Tag Archives: c diff research

Researchers Suggest a Portion Of C. diff. Cases In Europe Involve Infections Associated With Other Sources Outside of Healthcare-Associated Infections

As part of a multicenter study, investigators from the University of Oxford, the University of Leeds, Astellas Pharma Europe, and elsewhere used a combination of ribotyping, sequencing, phylogenetics, and geographic analyses to retrace the genetic diversity and potential sources of C. difficile isolates involved in infections in European hospitals.

Recent research suggests a proportion of Clostridium difficile cases in Europe involve not only hospital-acquired infections but also infections associated with other sources, such as food.

As stated in the article:

https://www.genomeweb.com/sequencing/clostridium-difficile-genetic-patterns-europe-point-possible-infection-sources-beyond?utm_source=Sailthru&utm_medium=email&utm_campaign=GWDN%20Mon%20PM%202017-04-24&utm_term=GW%20Daily%20News%20Bulletin

David Eyre, a clinical lecturer at the University of Oxford, was slated to present the work at the European Congress of Clinical Microbiology and Infectious Diseases annual 2017 meeting in Vienna this past weekend. The study was funded by Astellas Pharma’s Europe, Middle East, and Africa (EMEA) program.

“We don’t know much about how C. difficile might be spread in the food chain, but this research suggests it may be very widespread,” Eyre said in a statement. “If that turns out to be the case, then we need to focus on some new preventative strategies such as vaccination in humans once this is possible, or we might need to look at our use of animal fertilizers on crops.”

“This study doesn’t give us any definitive answers,” he explained, “but it does suggest other factors [than hospital infections] are at play in the spread of C. difficile and more research is urgently needed to pin them down.”

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Some of the strains clustered by locale, consistent with spread from one individual to the next, for example in a healthcare setting. But more unexpectedly, the team also saw strains smattered across seemingly unconnected sites. And because at least one of those strains had previously been linked to pig farming, the researchers speculated that some infections may have been transmitted through food sources.

 

To read the article in its entirety click on the following link:

https://www.genomeweb.com/sequencing/clostridium-difficile-genetic-patterns-europe-point-possible-infection-sources-beyond?utm_source=Sailthru&utm_medium=email&utm_campaign=GWDN%20Mon%20PM%202017-04-24&utm_term=GW%20Daily%20News%20Bulletin

Clostridium difficile Research Suggests That Positively Selected Sites In the Surface Layer Proteins May Play A Role In Driving the Emergence of Hyper-virulent Strains

  • Mark Lynch,
  • Thomas A. Walsh,
  • Izabela Marszalowska,
  • Andrew E. Webb,
  • Micheál MacAogain,
  • Thomas R. Rogers,
  • Henry Windle,
  • Dermot Kelleher,
  • Mary J. O’ConnellEmail author and
  • Christine E. Loscher

To Read Abstract/Article In Its Entirety Please Click On the Following Link:

https://bmcevolbiol.biomedcentral.com/articles/10.1186/s12862-017-0937-8

 

Abstract

Background

Clostridium difficile is a nosocomial pathogen prevalent in hospitals worldwide and increasingly common in the community.

Sequence differences have been shown to be present in the Surface Layer Proteins (SLPs) from different C. difficile ribotypes (RT) however whether these differences influence severity of infection is still not clear.

Results

We used a molecular evolutionary approach to analyse SLPs from twenty-six C. difficile RTs representing different slpA sequences. We demonstrate that SLPs from RT 027 and 078 exhibit evidence of positive selection (PS).

We compared the effect of these SLPs to those purified from RT 001 and 014, which did not exhibit PS, and demonstrate that the presence of sites under positive selection correlates with ability to activate macrophages.

SLPs from RTs 027 and 078 induced a more potent response in macrophages, with increased levels of IL-6, IL-12p40, IL-10, MIP-1α, MIP-2 production relative to RT 001 and 014. Furthermore, RTs 027 and 078 induced higher expression of CD40, CD80 and MHC II on macrophages with decreased ability to phagocytose relative to LPS.

Conclusions

These results tightly link sequence differences in C. difficile SLPs to disease susceptibility and severity, and suggest that positively selected sites in the SLPs may play a role in driving the emergence of hyper-virulent strains.

