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The Journal of Allergy and Clinical... Aug 2023A guideline identifying when inpatients with penicillin or cephalosporin antibiotic allergy labels (PCAAL) can receive β-lactam antibiotics increased β-lactam receipt...
BACKGROUND
A guideline identifying when inpatients with penicillin or cephalosporin antibiotic allergy labels (PCAAL) can receive β-lactam antibiotics increased β-lactam receipt at a large northeastern US health care system.
OBJECTIVE
To report outcomes of implementing a similar guideline and electronic order set (OS) at an independent academic health care system.
METHODS
Penicillin/cephalosporin receipt (percentage of inpatients receiving full doses) and alternative antibiotic use (days of therapy per 1000 patient-days [DOT/1000PD]) were compared over 3 periods before (February 1, 2017, to January 31, 2018) and after guideline implementation (February 1, 2018, to January 31, 2019), and after OS implementation (February 1, 2019, to January 31, 2020) among inpatients with PCAAL admitted on medical services with access to guideline/OS and education (Medical-PCAAL, n = 8721), surgical services with access to guideline/OS without education (Surgical-PCAAL, n = 5069), and obstetrics/gynecology services without interventions (Ob/Gyn-PCAAL, n = 798) and inpatients without PCAAL admitted on the same services (Medical-No-PCAAL, n = 50,840; Surgical-No-PCAAL, n = 29,845; Ob/Gyn-No-PCAAL, n = 6109). χ tests were used to compare categorical variables, and analysis of variance was used to compare continuous and interrupted time series analyses (ITSA) to investigate the guideline/OS implementation effect on penicillin/cephalosporin receipt.
RESULTS
In the Medical-PCAAL group, penicillin/cephalosporin receipt increased (58%-68%, P < .001), specifically for cefazolin (8%-11%, P = .02) and third- to fifth-generation cephalosporins (43%-48%, P = .04), and aztreonam use decreased (12 DOT/1000PD, P = .03). In the Medical-No-PCAAL group, penicillin/cephalosporin receipt increased (88%-90%, P = .004), specifically for penicillin (40%-44%, P < .001), without changes in aztreonam use. Significant changes were not observed in these outcomes on surgical or obstetrics/gynecology services. Per ITSA, guideline/OS implementation was associated with increased penicillin/cephalosporin receipt in the Medical-PCAAL group only.
CONCLUSION
Guideline and OS implementation was associated with improved antibiotic stewardship on inpatient services that also received allergy education.
Topics: Humans; Anti-Bacterial Agents; beta-Lactams; Inpatients; Aztreonam; Penicillins; Cephalosporins; Drug Hypersensitivity; Hypersensitivity; Retrospective Studies
PubMed: 37182569
DOI: 10.1016/j.jaip.2023.04.051 -
International Immunopharmacology Sep 2023Beta-lactam (BLM) antibiotics, including amino-penicillin and cephalosporins, are typically the first-choice treatment for bacterial infections. However, adverse... (Review)
Review
Beta-lactam (BLM) antibiotics, including amino-penicillin and cephalosporins, are typically the first-choice treatment for bacterial infections. However, adverse reactions to these antibiotics are frequently reported, causing non-allergist physicians to select alternative broad-spectrum antibiotics that can have harmful consequences. Patients with unclear histories of hypersensitivity reactions to BLMs should undergo an allergy workup to establish a firm diagnosis, particularly when different drugs are prescribed simultaneously. However, finding the safest, most precise, and cost-effective methods for confirming BLMs hypersensitivity and selecting the most appropriate alternative BLM is uncertain, particularly in severe delayed reactions. This review aims to provide data and recommendations on the availability and validity of skin tests (STs), drug provocation test (DPT) protocols, based on the latest published literature and guideline. To make the process more practical, we focused on cross-reactivity between BLMs and diagnostic tests. There are two main novel aspects of this document: 1) For T-cell-mediated reactions, patient stratification into high, moderate, and low-risk groups based on the mortality and morbidity of adverse drug reactions. 2) For IgE-mediated reactions, stratification of individuals with isolated limited urticarial without anaphylaxis in a low-risk group and removal of the extensive limitation.
Topics: Humans; Anti-Bacterial Agents; beta-Lactams; Drug Hypersensitivity; Penicillins; Skin Tests; Monobactams; Anaphylaxis; Cross Reactions
PubMed: 37413935
DOI: 10.1016/j.intimp.2023.110573 -
International Journal of Molecular... Aug 2023Drug hypersensitivity reactions are a serious concern in clinical practice because they can be severe and result in lifelong sequelae. An accurate diagnosis and... (Review)
Review
Drug hypersensitivity reactions are a serious concern in clinical practice because they can be severe and result in lifelong sequelae. An accurate diagnosis and identification of the culprit drug is essential to prevent future reactions as well as for the identification of safe treatment alternatives. Nonetheless, the diagnosis can be challenging. In vivo and in vitro tests can be helpful, although none are conclusive; therefore, the tests are not usually performed in isolation but as part of a diagnostic algorithm. In addition, some in vitro tests are only available in research laboratories, and standardization has not been fully accomplished. Collaborating research is needed to improve drug hypersensitivity reaction diagnosis. In this review, we update the current available in vivo and in vitro tools with their pros and cons and propose an algorithm to integrate them into clinical practice.
