Category Archives: C. diff. Research Community

Researchers Examined the Effect of Disinfectant on C. difficile Spores and How They Survived Afterwards On Surfaces Including Isolation Gowns, Stainless Steel and Vinyl Flooring

In lab studies, researchers found that C. diff spread easily from disposable gowns often employed in surgery or infection control to stainless steel and vinyl surfaces.

“The [bacteria] also transferred to vinyl flooring, which was quite disturbing. We didn’t realize they would,” said Tina Joshi, a lecturer in molecular microbiology at the University of Plymouth in the United Kingdom and lead author of the new study.

“These bugs evolve. These bugs like to stay one step ahead. And even though we’re using disinfectants and antibiotics appropriately, they still will become resistant in time. It’s inevitable,” Joshi said.

The bacteria, called Clostridioides difficile or C. diff., cause almost a half million infections every year in the United States, according to the Centers for Disease Control and Prevention.

The infection, which is spread by fecal to oral transmission, causes severe diarrhea, and can lead to intestinal inflammation and kidney failure. Those most at risk are people who have been given strong antibiotics, as well as those with long hospital stays, or those living in long-term care facilities like the elderly.

That means that keeping these facilities clean is incredibly important. But new research, published Friday (7/12/19)  in the journal Applied and Environmental Microbiology, shows how difficult that can be.

In lab studies, researchers found that C. diff spread easily from disposable gowns often employed in surgery or infection control to stainless steel and vinyl surfaces.

These bugs evolve. These bugs like to stay one step ahead. And even though we’re using disinfectants and antibiotics appropriately, they still will become resistant in time. It’s inevitable.

What’s more, the bacteria didn’t die when the researchers tried to kill them with concentrated chlorine disinfectant.

“Even if we applied 1,000 parts per million of chlorine, it would allow spores to survive in the gowns,” Joshi told NBC News.

It’s possible that increasing the amount of chlorine might kill the spores, but if the spores are indeed becoming resistant to the disinfectant, it will only be a matter of time before the stronger concentrations can’t kill them.

“These bugs evolve. These bugs like to stay one step ahead. And even though we’re using disinfectants and antibiotics appropriately, they still will become resistant in time. It’s inevitable,” Joshi said.

C. diff infections can occur when a patient is given broad spectrum antibiotics to tackle another infection.

If the bacteria aren’t killed, hospital patients or people in nursing homes can become infected when they come into contact with contaminated surfaces, such as a bedside food tray.

But if traditional disinfectants are ineffective, as the new research suggests, what works?

One option is UV light, which could be useful in killing the bacteria. However, it can be challenging to make sure all surfaces are fully exposed to the light. At this point, Joshi said, highly concentrated bleach appears to be the best option.

For those who care for patients with compromised immune systems at home, the C. Diff Foundation says alcohol-based hand sanitizers are ineffective against the bacteria.

On its website, the group recommends using a cleaning solution of one cup bleach to nine cups of water, and leaving the mixture on surfaces for a minimum of 10 minutes. (Basic & Generic, not EPA registered product).

Meanwhile, if C. diff spores can survive on gowns and other surfaces, it is likely also the case that they can live on doctor’s coats and scrubs worn by hospital personnel all day.  (C Diff Foundation agrees)

“That’s a real infection control hazard, because these spores can stick to fibers. We’ve proven that in this paper,” Joshi said.

Erika Edwards

Erika Edwards is the health and medical news writer/reporter for NBC News and Today.

 

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https://www.nbcnews.com/health/health-news/dangerous-bacteria-can-survive-disinfectant-putting-patients-risk-n1029231

 

 

CspC Plays a Critical Role in Regulating C. diff. Spore Germination in Response to Multiple Environmental Signals.


Abstract

The gastrointestinal pathogen, Clostridioides difficile, initiates infection when its metabolically dormant spore form germinates in the mammalian gut. While most spore-forming bacteria use transmembrane germinant receptors to sense nutrient germinants, C. difficile is thought to use the soluble pseudoprotease, CspC, to detect bile acid germinants. To gain insight into CspC’s unique mechanism of action, we solved its crystal structure. Guided by this structure, we identified CspC mutations that confer either hypo- or hyper-sensitivity to bile acid germinant. Surprisingly, hyper-sensitive CspC variants exhibited bile acid-independent germination as well as increased sensitivity to amino acid and/or calcium co-germinants. Since mutations in specific residues altered CspC’s responsiveness to these different signals, CspC plays a critical role in regulating C. difficile spore germination in response to multiple environmental signals. Taken together, these studies implicate CspC as being intimately involved in the detection of distinct classes of co-germinants in addition to bile acids and thus raises the possibility that CspC functions as a signaling node rather than a ligand-binding receptor

