Early detection of ICU-acquired infections using high-frequency electronic health record data.

Background: Nosocomial infections are a major cause of morbidity and mortality in the ICU. Earlier identification of these complications may facilitate better clinical management and improve outcomes. We developed a dynamic prediction model that leveraged high-frequency longitudinal data to estimate infection risk 48 h ahead of clinically overt deterioration.

Hurdles for the Delivery of Multinational Randomized Clinical Trials.

Importance: Ethical, administrative, regulatory, and logistical (EARL) procedures can hamper clinical trial delivery. Quantification of these hurdles is rare, prohibiting identification of areas for improvement.

Objective: To identify and quantify EARL hurdles in trial delivery before and during the COVID-19 pandemic.

Optimizing microbiological surveillance during selective digestive decontamination in the intensive care unit: an in silico simulation study.

Background: Selective Digestive Decontamination (SDD) prevents infections and reduces mortality in the intensive care unit (ICU). Microbiological surveillance is considered essential for effective decontamination and detecting antibiotic resistance. However, its optimal frequency is unclear.

Pathogen-specific host response in critically ill patients with blood stream infections: a nested case-control study.

Background: Knowledge of the contribution of the pathogen to the heterogeneity of the host response to infection is limited. We aimed to compare the host response in critically ill patients with a bloodstream infection (BSI).

Methods: RNA profiles were determined in blood obtained between one day before and after a positive blood culture.

[Biomarker guided antibiotic stewardship in community acquired pneumonia].

Objective: To investigate whether the duration of antibiotic therapy in patients with CAP can be reduced using a biomarker-guided algorithm.

Design: Randomized controlled multicentre study.

Method: A total of 468 non-ICU patients with CAP were randomized after 2-3 days into three groups (ratio 1:1:1): standard treatment, PCT-guided treatment, and CRP-guided treatment.

Characterization of genome-wide transpositions induced by colistin exposure in multi-drug-resistant .

Colistin is one of the last-line antibiotics against multi-drug-resistant (MDR) gram-negative pathogens, such as . Using long-read sequencing, we observed remarkable genome-wide transposition events in MDR exposed to colistin in patients receiving treatment for respiratory infections or as part of selective decolonization strategies and further confirmed these on selection experiments. These data add yet another dimension to the role of antibiotics in mediating specific processes in bacteria beyond antibiotic resistance.

Tocilizumab, sarilumab and anakinra in critically ill patients with COVID-19: a randomised, controlled, open-label, adaptive platform trial.

Introduction: Tocilizumab improves outcomes in critically ill patients with COVID-19. Whether other immune-modulator strategies are equally effective or better is unknown.

Methods: We investigated treatment with tocilizumab, sarilumab, anakinra and no immune modulator in these patients.

Impact of co-infection with SARS-CoV-2 and other respiratory viruses on illness: Pooled analyses of 11 COVID-19 cohorts.

Objective: This individual patient data meta-analysis investigates the impact of SARS-CoV-2 infection with or without other respiratory viruses on Acute Respiratory Illness (ARI) occurrence and severity.

Methods: We pooled individual participant data from 11 prospective COVID-19 community and healthcare cohorts (2020-2024). A subject's first respiratory sample was tested for SARS-CoV-2 and a panel of respiratory viruses.

Automated surveillance of hospital-onset bacteremia and fungemia: feasibility and epidemiological results from a Dutch multicenter study.

Objective: Hospital-onset bacteremia and fungemia (HOB) has been suggested as a suitable and automatable surveillance target to include in surveillance programs, however differences in definitions across studies limit interpretation and large-scale implementation. We aimed to apply an automated surveillance system for HOB in multiple hospitals using a consensus definition, and describe HOB rates.

Design And Setting: Retrospective cohort study in four Dutch hospitals: 1 tertiary hospital and 3 secondary hospitals.

Statistical documentation for multi-disease, multi-domain platform trials: our experience with the Staphylococcus aureus Network Adaptive Platform trial.

Platform trials have become widely adopted across multiple disease areas over recent years, however, guidelines for operationalising these trials have not kept pace. We outline a series of documents that summarise the statistical components, and implicit processes, of the Staphylococcus aureus Network Adaptive Platform (SNAP) trial to provide an informal template for other researchers and reviewers of platform trials. We briefly summarise the content and role of the core protocol, statistical appendix, domain-specific appendices, simulation report, statistical implementation guides, data safety and monitoring committee (DSMC) reports, and domain-specific statistical analysis plans and final reports, and a transparent governance structure that ensures separate blinded and unblinded statistical teams.

The blood transcriptional response in patients developing intensive care unit-acquired pneumonia.

Background: Immune response dysregulation has been implicated in the development of intensive care unit (ICU)-acquired pneumonia. We aimed to determine differences in the longitudinal blood transcriptional response between patients who develop ICU-acquired pneumonia (cases) and those who do not (controls).

Methods: We performed a case-cohort study in mechanically ventilated trauma and surgery patients with ICU stays >2 days, enrolled in 30 hospitals across Europe.

