Category Archives: C. diff. Research & Development

Researchers From Loyola Medicine Retrospectively Studied 100 Vancomycin Taper and Pulse Treatment Patients Treated For Recurrent C. difficile Infection

A tapered and pulsed regimen with vancomycin — with diligent follow-up — can achieve significant cure rates in recurrent Clostridium difficile (C. difficile) infected patients, according to a new study.

Researchers from Loyola Medicine retrospectively studied 100 vancomycin taper and pulse treatment patients treated for recurrent C. difficile infection between January 1, 2009 and December 31, 2014. Their clinic, the study authors wrote, has been a referral center for the infection for the past decade.

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

http://www.mdmag.com/medical-news/pulsed-and-tapered-vancomycin-likely-route-to-recurrent-clostridium-difficile-cure

However, despite the guidelines for treatment of recurrent C. difficile infection being not too different than recurrent episodes – except for the use of vancomycin when the case is severe – there have not been many studies on this vancomycin taper and pulsed dosing. 

The researchers observed that after a referral, the confirmed recurrent C. difficile patients were treated with a vancomycin taper and pulse regimen: a taper of vancomycin to once-daily, followed by alternate day dosing; or once-daily followed by alternate day dosing; followed by every third day, for at least 2 weeks. After this regimen, all patients had 90-day follow-up documentation.

On average, the patients in the clinic were on their third C. difficile diarrhea episode. Half of the patients had also received a standard course of vancomycin, while another third had received some type of vancomycin taper regimen, the researchers said.

Despite the fact that many of these patients were a “treatment experienced” population, 75% of the patients who received a supervised vancomycin taper and pulsed regimen achieved a cure,  study author Stuart Johnson  MD, . He added that the results were further improved for patients who received the expended pulse phase: 81% achieved a cure.

“The findings were not unexpected to us, but I think that many clinicians will be surprised how well a deliberate, prolonged vancomycin taper and pulse regimen – with careful follow up – works,” Johnson said.

There were no significant differences among the patients in terms of gender, age, concomitant antibiotics, proton pump inhibitor use, histamine receptor-2 blocker use, or patients with a regimen greater than 10 weeks in length, the researchers continued.

The researchers added that their finding of improved cure rates with alternate-day dosing plus every third day dosing over strictly alternate-day dosing is consistent with the hypothesis that pulsed dosing can promote a cyclical decrease in spore burden, they wrote. This can also permit the resetting of normal microbiota in the gut.

Johnson concluded that the clinical implications of the study show most recurrent C. difficile patients do not need fecal microbiota transplant (FMT).

“FMT has received an enormous amount of press and this procedure is now widely available throughout the US,” Johnson said. “FMT is attractive because it addresses one of the primary mechanisms involved with recurrent C. difficile infection, a marked disruption of the resident bacteria that populate the intestine and provide an important host defense against C. difficile.

Although physicians screen donor feces for “known pathogens,” not all is known of the potential complications to come from FMT, Johnson said.

“In addition, it appears that efficacy with a carefully supervised vancomycin taper and pulse regimen compare to that achieved with FMT,” Johnson said.

The study, “Vancomycin Taper and Pulsed Regimen with careful Follow up for Patients with Recurrent Clostridium difficile Infection,” was published in the journal Clinical Infectious Diseases.

Norman B. Javitt, M.D. Is Welcomed As a Member Of the C Diff Foundation, R & D Committee

We are pleased to welcome
Norman B. Javitt, M.D. to the
C Diff Foundation.

Dr. Javitt has an extensive professional career in health care.  New York University Medical Center: Instructor, then Assistant Professor Medicine where his career was devoted mostly to research in liver disease, specifically in inborn errors of cholesterol metabolism affecting newborns, and to teaching medical students.

Cornell University Medical School-New York Hospital:  Associate Professor of Medicine, then Professor of medicine and Chief, Division of Gastroenterology the research program continued to grow, attracting many fellows from all over the world.  Also provided care for private patients, both children and adults, with difficult liver problems.

