Author Archives: cdifffoundation

California Hemet Valley Medical Center Adds UV Technology to Enhance Patient Safety

Hemet Valley Medical Center has implemented innovative ultraviolet technology with the addition of the Clorox Healthcare® Optimum-UV® System. The system helps remove harmful bacteria and pathogens that can jeopardize health, providing patients, visitors and staff with an additional layer of safety and protection.

Researchers at Boston-based Massachusetts General Hospital, Ann Arbor-based University of Michigan and Cambridge-based Massachusetts Institute of Technology Are Developing Institution-Specific Models That Predict Patient’s Risk Of Acquiring C.diff. Infections

Researchers at Boston-based Massachusetts General Hospital, Ann Arbor-based University of Michigan and Cambridge-based Massachusetts Institute of Technology are developing hospital-specific machine learning models that predict patients’ risk of Clostridium difficile infections much sooner than current diagnostic methods allow, according to a study published in Infection Control & Epidemiology.

“Despite substantial efforts to prevent C. diff infection and to institute early treatment upon diagnosis, rates of infection continue to increase,” co-senior study author Erica Shenoy, MD, PhD, said in a press release. “We need better tools to identify the highest risk patients so that we can target both prevention and treatment interventions to reduce further transmission and improve patient outcomes.”

The study authors noted most previous approaches to C. diff  infection risk were limited in usefulness since they were not hospital-specific and were developed as “one-size-fits-all” models that only included a few risk factors.

Therefore, to predict a patient’s C. diff risk throughout the course of their hospital stay, the researchers took a “big data” approach that analyzed the entire EHR. This method allows for institution-specific models that could be tailored to different patient populations, different EHR systems and factors specific to each facility. 

“When data are simply pooled into a one-size-fits-all model, institutional differences in patient populations, hospital layouts, testing and treatment protocols, or even in the way staff interact with the EHR can lead to differences in the underlying data distributions and ultimately to poor performance of such a model,” said co-senior study author Jenna Wiens, PhD. “To mitigate these issues, we take a hospital-specific approach, training a model tailored to each institution.”

With this machine learning-based model, the researchers looked at de-identified data, which included individual patient demographics and medical history, details on admissions and daily hospitalization, and the likelihood of C. diff exposure. The data was gathered from the EHRs of roughly 257,000 patients admitted to either MGH or to Michigan Medicine over two-year and six-year periods, respectively.

The models proved to be highly successful at predicting patients who would ultimately be diagnosed with C. diff. In half of these infected patients, accurate predictions could have been made at least five days before collecting diagnostic samples, which would allow hospitals to focus on antimicrobial interventions on the highest-risk patients.

The study’s risk prediction score could guide early screening for C. diff if validated in subsequent studies. For patients who receive an earlier diagnosis, treatment initiation could curb illness severity, and patients with confirmed C. diff could be isolated to prevent transmission to other patients.

The algorithm code is freely available here for hospital leaders to review and adapt for their institutions. However, Dr. Shenoy notes facilities looking to apply similar algorithms to their own institutions must assemble the appropriate local subject-matter experts and validate the performance of the models in their institutions.

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

https://www.beckershospitalreview.com/quality/how-machine-learning-models-are-rapidly-predicting-c-diff-infections.html

Researchers From North Carolina State University Find That Antibiotics Give C.diff. Nutrient-Rich Environment

Using a mouse model, researchers from North Carolina State University have found that antibiotic use creates a “banquet” for Clostridium difficile (C. diff), by altering the native gut bacteria that would normally compete with C. diff for nutrients. The findings could lead to the development of probiotics and other strategies for preventing C. diff infection.

C. diff is a harmful bacterium that can cause severe, recurrent and sometimes fatal infections in the gut. Although the bacteria are commonly found throughout our environment, C. diff infections primarily occur in patients who are taking, or who have recently finished taking, antibiotics.

“We know that antibiotics are major risk factors for C. diff infection because they alter the gut microbiota, or composition of bacteria in the gut, by eliminating the bacteria that are normally there,” says Casey Theriot, assistant professor of infectious disease at NC State and corresponding author of a paper describing the research. “Our latest work suggests that the microbiota may provide natural resistance to C. diff colonization by competing with C. diff for nutrients in that environment; specifically, for an amino acid called proline.”

