Tag Archives: Are there Clostridioides difficile research studies?

Clostridioides diffiicle Thrives In an Inflammed Environement ….Research Study From North Carolina State University

Clostridioides difficile thrives in an inflamed environment by generating toxins that support prolonged infection, according to a study from North Carolina State University.

The study, published in Nature Communications, showed how C. diff produces toxins that cause inflammation, eliminating competing bacteria and releasing peptides and amino acids that support the growth of C. diff.

C. diff thrives when other microbes in the gut are absent – which is why it is more prevalent following antibiotic therapy,” corresponding author Casey Theriot, Ph.D., associate professor of infectious disease at North Carolina State University, said. “But when colonizing the gut,
C. diff. also produces two large toxins, TcdA and TcdB, which cause inflammation. We wanted to know if these inflammation-causing toxins actually give C. diff a survival benefit – whether the pathogen can exploit an inflamed environment in order to thrive.”

Investigators examined two variants of C. diff in vitro and in an antibiotic-treated mouse model. The variants included a wild type C. diff that produces toxins and a genetically modified variant that does not. They found that the wild type C. diff, associated with toxin production, generated more inflammation and tissue damage than the mutant.

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

https://www.contagionlive.com/view/clostridioides-difficile-thrives-in-inflamed-environment

Investigators also found changes in the expression of metabolic genes, with C. diff in the inflamed environment expressing more genes related to carbohydrate and amino acid metabolism that sustains growth.

C. diff’s toxins damage the cells that line the gut,” Theriot said. “These cells contain collagen, which is made up of amino acids and peptides. When collagen is degraded by toxins,
C. diff responds by turning on expression of genes that can use these amino acids for growth.”

Inflammation provided a second benefit to C. diff by creating an inhospitable environment for other bacteria that compete for nutrients. Bacteroidaceae were present in control groups that weren’t infected with toxin-producing C. diff, which was consistent with previous studies that found negative associations between C. diff and Bacteroidaceae.

“I always found it interesting that C. diff causes such intense inflammation,” first author Josh Fletcher, Ph.D., a former postdoctoral researcher at North Carolina State University, said. “Our research shows that this inflammation may contribute to the persistence of C. diff in the gut environment, prolonging infection.”

C. diff is the most significant cause of hospital-acquired diarrhea, causing more than 223,900 infections and 12,800 deaths in the US in 2017, according to a recent report.

The disease has two phases, a spore phase, and vegetative phase. Toxins are released during the vegetative phase, causing diarrhea and other symptoms. But the pathogen is often transmitted during the spore phase, during which it is hardy and isn’t susceptible to gastric acids and alcohol-based hand sanitizer, experts explained during a recent discussion of the disease.

Risks for infection include exposure to C. diff spores and antibiotic use. An investigational drug to prevent the disruption of the gut microbiota by antibiotics is among the most recent developments in the fight against a C diff. infection.

 

Please — Do Not Take Medicine Into Your Own Hands, You Are NOT Out Of Options

Do-It-Yourself Treatments Could Be Fatal……

You are NOT out of options………………………

During these unprecedented times, we understand the patient’s frustration and how this pandemic has created a halt to the readily accessible alternative treatment option in the FMT community.   The need for continued treatments for a C. diff. infection and recurrent C. diff. infections are real and necessary. We also understand how patients experiencing
recurrent C. difficile infections are desperately seeking the FMT alternative treatment.

C Diff Foundation is able to provide information about treatments available to safely treat  CDI’s and recurrent C. diff. infections.

Most home remedies or natural therapies, though, haven’t been put through the same rigorous clinical testing you expect from pharmaceutical medications.

In a world where you can fix almost anything with a do-it-yourself video on YouTube, you might think curing your own illness would be a piece of cake. It might be if it weren’t for a couple of (not so small) sticking points.  One, the home remedy recommended by your friend — or one of the many websites promoting “natural therapies” — might not work.1  Dr. Harriet Hall, a retired family physician, former Air Force flight surgeon, and author of the SkepDoc column in Skeptic magazine, is one of those leading the charge against medical “treatments” not supported by science.  Like others in the medical and scientific community, ……. There is the only medicine that has been tested and proven to work, and medicine that hasn’t,” Hall told Healthline. 1

Talk to your medical professional/s.

Discuss medications and clinical trials available.

Do Not Share Antibiotics.