New York University Medical Center:  Professor of Medicine and of Pediatrics, Division chairman Hepatic Diseases April, Research professor 2015-presnt.  At NYUMC Dr. Javitt has been focusing on C. difficile research  and teaching medical students and house staff.  His research interest has also expand to many areas of cholesterol synthesis and metabolism other than just liver disease.

Dr. Javitt has published research papers in age-related macular degeneration, in vitro fertilization, and Alzheimer’s disease.  He has also published more than 150 research papers, in addition to several books and review articles, and presented work at numerous professional meetings and symposia throughout the world.  His work has been supported by the National Institutes of Health, by private foundations and Pharmaceutical companies.  Dr. Javitt is welcomed by fellow researchers in the Research and Development Committee Chaired by Professor Simon M. Cutting, Ph.D…

C. diff. May Carry Risks in Preoperative and Postoperative Patients

 

There are risks for acquiring a C. difficile infection (CDI).

The risks range from the overuse of Antibiotics, Immunosuppressed patients, prolonged hospital stays, being a patient in a long-term care facility, and for the senior population.

There may also be a risk for the surgical patients and the following study explains the study and the results:

To read the article in its entirety please click on the following link: https://cdifffoundation.wordpress.com/wp-admin/post-new.php

A lengthy study of four surgical specialties has determined that Clostridium difficile infection (CDI) is a major risk factor for postoperative patients, although incidences varied.

Although it has been shown that CDI is associated with increased cost, morbidity and mortality in patients after surgery, this is the first to examine C. difficile rates across multiple surgical specialties (Infect Control Hosp Epidemiol 2017:1-4. doi: 10.1017/ice.2017.158).

“This study has great importance as the landscape of repayment for elective surgical procedures changes,” said the study’s lead author, James Bernatz, MD, a surgeon with the Department of Orthopedics and Rehabilitative Medicine at University of Wisconsin Hospital and Clinics, in Madison. “With more surgeries being reimbursed as bundled payments, hospitals are pressured to limit costs. As C. diff infection has been found to increase length of stay by one week and double the cost of care, it is clearly a postoperative complication to be avoided.”

Dr. Bernatz and his colleagues conducted the study at a 592-bed tertiary care academic center. They used the hospital’s quality improvement database to review admissions to the orthopedic surgery, neurosurgery, trauma surgery and general surgery units from January 2014 through July 2016. Those patients who underwent an inpatient surgical procedure, and did not meet the exclusion criteria, were surveyed.

Case patients were defined as those who underwent an inpatient procedure and subsequently developed a health care–associated CDI, which was defined as a positive polymerase chain reaction (PCR) test result for C. difficile toxin gene recorded more than 72 hours after admission and within 12 weeks of discharge.

They found 52 cases of CDI among 11,310 surgical admissions to four hospital units: general surgery, neurology, orthopedics and trauma. In all 52 cases, patients had a PCR-positive test result more than 72 hours after admission and within 12 weeks of discharge, making the incidence rate 0.80 cases per 1,000 patient-days. The trauma unit had the highest rate at 9.5 CDI cases per 1,000 admissions (11 cases over 1.160 admissions during the study period). General surgery had 30 cases among 3,447 admissions for a rate of 8.7; orthopedics had six cases among 4,339 admissions for a rate of 1.4; and neurology had five cases among 2,364 admissions for a rate of 2.1.

A number of risk factors were surveyed, including the use of antibiotics.

Regarding antibiotic use, the researchers found that the odds of CDI increased 3.34-fold when the perioperative antibiotic is continued more than 24 hours after surgery, outside of the perioperative window. Antibiotic use, other than the perioperative antibiotic, while in the hospital also was associated with 2.2 times greater odds of CDI. And exposure to antibiotics as long as six months before surgery increases the odds of CDI more than threefold.

