Molecular epidemiology and β-lactam resistance mechanisms of complex isolates obtained from bloodstream infections, Kyoto, Japan.

The complex (ECC) comprises multiple species that require genomic analysis for precise identification. They produce inducible AmpC β-lactamase and may carry acquired β-lactamases, which are responsible for cefotaxime and cefepime resistance. To determine the molecular epidemiology, antimicrobial resistance, and β-lactam resistance mechanisms of the ECC, we conducted whole-genome sequencing analysis, antimicrobial susceptibility testing, and mutation analysis on bloodstream ECC isolates from patients in Kyoto, Japan.

Antibiotic shortages: An overview by the alliance for the prudent use of antibiotics (APUA).

Background: Antibiotics have been among the drugs most affected by shortages over the last two decades, with harmful consequences that may persist over years. This position paper was designed by the Alliance for the Prudent Use of Antibiotics (APUA), an international multidisciplinary consortium of experts dedicated to combating antimicrobial resistance.

Methods: We performed a narrative review to examine the main causes and impacts of antibiotics shortages, and to identify the solutions that may be proposed to prevent and mitigate this public health threat.

Severe cases of local cytokine release syndrome (CRS); craniocervical edema soon after chimeric antigen T-cell (CAR-T) therapy.

Craniocervical edema appears soon after chimeric antigen receptor T-cell (CAR-T) therapy in some cases. This phenomenon is often observed right after systemic cytokine release syndrome (CRS), and it is called local CRS (L-CRS). In severe cases, L-CRS causes airway obstruction and asphyxia, but it is not yet well known among hematologists.

Epidemiology of respiratory viruses according to age group, 2023-24 winter season, Kyoto, Japan.

The seasonality and epidemiology of viral acute respiratory infections (ARIs) have changed since the coronavirus disease 2019 pandemic. However, molecular-based ARI surveillance has not been conducted in Japan. We developed a regional surveillance program to define the local epidemiology of ARIs.

Booster COVID-19 mRNA vaccination ameliorates impaired B-cell but not T-cell responses in older adults.

Age-associated differences in the effect of repetitive vaccination, particularly on memory T-cell and B-cell responses, remain unclear. While older adults (aged ≥65 years) exhibited enhanced IgG responses following COVID-19 mRNA booster vaccination, they produced fewer spike-specific circulating follicular helper T cells-1 than younger adults. Similarly, the cytotoxic CD8 T-cell response remained diminished with reduced PD-1 expression even after booster vaccination compared with that in younger adults, suggesting impaired memory T-cell activation in older adults.

Model-Informed Dosing Optimization of Tacrolimus for Concomitant Administration With Itraconazole to Japanese Lung Transplant Recipients.

Background: Tacrolimus is an immunosuppressant administered to patients undergoing lung transplantation. Itraconazole is often concomitantly used with tacrolimus to prevent fungal infections and increase tacrolimus concentration. However, the pharmacokinetics of tacrolimus in Japanese lung transplant recipients and the effect of itraconazole on its pharmacokinetics have not been adequately evaluated.

Complete genome sequence of three strains isolated from patients with skin diseases in Japan.

is a member of the human skin microbiota as a commensal organism but could be an important opportunistic pathogen for immunocompromised individuals. Here, we report the complete genome sequence of three . strains isolated from patients with skin diseases.

Clinical characteristics and analysis of prognostic factors in methicillin-resistant Staphylococcus aureus endocarditis: A retrospective multicenter study in Japan.

Background: Infective endocarditis (IE) caused by MRSA (methicillin-resistant Staphylococcus aureus) is associated with a high mortality rate. This study aimed to elucidate the characteristics of patients with MRSA-IE in Japan and identify the factors associated with prognosis.

Methods: This retrospective study included patients with a confirmed diagnosis of IE caused by MRSA, between January 2015 and April 2019.

Investigation of severe acute respiratory syndrome coronavirus 2 infection status in solid organ transplant recipients treated with tixagevimab/cilgavimab.

Introduction: Tixagevimab and cilgavimab (T/C) are neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be used to prevent SARS-CoV-2 infection in solid organ transplant (SOT) recipients. However, their neutralizing activity against recent variants was reduced, raising concerns regarding the emergence of breakthrough coronavirus diseases 2019 (COVID-19). This study aimed to investigate the status of the COVID-19 breakthrough after T/C administration.

Utilizing red blood cell distribution width (RDW) as a reliable biomarker to predict treatment effects after chimeric antigen receptor T cell therapy.

Chimeric antigen receptor T cell (CAR-T) therapy is an effective treatment for B cell malignancies. A certain fraction of patients, however, experience post-CAR-T relapse, and due to the difficulty of precise relapse prediction, biomarkers that can predict the strength and duration of CAR-T efficacy are needed before CAR-T infusion. Therefore, we performed a single-center cohort study including 91 diffuse large B cell lymphoma (DLBCL) patients treated with CAR-T in order to identify such a new prognostic biomarker.