Author summary

The major nosocomial pathogen Clostridioides difficile depends on spore germination to initiate infection. Interestingly, C. difficile’s germinant sensing mechanism differs markedly from other spore-forming bacteria, since it uses bile acids to induce germination and lacks the transmembrane germinant receptors conserved in almost all spore-forming organisms. Instead, C. difficile is thought to use CspC, a soluble pseudoprotease, to sense these unique bile acid germinants. To gain insight into how a pseudoprotease senses germinant and propagates this signal, we solved the crystal structure of C. difficile CspC. Guided by this structure, we identified mutations that alter the sensitivity of C. difficile spores to not only bile acid germinant but also to amino acid and calcium co-germinants. Taken together, our study implicates CspC in either directly or indirectly sensing these diverse small molecules and thus raises new questions regarding how C. difficile spores physically detect bile acid germinants and co-germinants.

Authors:

  • Amy E. Rohlfing ,
  • Brian E. Eckenroth ,
  • Emily R. Forster,
  • Yuzo Kevorkian,
  • M. Lauren Donnelly,
  • Hector Benito de la Puebla,
  • Sylvie Doublié,
  • Aimee Shen

To view the Abstract in its entirety – please click on the link provided below:

https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1008224

  • Published: July 5, 2019

On June 13th the U.S. Food and Drug Administration Warned of Infections From Fecal Microbiota Transplantation (FMT) Linked to a Patient’s Death

Dr. Peter Marks, director the Center for Biologics Evaluation and Research at the U.S. Food and Drug Administration stated, “While we support this area of scientific discovery, it’s important to note that fecal microbiota for transplantation does not come without risk,”

Two patients contracted severe infections, and one of them died, from fecal transplants that contained drug-resistant bacteria.

The agency said two patients received donated stool that had not been screened for drug-resistant germs, leading it to halt clinical trials until researchers prove proper testing procedures are in place.

After reports of serious, antibiotic-resistant infections linked to the procedures, the FDA wants “to alert all health care professionals who administer FMT [fecal microbiota transplant] about this potential serious risk so they can inform their patients.” said Dr. Peter Marks, director the Center for Biologics Evaluation and Research at the U.S. Food and Drug Administration.

Other samples from the same donor were tested after the patients got sick. The samples were found to harbor the same dangerous germs found in the patients, known as multi-drug-resistant organisms (MDRO). They were E. coli bacteria that produced an enzyme called extended-spectrum beta-lactamase, which makes them resistant to multiple antibiotics. The stool had not been tested for the germs before being given to the patients.

The F.D.A. on Thursday issued a warning to researchers that stool from donors in studies of fecal transplantation should be screened for drug-resistant microbes, and not used if those were present. It is also warning patients that the procedure can be risky, is not approved by the agency and should be used only as a last resort when C. difficile does not respond to standard treatments.

Dr. Marks said the agency was trying to strike a balance between giving patients who need the treatment access to it while also establishing safeguards to protect them from infection. In a statement, he said, “While we support this area of scientific discovery, it’s important to note that fecal microbiota for transplantation does not come without risk.”

Researchers are also looking into the use of fecal transplants to treat chronic gastrointestinal illnesses such as ulcerative colitis or irritable bowel syndrome.

The patients received treatment as part of a clinical trial, and the researchers conducting the trial reported the cases as adverse events to the F.D.A., which they are required to do. But the rules governing this kind of experiment prohibit the F.D.A. from revealing details about the treatment or who provided it.

 

SOURCE:  https://www.nytimes.com/2019/06/13/health/fecal-transplant-fda.html

Researchers Find Sulfated glycosaminoglycans and Low-Density Lipoprotein Receptor Contribute To Clostridioides difficile Toxin A Cell Entry

 