Topics: Humans; Algorithms; Causality; Disease Progression; Drug Hypersensitivity; Hypersensitivity
PubMed: 37628756
DOI: 10.3390/ijms241612577 -
Allergy Nov 2023Allopurinol (ALP) is a successful drug used in the treatment of gout. However, this drug has been implicated in hypersensitivity reactions that can cause severe to...
Allopurinol (ALP) is a successful drug used in the treatment of gout. However, this drug has been implicated in hypersensitivity reactions that can cause severe to life-threatening reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Individuals who carry the human leukocyte antigen (HLA)-B*58:01 allotype are at higher risk of experiencing a hypersensitivity reaction (odds ratios ranging from 5.62 to 580.3 for mild to severe reactions, respectively). In addition to the parent drug, the metabolite oxypurinol (OXP) is implicated in triggering T cell-mediated immunopathology via a labile interaction with HLA-B*58:01. To date, there has been limited information regarding the T-cell receptor (TCR) repertoire usage of reactive T cells in patients with ALP-induced SJS or TEN and, in particular, there are no reports examining paired αβTCRs. Here, using in vitro drug-treated PBMCs isolated from both resolved ALP-induced SJS/TEN cases and drug-naïve healthy donors, we show that OXP is the driver of CD8 T cell-mediated responses and that drug-exposed memory T cells can exhibit a proinflammatory immunophenotype similar to T cells described during active disease. Furthermore, this response supported the pharmacological interaction with immune receptors (p-i) concept by showcasing (i) the labile metabolite interaction with peptide/HLA complexes, (ii) immunogenic complex formation at the cell surface, and (iii) lack of requirement for antigen processing to elicit drug-induced T cell responsiveness. Examination of paired OXP-induced αβTCR repertoires highlighted an oligoclonal and private clonotypic profile in both resolved ALP-induced SJS/TEN cases and drug-naïve healthy donors.
Topics: Humans; Allopurinol; Oxypurinol; Stevens-Johnson Syndrome; CD8-Positive T-Lymphocytes; HLA-B Antigens
PubMed: 37452515
DOI: 10.1111/all.15814 -
The American Journal of Case Reports Oct 2023BACKGROUND Different medication classes have been implicated in cutaneous eruptions that may lead to significant morbidity and mortality. In drug reaction with...
BACKGROUND Different medication classes have been implicated in cutaneous eruptions that may lead to significant morbidity and mortality. In drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, the patient may initially present with a cutaneous eruption and hematologic abnormalities which can lead to acute visceral organ involvement if the offending drug is not discontinued. There is also a potential for long-term sequelae such as autoimmune disorders. CASE REPORT A 47-year-old woman with an unknown past medical history and no known drug allergies was admitted to the Behavioral Health Unit, where she was diagnosed with disorganized schizophrenia and started on olanzapine. On day 17 of admission, she developed a diffuse, macular, and erythematous rash on her abdomen, which spread to involve over 50% of her total body surface area. Occipital and posterior auricular lymphadenopathy was present. The patient was treated with prednisone and diphenhydramine. Olanzapine was subsequently discontinued and the patient's rash cleared up. CONCLUSIONS This case report highlights the challenges in diagnosing DRESS syndrome and the potential for antipsychotics to cause DRESS syndrome. DRESS syndrome is a clinical diagnosis augmented by laboratory tests with a wide range of patient presentations. Although there are probability criteria to assist with diagnosis, not all patients will fall exactly into these criteria, which can lead to missed diagnoses and poor patient outcomes. A challenge with DRESS syndrome diagnosis is the latency period between drug initiation and cutaneous eruption. Thus, in differential diagnoses for skin eruptions, temporal associations (minutes, days, weeks) with medications are crucial.
Topics: Female; Humans; Middle Aged; Drug Hypersensitivity Syndrome; Olanzapine; Exanthema; Eosinophilia; Disease Progression
PubMed: 37777823
DOI: 10.12659/AJCR.941379 -
Archives of Toxicology Jan 2024Idiosyncratic drug-induced liver injury (DILI) associated with drug reactions with eosinophilia and systemic symptoms (DRESS) is poorly characterized among patients of...