Longitudinal analysis of genomic mutations in SARS-CoV-2 isolates from persistent COVID-19 patient.

A primary reason for the ongoing spread of coronavirus disease 2019 (COVID-19) is the continuous acquisition of mutations by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the mechanism of acquiring mutations is not fully understood. In this study, we isolated SARS-CoV-2 from an immunocompromized patient persistently infected with Omicron strain BF.

Micro-patterned culture of iPSC-derived alveolar and airway cells distinguishes SARS-CoV-2 variants.

The emergence of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) variants necessitated a rapid evaluation system for their pathogenesis. Lung epithelial cells are their entry points; however, in addition to their limited source, the culture of human alveolar epithelial cells is especially complicated. Induced pluripotent stem cells (iPSCs) are an alternative source of human primary stem cells.

Autochthonous Cryptococcus gattii genotype VGIIb infection in a Japanese patient with anti-granulocyte-macrophage colony-stimulating factor antibodies.

A 31-year-old Japanese man presented with cerebral and pulmonary cryptococcosis. Cryptococcus gattii (C. gattii) genotype VGIIb was detected in the patient's sputum and cerebrospinal fluid specimens.

Comparison of the safety and cost-effectiveness of nebulized liposomal amphotericin B and amphotericin B deoxycholate for antifungal prophylaxis after lung transplantation.

Introduction: Fungal infection after lung transplantation can lead to poor clinical outcome, for which lung transplant recipients require prophylaxis. One of the antifungal agents used after lung transplantation is nebulized amphotericin B (AMB). Nebulized AMB causes adverse events such as dyspnea and airway irritation, and long-term use leads to high economic costs.

Development and evaluation of three automated media pooling and molecular diagnostic systems for the detection of SARS-CoV-2.

Pooled testing combined with molecular diagnostics for the detection of SARS-CoV-2 is a promising method that can increase testing capacities and save costs. However, pooled testing is also associated with the risks of decreased test sensitivity and specificity. To perform reliable pooled testing, we developed and validated three automated media pooling and molecular diagnostic systems.

Clinical Impact of Cytokine Release Syndrome on Prolonged Hematotoxicity after Chimeric Antigen Receptor T Cell Therapy: KyoTox A-Score, a Novel Prediction Model.

Prolonged hematotoxicity is the most common long-term adverse event in chimeric antigen receptor T cell therapy (CAR-T). To evaluate the impact on prolonged cytopenia of inflammatory status after CAR T infusion, we performed a single-center retrospective study and analyzed patients with B cell lymphomas after CAR-T. Among 90 patients analyzed at 90 days after infusion, the cumulative incidence was 57.

SARS-CoV-2-induced disruption of a vascular bed in a microphysiological system caused by type-I interferon from bronchial organoids.

Blood vessels show various COVID-19-related conditions including thrombosis and cytokine propagation. Existing blood vessel models cannot represent the consequent changes in the vascular structure or determine the initial infection site, making it difficult to evaluate how epithelial and endothelial tissues are damaged. Here, we developed a microphysiological system (MPS) that co-culture the bronchial organoids and the vascular bed to analyze infection site and interactions.

A population-based study of the trend in SARS-CoV-2 diagnostic modalities from the beginning of the pandemic to the Omicron surge in Kyoto City, Kyoto, Japan.

Background: The coronavirus disease 2019 (COVID-19) presents critical diagnostic challenges for managing the pandemic. We investigated the 30-month changes in COVID-19 testing modalities and functional testing sites from the early period of the pandemic to the most recent Omicron surge in 2022 in Kyoto City, Japan.

Methods: This is a retrospective-observational study using a local anonymized population database that included patients' demographic and clinical information, testing methods and facilities from January 2020 to June 2022, a total of 30 months.

Development and evaluation of the automated multipurpose molecular testing system PCRpack for high-throughput SARS-CoV-2 testing.

Accurate and fast molecular testing is important for the diagnosis and control of COVID-19. During patient surges in the COVID-19 pandemic, laboratories were challenged by a higher demand for molecular testing under skilled staff shortages. We developed an automated multipurpose molecular testing system, named PCRpack, for the rapid, high-throughput testing of infectious pathogens, including SARS-CoV-2.

Novel intrathoracic irrigation using ultrafine ozone bubbles in a rat empyema model.

Dissolved ozone is generally used for sanitization, but it has not been used for thoracic cavity sanitization because of its short half-life (< 20 min) and possible toxicity. We developed a novel solution containing ultrafine ozone bubbles (ozone-UFB) with a fivefold longer half-life than non-UFB ozone. Using an in vitro model, Staphylococcus aureus colonies were counted after exposure to ozone-UFB or non-UFB ozone at the same ozone concentration (0.