Abstract

Clostridium difficile toxin A (TcdA) is a major exotoxin contributing to disruption of the colonic epithelium during C. difficile infection. TcdA contains a carbohydrate-binding combined repetitive oligopeptides (CROPs) domain that mediates its attachment to cell surfaces, but recent data suggest the existence of CROPs-independent receptors. Here, we carried out genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9)-mediated screens using a truncated TcdA lacking the CROPs, and identified sulfated glycosaminoglycans (sGAGs) and low-density lipoprotein receptor (LDLR) as host factors contributing to binding and entry of TcdA. TcdA recognizes the sulfation group in sGAGs. Blocking sulfation and glycosaminoglycan synthesis reduces TcdA binding and entry into cells. Binding of TcdA to the colonic epithelium can be reduced by surfen, a small molecule that masks sGAGs, by GM-1111, a sulfated heparan sulfate analogue, and by sulfated cyclodextrin, a sulfated small molecule. Cells lacking LDLR also show reduced sensitivity to TcdA, although binding between LDLR and TcdA are not detected, suggesting that LDLR may facilitate endocytosis of TcdA. Finally, GM-1111 reduces TcdA-induced fluid accumulation and tissue damage in the colon in a mouse model in which TcdA is injected into the caecum. These data demonstrate in vivo and pathological relevance of TcdA-sGAGs interactions, and reveal a potential therapeutic approach of protecting colonic tissues by blocking these interactions.

To view abstract in its entirety please click on the following link to be redirected:  https://www.ncbi.nlm.nih.gov/pubmed/31160825?dopt=Abstract&utm_source=dlvr.it&utm_medium=twitter

National and State Healthcare-associated Infection (HAI) Progress Report from the CDC 2019

Between 2016 and 2017, healthcare-associated infections decreased in the United States, according to the most recent National and State HAI Progress Report   from the CDC.

The report includes a summary of rates for select HAIs across four settings: acute care hospitals, critical access hospitals, inpatient rehabilitation facilities and long-term acute care hospitals.

Key findings from the report include:

1. Central line-associated bloodstream infections saw a 9 percent decrease, with the largest decrease occurring in hospital wards.

2. Catheter-associated urinary tract infections dropped by 5 percent, with ICUs showing the largest decrease of 8 percent.

3. Methicillin-resistant Staphylococcus aureus bacteremia declined by 8 percent and Clostridioides difficile events reduced by 13 percent.

4. Ventilator-associated events and surgical site infections both decreased, by 3 percent and 1 percent respectively. The decrease in SSIs was related to 10 procedures tracked in the report.

5. There were no significant decreases or increases in abdominal hysterectomy SSIs and colon surgery SSIs.

 

Source:  https://www.beckershospitalreview.com/quality/hais-decreased-in-2017-c-diff-down-13-mrsa-down-8.html

Researchers Share Risk Factors for Recurrence of Clostridioides difficile (formally known as Clostridium difficile) Infection In Japan Real-World Analysis

 

 

 

 

Author information

Abstract

OBJECTIVE:

Recurrent Clostridioides (Clostridium) difficile infection (rCDI) is common and increases healthcare resource utilization. In this study, we assessed rCDI risk factors using an up-to-date, Japanese national hospital-based database.

METHODS:

C. difficile infection (CDI) episodes, occurring July 2014-June 2017, in patients aged ≥18 years were extracted from the database and a nested case-control analysis was performed. Cases were defined as rCDI episodes which required re-initiation of oral vancomycin or oral/intravenous metronidazole treatment within 8 weeks from the start of initial treatment. Cases were matched to 4 non-rCDI episodes at the timing of rCDI occurrence. Adjusted odds ratios (ORs) were estimated using multivariate conditional logistic regression model.

RESULTS:

Of 18,246 initial CDI episodes, 3250 (17.8%) had at least one rCDI. Approximately 90% of episodes occurred in inpatients and 65% were treated with metronidazole. Older age (<75 years vs 75-84 years and vs 85 + years) was associated with higher risk of rCDI (OR = 1.27, 95% confidence interval [1.15, 1.41] and 1.45 [1.30, 1.61], respectively). Use of systemic antibiotics (3.16 [2.90, 3.44]), probiotics (2.53 [2.32, 2.77]), chemotherapy (1.28 [1.08, 1.53]), or proton pump inhibitors (PPIs) (1.17 [1.07, 1.28]), and prior CDI history (1.22 [1.03, 1.43]) were also identified as rCDI risk factors. Vancomycin reduced the risk of rCDI compared with metronidazole treatment (0.83 [0.76, 0.91]).

CONCLUSION:

This large, multicenter, nationwide study confirmed that older age, PPIs, antibiotics, probiotics, chemotherapy, and prior CDI history are risk factors for rCDI in Japan. There was a 17% decrease of rCDI risk with vancomycin vs metronidazole treatment.

CLINICAL TRIAL REGISTRATION NUMBER:N/A.

