Clostridioides difficile Biofilm.

Clostridioides difficile infection (CDI), previously Clostridium difficile infection, is a symptomatic infection of the large intestine caused by the spore-forming anaerobic, gram-positive bacterium Clostridioides difficile. CDI is an important healthcare-associated disease worldwide, characterized by high levels of recurrence, morbidity, and mortality. CDI is observed at a higher rate in immunocompromised patients after antimicrobial therapy, with antibiotics disrupting the commensal microbiota and promoting C.

Clostridioides difficile infections; new treatments and future perspectives.

Purpose Of Review: As a significant cause of global morbidity and mortality, Clostridioides difficile infections (CDIs) are listed by the Centres for Disease Control and prevention as one of the top 5 urgent threats in the USA. CDI occurs from gut microbiome dysbiosis, typically through antibiotic-mediated disruption; however, antibiotics are the treatment of choice, which can result in recurrent infections. Here, we highlight new treatments available and provide a perspective on different classes of future treatments.

The effect of intestinal microbiota dysbiosis on growth and detection of carbapenemase-producing Enterobacterales within an in vitro gut model.

Background: Carbapenemase-producing Enterobacterales (CPE) can colonize the gut and are of major clinical concern. Identification of CPE colonization is problematic; there is no gold-standard detection method, and the effects of antibiotic exposure and microbiota dysbiosis on detection are unknown.

Aim: Based on a national survey we selected four CPE screening assays in common use.

Optimization of an Assay To Determine Colonization Resistance to Clostridioides difficile in Fecal Samples from Healthy Subjects and Those Treated with Antibiotics.

A healthy, intact gut microbiota is often resistant to colonization by gastrointestinal pathogens. During periods of dysbiosis, however, organisms such as can thrive. We describe an optimized colonization resistance assay for in stool (CRACS) and demonstrate the utility of this assay by assessing changes in colonization resistance following antibiotic exposure.

A Novel, Orally Delivered Antibody Therapy and Its Potential to Prevent Infection in Pre-clinical Models.

infection (CDI) is a toxin-mediated infection in the gut and a major burden on healthcare facilities worldwide. We rationalized that it would be beneficial to design an antibody therapy that is delivered to, and is active at the site of toxin production, rather than neutralizing the circulating and luminal toxins after significant damage of the layers of the intestines has occurred. Here we describe a highly potent therapeutic, OraCAb, with high antibody titers and a formulation that protects the antibodies from digestion/inactivation in the gastrointestinal tract.

Investigation of the effect of the adsorbent DAV131A on the propensity of moxifloxacin to induce simulated Clostridioides (Clostridium) difficile infection (CDI) in an in vitro human gut model.

Background: Clostridioides difficile infection (CDI) remains a high burden worldwide. DAV131A, a novel adsorbent, reduces residual gut antimicrobial levels, reducing CDI risk in animal models.

Objectives: We used a validated human gut model to investigate the efficacy of DAV131A in preventing moxifloxacin-induced CDI.

Method comparison for the direct enumeration of bacterial species using a chemostat model of the human colon.

Background: Clostridioides difficile infection (CDI) has a high recurrent infection rate. Faecal microbiota transplantation (FMT) has been used successfully to treat recurrent CDI, but much remains unknown about the human gut microbiota response to replacement therapies. In this study, antibiotic-mediated dysbiosis of gut microbiota and bacterial growth dynamics were investigated by two quantitative methods: real-time quantitative PCR (qPCR) and direct culture enumeration, in triple-stage chemostat models of the human colon.

Investigating the transient and persistent effects of heat on spores.

spores are extremely resilient to high temperatures. Sublethal temperatures are associated with the 'reactivation' of dormant spores, and are utilized to maximize spore recovery. Spore eradication is of vital importance to the food industry.

Dissemination of multiple carbapenem resistance genes in an in vitro gut model simulating the human colon.

Background: Carbapenemase-producing Enterobacteriaceae (CPE) pose a major global health risk. Mobile genetic elements account for much of the increasing CPE burden.

Objectives: To investigate CPE colonization and the impact of antibiotic exposure on subsequent resistance gene dissemination within the gut microbiota using a model to simulate the human colon.

Omadacycline Gut Microbiome Exposure Does Not Induce Clostridium difficile Proliferation or Toxin Production in a Model That Simulates the Proximal, Medial, and Distal Human Colon.

A clinically reflective model of the human colon was used to investigate the effects of the broad-spectrum antibiotic omadacycline on the gut microbiome and the subsequent potential to induce simulated infection (CDI). Triple-stage chemostat gut models were inoculated with pooled human fecal slurry from healthy volunteers (age, ≥60 years). Models were challenged twice with 10 CFU spores (PCR ribotype 027).

Biofilm-derived spores of Clostridioides (Clostridium) difficile exhibit increased thermotolerance compared to planktonic spores.

Biofilm-derived spores of strains of four ribotypes (001, 020, 027 & 078) of Clostridioides (Clostridium) difficile were found to exhibit increased thermotolerance compared to spores produced in planktonic culture. In addition, 'thick' and 'thin' exosporium morphotypes described previously were visualised by electron microscopy in both biofilm and planktonic spores.

Survey of screening methods, rates and policies for the detection of carbapenemase-producing Enterobacteriaceae in English hospitals.