Theriot and postdoctoral fellow Joshua Fletcher introduced C. diff to antibiotic-treated mice and monitored their gut environment at four intervals: 0, 12, 24, and 30 hours after introduction. They conducted metabolomic and RNA sequencing analysis of the gut contents and the C. diff at these time points to find out which nutrients the bacteria were “eating.” Metabolomics allowed the team to trace the abundance of the nutrients in the gut, and RNA analysis indicated which genes in the C. diff were active in metabolizing nutrients.

The researchers found that the amount of proline in the gut decreased as the population of C. diff increased. Additionally, the amount of a proline byproduct called 5-aminovalerate also increased, indicating that C. diff was metabolizing the proline. The RNA analysis further confirmed C. diff‘s use of proline, as genes related to proline metabolism in C. diff increased during the early stages of colonization, when proline was abundant.

“We’ve been able to show that in the absence of competition C. diff is metabolizing proline and other amino acids in the mouse model, using it as fuel to survive and thrive,” Theriot says. “Hopefully this information could lead to the development of better probiotics, or ‘good’ bacteria that can outcompete C. diff for nutrients in the gut. The ultimate goal is to control these bacteria in ways that don’t rely solely on antibiotics.”

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

https://www.sciencedaily.com/releases/2018/03/180328204122.htm

Rutgers University and International Scientists Have Determined the Molecular Target and Mechanism of the Antibacterial Drug fidaxomicin (Trade Name Dificid)

Fidaxomicin was approved in 2011 for treatment of the CDC “urgent threat” bacterial pathogen Clostridium difficile (C. diff) and currently is one of two front-line drugs for treatment of C. diff.

A team of Rutgers University and international scientists has determined the molecular target and mechanism of the antibacterial drug fidaxomicin (trade name Dificid).

Resource:  https://www.sciencedaily.com/releases/2018/03/180329141050.htm

Fidaxomicin also exhibits potent antibacterial activity against other CDC “serious threat” bacterial pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Staphylococcus aureus (VRSA), and the tuberculosis bacterium, Mycobacterium tuberculosis. However, the low solubility and low systemic bioavailability of fidaxomicin have precluded use of fidaxomicin for treatment of MRSA, VRSA, and tuberculosis.

To design next-generation fidaxomicin derivatives with improved clinical activity against C. diff and useful clinical activity against MRSA, VRSA, and tuberculosis, it is essential to know how the drug binds to and inhibits its molecular target, bacterial RNA polymerase, the enzyme responsible for bacterial RNA synthesis.

In a paper published in Molecular Cell today, the researchers report results of cryo-electron microscopy (cryo-EM) and single molecule spectroscopy analyses showing how fidaxomicin binds to and inhibits bacterial RNA polymerase.

The researchers report a cryo-EM structure of fidaxomicin bound to Mycobacterium tuberculosis RNA polymerase at 3.5 Å resolution. The structure shows that fidaxomicin binds at the base of the RNA polymerase “clamp,” a part of RNA polymerase that must swing open to allow RNA polymerase to bind to DNA and must swing closed to allow RNA polymerase to hold onto DNA. The structure further shows that fidaxomicin traps the RNA polymerase “clamp” in the open conformation.

The researchers also report results of single-molecule fluorescence spectroscopy experiments that confirm that fidaxomicin traps the RNA polymerase “clamp” in the open conformation and that define effects of fidaxomicin on the dynamics of clamp opening and closing.

The researchers show that fidaxomicin inhibits bacterial RNA polymerase through a binding site and mechanism that differ from those of rifamycins, another class of antibacterial drugs that target bacterial RNA polymerase. The finding that fidaxomicin inhibits bacterial RNA polymerase functions through a different, non-overlapping binding site and mechanism explains why fidaxomicin is able to kill bacterial pathogens resistant to rifamycins and why fidaxomicin is able to function additively when combined with rifamycins.

The new results enable rational, structure-based design of new, improved fidaxomicin derivatives with higher antibacterial potency, higher solubility, and higher systemic bioavailability. Based on the structure of fidaxomicin bound to its target, the researchers identified atoms of fidaxomicin that are not important for binding to the target and thus that can be modified without compromising the ability to bind to the target. The researchers then developed chemical procedures that allow selective attachment of new chemical groups at those atoms, including new chemical groups that can improve potency, solubility, or systemic bioavailability.