 

Clostridium difficile Infection Incidence In Mainland China – A Systematic Review

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In the news:

Author information

 Abstract

It has been widely reported that the incidence and severity of Clostridium difficile infection (CDI) have increased dramatically in North America and Europe. However, little is known about CDI in Mainland China. In this study, we aimed to investigate the incidence of CDI and the main epidemic and drug-resistant strains of C. difficile in Mainland China through meta-analysis of related studies published after the year 2010. A total of 51 eligible studies were included. The pooled incidence of toxigenic C. difficile among patients with diarrhoea was 14% (95% CI = 12-16%). In Mainland China, ST-37 and ST-3 were the most prevalent strains; fortunately, hypervirulent strains, such as ST-1 (BI/NAP1/027) and ST-11 (RT 078), have only occurred sporadically to date.

The rates of C. difficile resistance to ciprofloxacin (98.3%; 95% CI = 96.9-99.7%), clindamycin (81.7%; 95% CI = 76.1-87.3%) and erythromycin (80.2%; 95% CI = 73.5-86.9%) are higher than in other counties; however, none of the C. difficile isolates reported in Mainland China were resistant to metronidazole (n/N = 0/960), vancomycin (n/N = 0/960), tigecycline (n/N = 0/41) or piperacillin/tazobactam(n/N = 0/288).

To read this article in its entirety click on the following link to be redirected:

https://www.ncbi.nlm.nih.gov/pubmed/27897206?dopt=Abstract&utm_source=dlvr.it&utm_medium=twitter

Researchers At University of Texas Health Science Center and Graduate School of Biomedical Sciences in Houston Have Uncovered How C. difficile Produces the Toxins A and B That Are Responsible For Causing Disease

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In the battle against drug-resistant pathogens, genetic research holds promising answers to our toughest threats. A new study shows that the best tool for
treating Clostridium difficile
infections could be within the genome of the bacteria itself.

Researchers at the University of Texas Health Science Center and the Graduate School of Biomedical Sciences in Houston have uncovered an important new finding to learn just how the C. difficile bacteria produces toxins, offering some new direction for the development of non-antibiotic drugs to fight dangerous C. difficile infections (CDI).

Strain on already stressed healthcare industry —–   The bacteria are one of the more virulent and widespread drug-resistant pathogens responsible for healthcare associated infections around the world, costing acute care facilities nearly $4.8 billion dollars a year in excess healthcare costs in the United States.

HOW is C. diff. Acquired?   —-   CDIs are linked to the use of broad spectrum antibiotics, which when used to treat infections can also suppress the beneficial bacteria that live in our guts and protect us from infections.   When that intestinal microflora is compromised, individuals become more susceptible to CDIs when exposed to C. difficile bacteria on contaminated surfaces or other individuals who are carrying the bacteria.

CDC Report —    C. difficile works by producing two toxins, toxin A and toxin B, that cause life-threatening diarrhea as well as pseudomembranous colitis, toxic megacolon, perforations in the colon, sepsis and — death. According to a 2015 study from the Centers for Disease Control and Prevention (CDC), there are nearly half a million CDIs in the United States each year, and about 15,000 of those cases result in deaths. The CDC considers C. difficile a public threat needing urgent and aggressive action.

The authors of the new study from the University of Texas have uncovered just how                 C. difficile produces the toxins A and B that are responsible for causing disease.

They studied several strains of the bacteria and found that some encode two Agr loci in their genomes, designated agr1 and agr2. The agr1 locus is present in all of the C. difficile strains sequenced to date, whereas the agr2 locus is present in a few strains.

Until recently, the function of these loci were not known. To understand their roles in toxin regulation and pathogenesis, the researchers used allelic exchange to delete components of agr1 and agr2 and then examined the mutants for toxin production. In their results, they found that the agr1 mutant cannot produce toxins A and B – in their model the mutant was able to colonize but could not produce disease.

These findings offer a potential new approach to treating CDIs for a global medical community vexed by the dangerous pathogen and in need of a novel solution.

“The toxins have become promising non-antibiotic treatment targets,” write the authors. “Here, we have identified a pathway responsible for activating the production of the toxins.

This important finding opens up a unique therapeutic target for the development of a novel non-antibiotic therapy for C. difficile infections.”