Responses to an anonymous online questionnaire of 496 parents, researchers at the Cohen Children’s Medical Center of New York reported that 48 percent of the parents surveyed said they’ve held onto leftover antibiotics. More troubling to researchers was that of those parents, 73 percent reported giving those antibiotics to siblings, unrelated children, and unrelated adults.  This would sometimes occur months after the drugs were originally prescribed.
Dr. Ruth Milanaik, director of the neonatal neurodevelopment follow-up program at Cohen and senior author of the study, says the results show an “alarming” percentage of parents engaging in sharing or borrowing antibiotics, a practice known as prescription diversion.  “This is dangerous not only for those given antibiotics that weren’t prescribed for them but for entire populations of people who some antibiotics may no longer help when the bacteria they target become resistant to them,” Milanaik said in a statement. 2

Discuss Resources available.

Times are trying during these unprecedented times and you are not without hope – we would like to help you and not see you get hurt or even worse. Please take time to speak to your treating physician and consider contacting a C Diff Foundation Triage Nurse at 727-205-3922 to learn more about safe and effective treatments available and options available to you at this time of desperation.

Remember – You  Are Not Out of Options.

Stay safe – and please – Do NOT take medicine into your own hands.

Thank You!

Resources:
1 Foxnews.com
2 Healthline.com

 

 

MGB Biopharma Developing MGB-BP-3 a Treatment for CDI – Announces the Successful Completion of Its End-of-Phase 2 Meeting With the FDA

MGB Biopharmaa biopharmaceutical company developing MGB-BP-3, a novel antibacterial, for the treatment of Clostridioides difficile (CDI), today announces the successful completion of its End-of-Phase 2 (EOP2) meeting with the US Food and Drug Administration (FDA), an important milestone for the company and its lead product.

The EOP2 Meeting is a formal step at which companies seek confirmation that their product is considered safe to proceed to broader clinical studies and to explore any additional studies that may be required before entering into Phase 3.

At the meeting, the US FDA confirmed that the design and the endpoints of our two prospective Phase 3 studies were appropriate. The Phase 3 studies, which are expected to recruit approximately 900 patients, will include the superiority of MGB-BP-3 against vancomycin in the critical measure of sustained clinical response as one of their endpoints.

Dr Miroslav Ravic, CEO of MGB Biopharma, said, “The successful completion of the End-of-Phase 2 meeting with the FDA marks the culmination of solid scientific and clinical endeavor by the Company. The positive Phase 2 data showed that MGB-BP-3 provides high rates of Sustained Cure from CDI, a devastating disease.  We are very pleased with the guidance received from the FDA on key elements of the Phase 3 program that will support the submission of a New Drug Application (NDA).

“The global pandemic caused by COVID-19 has highlighted the importance of being adequately prepared for infectious diseases. CDI’s ongoing high mortality reminds us that this is a disease with a significant unmet medical need for which new treatments are urgently required. MGB-BP-3, with its unique mode of action, is perfectly positioned to meet the need and provide confidence to patients and clinicians that more effective treatments are just round the corner.”

Professor Thomas Louie, clinical professor at the Cumming School of Medicine at the University of AlbertaCalgary (Canada) and Principal Investigator said, “I am most pleased to have contributed to the success of the Phase 2 clinical study of MGB-BP-3. There is a real need for new agents to address CDI and it is gratifying to see this agent progressing onto its next phase of the study. CDI represents a major burden to the Canadian and US healthcare systems. A novel antibiotic that is able to kill this deadly pathogen before it is able to sporulate offers hope to patients and their families who suffer the pain and misery caused by this disease.”

MGB Biopharma is considering strategic options for the business and has engaged JMP Securities as its exclusive financial advisor.

About MGB-BP-3

MGB-BP-3 is a novel antibiotic that belongs to the Minor Groove Binder group, discovered at the University of Strathclyde, with a unique rapid bactericidal activity against Clostridioides difficile (CDI), a feature shared by no other treatment available. A recently completed Phase 2 clinical study in 33 CDI patients using three sequential ascending doses of MGB-BP-3 showed a high initial average cure of 94% in all dosages, a high average sustained cure of 95% in the 2 lower dosages, and preservation of the gut microbiota with the lower dosages. There were correspondingly low recurrence rates of less than 5% for the first two doses. MGB-BP-3 was shown to be safe and well-tolerated with no serious adverse events in either of Phase 1 or 2 clinical studies.

CDI is a serious and life-threatening infection of the large intestine and is the most frequent cause of diarrhea in hospitals and care homes. In the US alone, there are almost half a million cases every year associated with around 30,000 deaths; three people die of uncontrolled CDI each hour. CDI has been recognized as an urgent threat pathogen by the Centers for Disease Control and Prevention (CDC) in the US and is a common consequence of antibiotic treatment in hospitalized patients.

