Tag Archives: gut microbiome

Acurx Pharmaceuticals LLC Lead Product ACX-362E Has Successfully Completed First-In-Man Phase I Clinical Trial To Treat C.difficile Infection

 Acurx Pharmaceuticals, LLC is, a privately-held, clinical stage, biopharmaceutical company developing new antibiotics for difficult-to-treat bacterial infections, announced that its lead product candidate, ACX-362E, has successfully completed the 32-subject, double-blinded, placebo-controlled, single-ascending dose portion of this first-in-man Phase 1 clinical trial. ACX-362E is a novel, oral antibacterial agent for the treatment of Clostridioides difficile infection (CDI), an acute, serious, potentially life-threatening, intestinal infection.

ACX-362E is Acurx’s lead compound in a pipeline of molecules that target a previously unexploited mechanism of action, namely, inhibition of the bacterial enzyme DNA polymerase IIIC (pol IIIC).  Pol IIIC is required for DNA replication of many Gram-positive pathogens, including not only Clostridioides but also Enterococcus, Staphylococcus, and Streptococcus.  Although the trial data remain blinded, ongoing monitoring of the data show dose levels up to 600mg have been generally well tolerated. Blood levels of ACX-362E show low systemic exposure, as predicted by prior animal studies and desirable in treating CDI.  Additionally, fecal concentrations of ACX-362E at higher dose levels have exceeded the concentrations known to inhibit C. difficile by several hundred-fold.

“We are very encouraged by these initial data which corroborate our nonclinical findings, showing that at well-tolerated doses ACX-362E reaches concentrations in the colon that are projected to be therapeutically relevant for patients with CDI” said Robert J. DeLuccia, Co-Founder and Managing Partner of Acurx.  “This gives us confidence that the ongoing multiple-dose segment of the trial will provide data to guide selection of our Phase 2 dose and improve the probability of success and timeline efficiency of our Phase 2 clinical trial planned to start later this year.”

Dr. Kevin Garey, Professor, University of Houston College of Pharmacy and the Principal Investigator for microbiomic aspects of the Phase 1 clinical trial said: “The emerging fecal concentration data are comparable to those observed with precedent products that have advanced to demonstrate clinical success. I look forward to the multiple-dose safety data and to the results of the microbiomic analyses that our laboratory is performing which will form a template for a new paradigm in microbiome studies associated with drug discovery and development of CDI-directed antibiotics.”

About the Phase 1 Clinical Trial
This Phase 1 trial, conducted in the U.S., is a double-blinded, placebo-controlled study to determine safety, tolerability, pharmacokinetics and fecal concentrations of ACX-362E in healthy volunteers.  It is being conducted in two parts; first, single ascending doses are administered to four cohorts of 8 subjects each, and second, multiple ascending doses are given that simulate the anticipated clinical treatment regimen. Safety information is analyzed through assessment of adverse events and other standard safety measures, while concentrations of ACX-362E are determined in both the blood and the feces, the latter being the critical site of drug delivery for treating CDI.  In addition, Acurx has partnered with the laboratory of Dr. Kevin Garey at the University of Houston to perform state-of-the-art microbiomic testing of gastrointestinal flora in trial subjects.

About ACX-362E, FDA QIDP and Fast Track Designation
FDA Fast Track Designation is a process designed to facilitate the development and expedite the regulatory pathway of new drugs to treat serious or life-threatening conditions and that fill a high unmet medical need. ACX-362E is a novel, first-in-class, orally-administered antibacterial.  It is the first of a novel class of DNA polymerase IIIC inhibitors under development by Acurx to treat bacterial infections. Acurx acquired ACX-362E from GLSynthesis, Inc. in February 2018.

ACX-362E is a Qualified Infectious Disease Product (QIDP) for the treatment of patients with Clostridium difficile infection (CDI).  Under QIDP designation, ACX-362E will now be eligible to benefit from certain incentives for the development of new antibiotics provided under the Generating Antibiotic Incentives Now Act (the GAIN Act). These incentives include Priority Review and eligibility for Fast Track status. Further, if ultimately approved by the FDA, ACX-362E is eligible for an additional five-year extension of Hatch-Waxman marketing exclusivity. ACX-362E is being developed as a targeted, narrow spectrum oral antibiotic for the treatment of patients with CDI.  Acurx anticipates completing the Phase 1 clinical trial in the second quarter of 2019 and is planning to advance ACX-362E into a Phase 2 clinical trial in the fourth quarter of 2019. The CDC (Centers for Disease Control & Prevention) has designated Clostridium difficile bacteria as an urgent threat highlighting the need for new antibiotics to treat CDI.