Study author Charles Darkoh, PhD, explains how his team plans on building on their research findings. “By crippling their toxin-making machinery, C. diff cannot make toxins and thus cannot cause disease. My laboratory is already working on this and was awarded a 5-year National Institutes of Health grant to investigate and develop an oral compound we have identified that inactivate the toxins and block the toxin-making machinery
of C. diff by targeting this pathway.”

To read article in its entirety click on the link below:

C. diff. Researcher Leads Researchers To Suggest Secondary Bile Salts May Have Potential As a Novel Biomarker For CDI Recurrence

C.diff. Research and Development News:

Patients with recurrent Clostridium difficile infection had distinct bile acid and microbiome profiles compared with healthy controls and patients with first Clostridium difficile infection, according to research published in Alimentary Pharmacology and Therapeutics. These findings led researchers to suggest that secondary bile salts may have potential as a novel biomarker for recurrence.

“The mechanism of recurrent CDI remains unknown, though bile salts have been implicated. The intestinal microbiota metabolizes bile acids, a process that if disrupted by antibiotics may be critical to initiation of CDI,” Jessica R. Allegretti, MD, MPH, from the Crohn’s and Colitis Center and Harvard Medical School, Brigham and Women’s Hospital told Healio Gastroenterology. “This study aimed to assess bile salt profiles in three distinct groups of patients — recurrent CDI, first episode CDI and healthy controls — to better understand the role bile salts play in pathogenesis of recurrent CDI and to gain further understanding as to which bacteria may be responsible for this important function. Additionally, we performed random forest regression to identify predictors of group membership.”

Allegretti and colleagues collected blood and stool samples from 20 patients with first CDI, 19 patients with recurrent CDI being screened for fecal transplantation, and 21 controls. Samples from the first CDI arm were collected before patients received antibiotic treatment, whereas samples from the recurrent CDI arm were collected while they were receiving stable doses of chronic oral vancomycin. Participants in the control arm had not been exposed to antibiotics for at least 3 months.

Researchers then analyzed blood plasma and stool samples for bile salt metabolomics profiles, and performed 16S rRNA amplicon sequencing to determine the microbiota composition of the stool samples.

“We found that secondary bile acids, which are protective, were significantly elevated in controls compared with both CDI groups in stool and blood,” Allegretti said.

The median secondary bile acids lithocholate and deoxycholate were significantly higher in the stool samples of controls compared with both first CDI (P < .0001 and P = .0003, respectively) and recurrent CDI arms (both P < .0001). Deoxycholate was also significantly higher in first vs. recurrent CDI patients (P = .017).

Median deoxycholic acid was significantly higher in the blood samples of controls compared with both first CDI (P < .0001) and recurrent CDI patients (P = .05), and was also significantly higher in the blood samples of first vs. recurrent CDI patients (P = .003).

“Conversely, primary bile acids, which can induce germination, were elevated in the recurrent group,” Allegretti said.

The primary bile acids cholate and chenodeoxycholate were significantly higher in the stool samples of the recurrent CDI arm compared with controls (P = .0002 and P = .02, respectively).

16S rRNA gene analyses showed significant differences in microbial alpha diversity across groups, which were most pronounced in recurrent CDI patients vs. controls (adjusted P < .001), but also significant between first and recurrent CDI patients and between first CDI patients and controls (both adjusted P < .05). There were also significant differences in beta-diversity between all groups (P = .001) and significant differences in relative abundances at the taxa level.

Using PICRUSt analyses, the researchers also found significant differences in predicted abundances of bacterial bile salt hydrolase genes between groups. Finally, using random forest regression, the researchers differentiated recurrent and first CDI patients 84.2% of the time using bile acid ratios, with stool deoxycholate to glycoursodeoxycholate ratio as the best predictor.

“Plasma deoxycholate (a secondary bile acid) was a strong predictor of disease state and may be utilized as a possible biomarker of recurrence,” Allegretti said. “This study further elucidates the role of bile salts in the pathogenesis of recurrent CDI and identifies possible novel biomarkers for recurrent disease.”