“The results set the stage for development of improved fidaxomicin derivatives, particularly improved fidaxomicin derivatives having the solubility and systemic bioavailability needed for treatment of systemic infections, such as MRSA and tuberculosis,” said Ebright, Board of Governors Professor of Chemistry and Chemical Biology and Laboratory Director at the Waksman Institute of Microbiology at Rutgers, who led the research.

In addition to Richard H. Ebright, the research team included Wei Lin, David Degen, Abhishek Mazumder, Dongye Wang, Yon W. Ebright, Richard Y. Ebright, Elena Sineva, Matthew Gigliotti, Aashish Srivastava, Sukhendu Mandal, Yi Jiang, Ruiheng Yin, and Dennis Thomas from Rutgers University; Kalyan Das from KU Leuven; Zhening Zhang and Edward Eng from the National Resource for Automated Molecular Microscopy and the Simons Electron Microscopy Center; Stefano Donadio from NAICONS Srl.; Haibo Zhang and Changsheng Zhang from the Chinese Academy of Sciences Guangzhou.

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

https://www.sciencedaily.com/releases/2018/03/180329141050.htm

C Diff Foundation ‘Making a Difference’ Award Presented to CutisPharma Inc.

The C Diff Foundation today announced that it presented CutisPharma, Inc., its “Making a Difference” award as a special recognition of the significant contribution that CutisPharma has made to the C.diff. Community: helping the advancement of C.diff. awareness as well as expanding treatment options for C.diff. patients.

C Diff Foundation

C Diff Foundation’s ‘Making a Difference’ Award Presented at CutisPharma’s Pre-Launch Celebration for Newly Approved C.diff. Drug FIRVANQ

(NEW PORT RICHEY, Fla.) — NEWS: The C Diff Foundation announced today that it presented CutisPharma, Inc., its “Making a Difference” award as a special recognition of the significant contribution that CutisPharma has made to the C.diff. Community: helping the advancement of C.diff. awareness as well as expanding treatment options for C.diff. patients.

The award was presented at CutisPharma’s celebration of its upcoming launch of FIRVANQ(TM), recently approved by the FDA for the treatment of Clostridium difficile associated diarrhea and enterocolitis caused by Staphylococcus aureus, including methicillin-resistant strains. Upon launch, FIRVANQ(TM) will be the only FDA-approved oral vancomycin solution treatment commercially available, improving patient access and reducing pharmacist burden by no longer having to compound oral liquid formulations.

“CutisPharma has been a committed partner of our Foundation and has furthered our mission to increase C.diff. awareness and support the research and development of new treatment options,” said Nancy C. Caralla, Foundress and Executive Director of the C Diff Foundation. “In recognition of CutisPharma’s efforts, we are pleased to grant them the ‘Making a Difference’ award at this special moment in the Company’s 20th anniversary year.”

“We are very grateful to receive such a special distinction from the C Diff Foundation,” said Neal I. Muni, MD, MSPH, and Chief Executive Officer of CutisPharma. “For 20 years, we have been committed to improving the lives of patients who are not well-served by existing therapies and would benefit from high-quality, cost-effective new treatment options. We greatly value our partnership with the C Diff Foundation and look forward to continuing to support their mission.”

In the USA: Nearly half a million Americans suffer from Clostridium difficile (C. diff.) infections in a single year according to a study released in 2015 by the Centers for Disease Control and Prevention (CDC). Approximately 29,000 patients died within 30 days of the initial diagnosis of C. difficile. Of those, about 15,000 deaths were estimated to be directly attributable to C. difficile infections making C. difficile a very important cause of infectious disease death in the United States.

About the C Diff Foundation:

The C Diff Foundation, a 501(c)(3)non-profit organization, established in 2012, is comprised of 100 percent volunteering professionals dedicated to supporting public health initiatives for C. difficile infection prevention, treatments, environmental safety, and support worldwide. For more information, visit: https://cdifffoundation.org/.