Idiosyncratic drug-induced liver injury (DILI) associated with drug reactions with eosinophilia and systemic symptoms (DRESS) is poorly characterized among patients of Western countries. We aimed to comprehensively assess the clinical characteristics, outcomes, and causative agents in a prospective, well-vetted cohort of DILI patients with DRESS (DILI-DRESS). We identified 53 DILI-DRESS cases from the Spanish DILI Registry and the Latin American DILI Network. For comparison purposes, we defined a group of DILI patients (n = 881). DILI-DRESS cases were younger (47 vs. 53 years, respectively; p = 0.042) and presented more frequently with cholestatic/mixed damage (p = 0.018). Most DILI-DRESS patients showed moderate liver injury, 13% developed severe damage, and only one patient (with hepatocellular injury due to anti-tuberculosis drugs) progressed to acute liver failure and died. DILI-DRESS cases showed a distinctive causative drug pattern compared to DILI cases. The most frequent drugs were carbamazepine (13%), anti-tuberculosis drugs (13%), amoxicillin-clavulanate (11%), and allopurinol and lamotrigine (7.6% each). Among all cases of DILI due to allopurinol and lamotrigine, 67% presented with a DILI-DRESS phenotype, respectively. Higher total bilirubin (TBL) levels at DILI recognition (odds ratio [OR] 1.23; 95% confidence interval [CI] 1.04-1.45) and absence of eosinophilia (OR 8.77; 95% CI 1.11-69.20) increased the risk for developing a severe-fatal injury in DILI-DRESS patients. DILI-DRESS patients have a more frequent cholestasis/mixed pattern of injury at presentation, with antiepileptics as distinctive causative drug class. Most of the lamotrigine and allopurinol cases present with this phenotype. Higher TBL levels and absence of eosinophilia at DILI recognition are markers of poor outcomes.
Topics: Humans; Drug Hypersensitivity Syndrome; Allopurinol; Prospective Studies; Lamotrigine; Eosinophilia; Chemical and Drug Induced Liver Injury; Cholestasis; Anticonvulsants; Antitubercular Agents; Registries
PubMed: 38051367
DOI: 10.1007/s00204-023-03630-0 -
Clinical Reviews in Allergy & Immunology Dec 2023Sulfonamides, which are drugs commonly prescribed in hospital and outpatient settings, have historically been associated with a high incidence of hypersensitivity... (Review)
Review
Sulfonamides, which are drugs commonly prescribed in hospital and outpatient settings, have historically been associated with a high incidence of hypersensitivity reactions. It is believed that there is an increased risk of cross-reactions with other drugs that contain this functional group in their structure. However, it has not been conclusively established that the sulfonamide group is the sole cause of hypersensitivity reactions, as non-antibiotic sulfonamides do not share the same accessory groups with antibiotic sulfonamides. Therefore, cross-reactivity between different types of sulfonamides and sulfonamide-type antibiotics is not clearly demonstrated, and allergic reactions may involve other mechanisms. Misinformation about this topic can lead to inappropriate use of alternative antibiotics with lower efficacy or higher adverse effects, contributing to antibiotic resistance. It is crucial to individualize and monitor patients with a history of allergies to sulfonamide-type antibiotics when introducing a new drug containing sulfa and manage any adverse reactions promptly. Desensitization protocols may be a viable option for patients who specifically benefit from these antibiotics, particularly those who are immunosuppressed. This article provides a descriptive bibliographic review to update information on sulfa allergy, its prevalence, management, and recommendations to prevent such reactions and optimize pharmacotherapy, without underusing these drugs.
Topics: Humans; Drug Hypersensitivity; Sulfonamides; Anti-Bacterial Agents; Sulfanilamide; Cross Reactions
PubMed: 38175321
DOI: 10.1007/s12016-023-08978-w -
Current Opinion in Allergy and Clinical... Aug 2023Serum tryptase, a mast cell marker, provides clues for the mechanism, severity, and management of drug hypersensitivity induced by immunoglobulin E dependent or...
PURPOSE OF REVIEW
Serum tryptase, a mast cell marker, provides clues for the mechanism, severity, and management of drug hypersensitivity induced by immunoglobulin E dependent or independent mast cell activation.
RECENT FINDINGS
The interpretation of serum tryptase levels has been challenged during the last 2 years by major advances in tryptase genetics and their rapid incorporation into clinical practice. On the contrary, new pathophysiological insight into nonmast cell-dependent immediate hypersensitivity has been gained.
SUMMARY
This review provides up-to-date information on the pathophysiology and recommended use and interpretation of tryptase in the context of drug hypersensitivity reactions as a function of their endotype.
