Epidemiology of invasive disease in adults in England, 2013-2017.

Extraintestinal pathogenic (ExPEC) causes invasive disease (IED), including bacteraemia and (uro)sepsis, resulting in a high disease burden, especially among older adults. This study describes the epidemiology of IED in England (2013-2017) by combining laboratory surveillance and clinical data. A total of 191 612 IED cases were identified.

Safety, reactogenicity, and immunogenicity of different doses of 10-valent Extraintestinal Pathogenic Escherichia Coli (ExPEC10V) bioconjugate vaccine (VAC52416) in healthy Japanese adults aged 60-85 years in a randomized, double-blind, phase 1 study.

Aim: This phase 1 study (NCT04306302) evaluated the safety, reactogenicity, and immunogenicity of ExPEC10V (VAC52416) in healthy Japanese adults.

Method: The randomized, double-blind, single-center study included 28-day screening, vaccination (Day 1), 30-day safety and immunogenicity follow-up and 181-day serious adverse events (SAEs) follow-up. Participants (60-85 years) were enrolled in dose-ascending approach and randomized to medium- and high-doses of ExPEC10V (n = 8 in each dose group) and placebo (n = 8).

Unbiased identification of risk factors for invasive Escherichia coli disease using machine learning.

Background: Invasive Escherichia coli disease (IED), also known as invasive extraintestinal pathogenic E. coli disease, is a leading cause of sepsis and bacteremia in older adults that can result in hospitalization and sometimes death and is frequently associated with antimicrobial resistance. Moreover, certain patient characteristics may increase the risk of developing IED.

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.

A randomized phase 1/2a trial of ExPEC10V vaccine in adults with a history of UTI.

The safety, reactogenicity, and immunogenicity of 3 doses of ExPEC10V (VAC52416), a vaccine candidate to prevent invasive Escherichia coli disease, were assessed in a phase 1/2a study (NCT03819049). In Cohort 1, ExPEC10V was well tolerated; the high dose was selected as optimal and further characterized in Cohort 2. Cohort 2 comprised a maximum 28-day screening, vaccination (Day 1), double-blind 181-day follow-up, and open-label long-term follow-up until Year 1.

Clinical presentation and antimicrobial resistance of invasive Escherichia coli disease in hospitalized older adults: a prospective multinational observational study.

Background: Clinical data characterizing invasive Escherichia coli disease (IED) are limited. We assessed the clinical presentation of IED and antimicrobial resistance (AMR) patterns of causative E. coli isolates in older adults.

Feasibility of tracking invasive Escherichia coli disease among older adults in a community setting: A prospective observational study.

Purpose: Invasive Escherichia coli disease (IED) encompasses a diverse range of sterile site infections. This study evaluated the feasibility of capturing IED among community-dwelling older adults to inform the implementation of a phase 3 efficacy trial of a novel vaccine against IED (NCT04899336).

Methods: EXPECT-1 (NCT04087681) was a prospective, multinational, observational study conducted in medically stable participants aged ≥ 60 years.

Safety, Reactogenicity, Immunogenicity, and Dose Selection of 10-Valent Extraintestinal Pathogenic Bioconjugate Vaccine (VAC52416) in Adults Aged 60-85 Years in a Randomized, Multicenter, Interventional, First-in-Human, Phase 1/2a Study.

Background: ExPEC10V is a bioconjugate vaccine containing O-antigen polysaccharides of 10 extraintestinal pathogenic (ExPEC) serotypes. This phase 1/2a study (NCT03819049) assessed the safety, reactogenicity, and immunogenicity of ExPEC10V (VAC52416) to prevent invasive disease in elderly adults.

Methods: The observer-blind, active-controlled design included a 28-day screening, vaccination, 181-day follow-up, and 1-year follow-up.

Colonization with ST131-30R (30R) Corresponds with Increased Serum Anti-O25 IgG Levels and Decreased TNFα and IL-10 Responsiveness to 30R.

An exceptional gut-colonizing ability may underlie the dramatic epidemiological success of the multidrug-resistant 30R subclone of sequence type 131 (O25b:K+:H4). In order to inform the development of colonization-preventing measures, we studied systemic immune correlates of 30R intestinal colonization. Human volunteers' fecal samples were screened for 30R by selective culture and PCR.

Epidemiology, Clinical Features, and Antimicrobial Resistance of Invasive Disease in Patients Admitted in Tertiary Care Hospitals.

Background: Invasive disease (IED), including bloodstream infection, sepsis, and septic shock, can lead to high hospitalization and mortality rates. This multinational study describes the clinical profile of patients with IED in tertiary care hospitals.

Methods: We applied clinical criteria of systemic inflammatory response syndrome (SIRS), sepsis, or septic shock to patients hospitalized with culture-confirmed from urine or a presumed sterile site.

Genomics and pathotypes of the many faces of Escherichia coli.

Escherichia coli is the most researched microbial organism in the world. Its varied impact on human health, consisting of commensalism, gastrointestinal disease, or extraintestinal pathologies, has generated a separation of the species into at least eleven pathotypes (also known as pathovars). These are broadly split into two groups, intestinal pathogenic E.

Global Distribution of O Serotypes and Antibiotic Resistance in Extraintestinal Pathogenic Escherichia coli Collected From the Blood of Patients With Bacteremia Across Multiple Surveillance Studies.

Background: Extraintestinal pathogenic Escherichia coli (ExPEC) is the leading cause of bacteremia worldwide, with older populations having increased risk of invasive bacterial disease. Increasing resistance to first-line antibiotics and emergence of multidrug-resistant (MDR) strains represent major treatment challenges. ExPEC O serotypes are key targets for potential multivalent conjugate vaccine development.