About CutisPharma:

CutisPharma, Inc., based in Wilmington, Mass., is privately held, specialty pharmaceutical company that has been the industry leader for 20 years in providing innovative solutions to pharmacists. CutisPharma’s FIRST(r) Unit-of-Use Compounding Kits have benefited millions of patients who are unable to swallow conventional oral dosage forms such as tablets and capsules and whose needs are not served by commercially available therapies. The Company’s first FDA-approved Kit, FIRVANQ(TM), will allow significantly broader patient access, convenience to pharmacists and patients alike by reducing the need for compounding, and serve as a potential cost-saving option to existing treatments. For more information, visit: https://cutispharma.com/.

 

Source:   https://enewschannels.com/c-diff-foundation-making-a-difference-award-presented-to-cutispharma-inc/

Immuron Announced First Patients Enrolled In Phase 1/2 (first-in-human) Clinical Trials For Immuron’s IMM-529 For Treatment of C.difficile Infections

The Australian biopharmaceutical company Immuron announced that the first patients have enrolled in phase 1/2 (first-in-human) clinical trials for Immuron’s IMM-529, an oral immunotherapeutic medication for treatment of Clostridium difficile infections (CDI).

As published in MD Mag February 16, 2018

To review this publication in its entirety please click on the following link to be redirected:

http://www.mdmag.com/medical-news/a-powerful-new-weapon-in-the-fight-against-clostridium-difficile-infection

According to Dan Peres, MD, senior vice president and head of medical development at Immuron, IMM-529 “has shown promise in successfully treating Clostridium-difficile” through its “unique delivery of antibodies.”

If the trials are successful, IMM-529 may be a powerful new weapon in the global fight against CDI. Peres reports that IMM-529 that has been effective in preclinical studies for prophylactic use, treatment of disease, and the prevention of recurrence in relation to CDI, and that the company is excited to enroll the first patients.

The placebo-controlled study to test the safety, tolerability and efficacy of IMM-529 will take place at Hadassah Medical Center in Jerusalem and include 60 CDI diagnosed patients in the 28 day study.

Patients enrolled in the study, led by Yoseph Caraco, MD, head of the clinical pharmacology unit at Hadassah Medical Center, will receive IMM-529 or a placebo 3 times a day during the 28 -day trial period, and be monitored for 2 additional months, determining any recurrence of the disease.

In a statement, Caraco said that he was optimistic about IMM-529 based on pre-clinical trial results and that IMM-529 could “be the answer we’re all looking for” when it comes to treatment of CDI.

IMM-529 targets CDI in 2 ways: by neutralizing toxin B (TcdB), a cytotoxin responsible for inflammation and diarrhea that characterizes CDI, and by binding Clostridium difficile spores and vegetative cells preventing further colonization. Caraco reported that IMM-529 approaches CDI by “targeting the main virulence factors of the disease with only minor disturbance to the natural biome” which could be extremely valuable in treating CDI.

In the earlier pre-clinical proof-of-concept study by led by Dena Lyras, MD, PhD with Monash University in Melbourne, Australia, IMM-529 was shown to be 80% effective in both the treatment of and prevention of CDI without the use of antibiotics.

In a December 2015 statement from Immuron, Lyras stated that she was “excited by the potential of these therapeutics in treating patients with both the acute and the relapse phase, of the disease.”

According to data supplied by the American Gastroenterological Association, approximately 500,000 people in the US are diagnosed with CDI each year, and CDI-associated deaths range from 14,000 to 30,000 per year.

In the European Union, according to a 2016 study led by Alessandro Cassini, MD, with the European Centre for Disease Prevention and Control in Stockholm, Sweden, more than 150,000 cases of hospital-acquired CDI infections (134,053–173,089; 95% CI) occur each year.

According to Immuron, the cost of CDI globally (calculated by CIDRAP, the Center for Infectious Disease and Policy at the University of Minnesota) is an estimated annual economic burden of more than $10 billion and increases in hypervirulent and antibiotic-resistant strains have led to CDI becoming a major medical concern.

Caraco stated that CDI poses “a growing risk amongst a greater population of patients, including those recently treated with antibiotics, the elderly, institutionalized and hospitalized.”

If IMM-529 is found to be safe and effective in clinical trials, it could prove a significant boon to the global fight against CDI at all 3 stages of the disease.

