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.

Performance of the Cepheid Methicillin-Resistant Staphylococcus aureus/S. aureus Skin and Soft Tissue Infection PCR Assay on Respiratory Samples from Mechanically Ventilated Patients for S. aureus Screening during the Phase 2 Double-Blind SAATELLITE Study.

We investigated the performance of the Xpert methicillin-resistant Staphylococcus aureus (MRSA)/S. aureus skin and soft tissue (SSTI) quantitative PCR (qPCR) assay in SAATELLITE, a multicenter, double-blind, phase 2 study of suvratoxumab, a monoclonal antibody (MAb) targeting S. aureus alpha-toxin, for reducing the incidence of S.

Validation and performance of a multiplex serology assay to quantify antibody responses following SARS-CoV-2 infection or vaccination.

Objectives: Robust, quantitative serology assays are required to accurately measure antibody levels following vaccination and natural infection. We present validation of a quantitative, multiplex, SARS-CoV-2, electrochemiluminescent (ECL) serology assay; show correlation with two established SARS-CoV-2 immunoassays; and present calibration results for two SARS-CoV-2 reference standards.

Methods: Precision, dilutional linearity, ruggedness, analytical sensitivity and specificity were evaluated.

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.

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.

Global Molecular Epidemiology of Respiratory Syncytial Virus from the 2017-2018 INFORM-RSV Study.

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection among infants and young children, resulting in annual epidemics worldwide. INFORM-RSV is a multiyear clinical study designed to describe the global molecular epidemiology of RSV in children under 5 years of age by monitoring temporal and geographical evolution of current circulating RSV strains, F protein antigenic sites, and their relationships with clinical features of RSV disease. During the pilot season (2017-2018), 410 RSV G-F gene sequences were obtained from 476 RSV-positive nasal samples collected from 8 countries (United Kingdom, Spain, The Netherlands, Finland, Japan, Brazil, South Africa, and Australia).

Two Distinct Mechanisms of Inhibition of LpxA Acyltransferase Essential for Lipopolysaccharide Biosynthesis.

The lipopolysaccharide biosynthesis pathway is considered an attractive drug target against the rising threat of multi-drug-resistant Gram-negative bacteria. Here, we report two novel small-molecule inhibitors (compounds and ) of the acyltransferase LpxA, the first enzyme in the lipopolysaccharide biosynthesis pathway. We show genetically that the antibacterial activities of the compounds against efflux-deficient are mediated by LpxA inhibition.

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.

Atopic Dermatitis Endotypes Based on Allergen Sensitization, Reactivity to Staphylococcus aureus Antigens, and Underlying Systemic Inflammation.

Background: Atopic dermatitis (AD) is a chronic inflammatory disease with significant local and systemic inflammation and barrier disruption. AD is associated with increased risk of allergen sensitization and skin colonization by Staphylococcus aureus. The heterogeneity of AD is unknown, and its complexity suggests its subdivision into several endotypes.

Associations of pathogen-specific and host-specific characteristics with disease outcome in patients with bacteremic pneumonia.

Objective: To understand the relationships of (SA) bacteremic pneumonia (SABP) outcome with patient-specific and SA-specific variables.

Methods: We analysed SA bloodstream isolates and matching sera in SABP patients by sequencing SA isolates ( = 50) and measuring AT production, haemolytic activity and expression of ClfA and ClfB. Controls were sera from gram-negative bacteremia patients with or without pneumonia and uninfected subjects.

Emergence of new antigenic epitopes in the glycoproteins of human respiratory syncytial virus collected from a US surveillance study, 2015-17.

Respiratory syncytial virus (RSV) is a significant cause of lower respiratory tract infection in infants and elderly. To understand the evolution of neutralizing epitopes on the RSV glycoprotein (G) and fusion (F) proteins, we conducted a multi-year surveillance program (OUTSMART-RSV) in the US. Analysis of 1,146 RSV samples from 2015-2017 revealed a slight shift in prevalence from RSV A (58.

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 .

Interplay of Klebsiella pneumoniae and Mutations Leads to LpxC Inhibitor-Dependent Growth Resulting from Loss of Membrane Homeostasis.

Tight coordination of inner and outer membrane biosynthesis is very important in Gram-negative bacteria. Biosynthesis of the lipid A moiety of lipopolysaccharide, which comprises the outer leaflet of the outer membrane has garnered interest for Gram-negative antibacterial discovery. In particular, several potent inhibitors of LpxC (the first committed step of the lipid A pathway) are described.

Mode of Action of the Monobactam LYS228 and Mechanisms Decreasing Susceptibility in Escherichia coli and Klebsiella pneumoniae.

The monobactam scaffold is attractive for the development of new agents to treat infections caused by drug-resistant Gram-negative bacteria because it is stable to metallo-β-lactamases (MBLs). However, the clinically used monobactam aztreonam lacks stability to serine β-lactamases (SBLs) that are often coexpressed with MBLs. LYS228 is stable to MBLs and most SBLs.

Characterization of circulating RSV strains among subjects in the OUTSMART-RSV surveillance program during the 2016-17 winter viral season in the United States.

Background: Respiratory syncytial virus (RSV) is an established cause of serious lower respiratory disease in infants, elderly and high-risk populations. The OUTSMART surveillance program aims to characterize patient populations and currently circulating RSV strains, and monitor temporal and geographic evolution of RSV F and G proteins in the U.S.

Activity of LYS228, a Novel Monobactam Antibiotic, against Multidrug-Resistant Enterobacteriaceae.

LYS228 is a novel monobactam with potent activity against LYS228 is stable to metallo-β-lactamases (MBLs) and serine carbapenemases, including carbapenemases (KPCs), resulting in potency against the majority of extended-spectrum β-lactamase (ESBL)-producing and carbapenem-resistant strains tested. Overall, LYS228 demonstrated potent activity against 271 strains, including multidrug-resistant isolates. Based on MIC values, LYS228 (MIC, 1 μg/ml) was ≥32-fold more active against those strains than were aztreonam, ceftazidime, ceftazidime-avibactam, cefepime, and meropenem.

Characterisation of anti-alpha toxin antibody levels and colonisation status after administration of an investigational human monoclonal antibody, MEDI4893, against alpha toxin.

Objectives: MEDI4893 is a novel, long-acting human monoclonal antibody targeting (SA) alpha toxin (AT). This report presents the results of the exploratory analyses from a randomised phase 1 dose-escalation study in healthy human subjects receiving single intravenous MEDI4893 doses or placebo.

Methods: Anti-AT antibodies and AT expression were measured as described previously.

Prevalence of IgG and Neutralizing Antibodies against Staphylococcus aureus Alpha-Toxin in Healthy Human Subjects and Diverse Patient Populations.

causes an array of serious infections resulting in high morbidity and mortality worldwide. This study evaluated naturally occurring serum anti-alpha-toxin (anti-AT) antibody levels in human subjects from various age groups, individuals with dialysis and surgical-site infections, and -colonized versus noncolonized subjects. Anti-AT immunoglobulin G (IgG) and neutralizing antibody (NAb) levels in infants (aged ≤1 year) were significantly lower than those in other populations.

In vitro selection, via serial passage, of Clostridium difficile mutants with reduced susceptibility to fidaxomicin or vancomycin.

Objectives: Current treatments for Clostridium difficile infection include vancomycin, metronidazole and fidaxomicin. LFF571 is an experimental agent undergoing evaluation in humans for the treatment of moderate C. difficile infection.