Bezlotoxumab for prevention of Clostridium difficile infection recurrence: Distinguishing relapse from reinfection with whole genome sequencing.

Background: Bezlotoxumab has been shown to prevent Clostridium difficile infection recurrence (rCDI) in high-risk patients.

Methods: We used whole genome sequencing to estimate the impact of bezlotoxumab on same-strain relapse or new-strain reinfection in MODIFY I/II trials. Reinfection with a new strain and relapse with the same strain were differentiated by the comparison of ribotype (RT) and pair-wise single-nucleotide whole genome sequencing (WGS) variations (PWSNV).

Effect of Endogenous Clostridioides difficile Toxin Antibodies on Recurrence of C. difficile Infection.

Background: Endogenous antibodies (eAbs) against Clostridioides (Clostridium) difficile toxins may protect against recurrence of C. difficile infection (rCDI). This hypothesis was tested using placebo group data from MODIFY (Monoclonal Antibodies for C.

Generation of Markerless Deletions in the Nosocomial Pathogen by Induction of DNA Double-Strand Breaks.

is an important nosocomial pathogen associated with potentially fatal disease induced by the use of antibiotics. Genetic characterization of such clinically important bacteria is often hampered by lack of availability of suitable tools. Here, we describe the use of I-SceI to induce DNA double-strand breaks, which increase the frequency of allelic exchange and enable the generation of markerless deletions in The usefulness of the system is illustrated by the deletion of genes encoding putative AddAB homologues.

Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection.

Background: Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy. Actoxumab and bezlotoxumab are human monoclonal antibodies against C.

International Clostridium difficile animal strain collection and large diversity of animal associated strains.

Background: Clostridium difficile is an important cause of intestinal infections in some animal species and animals might be a reservoir for community associated human infections. Here we describe a collection of animal associated C. difficile strains from 12 countries based on inclusion criteria of one strain (PCR ribotype) per animal species per laboratory.

A prospective study of community-associated Clostridium difficile infections: the role of antibiotics and co-infections.

Objectives: This prospective study was performed to determine the incidence, risk factors, severity and outcomes of community-associated Clostridium difficile infection (CA-CDI) in the SE of Scotland.

Methods: All patients (335) diagnosed with laboratory confirmed CDI in the city of Edinburgh, East Lothian and Midlothian regions of Scotland between August 2010 and July 2011 were followed up for one year after diagnosis. Clinical details and laboratory markers were recorded.

Clostridium difficile infections in South East Scotland: mortality and recurrence in a region without PCR ribotype 027.

Three hundred and thirty-five patients with laboratory-confirmed Clostridium difficile infections (CDIs) were studied for epidemiological features, clinical presentation and laboratory markers. They were followed up for 1 year to determine recurrence and mortality. Four hundred and thirty-two episodes were recorded.

The changing faces of Clostridium difficile: a personal reflection of the past 34 years.

Late in 1978 my boss gave me a folder with "Clostridium difficile (diffikilé)" written on it. Inside were a few recent and now classic papers by Bartlett, Larson and co. It was suggested that this might be an interesting research topic.

Induction of cytokines in a macrophage cell line by proteins of Clostridium difficile.

Clostridium difficile is a major cause of nosocomial diarrhoea. The toxins produced by C. difficile are responsible for the characteristic pathology observed in C.

Efficacy of decontaminants and disinfectants against Clostridium difficile.

Clostridium difficile is a common nosocomial pathogen transmitted mainly via its spores. These spores can remain viable on contaminated surfaces for several months and are resistant to most commonly used cleaning agents. Thus, effective decontamination of the environment is essential in preventing the transmission of C.

Comparison of toxin and spore production in clinically relevant strains of Clostridium difficile.

Clostridium difficile is a major cause of nosocomial diarrhoea. The toxins that it produces (TcdA and TcdB) are responsible for the characteristic pathology of C. difficile infection (CDI), while its spores persist in the environment, causing its widespread transmission.

A proposed nomenclature for cell wall proteins of Clostridium difficile.

Strains of Clostridium difficile produce a number of surface-localized proteins, including the S-layer proteins (SLPs) and other proteins that have suspected roles in pathogenesis. During the Third International C. difficile Symposium (Bled, Slovenia, September 2010) discussions were held on standardization of nomenclature.

Fidaxomicin: a new macrocyclic, RNA polymerase-inhibiting antibiotic for the treatment of Clostridium difficile infections.