Rebiotix In Partnership With BioRankings® Develops Microbiome Health Index™ (MHI™) to Identify Indicators for Microbiome Restoration

Rebiotix Inc., a clinical-stage microbiome company focused on harnessing the power of the human microbiome to treat debilitating diseases, announced  on February 12, 2018 — the development of the Microbiome Health Index™ (MHI™) to provide the microbiome research community with a standardized metric to quantify the rehabilitation of the human microbiome.

MHI was established in partnership with data analytics firm, BioRankings®, to enable a non-biased comparison of the efficacy of microbiome-based therapeutics.

New MHI data will be presented at the 28th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2018) in April.

“In developing the Microbiome Health Index, our aim is to provide an objective, universal tool to measure the restoration of a dysbiotic microbiome across different trial designs, sequencing methods and across multiple drug technologies,” stated Ken F. Blount, Ph.D., Chief Scientific Officer of Rebiotix.  “Initial analyses using MHI in Clostridium difficile (C. diff) infections have demonstrated its significant potential to quantify and differentiate dysbiotic from healthier microbiomes.  As presented at ACG2017, MHI was able to quantify the relationship between four key bacterial classes into a single metric that can distinguish patients with dysbiosis resulting from C. diff. From this, we were able to gain valuable insight into the mechanism of action by which Rebiotix’s Phase 3 microbiota drug, RBX2660, is able to rehabilitate a dysbiotic microbiome to a healthier state.”

Blount continued, “MHI is now being employed to analyze microbiome profile data gathered in the ongoing Phase 1 clinical trial of RBX7455, Rebiotix’s lyophilized, non-frozen oral capsule formulation. The intent with this research is to further strengthen and refine MHI and confirm the RBX2660 analysis. Additionally, we will look to utilize MHI in new diseases states being studied.”

Bill Shannon, Ph.D., MBA, Co-Founder and Managing Partner of Analytics at BioRankings said, “The human microbiome is a new frontier where very little analytical methodology or rigorous statistical methods have been developed specifically for this type of data.  Analytical tools such as MHI will be critical to advance translational clinical microbiome research, and we are emboldened by the MHI data that have been reported and continuing to be collected.  Our vision is for MHI to become a standard measure for microbiome research, potentially serving as a validated endpoint for clinical trials and providing both a predictive measure and actionable data.”

MHI provides a unidimensional expression of changes in four taxonomic classes known to have relevance to microbiome health and colonization resistance – Bacteriodia, Clostridia, Gammaproteobacteria and Bacilli.

Utilizing microbiome profiles of patients from the PUNCH CD2 Phase 2b trial of RBX2660, researchers determined that MHI can effectively distinguish patients with dysbiosis from healthier patients, as defined by the RBX2660 product profile and the Human Microbiome Project.  Notably following RBX2660 treatment, MHI significantly increased as early as seven days in responders compared to baseline and continued to increase at day 30 and day 60.

About BioRankings®

BioRankings is a contract analytics firm that works with clients to extract actionable results from their data. Their business philosophy centers on providing clients and partners with the methods, software, and support they need to make full use of their data and design accurate, cost-efficient experiments.  For more information on BioRankings, please visit http://www.biorankings.com.

About Rebiotix Inc.

Rebiotix Inc. is a late-stage clinical microbiome company focused on harnessing the power of the human microbiome to revolutionize the treatment of challenging diseases. Rebiotix possesses a deep and diverse clinical pipeline, with its lead drug candidate, RBX2660, in Phase 3 clinical development for the prevention of recurrent Clostridium difficile (C. diff) infection.  RBX2660 has been granted Fast Track status, Orphan Drug and Breakthrough Therapy designation from the FDA for its potential to prevent recurrent C. diff. infection. Rebiotix’s clinical pipeline also features RBX7455, a lyophilized, non-frozen, oral capsule formulation, which is currently the subject of an investigator-sponsored Phase 1 trial for the prevention of recurrent C. diff. infection.  In addition, Rebiotix is targeting several other disease states with drug products built on its pioneering Microbiota Restoration Therapy™ (MRT™) platform.  MRT is a standardized, stabilized drug technology that is designed to rehabilitate the human microbiome by delivering a broad consortium of live microbes into a patient’s intestinal tract via a ready-to-use and easy-to-administer format. For more information on Rebiotix and its pipeline of human microbiome-directed therapies, visit http://www.rebiotix.com.