Synergistic combination of orally available safe-in-man pleconaril, AG7404, and mindeudesivir inhibits enterovirus infections in human cell and organoid cultures.

Enteroviruses can infect various human organs, causing diseases such as meningitis, the common cold, hand-foot-and-mouth disease, myocarditis, pancreatitis, hepatitis, poliomyelitis, sepsis, and type 1 diabetes. Currently, there are no approved treatments for enterovirus infections. In this study, we identified a synergistic combination of orally available, safe-in-man pleconaril, AG7404, and mindeudesivir, that at non-toxic concentrations effectively inhibited enterovirus replication in human cell and organoid cultures.

Leveraging explainable artificial intelligence for early prediction of bloodstream infections using historical electronic health records.

Bloodstream infections (BSIs) are a severe public health threat due to their rapid progression into critical conditions like sepsis. This study presents a novel eXplainable Artificial Intelligence (XAI) framework to predict BSIs using historical electronic health records (EHRs). Leveraging a dataset from St.

Identification and characterisation of carbapenem-resistant sp. nov. isolated from blood culture.

Background: This study aimed to investigate a highly resistant strain of sp. isolated from a patient with bloodstream infection and determine its taxonomic classification.

Methods: The strain was isolated from blood culture from a 65-year-old male patient admitted to St.

In-hospital mortality, readmission, and prolonged length of stay risk prediction leveraging historical electronic patient records.

Objective: This study aimed to investigate the predictive capabilities of historical patient records to predict patient adverse outcomes such as mortality, readmission, and prolonged length of stay (PLOS).

Methods: Leveraging a de-identified dataset from a tertiary care university hospital, we developed an eXplainable Artificial Intelligence (XAI) framework combining tree-based and traditional machine learning (ML) models with interpretations and statistical analysis of predictors of mortality, readmission, and PLOS.

Results: Our framework demonstrated exceptional predictive performance with a notable area under the receiver operating characteristic (AUROC) of 0.

A Genome-wide Association Study of Susceptibility to Upper Urinary Tract Infections.

Background: Our goal was to identify genetic and modifiable risk factors for upper urinary tract infections (UTIs).

Methods: We used data from UK Biobank, the Trøndelag Health Study, and the Michigan Genomics Initiative to conduct genome-wide association studies and sex-stratified analyses on upper UTI. Mendelian randomization (MR) analyses were conducted to examine potential causal relationships between cardiometabolic risk factors and upper UTIs.

Enteroaggregative Escherichia coli in mid-Norway: A prospective, case control study.

Background: The use of molecular methods has led to increased detection of Enteroaggregative Escherichia coli (EAEC) in faecal samples. Studies have yielded conflicting results regarding the clinical relevance of this finding. The objective of this study was to investigate the prevalence of EAEC in faecal samples from patients with diarrhoea and healthy controls and describe characteristics of EAEC positive persons.

Risk of death in Klebsiella pneumoniae bloodstream infections is associated with specific phylogenetic lineages.

Background: Klebsiella pneumoniae species complex (KpSC) bloodstream infections (BSIs) are associated with considerable morbidity and mortality, particularly in elderly and multimorbid patients. Multidrug-resistant (MDR) strains have been associated with poorer outcome. However, the clinical impact of KpSC phylogenetic lineages on BSI outcome is unclear.

Incidence of invasive infections with Group B streptococcus in adults in Norway 1996-2019: a nationwide registry-based case-control study.

Purpose: Group B streptococcus (GBS) colonizes the gastrointestinal and vaginal mucosa in healthy adults, but has also become an increasing cause of invasive infection. The aims of this study were to describe the incidence and factors associated with the occurrence of invasive GBS disease in adults in Norway.

Methods: We performed a nationwide retrospective case-control study of invasive GBS infections during 1996-2019, with two control groups; invasive Group A streptococcal disease (GAS) to control for changes in surveillance and diagnostics, and a second representing the general population.

Insights from a decade of surveillance: Molecular epidemiology of methicillin-resistant Staphylococcus aureus in Norway from 2008 to 2017.

Aim: Norway has a low prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and reporting of all MRSA cases has been mandatory, including infections and carriage, since 1995 and 2005 accordingly. This provides a unique window to study the spread of MRSA in Norway over time. The aim of this study was to analyze the nationwide trends in the molecular epidemiology of MRSA in Norway over a period of 10 years.

The combination of pleconaril, rupintrivir, and remdesivir efficiently inhibits enterovirus infections in vitro, delaying the development of drug-resistant virus variants.

Enteroviruses are a significant global health concern, causing a spectrum of diseases from the common cold to more severe conditions like hand-foot-and-mouth disease, meningitis, myocarditis, pancreatitis, and poliomyelitis. Current treatment options for these infections are limited, underscoring the urgent need for effective therapeutic strategies. To find better treatment option we analyzed toxicity and efficacy of 12 known broad-spectrum anti-enterovirals both individually and in combinations against different enteroviruses in vitro.

Coding practice for sepsis 2008-21.