Multi-drug-resistant Gram-negative bacteria are of major clinical concern. The increasing prevalence of carbapenemase-producing Enterobacteriaceae (CPE), resistant to all beta-lactams including carbapenems and able to colonize the large intestine, represents a key threat. Rapid, accurate detection of intestinal CPE colonization is critical to minimize transmission, and hence reduce costly, difficult-to-treat CPE infections.

Investigating the effect of supplementation on Clostridioides (Clostridium) difficile spore recovery in two solid agars.

Background: A variety of supplemented solid media are used within Clostridium difficile research to optimally recover spores. Our study sought to investigate different media and additives, providing a method of optimised C. difficile spore recovery.

Clostridium difficile Biofilm.

Clostridium difficile infection (CDI) is an important healthcare-associated disease worldwide, mainly occurring after antimicrobial therapy. Antibiotics administered to treat a number of infections can promote C. difficile colonization of the gastrointestinal tract and, thus, CDI.

Microbiologic factors affecting Clostridium difficile recurrence.

Background: Recurrent Clostridium difficile infection (rCDI) places a huge economic and practical burden on healthcare facilities. Furthermore, rCDI may affect quality of life, leaving patients in an rCDI cycle and dependant on antibiotic therapy.

Aims: To discuss the importance of microbiologic factors in the development of rCDI.

Evaluation of Whole Genome Mapping as a Fast and Automated Molecular Epidemiological Tool for the Study of Cronobacter spp. in Powdered Infant Formula Processing Facilities.

Cronobacter has been identified as the causative agent of outbreaks or sporadic cases of meningitis, necrotizing enterocolitis, and septicemia associated with powdered infant formula. Food processing environments may provide a possible contamination route. The purpose of this study was to evaluate whole genome mapping (WGM) as a fast and automated molecular epidemiological method for characterizing Cronobacter spp.

Association of Fidaxomicin with C. difficile Spores: Effects of Persistence on Subsequent Spore Recovery, Outgrowth and Toxin Production.

Background: We have previously shown that fidaxomicin instillation prevents spore recovery in an in-vitro gut model, whereas vancomycin does not. The reasons for this are unclear. Here, we have investigated persistence of fidaxomicin and vancomycin on C.

An In Vitro Model of the Human Colon: Studies of Intestinal Biofilms and Clostridium difficile Infection.

The in vitro gut model is an invaluable research tool to study indigenous gut microbiota communities, the behavior of pathogenic organisms, and the therapeutic and adverse effect of antimicrobial administration on these communities. The model has been validated against the intestinal contents of sudden death victims to reflect the physicochemical and microbiological conditions of the proximal to distal colon, and has been extensively used to investigate the interplay between gut microbiota populations, antibiotic exposure, and Clostridium difficile infection. More recently the gut model has been adapted to additionally model intestinal biofilm.

Potential of lactoferrin to prevent antibiotic-induced Clostridium difficile infection.

Objectives: Clostridium difficile infection (CDI) is a global healthcare problem. Recent evidence suggests that the availability of iron may be important for C. difficile growth.

Efficacy of vancomycin extended-dosing regimens for treatment of simulated Clostridium difficile infection within an in vitro human gut model.

Objectives: Effects of two vancomycin extended-dosing regimens on microbiota populations within an in vitro gut model of simulated Clostridium difficile infection (CDI) were evaluated.

Methods: Two chemostat gut models were inoculated with faecal emulsion and clindamycin instilled to induce CDI. Simulated CDI was treated with vancomycin (125 mg/L four times daily, 7 days) followed by different vancomycin dosing extensions totalling 7 g (lower dose) or 9.

Efficacy of alternative fidaxomicin dosing regimens for treatment of simulated Clostridium difficile infection in an in vitro human gut model.

Background: Fidaxomicin treatment reduces the risk of recurrent Clostridium difficile infection (CDI) compared with vancomycin. Extending duration of fidaxomicin therapy may further reduce recurrence. We compared the efficacy of four extended fidaxomicin regimens in an in vitro model of CDI.

Recurrence of dual-strain Clostridium difficile infection in an in vitro human gut model.

Background: Clostridium difficile infection (CDI) is still a major challenge to healthcare facilities. The detection of multiple C. difficile strains has been reported in some patient samples during initial and recurrent CDI episodes.

In vitro susceptibility of Clostridium difficile to SMT19969 and comparators, as well as the killing kinetics and post-antibiotic effects of SMT19969 and comparators against C. difficile.

Objectives: SMT19969 is a novel antimicrobial under clinical development for the treatment of Clostridium difficile infection (CDI). The objective was to determine the comparative susceptibility of 82 C. difficile clinical isolates (which included ribotype 027 isolates and isolates with reduced metronidazole susceptibility) to SMT19969, fidaxomicin, vancomycin and metronidazole and to determine the killing kinetics and post-antibiotic effects of SMT19969, fidaxomicin and vancomycin against C.

Efficacy of surotomycin in an in vitro gut model of Clostridium difficile infection.

Objectives: We investigated the efficacy of the cyclic lipopeptide surotomycin in treating clindamycin-induced Clostridium difficile infection (CDI) using an in vitro gut model.

Methods: Two three-stage chemostat gut models were inoculated with human faeces, spiked with C. difficile spores (∼10(7) cfu/mL, PCR ribotype 027 or 001).