Clostridium difficile infection is now a major concern throughout the developed world and its occurrence is a consequence of broad-spectrum antibiotic therapy primarily in the elderly in-patient population and high spore loads in hospitals in these regions. With the emergence of a hypervirulent, endemic strain, more severe disease is being recognized and is occurring in previously considered unusual patient groups. Vancomycin and metronidazole are the current mainstays for therapy of severe and nonsevere disease, respectively.

Changes in antibiotic susceptibility and ribotypes in Clostridium difficile isolates from southern Scotland, 1979-2004.

An increase in the incidence of clinical cases of Clostridium difficile infection has been reported in recent years, but few studies have examined changes in molecular epidemiology and antibiotic resistance over a long period of time. A collection of 179 isolates of C. difficile obtained from symptomatic adult patients in southern Scotland between 1979 and 2004 was used to determine changes in the prevalence of epidemiological types and antibiotic susceptibilities to common antibiotics.

Potential use of a liposome-encapsulated mixture of lipopolysaccharide core types (R1, R2, R3 and R4) of Escherichia coli in controlling colisepticaemia in chickens.

Infections caused by Escherichia coli have an economically significant impact on the poultry industry and a non-serotype-specific vaccine appears to be the most logical method of controlling them. The core oligosaccharide-lipid A region of bacterial lipopolysaccharide (LPS) is well conserved and highly immunogenic but toxic. This study determined the possible use of a liposome-encapsulated mixture of rough LPSs of core types R1, R2, R3 and R4 in controlling infections caused by E.

Bacteroides fragilis signals through Toll-like receptor (TLR) 2 and not through TLR4.

Although it is desirable to identify the interactions between endotoxin/LPS and the innate immune mechanism, it is often not possible to isolate these interactions from other cell wall-related structures of protein or polysaccharide origin. There is no universally accepted method to extract different LPSs from different bacteria, and their natural state will be influenced by their interactions with the associated molecules in the bacterial outer membrane. It is now believed that Toll-like receptor (TLR) 4 is the main signal transducer of classical LPS (i.

Enhancement of the cytotoxic activity of Clostridium difficile toxin A by surface-associated antigens.

Cell-surface antigens of Clostridium difficile and LPS from Escherichia coli were investigated for modulating effects on the activity of C. difficile toxin A on Vero and Caco2 cells. The antigens of C.

Systemic antibody response to Clostridium difficile in colonized patients with and without symptoms and matched controls.

It has been proposed that patients who develop Clostridium difficile-associated disease (CDAD) do so because they are unable to mount an adequate immune response. Serum was collected from three groups of elderly in-patients: (i) cases (n=21) of CDAD, being toxin A/B-positive; (ii) carriers (n=21) asymptomatic for CDAD (no diarrhoea) but at least toxin or culture positive; and (iii) controls (n=26) asymptomatic for CDAD and negative for both C. difficile toxin and culture.

Molecular characterization and antimicrobial susceptibility patterns of Clostridium difficile strains isolated from hospitals in south-east Scotland.

Clostridium difficile isolates (n=149) collected in south-east Scotland between August and October 2005 were typed by four different methods and their susceptibility to seven different antibiotics was determined. The aims were to define the types of strain occurring in this region and to determine whether there were any clonal relationships among them with respect to genotype and antibiotic resistance pattern. Ribotyping revealed that 001 was the most common type (n=113, 75.

A PCR approach to determine the distribution of toxin genes in closely related Clostridium species: Clostridium botulinum type C and D neurotoxins and C2 toxin, and Clostridium novyi alpha toxin.

The closely related Clostridium novyi and Clostridium botulinum types C and D are of current interest because of their association with serious infections in injecting drug users (C. novyi type A) and equine and feline dysautonomias (C. botulinum types C/D).

Acinetobacter baumannii lipopolysaccharides are potent stimulators of human monocyte activation via Toll-like receptor 4 signalling.

Acinetobacter baumannii is a major nosocomial pathogen and frequent cause of hospital-acquired pneumonia, surgical wound infections and sepsis. As very little is known of the endotoxic potential of A. baumannii lipopolysaccharide (LPS) with respect to human cells or of its ability to stimulate inflammatory signalling via human Toll-like receptors (TLRs), the biological activity of these endotoxins was investigated in human monocytic THP-1 cells and in TLR-deficient HEK-293 cells transfected with human TLR2 and TLR4 constructs.

"Dirty little secrets"--endotoxin contamination of recombinant proteins.

The identification of Toll-like receptors has revolutionised our understanding of innate immunity. TLR4 transduces the LPS signal and that of a number of structurally and functionally unrelated agonists. However, recent evidence adds to longstanding concerns that endotoxin contamination of bacterially derived recombinant TLR4 agonists is responsible for effects attributed to these molecules.