Topics: Humans; Tryptases; Anaphylaxis; Drug Hypersensitivity; Mast Cells; Hypersensitivity, Immediate
PubMed: 37357783
DOI: 10.1097/ACI.0000000000000916 -
The Journal of Hospital Infection Nov 2023There is a lack of understanding of the barriers reported by healthcare providers when evaluating beta-lactam allergies, but knowledge of these barriers is required for...
BACKGROUND
There is a lack of understanding of the barriers reported by healthcare providers when evaluating beta-lactam allergies, but knowledge of these barriers is required for practical and effective implementation interventions.
METHODS
Twenty-five healthcare providers, consisting of physicians, nurses and pharmacists practicing in the areas of intensive care, emergency medicine, infectious disease and general hospital practice, were interviewed between September 2021 and July 2023. Twenty-three of these providers were practising in the USA. A semi-structured interview guide grounded in the Theoretical Domain Framework was used for the interviews. Deductive and inductive analysis was performed on the interview transcripts, and translated into intervention recommendations using the Behaviour Change Wheel.
RESULTS
Widely held beliefs included a lack of clear policy for the evaluation of allergies, confusing or missing documentation of allergy information, confidence in their own and their colleagues' ability to evaluate allergies when information is available, and pharmacists as the provider most equipped to evaluate beta-lactam allergies.
CONCLUSIONS
Health systems should adopt and disseminate policies for the evaluation of beta-lactam allergies, and promote the use of pharmacists in the evaluation of drug allergies when possible. Allergy sections of electronic health records should be reworked to encourage unambiguous documentation of allergy reactions and support using previously tolerated beta-lactam antibiotics.
Topics: Humans; beta-Lactams; Anti-Bacterial Agents; Hypersensitivity; Drug Hypersensitivity; Pharmacists
PubMed: 37574018
DOI: 10.1016/j.jhin.2023.07.024 -
Endocrine, Metabolic & Immune Disorders... 2024Hypersensitivity reactions to non-steroidal anti-inflammatory drugs (HR-NSAIDs) are common adverse events related to the widespread use of over-the-counter NSAIDs for... (Review)
Review
BACKGROUND
Hypersensitivity reactions to non-steroidal anti-inflammatory drugs (HR-NSAIDs) are common adverse events related to the widespread use of over-the-counter NSAIDs for the treatment of a variety of inflammatory conditions. Urticaria is the most commonly reported immediate cutaneous clinical sign of HR-NSAIDs, but it can be a manifestation of pathophysiologically different clinical entities that require different therapeutic strategies. The aim of this study is to ease the identification of the correct phenotype of HR-NSAIDs in patients reporting urticaria associated with the intake of NSAIDs and provide updated information about their diagnosis and management.
METHODS
The study is a narrative review conducted by collecting the most relevant and up-todate data related to the classification, pathophysiology, severity, and prognosis of NSAID hypersensitivity reactions. PubMed and Embase scientific databases were used as search engines to select relevant articles.
RESULTS
Patients developing HR-NSAIDs can be divided into two categories: selective responders (SR), who develop reactions after the administration of a single specific NSAID due to an underlying IgE or T-cell mediated hypersensitivity mechanism, or cross-intolerant (CI), who develop reactions to more than one chemically unrelated NSAIDs due to abnormalities in the biochemical pathways related with prostaglandin metabolism, independently from an underlying immunological mechanism. Five major different categories of HR-NSAIDs have been identified: NSAIDs-exacerbated cutaneous disease (NECD), NSAIDs-induced urticaria/angioedema with/without respiratory and systemic symptoms of anaphylaxis (NIUAA), and NSAIDsexacerbated respiratory disease (NERD), which are developed by CI patients, and single NSAIDs-induced urticaria, angioedema and/ or anaphylaxis (SNIUAA) and single NSAIDsinduced delayed hypersensitivity reactions (SNIDHR), which are developed by CI patients. In vivo and in vitro diagnostic tests have rarely been shown to be reliable in all these entities and therefore are not routinely used in clinical practice. The management in SR patients consists of strict avoidance of the culprit drug, while for cross-intolerance reactions oral tolerance tests with safe alternative drugs (e.g. weak COX-1 inhibitors or selective COX-2 inhibitors) can be performed.
CONCLUSION
HR-NSAIDs are being observed with increasing frequency, however, the pathogenesis behind some NSAIDS-associated clinical entities is still unclear. Diagnosis is mostly based on a thorough clinical history and confirmed by a drug challenge test. Clinical management is based on strict avoidance and use of alternative tolerated medications. Overall, all therapeutic decisions depend on the correct identification of the type of reaction the patient experienced.
Topics: Humans; Anti-Inflammatory Agents, Non-Steroidal; Urticaria; Drug Hypersensitivity
PubMed: 37691219
DOI: 10.2174/1871530323666230907112453