Impact of Pseudomonas aeruginosa carriage on intensive care unit-acquired pneumonia: a European multicentre prospective cohort study.

Objectives: Pseudomonas aeruginosa (PA) is a common causative pathogen of pneumonia acquired in the intensive care unit (ICU). The aim of this study was to determine the incidence of PA ICU pneumonia (PAIP) and to quantify its independent association with PA colonization at different body sites.

Methods: Adult patients on mechanical ventilation at ICU admission were prospectively enrolled across 30 European ICUs.

Association of Bacterial Load and Colonization Sites With the Risk of Postoperative Infection.

Background: The independent effects of extranasal-only carriage, carriage at multiple bodily sites, or the bacterial load of colonizing (SA) on the risk of developing SA surgical site infections and postoperative bloodstream infections (SA SSI/BSIs) are unclear. We aimed to quantify these effects in this large prospective cohort study.

Methods: Surgical patients aged 18 years or older were screened for SA carriage in the nose, throat, or perineum within 30 days before surgery.

Postoperative Staphylococcus aureus Infections in Patients With and Without Preoperative Colonization.

Importance: Staphylococcus aureus surgical site infections (SSIs) and bloodstream infections (BSIs) are important complications of surgical procedures for which prevention remains suboptimal. Contemporary data on the incidence of and etiologic factors for these infections are needed to support the development of improved preventive strategies.

Objectives: To assess the occurrence of postoperative S aureus SSIs and BSIs and quantify its association with patient-related and contextual factors.

Mixed strain pathogen populations accelerate the evolution of antibiotic resistance in patients.

Antibiotic resistance poses a global health threat, but the within-host drivers of resistance remain poorly understood. Pathogen populations are often assumed to be clonal within hosts, and resistance is thought to emerge due to selection for de novo variants. Here we show that mixed strain populations are common in the opportunistic pathogen P.

Plasma protein biomarkers reflective of the host response in patients developing Intensive Care Unit-acquired pneumonia.

Background: Immune suppression has been implicated in the occurrence of pneumonia in critically ill patients. We tested the hypothesis that Intensive Care Unit (ICU)-acquired pneumonia is associated with broad host immune aberrations in the trajectory to pneumonia, encompassing inflammatory, endothelial and coagulation responses. We compared plasma protein biomarkers reflecting the systemic host response in critically ill patients who acquire a new pneumonia (cases) with those who do not (controls).

Gut to lung translocation and antibiotic mediated selection shape the dynamics of Pseudomonas aeruginosa in an ICU patient.

Bacteria have the potential to translocate between sites in the human body, but the dynamics and consequences of within-host bacterial migration remain poorly understood. Here we investigate the link between gut and lung Pseudomonas aeruginosa populations in an intensively sampled ICU patient using a combination of genomics, isolate phenotyping, host immunity profiling, and clinical data. Crucially, we show that lung colonization in the ICU was driven by the translocation of P.

Susceptibility profiles and resistance genomics of Pseudomonas aeruginosa isolates from European ICUs participating in the ASPIRE-ICU trial.

Objectives: To determine the susceptibility profiles and the resistome of Pseudomonas aeruginosa isolates from European ICUs during a prospective cohort study (ASPIRE-ICU).

Methods: 723 isolates from respiratory samples or perianal swabs of 402 patients from 29 sites in 11 countries were studied. MICs of 12 antibiotics were determined by broth microdilution.

Evaluation of GeneXpert PA assay compared to genomic and (semi-)quantitative culture methods for direct detection of Pseudomonas aeruginosa in endotracheal aspirates.

Introduction: Pseudomonas aeruginosa is a common cause of ventilator-associated pneumonia (VAP). Rapid and accurate detection of lower respiratory tract colonization and/or infection with P. aeruginosa may advise targeted preventive (antibody-based) strategies and antibiotic therapy.

COMBACTE LAB-Net: building a European laboratory network for clinical trials on anti-infectives.

LAB-Net, the laboratory network of COMBACTE, has established itself as an indispensable network for clinical trials in infectious diseases that plays a crucial part across 30 clinical studies not only within, but also outside the COMBACTE consortium. Since its official launch in January 2013, LAB-Net has expanded more than threefold and in Q4 2020 it encompasses 841 labs across 41 countries in Europe. In addition, LAB-Net has crossed the European borders and collaborates with more than 300 laboratories spread across the globe.

Efficacy and safety of suvratoxumab for prevention of Staphylococcus aureus ventilator-associated pneumonia (SAATELLITE): a multicentre, randomised, double-blind, placebo-controlled, parallel-group, phase 2 pilot trial.

Background: Staphylococcus aureus remains a common cause of ventilator-associated pneumonia, with little change in incidence over the past 15 years. We aimed to evaluate the efficacy of suvratoxumab, a monoclonal antibody targeting the α toxin, in reducing the incidence of S aureus pneumonia in patients in the intensive care unit (ICU) who are on mechanical ventilation.

Methods: We did a multicentre, randomised, double-blind, placebo-controlled, parallel-group, phase 2 pilot trial at 31 hospitals in Belgium, the Czech Republic, France, Germany, Greece, Hungary, Portugal, Spain, and Switzerland.

Exploring Virulence Factors and Alternative Therapies against Pneumonia.

Pneumonia is an acute pulmonary infection associated with high mortality and an immense financial burden on healthcare systems. is an opportunistic pathogen capable of inducing pneumonia (SAP), with some lineages also showing multidrug resistance. Given the high level of antibiotic resistance, much research has been focused on targeting virulence factors, including toxins and biofilm-associated proteins, in an attempt to develop effective SAP therapeutics.