Background: Sepsis has a high incidence and mortality rate. Accurate data are needed for health service planning and for research, and there is a need to identify coding practices in Norway.

Material And Method: All patients over 17 years of age who had been admitted to Norwegian hospitals with sepsis in the period 2008-21 were identified using diagnostic codes for infection plus organ failure, and specific codes for sepsis, from the Norwegian Patient Registry.

Role of fungal burden in risk stratification of HIV-negative patients with Pneumocystis pneumonia: A 12-year, retrospective, observational, multicenter cohort.

Objectives: This study aimed to explore the role of fungal burden in risk stratification of patients without HIV-negative patients with Pneumocystis pneumonia (PCP).

Methods: This was a retrospective analysis of the characteristics associated with 30-day mortality in patients who were positive for P. jirovecii using polymerase chain reaction in bronchoalveolar lavage fluid between 2006 and 2017 in a multicenter cohort from Central Norway.

Mortality and neurodevelopmental outcome after invasive group B streptococcal infection in infants.

Aim: To assess case fatality rate (CFR), infant mortality, and long-term neurodevelopmental disorders (NDDs) after invasive group B streptococcal (GBS; Streptococcus agalactiae) infection in infants.

Method: Children born in Norway between 1996 and 2019 were included. Data on pregnancies/deliveries, GBS infection, NDDs, and causes of death were retrieved from five national registries.

Novel Synergistic Anti-Enteroviral Drug Combinations.

Enterovirus infections affect people around the world, causing a range of illnesses, from mild fevers to severe, potentially fatal conditions. There are no approved treatments for enterovirus infections. We have tested our library of broad-spectrum antiviral agents (BSAs) against echovirus 1 (EV1) in human adenocarcinoma alveolar basal epithelial A549 cells.

Empirical antimicrobial therapy for bloodstream infections not compliant with guideline was associated with discordant therapy, which predicted poorer outcome even in a low resistance environment.

Objectives: To characterise all bloodstream infections (BSIs) in a low antimicrobial resistance (AMR) prevalence setting with regard to the appropriateness of empirical antimicrobial therapy, compliance with the national clinical practice guideline, de-escalation practice and outcome.

Methods: A retrospective observational study including patients aged 18 years admitted to a university hospital in central Norway with positive blood culture in 2019.

Results: We included 756 BSI episodes in our analysis.

The Streptococcus agalactiae R3 surface protein is encoded by sar5.

Streptococcus agalactiae (group B streptococcus; GBS) is an important human pathogen causing pneumonia, sepsis and meningitis in neonates, as well as infections in pregnant women, immunocompromised individuals, and the elderly. For the future control of GBS-inflicted disease, GBS surface exposed proteins are particularly relevant as they may act as antigens for vaccine development and/or as serosubtype markers in epidemiological settings. Even so, the genes encoding some of the surface proteins established as serosubtype markers by antibody-based methods, like the R3 surface protein, are still unknown.

Detailed stratified GWAS analysis for severe COVID-19 in four European populations.

Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended genome-wide association meta-analysis of a well-characterized cohort of 3255 COVID-19 patients with respiratory failure and 12 488 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.

Phenotypic and genotypic characterisation of thymine auxotrophy in Escherichia coli isolated from a patient with recurrent bloodstream infection.

Introduction: Thymine auxotrophic in vitro mutants of Escherichia coli were first reported in the mid-20th century. Later, thymine-dependent clinical strains of E. coli as well as other Enterobacterales, Enterococcus faecalis and Staphylococcus aureus have been recognized as the cause of persistent and recurrent infections.

High levels of discordant antimicrobial therapy in hospital-acquired bloodstream infections is associated with increased mortality in an intensive care, low antimicrobial resistance setting.

Background: Bloodstream infections (BSI) occur frequently and are associated with severe outcomes. In this study we aimed to investigate proportions of patients that received discordant empirical antimicrobial therapy and its association to mortality.

Methods: A retrospective cohort study model was undertaken to outline BSI in an intensive care, single centre, and low antimicrobial resistance prevalence setting.

Use of Sysmex UF-5000 flow cytometry in rapid diagnosis of urinary tract infection and the importance of validating carryover rates against bacterial count cut-off.

Urinary tract infections are common bacterial infections worldwide. Urine culture is the gold standard method to identify and quantify the presence or absence of bacteria in urine. Flow cytometry, which can differentiate and quantify multiple particles (including bacteria) in the urine, presents an alternative method for rapid screening to rule out bacteriuria.

Semiquantitative Real-Time PCR to Distinguish Pneumocystis Pneumonia from Colonization in a Heterogeneous Population of HIV-Negative Immunocompromised Patients.

Pneumocystis jirovecii is a threat to iatrogenically immunosuppressed individuals, a heterogeneous population at rapid growth. We assessed the ability of an in-house semiquantitative real-time PCR assay to discriminate Pneumocystis pneumonia (PCP) from colonization and identified risk factors for infection in these patients. Retrospectively, 242 PCR-positive patients were compared according to PCP status, including strata by immunosuppressive conditions, human immunodeficiency virus (HIV) infection excluded.