in the correct labeling DH/DA in electronic health records and official statistics. More accurate definitions, classification and coding may contribute to a better-quality MMS thanks to the ICD-11, under implementation worldwide. Improving the quality of epidemiological data related to DH/DA should clarify areas of uncertainty, which would lead to better strategies to reduce the burden of these conditions. As knowledge derived from populations is key information for more realistic decision-making, the construction of the new section addressed to DH/DA in the ICD-11 will allow the collection of more accurate epidemiological data to support quality management of patients, and facilitate healthcare planning to implement public health measures to prevent and reduce the morbidity and mortality attributable to these conditions.
Topics: Humans; Drug Hypersensitivity; International Classification of Diseases
PubMed: 38873859
DOI: 10.1097/ACI.0000000000001003 -
Current Opinion in Allergy and Clinical... Aug 2023Recent studies have been clarifying the pathogenesis and early diagnostic markers of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Additionally,... (Review)
Review
PURPOSE OF REVIEW
Recent studies have been clarifying the pathogenesis and early diagnostic markers of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Additionally, the efficacy of tumor necrosis factor alpha inhibitors is attracting attention. This review provides) recent evidence for the diagnosis and management of SJS/TEN.
RECENT FINDINGS
Risk factors for the development of SJS/TEN have been identified, particularly the association between HLA and the onset of SJS/TEN with specific drugs, which has been intensively studied. Research on the pathogenesis of keratinocyte cell death in SJS/TEN has also progressed, revealing the involvement of necroptosis, an inflammatory cell death, in addition to apoptosis. Diagnostic biomarkers associated with these studies have also been identified.
SUMMARY
The pathogenesis of SJS/TEN remains unclear and effective therapeutic agents have not yet been established. As the involvement of innate immunity, such as monocytes and neutrophils, in addition to T cells, has become clear, a more complex pathogenesis is predicted. Further elucidation of the pathogenesis of SJS/TEN is expected to lead to the development of new diagnostic and therapeutic agents.
Topics: Humans; Stevens-Johnson Syndrome; Immunologic Factors
PubMed: 37284785
DOI: 10.1097/ACI.0000000000000914