Clinical characteristics and outcomes of Clostridioides difficile infection in the intensive care unit: A KASID multicenter study - PubMed
High-risk patients in the ICU had a higher mortality rate and a lower cure rate of CDI. Further research is required to provide more accurate prediction scoring systems and better clinical outcomes.
Type IV pili are involved in phenotypes associated with Clostridioides difficile pathogenesis - PubMed
Clostridioides difficile is a Gram-positive, spore-forming, rod-shaped, obligate anaerobe that is the leading cause of antibiotic-associated diarrhea. Type IV pili (T4P) are elongated appendages on the surface of C. difficile that are polymerized from many pilin proteins. T4P play an i …
Fungal-bacterial gut microbiota interactions in patients with Clostridioides difficile colonisation and infection
Objectives: The bacterial microbiota is well-recognised for its role in Clostridioides difficile colonization and infection, while fungi and yeasts remain understudied. The aim of this study was to analyse the mycobiota and its interactions with the bacterial microbiota in light of C. difficile colonization and infection. Methods: The mycobiota was profiled by ITS2 sequencing of faecal DNA from infected patients (CDI; n = 29), asymptomatically colonised patients (CDC; n = 38) and hospitalised controls with C. difficile negative stool culture (Controls; n = 38). Previously published 16S rRNA gene sequencing data of the same cohort were used additionally for machine learning and fungal-bacterial network analysis. Results: CDI patients were characterised by a significantly higher abundance of Candida spp. (MD 0.270 +/- 0.089, P = 0.002) and Candida albicans (MD 0.165 +/- 0.082, P = 0.023) compared to Controls. Additionally, they were deprived of Aspergillus spp. (MD -0.067 +/- 0.026, P = 0.000) and Penicillium spp. (MD -0.118 +/- 0.043, P = 0.000) compared to CDC patients. Network analysis revealed a positive association between several fungi and bacteria in CDI and CDC, although the analysis did not reveal a direct association between Clostridioides spp. and fungi. Furthermore, the microbiota machine learning model outperformed the models based on the mycobiota and the joint microbiota-mycobiota model. The microbiota classifier successfully distinguished CDI from CDC (AUROC = 0.884) and CDI from Controls (AUROC = 0.905). Blautia and Bifidobacterium were marker genera associated with CDC patients and Controls. Conclusions: The gut mycobiota differs between CDI, CDC, and Controls, and may affect Clostridioides spp. through indirect interactions. The identification of bacterial marker genera associated with CDC and controls warrants further investigation. Although the mycobiota's predictive value of C. difficile status was low, fungal-bacterial interactions might be considered when diagnosing and treating C. difficile infection.
### Competing Interest Statement
This work was supported by the Netherlands Organization for Health Research and Development, ZonMw Grant 522008007.
Identification of DraRS in Clostridioides difficile, a Two-Component Regulatory System That Responds to Lipid II-Interacting Antibiotics - PubMed
Clostridioides difficile is a Gram-positive opportunistic pathogen that results in 220,000 infections, 12,000 deaths, and upwards of $1 billion in medical costs in the United States each year. C. difficile is highly resistant to a variety of antibiotics, but we have a poor understanding of how C. di …
Community-Acquired Severe Clostridium difficile Enteritis Complicated by Metabolic Acidosis and Acute Kidney Injury
Clostridium difficile (CD) is known to be pathogenic when the balance of intestinal microbiota is disrupted by the administration of broad-spectrum antimicrobial agents. Therefore, CD enteritis ...
Colon Cancer Risk Following Intestinal Clostridioides difficile Infection: A Longitudinal Cohort Study - PubMed
This is the first epidemiological study associating Cdiff with an increased risk for colon cancer. Future studies should further evaluate this relationship.
