International Network of Antibiotic Allergy Nations (iNAAN): Protocol for a type 2 hybrid effectiveness-implementation multicentre prospective cohort and target trial emulation study evaluating penicillin allergy delabeling via direct oral challenge.

Background: Penicillin allergies are reported in 1 in 10 hospitalised patients globally and are associated with inferior patient and health service outcomes. However, more than 95% of low-risk penicillin allergies can be removed by direct oral challenge (DOC).

Objective: The International Network of Antibiotic Allergy Nations (iNAAN) aims to evaluate the utility of an audit and feedback (A&F) and education implementation strategy to increase the adoption of penicillin DOC in patients with a low-risk penicillin allergy, while concurrently assessing the impact of penicillin DOC on antibiotic prescribing and health service outcomes.

Analysis of skin immune cells in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).

Examination of the immune content in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) lesions reveals the putative role of skin-localised cytotoxic CD8 T cells in disease pathogenesis.

HLA-B*15:01-positive severe COVID-19 patients lack CD8 T cell pools with highly expanded public clonotypes.

Understanding host factors driving asymptomatic versus severe disease outcomes is of key importance if we are to control emerging and re-emerging viral infections. HLA-B*15:01 has been associated with asymptomatic SARS-CoV-2 infection in nonhospitalized individuals of European ancestry, with protective immunity attributed to preexisting cross-reactive CD8 T-cells directed against HLA-B*15:01-restricted Spike-derived S peptide (B15/SCD8 T-cells). However, fundamental questions remained on the abundance and clonotypic nature of CD8 T-cell responses in HLA-B*15:01-positive patients who succumbed to life-threatening COVID-19.

The role of skin testing, drug challenge and IFN-γ ELISpot in delayed hypersensitivity to iodinated contrast media.

Background: The use of in vivo and ex vivo diagnostic tools for delayed hypersensitivity reactions (DHRs) associated with iodinated contrast media (ICM) is currently ill-defined.

Objective: To evaluate the role of in vivo and ex vivo diagnostic tools for DHRs occurring >6 h following intravenous low-osmolality ICM.

Methods: We conducted a prospective, multicenter, international cohort study.

Tackling antimicrobial resistance in people who are immunocompromised: leveraging diagnostic and antimicrobial stewardship.

Antimicrobial resistance (AMR) disproportionately affects people who are immunocompromised due to their frequent encounters with the health-care system and repeated, prolonged exposure to antibiotics. AMR threatens to undermine continued advances in cancer care, haematopoietic cell transplantation, and solid organ transplantation by severely restricting therapeutic options. The convergence of several factors in the diagnostic evaluation of infection among individuals with immunocompromising conditions contributes to excess and inappropriate antibiotic use.

HLA-B Alleles With Shared Peptide Binding Specificities Define Global Risk of Co-trimoxazole-Induced Severe Cutaneous Adverse Drug Reactions.

Background: Co-trimoxazole is a leading global cause of severe cutaneous adverse drug reactions (SCAR) including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS). Co-trimoxazole-induced SCAR are associated with HLA class I alleles including HLA-B∗13:01 and HLA-B∗38:02 in Southeast Asian (SEA) populations. However, the global generalizability of these associations is unknown but critical for population-appropriate risk stratification and diagnosis.

Global Approach for Severe Cutaneous Adverse Reactions (GRASS) Survey.

Background: Consensus guidelines outline the recommended management of delayed drug hypersensitivity reactions (DHR), but clinical practices are largely expert-based and may vary significantly across populations and regions. This study evaluated the approach and management of healthcare specialists globally regarding DHR, including severe cutaneous adverse reactions (SCARs).

Objective: To assess the current practices, knowledge, and availability of allergy testing for DHR, including SCARs, among relevant healthcare professionals globally.

Influenza-Specific T-Cell Responses to Vaccination Are Independent of Underlying Hematological Malignancy: Analysis of a Randomized Influenza Vaccination Trial.

Background: There are few in-depth immunogenicity analyses of novel influenza vaccination strategies in high-risk patients with hematological malignancy (HM).

Methods: Participants receiving treatment for active HM (multiple myeloma [MM], chronic lymphocytic leukemia [CLL], or non-Hodgkin lymphoma [NHL]) in a randomized controlled trial of 2 doses of adjuvanted quadrivalent inactivated influenza vaccine (QIV) versus 2 doses of standard-dose QIV during 2022 were included. Hemagglutination (HA) inhibition assay and HA probe-specific B-cells were compared at baseline and 1, 2, and 6 months after the first vaccine dose (visits 1-4).

Genetic markers of enhanced functional antibody responses to COVID-19 vaccination.

Introduction: Substantial population-level variation in vaccine-specific antibody responses has been observed following global coronavirus disease 2019 (COVID-19) vaccination efforts. Beyond the influence of clinical and demographic features, immunogenetic variation is suggested to underlie divergent serological responses following COVID-19 vaccination of distinct populations.

Methods: Immunoglobulin G1 (IgG1) allotypic markers (G1m) for 121 COVID-19 vaccinated healthy adults were genotyped via Sanger sequencing.