To view this article in its entirety please click on the following link:

http://www.healio.com/gastroenterology/infection/news/online/%7B6ea00ba3-4f82-4541-8466-dd5ad2a3e34c%7D/secondary-bile-salts-may-be-novel-biomarkers-of-c-difficile-recurrence?utm_content=31543239&utm_medium=social&utm_source=twitter

by Adam Leitenberger

Hospital C. diff. Study; CDI Rates and Prediction of Length of Stay in Patients Without C. diff. Infection

Clostridium-difficile_456px

Hospital Clostridium difficile Infection Rates and Prediction of Length of Stay in Patients Without  C. difficile Infection (CDI)

> C Diff Foundation > C. diff. Research Community April 2016

Abstract

BACKGROUND Inpatient length of stay (LOS) has been used as a measure of hospital quality and efficiency. Patients with Clostridium difficile infections (CDI) have longer LOS.

OBJECTIVE To describe the relationship between hospital CDI incidence and the LOS of patients without CDI.

DESIGN Retrospective cohort analysis.

METHODS We predicted average LOS for patients without CDI at both the hospital and patient level using hospital CDI incidence. We also controlled for hospital characteristics (eg, bed size) and patient characteristics (eg, comorbidities, age).

SETTING Healthcare Cost and Utilization Project Nationwide Inpatient Sample, 2009–2011.

PATIENTS The Nationwide Inpatient Sample includes patients from a 20% sample of all nonfederal US hospitals.

RESULTS Inpatient LOS was significantly longer (P<.001) at hospitals with greater CDI incidence at both the hospital and individual level.

At a hospital level, a percentage point increase in the CDI incidence rate was associated with more than an additional day’s stay (between 1.19 and 1.61 days).

At the individual level, controlling for all observable variables, a percentage point increase in the CDI incidence rate at their hospital was also associated with longer LOS (between 0.6 and 1.05 additional days).

Hospital CDI incidence had a larger impact on LOS than many other commonly used predictors of LOS.

CONCLUSION CDI rates are a predictor of LOS in patients without CDI at an individual and institutional level. CDI rates are easy to measure and report and thus may provide an important marker for hospital efficiency and/or quality.

Infect. Control Hosp. Epidemiol. 2016;37(4):404–410

Aaron C. Millera1, Linnea A. Polgreena2, Joseph E. Cavanaugha2 and Philip M. Polgreena2 c1

a1 Cornell College, Mount Vernon, Iowa

a2 University of Iowa, Iowa City, Iowa

Clostridium difficile Research: Bacteriophage Combinations Significantly Reduce C. diff. Growth

Microscope - 5

 

Bacteriophage Combinations Significantly Reduce Clostridium difficile Growth In Vitro and Proliferation In Vivo

 

 

The microbiome dysbiosis caused by antibiotic treatment has been associated with both susceptibility to and relapse of Clostridium difficile infection (CDI). Bacteriophage (phage) therapy offers target specificity and dose amplification in situ, but few studies have focused on its use in CDI treatment. This mainly reflects the lack of strictly virulent phages that target this pathogen. While it is widely accepted that temperate phages are unsuitable for therapeutic purposes due to their transduction potential, analysis of seven C. difficile phages confirmed that this impact could be curtailed by the application of multiple phage types. Here, host range analysis of six myoviruses and one siphovirus was conducted on 80 strains representing 21 major epidemic and clinically severe ribotypes. The phages had complementary coverage, lysing 18 and 62 of the ribotypes and strains tested, respectively. Single-phage treatments of ribotype 076, 014/020, and 027 strains showed an initial reduction in the bacterial load followed by the emergence of phage-resistant colonies. However, these colonies remained susceptible to infection with an unrelated phage. In contrast, specific phage combinations caused the complete lysis of C. difficile in vitro and prevented the appearance of resistant/lysogenic clones. Using a hamster model, the oral delivery of optimized phage combinations resulted in reduced C. difficile colonization at 36 h postinfection. Interestingly, free phages were recovered from the bowel at this time. In a challenge model of the disease, phage treatment delayed the onset of symptoms by 33 h compared to the time of onset of symptoms in untreated animals. These data demonstrate the therapeutic potential of phage combinations to treat CDI.

 

To read the article in its entirety please click on the following link:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4750681/

 

Article shared by Dr. Martha Clokie, Ph.D., Member of the C Diff Foundation
Research and Development Committee