Decoding a cryptic mechanism of metronidazole resistance among globally disseminated fluoroquinolone-resistant Clostridioides difficile - PubMed
Severe outbreaks and deaths have been linked to the emergence and global spread of fluoroquinolone-resistant Clostridioides difficile over the past two decades. At the same time, metronidazole, a nitro-containing antibiotic, has shown decreasing clinical efficacy in treating C. difficile infection ( …
Investigating the Correlation Between Clostridioides difficile Infection and Vitamin D Deficiency - PubMed
CDI patients with comorbid VDD are at higher risk for the recurrence of CDI. This is likely due to the role of vitamin D in the expression of intestinal epithelial antimicrobial peptides, macrophage activation, and maintenance of tight junctions between gut epithelial cells. Furthermore, vitamin D p …
Effects of sexual dimorphism and estrous cycle on C. difficile infections in rodent models
Clostridioides difficile infection (CDI) is responsible for the majority of identifiable hospital-related antibiotic-associated diarrhea. Susceptibility to CDI and severity of disease varies depending on a variety of factors such as aggressive use of broad-spectrum antibiotics, age, and immune status. Epidemiological studies have consistently shown that female patients are more at risk for CDI than their male counterparts. In this study, we show that female mice developed more severe CDI than their male counterparts when challenged with spores from three different C. difficile strains. CDI sexual dimorphism was still apparent when animals were placed under diet conditions that exacerbated CDI severity. Unlike male mice, females undergo the estrous cycle. Thus, female mice were challenged with C. difficile spores when they were at the estrus, metestrus, diestrus, late diestrus/early proestrus, proestrus, or late proestrus/early estrus stages. Animals were scored for CDI sign severity while continuously monitoring their estrous cycle stages. The resulting data showed a striking spike in CDI severity when animals were in proestrus the day before sign scoring. In contrast, animals who were in estrus the day before signs scoring were protected from CDI. Prophylactic treatment of CDI also showed sexual dimorphism with females responding better to treatment than males. Interestingly, infection sexual dimorphism was reversed in hamsters, with male hamsters developing more severe CDI signs than females. In conclusion, we have shown that mice recreate many of the conditions of sexual dimorphism of human CDI.
### Competing Interest Statement
The authors have declared no competing interest.
Genomic Analysis of Clostridioides difficile Recovered from Horses in Western Australia
Clostridioides difficile poses an ongoing threat as a cause of gastrointestinal disease in humans and animals. Traditionally considered a human healthcare-related disease, increases in community-associated C. difficile infection (CDI) and growing evidence of inter-species transmission suggest a wider perspective is required for CDI control. In horses, C. difficile is a major cause of diarrhoea and life-threatening colitis. This study aimed to better understand the epidemiology of CDI in Australian horses and provide insights into the relationships between horse, human and environmental strains. A total of 752 faecal samples from 387 Western Australian horses were collected. C. difficile was isolated from 104 (30.9%) horses without gastrointestinal signs and 19 (37.8%) with gastrointestinal signs. Of these, 68 (55.3%) harboured one or more toxigenic strains, including C. difficile PCR ribotypes (RTs) 012 (n = 14), 014/020 (n = 10) and 087 (n = 7), all prominent in human infection. Whole-genome analysis of 45 strains identified a phylogenetic cluster of 10 closely related C. difficile RT 012 strains of equine, human and environmental origin (0–62 SNP differences; average 23), indicating recent shared ancestry. Evidence of possible clonal inter-species transmission or common-source exposure was identified for a subgroup of three horse and one human isolates, highlighting the need for a One Health approach to C. difficile surveillance.
A Systematic Review and Meta-Analysis: A Prior Appendectomy Does Not Increase the Risk of Severe Clostridioides difficile Infection or Recurrence - PubMed
Patients with appendectomy are not at increased risk for developing severe Clostridioides difficile infection or recurrence. Further prospective studies are needed to establish these associations.
An intact S-layer is advantageous to Clostridioides difficile within the host - PubMed
Clostridioides difficile is responsible for substantial morbidity and mortality in antibiotically-treated, hospitalised, elderly patients, in which toxin production correlates with diarrhoeal disease. While the function of these toxins has been studied in detail, the contribution of other factors, i …
An intact S-layer is advantageous to Clostridioides difficile within the host - PubMed
Clostridioides difficile is responsible for substantial morbidity and mortality in antibiotically-treated, hospitalised, elderly patients, in which toxin production correlates with diarrhoeal disease. While the function of these toxins has been studied in detail, the contribution of other factors, i …
Myeloid cell specific deletion of PDGFR-α promotes dysbiotic intestinal microbiota and thus increased colitis susceptibility - PubMed
Taken together, our results indicate a protective role for myeloid PDGFR-α in maintaining gut homeostasis by promoting a protective intestinal microbiota and providing an anti-inflammatory macrophage phenotype.