“Although the surgeon cannot necessarily control the antibiotics prescribed to their patients in the year leading up to surgery, they can control antibiotic administration in the perioperative and postoperative period,” Dr. Bernatz said. “Antibiotics should be limited to one prophylactic preoperative dose, unless 24 hours of antibiotics are indicated. In the immediate postoperative period, antibiotics should be used judiciously.”

Other significant risk factors included number of hospital admissions in the past year and proton pump inhibitor or histamine type 2 receptor blocker use in the previous six months. “Previous studies have shown a correlation between CDI and hospital admission in the previous 3 months,” the researchers wrote. “Our study reports that this association extends to 12 months. We found that the number of hospital admissions in the past year increases the odds of CDI by 133% for each admission.”

A higher American Society of Anesthesiologists (ASA) physical status classification also was a significant risk factor for CDI; ASA IV or V patients were 15 times more likely to develop CDI than those with ASA class I or II disease, according to the researchers.

Dr. Bernatz said additional research is needed to further reveal these links. “Other studies could examine the rate of C. diff infection between operations within one subspecialty to determine if certain operative variables or patient characteristics affect the postoperative risk of C. diff infection,” he said.

The Latest Developments in C. diff Research and Treatment

 

 

 

 

 

The Program Podcast is Now Available —

Listen at your leisure as our guest, Dr Mary Beth Dorr, PhD, Clinical Director, Clinical Research, Infectious Diseases, and he product development team lead for bezlotoxumab, Merck & Co., Inc.  provided us with an overview of a C. diff. infection, the challenges of recurrence, the latest clinical research overview, current treatment landscape, and pending new C. diff infection treatment guidelines from the Infectious Diseases Society of America (IDSA) that are anticipated to be released fall of 2017.

Click on the C. diff. Spores and More Logo to be connected to the podcast

C. diff. Infection (CDI) In Hospitalized Adults with Inflammatory Bowel Disease (IBD)

 

The incidence and outcomes from Clostridium difficile infection in hospitalized adults with inflammatory bowel disease.

 Abstract
OBJECTIVES:

Clostridium difficile infection (CDI) may worsen outcomes in patients with inflammatory bowel disease (IBD), but large database-driven studies have conflicting results. The study objective is to analyze clinical features and outcomes in patients with CDI and IBD using the National Hospital Discharge Survey (NHDS) database from 2005 to 2009.

MATERIALS AND METHODS:

NHDS collects the clinical information on patients dismissed from non-Federal short-stay United States hospitals. CDI and IBD patients were identified using ICD-9 codes. Demographics, diagnoses, procedures, length of stay (LOS) and dismissal information were abstracted.

RESULTS:

Of an estimated 162 million hospitalizations; 5.62 × 105 were for IBD (0.35%); 53.2% were female. CDI developed in 3.7% of hospitalized IBD patients as compared to 0.78% of all adults (OR, 3.9; 95% CI, 3.3-4.6; p < .0001). African-Americans with IBD had a higher likelihood of CDI compared to Caucasians with IBD (OR, 1.67; 95% CI, 1.59-1.75; p < .0001). After adjusting for age, sex and comorbidities, IBD patients with CDI had a longer LOS (mean difference 1 day, p < .0001), higher all-cause, in-hospital mortality (adjusted OR, 4.5; 95% CI, 4.2-4.9; p < .0001), and a higher risk of dismissal to a care facility (adjusted OR, 2.3; 95% CI, 2.2-2.4; p < .0001).

CONCLUSIONS:

CDI in IBD patients prolonged hospitalization and increased in-hospital mortality and likelihood of dismissal to a care-facility as compared to IBD patients without CDI. CDI was more common among African-American IBD patients compared to IBD patients of other races.