Combined effects of glycan chain length and linkage type on the immunogenicity of glycoconjugate vaccines.

The development and use of antibacterial glycoconjugate vaccines have significantly reduced the occurrence of potentially fatal childhood and adult diseases such as bacteremia, bacterial meningitis, and pneumonia. In these vaccines, the covalent linkage of bacterial glycans to carrier proteins augments the immunogenicity of saccharide antigens by triggering T cell-dependent B cell responses, leading to high-affinity antibodies and durable protection. Licensed glycoconjugate vaccines either contain long-chain bacterial polysaccharides, medium-sized oligosaccharides, or short synthetic glycans.

Vaccination With Detoxified Leukocidin AB Reduces Bacterial Load in a Staphylococcus aureus Minipig Deep Surgical Wound Infection Model.

Vaccines against Staphylococcus aureus have eluded researchers for >3 decades while the burden of staphylococcal diseases has increased. Early vaccine attempts mainly used rodents to characterize preclinical efficacy, and all subsequently failed in human clinical efficacy trials. More recently, leukocidin AB (LukAB) has gained interest as a vaccine antigen.

Epidemiology and O-Serotypes of Extraintestinal Pathogenic Disease in Patients Undergoing Transrectal Ultrasound Prostate Biopsy: A Prospective Multicenter Study.

Purpose: Extraintestinal pathogenic (ExPEC) are a leading cause of invasive infections in adults. The study aimed to evaluate the incidence of microbiologically confirmed invasive ExPEC disease in patients undergoing transrectal ultrasound-guided prostate needle biopsy (TRUS-PNB), O-serotype distribution and antibiotic resistance profiles of associated isolates.

Materials And Methods: Adult men (≥18 years) undergoing TRUS-PNB were enrolled.

Expanding the role of bacterial vaccines into life-course vaccination strategies and prevention of antimicrobial-resistant infections.

A crisis in bacterial infections looms as ageing populations, increasing rates of bacteraemia and healthcare-associated infections converge with increasing antimicrobial resistance and a paucity of new antimicrobial classes. New initiatives are needed to develop bacterial vaccines for older adults in whom immune senescence plays a critical role. Novel vaccines require an expanded repertoire to prevent mucosal diseases such as pneumonia, skin and soft tissue infections and urinary tract infections that are major causes of morbidity and mortality in the elderly, and key drivers of antimicrobial resistance.

[Bacterial vaccines].

Vaccines were originally developed to prevent potentially deadly childhood diseases, but during the 21st century attention broadened to include prevention of infection in all stages of life. Prevention and treatment of bacterial infections are two of the biggest public health challenges of the 21st century. A crisis threatens to arise as the ageing of the population and the associated increase in cases of life-threatening bacteraemia and healthcare-associated infection coincides with an increase in antimicrobial resistance.

Characterization of Escherichia coli isolates potentially covered by ExPEC4V and ExPEC10V, that were collected from post-transrectal ultrasound-guided prostate needle biopsy invasive urinary tract and bloodstream infections.

There is an increasing incidence of infectious complications caused by extraintestinal pathogenic Escherichia coli (ExPEC) after transrectal ultrasound-guided prostate needle biopsy (TRUS-PNB), and a need for prophylaxis methods effective against associated antibiotic-resistant organisms. We aimed to identify the O-serotypes of ExPEC isolates collected in a sample of 60 patients with invasive ExPEC disease (IED) after TRUS-PNB, by serotype-specific agglutination and polymerase chain reaction (PCR) assays. The prevalence of O-serotypes included in a tetravalent ExPEC vaccine was 38.

Epidemiology of Escherichia coli Bacteremia: A Systematic Literature Review.

Background: Escherichia coli is the most common cause of bacteremia in high-income countries. To enable the development and implementation of effective prevention strategies, a better understanding of the current epidemiology of invasive E. coli infections is needed.

Safety and immunogenicity of a vaccine for extra-intestinal pathogenic Escherichia coli (ESTELLA): a phase 2 randomised controlled trial.

Background: ExPEC4V (JNJ-63871860) is a bioconjugate vaccine, containing O-antigens from Escherichia coli serotypes O1A, O2, O6A, and O25B, developed for the prevention of invasive extra-intestinal pathogenic E coli (ExPEC) disease. We aimed to assess safety, reactogenicity, and immunogenicity of ExPEC4V in healthy adults.

Methods: In this phase 2 randomised, double-blind placebo-controlled study, we recruited healthy adults (≥18 years with a body-mass index of 35 kg/m or less) between Nov 16, 2015, and Aug 8, 2017, and randomly assigned them to receive a single dose of ExPEC4V (antigen O1A:O2:O6A:O25B content 4:4:4:4 μg [group 1]; 4:4:4:8 μg [group 2], 8:8:8:8 μg [group 3], 8:8:8:16 μg [group 4], or 16:16:16:16 μg [group 5]) or placebo.

Increasing FIM2/3 antigen-content improves efficacy of Bordetella pertussis vaccines in mice in vivo without altering vaccine-induced human reactogenicity biomarkers in vitro.

Current acellular-pertussis (aP) vaccines appear inadequate for long-term pertussis control because of short-lived efficacy and the increasing prevalence of pertactin-negative isolates which may negatively impact vaccine efficacy. In this study, we added fimbriae (FIM)2 and FIM3 protein to licensed 2-, 3- or 5-component aP vaccines (Pentavac®, Boostrix®, Adacel®, respectively) to assess whether an aP vaccine with enhanced FIM content demonstrates enhanced efficacy. Vaccine-induced protection was assessed in an intranasal mouse challenge model.