Research reveals how microorganisms found in the gut can worsen C. difficile infections
New research from the University of Virginia School of Medicine and collaborators reveals how microorganisms found in our guts can worsen dangerous C. difficile infections.
The Brief Case: a White-Colony-Producing Clostridioides difficile Ribotype 020 Strain | Journal of Clinical Microbiology
A bedridden elderly female patient with right hemiparesis was admitted to Siriraj
Hospital, Bangkok, Thailand, with acute pyelonephritis. Considering the patient’s
history of frequent hospitalization, intravenous meropenem (2 g, every 8 h) was given
empirically. An extended-spectrum β-lactamase (ESBL)-producing Escherichia coli isolate was later isolated from her urine, and meropenem was continued for 10 days.
The patient responded well; however, 6 days after admission, she developed watery
diarrhea. At the time, she was receiving colchicine and senna, which were discontinued;
however, the diarrhea did not resolve after 2 days. The patient’s stool was tested
and was positive for the Clostridioides difficile tcdB gene using the BD Max platform (Becton, Dickinson, USA). She was thus diagnosed with
mild C. difficile infection (CDI) and treated with oral metronidazole (400 mg, every 8 h) for 7 days
while continuing meropenem. She responded well to treatment and was later discharged
from the hospital without further complications.
Oligomerization and Adjuvant Activity of Peptides Derived from the VirB4-like ATPase of Clostridioides difficile - PubMed
In a previous study, we demonstrated that the Clostridioides difficile VirB4-like ATPase forms oligomers in vitro. In the current investigation, to study the observed phenomenon in more detail, we prepared a library of VirB4-derived peptides (delVirB4s) fused to a carrier maltose-binding prot …
Domperidone Protects Cells from Intoxication with Clostridioides difficile Toxins by Inhibiting Hsp70-Assisted Membrane Translocation - PubMed
Clostridioides difficile infections cause severe symptoms ranging from diarrhea to pseudomembranous colitis due to the secretion of AB-toxins, TcdA and TcdB. Both toxins are taken up into cells through receptor-mediated endocytosis, autoproteolytic processing and translocation of their enzyme …
Pre-colonization with the fungus Candida glabrata exacerbates infection by the bacterial pathogen Clostridioides difficile in a murine model - PubMed
The contributions of commensal fungi to human health and disease are not well understood. Candida species such as C. albicans and C. glabrata are opportunistic pathogenic fungi and common colonizers of the human intestinal tract. They have been shown to affect the host immune sy …
Comparison of DNA extraction methods for 16S rRNA gene sequencing in the analysis of the human gut microbiome - PubMed
The gut microbiome is widely analyzed using high-throughput sequencing, such as 16S rRNA gene amplicon sequencing and shotgun metagenomic sequencing (SMS). DNA extraction is known to have a large impact on the metagenomic analyses. The aim of this study was to compare DNA extraction protocols for 16 …
This case report discusses a nine-year-old female that presented with abdominal pain, diarrhea, and weight loss, suggestive of inflammatory bowel disease (IBD). She had an older brother previous...
Intestinal C. Difficile Infection Supported by Antibiotic-Resistant Gut Bacteria
Study showed how Enterococcus fine tunes the environment around C. diff, restricting some nutrients and supplying others, to increase its fitness and virulence.
The gut microbes in inflammatory bowel disease: Future novel target option for pharmacotherapy - PubMed
Gut microbes constitute the main microbiota in the human body, which can regulate biological processes such as immunity, cell proliferation, and differentiation, hence playing a specific function in intestinal diseases. In recent years, gut microbes have become a research hotspot in the pharmaceutic …
Increased intestinal permeability and downregulation of absorptive ion transporters Nhe3, Dra, and Sglt1 contribute to diarrhea during Clostridioides difficile infection - PubMed
CDI increases intestinal permeability and decreases apical abundance of NHE3, SGLT1, and DRA. This combination likely leads to dysfunctional water and solute absorption in the large bowel, causing osmotic diarrhea. These findings provide insights into the pathophysiological mechanisms underlying dia …
This case report discusses a nine-year-old female that presented with abdominal pain, diarrhea, and weight loss, suggestive of inflammatory bowel disease (IBD). She had an older brother previous...