About MGB Biopharma

MGB Biopharma is a clinical-stage company developing a novel class of anti-infectives. Its lead candidate, MGB-BP-3, is an antibacterial that is active against a broad range of important multi-resistant and susceptible Gram-positive pathogens. The Company is developing an oral formulation of MGB-BP-3 for the treatment of Clostridioides difficile Infection (CDI).

In addition to its C. difficile programme, MGB Biopharma has a pipeline of early preclinical compounds against Gram-positive, Gram-negative, anti-fungal, anti-viral and anti-parasitic pathogens.

MGB Biopharma acquired rights to the proprietary minor groove binder (MGB) platform, developed at the University of StrathclydeGlasgow, with exclusive worldwide licensing rights for all anti-infective fields. This platform provides an opportunity to develop various compounds with a completely new mode of action that are distinct from the antimicrobial drugs used in clinical practice today. As a result, many MGB-based drugs could have the potential to offer significant advantages over existing anti-infectives.

The Company, founded in 2010 and headquartered in Glasgow, Scotland, is backed by Scottish investors including Archangel Investors Limited, Barwell, TRICAPITAL, Syndicate Room, and the Scottish Investment Bank, Scottish Enterprise. The company also received significant support for its clinical programme from Innovate UK.

For more information, please visit www.mgb-biopharma.com

CDI and Recurrence; Microbiome – Based Therapy Publication

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

To read the article in its entirety, please download the .pdf format below

2021-MicrobiomeBasedTherapyCDI

 

 

Researchers Perform A Systematic Review and Meta-Analysis In Order to Summarize Data on Antimicrobial Resistance to C. difficile Derived from Humans

 

 

 

 

 

 

 

Mohammad Sholeh1Marcela Krutova2Mehdi Forouzesh3Sergey Mironov4Nourkhoda Sadeghifard5Leila Molaeipour6Abbas Maleki5Ebrahim Kouhsari789
  • PMID: 32977835
  • PMCID: PMC7517813
  • DOI: 10.1186/s13756-020-00815-5

Free PMC article

Abstract

Background: Clostridioides (Clostridium) difficile is an important pathogen of healthcare-associated diarrhea, however, an increase in the occurrence of C. difficile infection (CDI) outside hospital settings has been reported. The accumulation of antimicrobial resistance in C. difficile can increase the risk of CDI development and/or its spread. The limited number of antimicrobials for the treatment of CDI is a matter of some concern.

Objectives: In order to summarize the data on antimicrobial resistance to C. difficile derived from humans, a systematic review and meta-analysis were performed.

Methods: We searched five bibliographic databases: (MEDLINE [PubMed], Scopus, Embase, Cochrane Library, and Web of Science) for studies that focused on antimicrobial susceptibility testing in C. difficile and were published between 1992 and 2019. The weighted pooled resistance (WPR) for each antimicrobial agent was calculated using a random-effects model.

Results: A total of 111 studies were included. The WPR for metronidazole and vancomycin was 1.0% (95% CI 0-3%) and 1% (95% CI 0-2%) for the breakpoint > 2 mg/L and 0% (95% CI 0%) for breakpoint ≥32 μg/ml. Rifampin and tigecycline had a WPRs of 37.0% (95% CI 18-58%) and 1% (95% CI 0-3%), respectively. The WPRs for the other antimicrobials were as follows: ciprofloxacin 95% (95% CI 85-100%), moxifloxacin 32% (95% CI 25-40%), clindamycin 59% (95% CI 53-65%), amoxicillin/clavulanate 0% (0-0%), piperacillin/tazobactam 0% (0-0%) and ceftriaxone 47% (95% CI 29-65%). Tetracycline had a WPR 20% (95% CI 14-27%) and meropenem showed 0% (95% CI 0-1%); resistance to fidaxomicin was reported in one isolate (0.08%).

Conclusion: Resistance to metronidazole, vancomycin, fidaxomicin, meropenem, and piperacillin/tazobactam is reported rarely. From the alternative CDI drug treatments, tigecycline had a lower resistance rate than rifampin. The high-risk antimicrobials for CDI development showed a high level of resistance, the highest was seen in the second generation of fluoroquinolones and clindamycin; amoxicillin/clavulanate showed almost no resistance. Tetracycline resistance was present in one-fifth of human clinical C. difficile isolates.

Keywords: Antimicrobial resistance; Clostridioides difficile; Meta-analysis; Metronidazole; Vancomycin.

Conflict of interest statement

The authors report no conflicts of interest in this work.

To review this Abstract in its entirety please click on the following link to be redirected.  Thank you.

https://pubmed.ncbi.nlm.nih.gov/32977835/