HLA-B Alleles with Shared Peptide Binding Specificities Define Global Risk of Cotrimoxazole-induced SCAR.

Background: Co-trimoxazole is a leading global cause of severe cutaneous adverse drug reactions (SCAR) including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS). Co-trimoxazole-induced SCAR are associated with HLA class I alleles including HLA-B*13:01 and HLA-B*38:02 in Southeast Asian (SEA) populations. However, the global generalizability of these associations is unknown but critical for population-appropriate risk stratification and diagnosis.

The role of penicillin major and minor determinants in skin testing for suspected penicillin hypersensitivity.

Background: In the evaluation of patient-reported penicillin allergy labels (PALs), the utility of skin testing to the penicillin major determinant, known as penicilloyl polylysine (PPL), and to the minor determinant mixture (MDM), has been questioned.

Methods: A review of a clinical antibiotic allergy database from April 2015 to December 2023 at Austin Health (Melbourne, Australia) was performed. Patients with PALs who underwent skin prick testing (SPT) and intradermal testing (IDT) to a previously-published standardised beta-lactam panel were selected.

Outcomes of Invasive Aspergillosis in Liver Transplant Recipients From an Institution Using Targeted Antifungal Prophylaxis and an Antifungal Stewardship Program.

Background: Recent evidence suggests liver transplant recipients (LiTRs) with invasive aspergillosis (IA) have lower rates of dissemination and mortality compared to historical data. However, contemporary data from other centers remain scarce. We aimed to evaluate modern IA outcomes at our institution, where targeted perioperative echinocandin prophylaxis and an active antifungal stewardship program (AFSP) have been implemented.

Antibiotic Exposure and Risk of Allograft Rejection and Survival After Liver Transplant: An Observational Cohort Study From a Tertiary Referral Centre.

Introduction: Our goal is to understand whether there is an association between Abx exposure-and the inferred downstream damage to the intestinal microbiome-and the key patient outcomes of overall survival and rejection following liver transplant.

Methods: We conducted a retrospective cohort study of 462 liver transplant recipients treated at a multistate liver transplant (LTx) service during a 7-year period. The association between antibiotic exposure and outcome was tested across models that addressed antibiotic spectrum, duration, and timing relative to transplant.

Perioperative Penicillin and Cephalosporin Antibiotic Allergy Assessment and Testing: The PREPARE Pilot Randomized Clinical Trial.

Importance: Antibiotic allergy labels (AALs) impact patient health and perioperative outcomes. Antibiotic allergy delabeling could improve antibiotic prescribing and infection-related outcomes perioperatively.

Objective: To assess the feasibility and safety of antibiotic allergy assessment and delabeling in anesthesiologist-led preoperative assessment clinics and expand delabeling efforts outside of specialist allergy clinics.

Increased SARS-CoV-2 IgG4 has variable consequences dependent upon Fc function, Fc receptor polymorphism, and viral variant.

Repeated mRNA COVID-19 vaccination increases spike-specific immunoglobulin G4 (IgG4) titers. Here, we characterized the influence of increased IgG4 titers on a range of Fc-mediated responses. Elevated spike-specific IgG4 reduced binding to FcγRIIIa and decreased antibody-dependent cellular cytotoxicity.

Discrepancies in Beta-Lactam Antibiotics Cross-Reactivity: Implications for Clinical Practice.

Background: In patients with a beta-lactam antibiotic (BA) allergy label, avoidance of the whole group of BAs leads to displacement of first-line therapies potentially influencing patient outcomes and antimicrobial resistance. Studies previously published on BA cross-reactivity use different sets of BA and seem to contain conflicting recommendations on safe BA alternatives in case of (suspected) BA allergy.

Methods: The objectives were (i) to identify discrepancies between studies regarding cross-allergy in BA and (ii) to identify research gaps.

Exploring cytokine outputs for diagnostics in drug reaction with eosinophilia and systemic symptoms (DRESS).

Background: In an exploratory study to assess the potential to individualize T-cell diagnostics in antibiotic-associated severe T-cell mediated hypersensitivity, we focused on drug reaction with eosinophilia and systemic symptoms (DRESS) and the related cytokine outputs IL-4 and IL-5.

Methods: Patients with well-phenotyped RegiSCAR ≥4 DRESS, positive intradermal skin testing, and a previous negative IFN-γ Enzyme-Linked ImmunoSpot (ELISpot) assay were prospectively recruited. We specifically performed an ELISpot assay with IL-4 and IL-5 cytokine outputs.

Global differences and risk factors influencing drug hypersensitivity quality of life: A multicenter, multiethnic study of drug allergy across 3 continents.

Background: Penicillin allergy labels are associated with many adverse outcomes. Fear and restriction of future medication use also have an impact on health-related quality of life (HR-QoL). However, the impact of a drug allergy on HR-QoL and its associated factors remains unknown.

Adult penicillin allergy programmes in Australian hospitals: a practical guide from the National Antibiotic Allergy Network.

Penicillin allergy is a significant burden on patient, prescribing and hospital outcomes. There has been increasing interest in the incorporation of penicillin allergy testing (i.e.