Longitudinal assessment of immunoglobulin response and disease progression in critically ill patients with community acquired pneumonia.

Background: Low endogenous immunoglobulin(Ig)-levels are common in critically ill patients with sepsis, but it is unknown whether low Ig-levels are associated with poor outcome, and in which patients Ig-replacement therapy (IgRT) improves outcome. Given the crucial role of immunoglobulins in eliminating certain encapsulated pathogens, we examined the relationship between serial Ig-levels and disease course in critically ill patients with community acquired pneumonia (sCAP) caused by encapsulated or other pathogens.

Methods: We included a cohort of consecutive critically ill patients with CAP, and PaO/FiO-ratio < 200 with or without septic shock, from an existing biorepository where microbiological causes of infection had been adjudicated in a protocolized manner.

The effect of BCG vaccination in the elderly on infectious and non-infectious immune-mediated diseases.

Objectives: Previous research has suggested beneficial heterologous effects of the Bacillus Calmette-Guérin (BCG) vaccine on non-mycobacterial infections and other immune-mediated diseases. During the COVID-19 pandemic, randomized controlled trials BCG-PRIME (n = 5349) and BCG-CORONA-ELDERLY (n = 1907) investigated the impact of BCG on SARS-CoV-2 infections in older individuals. We extended the follow-up in these studies by one year (BCG-Long Term study), to assess the overall effects of BCG vaccination on infectious and immune-mediated diseases in individuals aged over 60.

Glycan-specific IgM is critical for human immunity to Staphylococcus aureus.

Staphylococcus aureus is a major human pathogen, yet the immune factors that protect against infection remain elusive. High titers of opsonic IgG antibodies, achieved in preclinical animal immunization studies, have consistently failed to provide protection in humans. Here, we investigate antibody responses to the conserved S.

Antecedent and persistent symptoms in COVID-19 and other respiratory illnesses: Insights from prospectively collected data in the BRACE trial.

Background: Some individuals have a persistence of symptoms following both COVID-19 (post-acute COVID-19 syndrome; PACS) and other viral infections. This study used prospectively collected data from an international trial to compare symptoms following COVID-19 and non-COVID-19 respiratory illness, to identify factors associated with the risk of PACS, and to explore symptom patterns before and after COVID-19 and non-COVID-19 respiratory illnesses.

Methods: Data from a multicentre randomised controlled trial (BRACE trial) involving healthcare workers across four countries were analysed.

Biomarker guided antibiotic stewardship in community acquired pneumonia: A randomized controlled trial.

Background: In community-acquired pneumonia (CAP), the role of biomarkers to shorten duration of antibiotic treatment has not been firmly established. We assessed the effectiveness of active feedback of treatment algorithms based on procalcitonin (PCT) and C-reactive protein (CRP), compared to standard care, on the duration of antibiotic treatment in patients hospitalized with community-acquired pneumonia (CAP) in non-ICU wards.

Methods And Findings: We performed a randomised, open label, parallel group, multi-centre trial in 3 Dutch teaching hospitals.

BCG vaccination of healthcare workers for protection against COVID-19: 12-month outcomes from an international randomised controlled trial.

Objectives: Bacille Calmette-Guérin (BCG) vaccine has immunomodulatory effects that may provide protection against unrelated infectious diseases. We aimed to determine whether BCG vaccination protects adults against COVID-19.

Design: Phase III double-blind randomised controlled trial.

A microbiological and genomic perspective of globally collected Escherichia coli from adults hospitalized with invasive E. coli disease.

Objectives: Escherichia coli can cause infections in the urinary tract and in normally sterile body sites leading to invasive E. coli disease (IED), including bacteraemia and sepsis, with older populations at increased risk. We aimed to estimate the theoretical coverage rate by the ExPEC4V and 9V vaccine candidates.

Risk factors for bloodstream infections due to carbapenem-resistant Enterobacterales: a nested case-control-control study.

Background: Carbapenem-resistant Enterobacterales (CRE) bloodstream infections (BSIs) are a major threat to patients. To date, data on risk factors have been limited, with low internal and external validity. In this multicentre study, risk factors for CRE BSI were determined by comparison with two control groups: patients with carbapenem-susceptible Enterobacterales (CSE) BSI, and patients without Enterobacterales infection (uninfected patients).

Determinants of Systemic SARS-CoV-2-Specific Antibody Responses to Infection and to Vaccination: A Secondary Analysis of Randomised Controlled Trial Data.

SARS-CoV-2 infections elicit antibodies against the viral spike (S) and nucleocapsid (N) proteins; COVID-19 vaccines against the S-protein only. The BCG-Corona trial, initiated in March 2020 in SARS-CoV-2-naïve Dutch healthcare workers, captured several epidemic peaks and the introduction of COVID-19 vaccines during the one-year follow-up. We assessed determinants of systemic anti-S1 and anti-N immunoglobulin type G (IgG) responses using trial data.