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https://www.ncbi.nlm.nih.gov/pubmed/30987950?dopt=Abstract&utm_source=dlvr.it&utm_medium=twitter

University of Virginia School of Medicine Researchers Find Why Certain Patients Are Highly Susceptible to C.diff. Infections

The new finding from the University of Virginia School of Medicine (UVA) explains why certain patients are highly susceptible

to C. diff infections, provides doctors with a way to predict disease severity and points to a new way to treat the often-deadly condition.

The UVA researchers found that the immune response to C. diff causes tissue damage and even death through a type of immune cell called Th17. This solves a longstanding mystery about why disease severity does not correlate with the amount of bacteria in the body but, instead, to the magnitude of the immune response. It also explains why patients with inflammatory bowel disease are more likely to suffer severe C. diff infections and more likely to die from them.

Lingering Effects

The bowel condition colitis, the researchers determined, has a lingering effect on the immune system, priming the patient for a worse C. diff infection.

While scientists have known that C. diff and other bacteria produce toxins that are harmful to the body, they assumed this was a simple matter: more toxin, more sickness.

But UVA’s research reveals that the truth is far more complex. Oftentimes, the type of immune response generated by the body can dictate the outcome of disease independent of bacterial toxin.

“When we, as a lab, started working on this, we were actively discouraged from working

on C. difficile because [some] people in the field thought, ‘Oh, this is a toxin-mediated disease. You don’t need to understand anything more than the fact that the bacteria make toxins,’” UVA’s Dr. William A. Petri Jr. said. “So, it’s been a wonderful opportunity for us because we went in and we sort of countered the prevailing wisdom. Yes, the toxins are important, but the toxins are important because they affect the immune system in dramatic ways.”

Inflammatory Bowel Disease

Seeking to understand why patients with inflammatory bowel disease are so susceptible to C. diff, researcher Mahmoud Saleh created a mouse model of colitis, one of the common forms of inflammatory bowel disease. He was able to determine that mice that recovered from colitis actually had changes in their immune system – an adaptive immune response. Immune cells known as Th17 cells had become hyper-charged, primed to cause a severe reaction to subsequent C. difficile infection. Even the same amount of the bacteria would now cause a dangerous, outsized response. “If we infect a month later, we see that these [T helper cells] alone can cause severe infection,” Saleh said. “So, these cells are sufficient for that increased severity of C. difficile infection.”

The researchers then looked at human samples to determine if their finding would hold true. It did, and they were able to use substances in the blood, including a protein known as interleukin 6 (IL-6), to predict disease severity. Patients with high amounts of IL-6 were almost eight times more likely to die from C. difficile than those with low levels.

Petri, of UVA’s Division of Infectious Diseases and International Health, explained: “Now we know from Mahmoud’s work that if I, as a physician, measure IL-6 in one of my patients with inflammatory bowel disease, I’ll be able to know how severe disease will be in that person and I can make the decision about whether the person needs to be admitted to the hospital … or even go to the intensive care unit.”

Preventing C. diff

The research also suggests a potential new way to treat or prevent severe C. difficile relapses. “We know that in mice by targeting T cells we protect from disease, and that leads to the question, could we do something similar and people to provide better therapy?” Petri said. “It is an interesting and terrible situation right now that C. diff is not resistant to antibiotics, but is resistant to treatment. And so even though we have very, very good antibiotics for this, the [body’s] response is so severe that even though we’re killing the bacteria with the antibiotics, patients are suffering from their own immune response.”

While more research will need to be done to create such a treatment, Petri and Saleh are proud to have solved a big mystery about C. difficile. “When you look at how much bacteria are growing or how much toxin is being produced, a lot of time there is no direct correlation,” Saleh said. “Now we know that what’s making that difference is this immune response.”

Findings Published

The researchers have published their findings in the scientific journal Cell Host & Microbe. The research team consisted of Saleh, Alyse L. Frisbee, Jhansi L. Leslie, Erica L. Buonomo, Carrie A Cowardin, Jennie Z. Ma, Morgan E. Simpson, Kenneth W. Scully, Mayuresh M. Abhyankar and Petri.

The research was supported by the National Institutes of Health, grants T32GM008715, T32AI007496, T32AI007496, T32AI07496, 5F31AI114203, 1R21AI114734 and 1R01AI124214; and the UVA Wagner Fellowship.

 

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https://news.virginia.edu/content/revealed-secret-superpower-makes-c-difficile-so-deadly?utm_source=dlvr.it&utm_medium=twitter