 

Resource:

https://www.ncbi.nlm.nih.gov/pubmed/28782372?dopt=Abstract&utm_source=dlvr.it&utm_medium=twitter

First Patient Is Enrolled In Rebiotix Phase 3 Clinical Trial of RBX2660 For the Prevention of Recurrent C. difficile Infection

REBIOTIX

 

Phase 3 Clinical Trial of RBX2660 for the Prevention of

Recurrent Clostridium difficile Infection

Phase 3 Initiation Advances Development of Lead Microbiome-based Drug, RBX2660, Following Completion of Three Separate Phase 2 Trials

Rebiotix Inc., a clinical-stage microbiome company focused on harnessing the power of the human microbiome to treat challenging diseases, announced today that it has enrolled the first patient in a Phase 3 clinical trial of RBX2660 for the prevention of recurrent Clostridium difficile (C. diff) infection.

RBX2660 is Rebiotix’s most clinically advanced drug product developed from the company’s Microbiota Restoration Therapy™ (MRT) platform. MRT is a standardized, stabilized drug technology that is designed to deliver a broad consortium of spore and non-spore forming microbes into a patient’s intestinal tract to restore a dysbiotic gut to a healthier state.

The randomized, double-blind, placebo-controlled Phase 3 clinical trial will evaluate the efficacy and safety of RBX2660 for the prevention of recurrent Clostridium difficile (C. diff) infection. The primary endpoint of the trial compares the proportion of subjects with treatment success following a blinded treatment with RBX2660 compared to the blinded placebo arm. Treatment success is defined as preventing recurrent C. diff infection for eight weeks. The multicenter Phase 3 clinical trial of RBX2660 will be conducted in the United States and Canada and is designed to support a Biologics License Application (BLA) with the U.S. Food and Drug Administration (FDA).

“Patients with debilitating, recurrent C. diff need solutions. We plan to continue our strong momentum generated by our Phase 2 results in this Phase 3 trial as we seek to advance RBX2660 toward registration and potential approval so patients have an option for this unmet medical need,” said Ms. Lee Jones, President and CEO of Rebiotix. “Initiating the Phase 3 clinical study of RBX2660 is a significant milestone for Rebiotix and showcases the potential of our Microbiota Restoration Therapy™ (MRT) platform to enable the development of microbiome-directed drug products.”

“It’s exciting to see RBX2660 begin a Phase 3 trial for recurrent C. diff infection,” said Dale Gerding, MD, MACP, FIDSA, Professor of Medicine at Loyola University Chicago and Chief Medical Officer of Rebiotix. “This disease is especially challenging to treat and having this microbial therapy available to physicians could dramatically change how we manage the vexing problem of recurrences of this leading healthcare-associated infection.”

RBX2660 is the first drug product in clinical study from the Microbiota Restoration Therapy (MRT) platform The initiation of the Phase 3 clinical trial follows a Phase 2 program that evaluated the safety and efficacy of RBX2660 for the prevention of recurrent C. diff infection. The Phase 2 program consisted of three separate Phase 2 studies, including a randomized, double-blind, placebo controlled Phase 2b trial. The drug has been tested in approximately 300 patients with many followed to 24 months post treatment. Rebiotix is also advancing RBX7455, a lyophilized, room-temperature stable, oral capsule formulation of its MRT technology in an investigator sponsored Phase 1 study

For more information on Rebiotix and its pipeline of human microbiome directed therapies, visit

www.rebiotix.com.

Researchers Find Key Role of Excess Calcium In the Gut In C. difficile infections (CDI)

New research shows, it can’t make this last, crucial move without enough of a humble nutrient: calcium.

And that new knowledge about Clostridium difficile (a bacterium also known as “C. diff“) may lead to better treatment for the most vulnerable patients.

The discovery, made in research laboratories at the University of Michigan Medical School and the U.S. Food and Drug Administration, is published in the online journal PLoS Pathogens.

It helps solve a key mystery about C. diff: What triggers it to germinate, or break its dormancy, from its hard spore form when it reaches the gut.

Though the findings were made in mice, not humans, the researchers say the crucial role of calcium may help explain another mystery: Why some hospital patients and nursing home residents have a much higher risk of contracting C. diff infections and the resulting diarrhea that carries its spores out of the body.

