Tag Archives: 2016 Early Diagnosis Prevention and Treatment of Clostridium difficile

David Kirk and Ben Bradley Explain the Gut Microbiome and Clostridium difficile

It has access to the largest surface area of the body, alters drugs before they even enter the blood stream and could be a potent medicinal weapon… yet there is much we still don’t understand about the microbiome.

Here David Kirk and Ben Bradley tell us about their attempts to heal us from within

We are not alone. We are inhabited by hundreds of species of microbes, which represent millions of genes. Together, these microscopic organisms – bacteria, fungi, archaea and viruses ­– and their collective genomes make up the microbiome.

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

https://www.labnews.co.uk/interviews/guestbook/therapeutics-live-21-05-2018/

In the gut, microbes break down otherwise indigestible dietary fibres and release nutrients, such as B-vitamins and short chain fatty acids, which can be absorbed by the intestines. They secrete other small molecules or peptides which interact with the body via the bloodstream and immune system. The majority of these have yet to be identified and characterised. In addition, commensal microbes deter opportunistic pathogens from invading the competitive niche of the intestinal tract.

LBPs are a recent concept and have their origins in a novel treatment for C. difficile infection: the faecal microbiota transplant… this is exactly what you think it is

The disruption of the microbiome, termed dysbiosis, is associated with an ever-growing list of conditions. Obesity and metabolic syndrome, for instance, are associated with a microbiome less diverse than that of a healthy individual. Inflammatory bowel disease (IBD) and colorectal cancer are associated with a decrease in butyrate-producing bacteria like Clostridia, and an increase in Enterobacteriaceae and Bacilli.

An air of scepticism comes with the phrase “associated”. Microbiome research is still a developing field, and the presence or absence of a single species or genus cannot be directly blamed for conditions like obesity or IBD in all patients. The complex interplay between host and microbiome depends as much on the host’s genetic susceptibility and environment as on the dysbiosis or lack of diversity in the microbiome. The million dollar question remains: What exactly constitutes a ‘healthy microbiome’?

A powerful tool
The microbiome is adaptive and changes in response to diet, environment and disease. It has become increasingly clear that many drugs interact with the microbiome, with some requiring microbiota derived enzymes for activation and others being rendered non-functional or even toxic via microbiota dependant conversion. As research in host-microbe interaction continues, more accurate relationships between the microbiome and human illness will be uncovered.

The gut microbiome presents an interesting medicinal target in itself. It interacts directly with one of the largest surface areas of the body. Therefore it has easy access to the bloodstream through diffusion of nutrients and small molecules, and via a mucosal layer rich in multiple cell types of the adaptive and innate immune systems. Due to the powerful delivering capacity of the gut, most microbial-based treatments in development aim to add to the microbiome rather than take away from it.

Microbial therapies using living organisms are known as live biotherapeutic products (LBPs). LBPs are a recent concept and have their origins in a novel treatment for C. difficile infection (CDI): the faecal microbiota transplant.

This is exactly what you think it is.

CDI occurs when the gut microbiome is wiped out by antibiotic use and becomes infected by C. difficile, an organism that is normally unable to compete against the natural microbiota. This illness may recur in spite of further antibiotic treatments, and can be fatal. The most effective treatment, in extreme cases, is a faecal transplant into the infected recipient. Transplanted microbes thrive and outcompete C. difficile, effectively reversing the infection in over 90% of cases. But due to the uncertainty of what constitutes a ‘healthy microbiome’, a faecal transplant cannot be considered a cure-all for dysbiosis-associated illness.

Daunting clinical trials
This “unknown” of host-microbe interaction sparked the need to develop defined microbiome therapies. Naturally, CDI was one of the first targets for a defined treatment. Several companies are developing and trialling defined cocktails of bacteria known to safely inhabit the gut with the goal of outcompeting C. difficile with Seres Therapeutics and Rebiotix entering phase 3 trials in 2018.

CHAIN Biotech is developing technology to deliver therapeutics to the gut microbiome using engineered Clostridium, a spore forming bacterium, and have a lead candidate targeting IBD. IBD is a collection of inflammatory diseases of the gut, commonly treated with steroid injections which cause numerous unpleasant side effects. Our approach is to deliver an LBP directly to the gut, where it can produce an anti-inflammatory in situ. We also make use of this species’ natural ability to produce spores, which survive the acidic environment of the stomach and germinates into therapeutic-producing cells only in the anaerobic environment of the lower intestine.

This elementary approach – adding one organism with a safe history of use in the human gut, and having it produce one novel product – minimizes the risk of disruption to the microbiome and delivers the treatment directly to the affected area. The next stages, taking LBPs to clinical trial, are daunting. A lot of unknowns exist around the human gut microbiome and these kinds of treatments. Few microbiome companies have LBPs in late-stage clinical trial, but those that do give hope to both patients and us that LBPs will someday heal us from within.

Clostridium difficile (C. diff. ) Review: Early Diagnosis, Prevention, and Treatment

C. difficile Review: Early Diagnosis, Prevention, and Treatment

March 2016

NewsSpeaker

An update on the 2011 comparative effectiveness review on the early diagnosis, prevention, and treatment of Clostridium difficile was released to aid healthcare professionals, patients, policymakers, and others in well-informed decision-making.Researchers aimed to highlight the differences in accuracy of diagnostic tests and the effects of interventions to prevent and treat C. diff infection (CDI) in adults. Data was analyzed from searches in Medline, the Cochrane Clinical Trials Registry, and Embase from 2010–April 2015 as well as referenced studies and recent systematic reviews.Studies for inclusion looked at sensitivity and specificity for diagnostic tests in at-risk patients for CDI. Randomized controlled studies or high-quality cohort studies that evaluated adults with CDI or suspected CDI for treatment interventions were included. A total of 37 diagnostic studies and 56 prevention or treatment intervention studies were included for the review update.

RELATED: 6 Antibiotic-Resistant Threats Examined in CDC’s New Superbug Report

High-strength evidence indicated that nucleic amplification tests were sensitive and specific for CDI when cultures were used as the reference standard. High-strength evidence also showed that in treating CDI, vancomycin was more effective than metronidazole and the effect did not vary by severity (moderate-strength).

Fidaxomicin remained noninferior to vancomycin for initial CDI cure (moderate-strength) but proved superior in the prevention of recurrent CDI (high-strength).

Low-strength evidence suggested that fecal microbiota transplantation (FMT) may exert a significant effect on reducing recurrent CDI. In addition, lactobaccilus strains and multiorganism probiotic can also reduce recurrent CDI. Saccharomyces boulardii, however, did not prove more effective than placebo in the prevention of recurrent CDI.

The review was prepared by the Minnesota Evidence-based Practice Center for the Agency for Healthcare Research and Quality of the U.S. Department of Health and Human Services.

 

To access the .pdf report format please click on the link below:

https://www.effectivehealthcare.ahrq.gov/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productID=2208

 

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

http://www.empr.com/news/updated-review-includes-new-c-diff-diagnosis-treatment-guidance/article/486399/