Mechanical Ventilation Impairs IL-17 Cytokine Family Expression in Ventilator-Associated Pneumonia.

Mechanical ventilation (MV) is the primary risk factor for the development of ventilator-associated pneumonia (VAP). Besides inducing a pro-inflammatory T-helper (Th)-1 cytokine response, MV also induces an anti-inflammatory Th2 cytokine response, marked by increased IL-4 secretion and reduced bacterial phagocytic capacity of rodent lung macrophages. Since IL-4 is known to downregulate both Th1 and Th17 cytokines, the latter is important in mediating mucosal immunity and combating bacterial and fungal growth, we studied and showed here in a rat model of MV that Th17 cytokines (IL-17A, IL-17F, and IL-22) were significantly upregulated in the lung as a response to different MV strategies currently utilized in clinic.

Comparison of GeneXpert MRSA/SA ETA assay with semi-quantitative and quantitative cultures and gene-based qPCR for detection of in endotracheal aspirate samples.

Introduction: is a common cause of ventilator-associated pneumonia. Rapid and accurate detection of lower respiratory tract colonization and/or infection with may inform targeted preventive and therapeutic strategies. To investigate this, we compared semi-quantitative (SQ)-culture results from 79 endotracheal aspirates (ETA) collected from mechanically-ventilated patients, to two culture and two non-culture-based methods for detection of .

Detection and prevalence of carbapenem-resistant Gram-negative bacteria among European laboratories in the COMBACTE network: a COMBACTE LAB-Net survey.

Antimicrobial resistance (AMR) represents a global public health threat that jeopardises the progress medicine has made over the last century. To confront AMR, the Innovative Medicines Initiative (IMI) has supported the development of a large network of hospitals and laboratories in Europe as part of the New Drugs for Bad Bugs (ND4BB) programme and the COMBACTE projects. COMBACTE LAB-Net conducted a pilot survey on distribution and usage of carbapenem resistance detection methods among laboratories in the COMBACTE network in two clinical trials as part of the COMBACTE-CARE project.

Rationale and design of ASPIRE-ICU: a prospective cohort study on the incidence and predictors of Staphylococcus aureus and Pseudomonas aeruginosa pneumonia in the ICU.

Background: The epidemiology of ICU pneumonia caused by Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) is not fully described, but is urgently needed to support the development of effective interventions.

Non-toxic perfringolysin O and α-toxin derivatives as potential vaccine candidates against bovine necrohaemorrhagic enteritis.

Bovine necrohaemorrhagic enteritis is a fatal Clostridium perfringens type A-induced disease that is characterised by sudden death. Recently the involvement of perfringolysin O and α-toxin in the development of necrohaemorrhagic lesions in the gut of calves was suggested, and thus derivatives of these toxins are potentially suitable as vaccine antigens. In the current study, the perfringolysin O derivative PFO, alone or in combination with α-toxin derivative GST-cpa, was evaluated as possible vaccine candidate, using in vitro assays.

Toxin-neutralizing antibodies protect against Clostridium perfringens-induced necrosis in an intestinal loop model for bovine necrohemorrhagic enteritis.

Background: Bovine necrohemorrhagic enteritis is caused by Clostridium perfringens type A. Due to the rapid progress and fatal outcome of the disease, vaccination would be of high value. In this study, C.

The C-terminal domain of Clostridium perfringens alpha toxin as a vaccine candidate against bovine necrohemorrhagic enteritis.

Bovine necrohemorrhagic enteritis is caused by Clostridium perfringens and leads to sudden death. Alpha toxin, together with perfringolysin O, has been identified as the principal toxin involved in the pathogenesis. We assessed the potential of alpha toxin as a vaccine antigen.

Veal Calves Produce Less Antibodies against C. Perfringens Alpha Toxin Compared to Beef Calves.

Enterotoxaemia is a disease with a high associated mortality rate, affecting beef and veal calves worldwide, caused by C. perfringens alpha toxin and perfringolysin. A longitudinal study was conducted to determine the dynamics of antibodies against these toxins in 528 calves on 4 beef and 15 veal farms.

Perfringolysin O: The Underrated Clostridium perfringens Toxin?

The anaerobic bacterium Clostridium perfringens expresses multiple toxins that promote disease development in both humans and animals. One such toxin is perfringolysin O (PFO, classically referred to as θ toxin), a pore-forming cholesterol-dependent cytolysin (CDC). PFO is secreted as a water-soluble monomer that recognizes and binds membranes via cholesterol.

The mycotoxin deoxynivalenol predisposes for the development of Clostridium perfringens-induced necrotic enteritis in broiler chickens.

Both mycotoxin contamination of feed and Clostridium perfringens-induced necrotic enteritis have an increasing global economic impact on poultry production. Especially the Fusarium mycotoxin deoxynivalenol (DON) is a common feed contaminant. This study aimed at examining the predisposing effect of DON on the development of necrotic enteritis in broiler chickens.

Progress and problems in vaccination against necrotic enteritis in broiler chickens.

Necrotic enteritis in broilers is caused by Clostridium perfringens type A strains that produce the NetB toxin. Necrotic enteritis is one of the gastrointestinal diseases in poultry that has gained worldwide importance during the last decade due to efforts to improve broiler performance. Prevention strategies include avoiding predisposing factors, such as coccidiosis, and in-feed supplementation with a variety of feed additives.