That group includes people whose guts are flooded with extra calcium because they’re taking certain medications or supplements, have low levels of Vitamin D in their blood or have gut diseases that keep them from absorbing calcium.

The new discovery shows that C. diff can recognize this extra calcium, along with a substance called bile salt produced in the liver, to trigger its awakening and the breaking of its shell.

Previous research had suggested it couldn’t do this without another key component, an amino acid called glycine. But the new findings show calcium and the bile salt called taurochlorate alone are enough. Mouse gut contents that were depleted of gut calcium had a 90 percent lower rate of C. diff spore germination.

“These spores are like armored seeds, and they can pass through the gut’s acidic environment intact,” says Philip Hanna, Ph.D., senior author of the new paper and a professor of microbiology and immunology at U-M. “Much of the spore’s own weight is made of calcium, but we’ve shown that calcium from the gut can work with bile salts to trigger the enzyme needed to activate the spore and start the germination process.”

Ironically, the researchers say, one way to use this new knowledge in human patients might be to add even more calcium to the system.

That could awaken all the dormant C. diff spores in a patient’s gut at once, and make them vulnerable to antibiotics that can only kill the germinated form. That could also prevent the transmission of more spores through diarrhea to the patient’s room. That could slow or stop the cycle of transmission that could threaten them or other patients in the future.

Hanna’s graduate student, Travis Kochan, made a key observation that led to the discovery. He noted that the fluid “growth medium” that the researchers typically grow C. diff in for their studies had calcium in it. He realized this could artificially alter the results of their experiments about what caused C. diff spores to germinate.

So, he used a chemical to remove the calcium while leaving all the other nutrients that                  keep C. diff growing. The result: no new spore germination happened in the calcium-free growth medium.

FDA’s Center for Biologics Evaluation and Research conducted further research in laboratory dishes and in the guts of mice. FDA’s Paul Carlson, Ph.D., a former U-M research fellow, and fellow FDA scientists in his laboratory found that C. diff spores that were mutated so that glycine couldn’t act on them could still germinate and colonize mice. This suggested that calcium, and not glycine, was critical for this process.

Both mutant and regular forms of the bacteria could still activate an enzyme inside the C. diff spore that led the bacteria to start dissolving their hard shell. This released the store of calcium that the spore had been harboring inside itself, and increases the local level of the nutrient even further.

“These spores don’t want to germinate in the wrong place,” says Kochan, whose grandfather suffered from a severe C. diff infection which ultimately led to his death. “C. diff spores have specialized to germinate in the gut environment, especially in the environment of the small intestine, where calcium and the bile salt injection from the liver comes in.”

Hanna notes that the bile salt connection to C. diff spore germination was first discovered at U-M in 1982 by a team led by Ken Wilson, M.D.

Calcium and the gut

Certain ailments and treatments cause defects in calcium absorption, but are also risk factors for C. diff infections. For example, patients with vitamin D deficiency are five times more likely to get C. diff.

Medications aimed at calming acid reflux – such as proton pump inhibitors – and steroids can increase the amount of calcium in the gut. A Vitamin D deficiency can keep the body from reabsorbing calcium through the gut wall, allowing it to build up.

And people with inflammatory bowel diseases such as Crohn’s and colitis also have a harder time absorbing calcium from food through their gut walls.

Older adults are also often counseled to take calcium supplements to compensate for lower calcium levels and protect their bones from fracturing.

Hanna cautions that the new findings should not cause any patients to stop taking their medications or doctor-recommended supplements, or to start taking new ones. But he hopes to work with clinicians at U-M and beyond to test the new knowledge in a clinical setting. Meanwhile, he and Kochan and their FDA and U-M colleagues will continue to study C. diff germination in mice and look for ways to block the enzymes crucial to spore germination.

 

To read the article in its entirety – please click on the following link to be re-directed:

http://www.news-medical.net/news/20170713/Scientists-reveal-key-role-of-excess-gut-calcium-in-C-diffc2a0infections.aspx?utm_source=dlvr.it&utm_medium=twitter