RESOURCE:  https://www.acurxpharma.com/news-media/press-releases/detail/8/acurx-announces-first-in-man-clinical-trial-data-of

 

 

Researchers Find Gut Microbes Linked to Depression

Mice experiments and small studies of people with depression have suggested the involvement of the gut microbiome in both behavior and depression, respectively. However, human research addressing how gut microorganisms might contribute to depression—in large samples and considering confounding factors that can affect the microbiota—is lacking.

A new study of two large groups of Europeans, led by Dr. Sara Vieira-Silva and Dr. Jeroen Raes from the Catholic University of Leuven (Belgium), has found new links between gut microbes and depression.

The researchers used 16S ribosomal ribonucleic acid (rRNA) gene sequencing to analyze the fecal microbiota of 1,054 Belgians enrolled in the Flemish Gut Flora Project, aimed at studying gut microbiome variation at population level. Furthermore, microbial taxa were correlated with the participants’ quality of life and incidence of depression, using a self-reported quality of life questionnaire and general practitioner-supplied diagnoses of the latter. The researchers also validated the associations in an independent cohort of 1,063 individuals from the Netherlands’ LifeLines DEEP (LLD) project.

Ten genus abundances were correlated with quality of life scores, including both mental and physical scores. Among these bacterial genera, Faecalibacterium, Coprococcus, Dialister, Butyrivibrio, Gemmiger, Fusicatenibacter and Prevotella were consistently associated with higher quality of life scores, whereas Parabacteroides, Streptococcus and Flavonifractor showed negative associations. After controlling for a wealth of confounding factors, the authors validated some of these associations in the LLD cohort.

The researchers found that Dialister and Coprococcus genera were reduced in people with depression, after taking into account antidepressant drugs as confounders. Furthermore, the authors described an association between enterotype distribution in relation to quality of life scores and diagnosis of depression in the Flemish cohort. For instance, a higher prevalence of Bacteroides enterotype 2 was linked to lower quality of life and depression.

Finally, the authors dug through metagenomic data to create a catalogue describing the gut microbiota’s ability to synthetize or degrade molecules that can cross-talk with the human nervous system. With this aim, Raes and colleagues assessed the distribution of 56 compounds that play an important role in proper nervous system function, which gut microbes either synthesize or metabolize, in human gut-associated microbial genomes (n=532).

Certain neuroactive compounds might explain the beneficial relationship between gut microbes and quality of life. The researchers found, for example, that GABA and tryptophan metabolism pathways were expressed in human gut-associated microorganisms.

Furthermore, some positive correlations were also observed between quality of life and the potential ability of the gut microbiome to produce 3,4-dihydroxyphenyalcetic acid -a breakdown product of the neurotransmitter dopamine-, isovaleric acid and histamine. Of these, the association between 3,4-dihydroxyphenylacetic acid and quality of life was also replicated in the LLD cohort. As neurotransmitters and neuroactive compounds can also have an impact on bacterial growth, further research is needed to disentangle the contribution of microbe-derived neuroactive molecules to a person’s behavior.

This is the first approach to build a database for studying the gut microbiome’s neuroactive potential and it will help future research to interpret microbiome-gut-mental axis research in a clearer way, supporting the translation of such complex research from the bench to the clinic.

Although these new findings do not prove cause and effect due to the observational design of the study, this research contributes to mounting evidence about mechanisms by which the “microbiome-gut-brain axis” is involved in the development of depression. Further options to experimentally prove the association between the gut microbiota and depression might include rodent models and large studies with enough follow-up periods that explore the role of probiotics, prebiotics, a healthy diet and fecal microbiota transplantation for recovering microbiota, considering the confounding effects of microbiome covariates.

On the whole, this new study strengthens the link between gut bacteria and depression. This is a first step towards understanding how the gut microbiome and its metabolites might affect mood in humans

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

https://www.gutmicrobiotaforhealth.com/en/a-large-study-of-belgian-and-dutch-people-finds-new-associations-between-gut-microbes-and-depression/

Rebiotix Features Three Posters Highlighting RBX2660 Clinical and Microbiome Data at ID Week™ 2017 in San Diego, October 4th – 8th

Positive Topline Data from Open-Label Phase 2 Trial of RBX2660 in Recurrent Clostridium
difficile to be Presented for First Time

 

 

 

Rebiotix Inc., a clinical-stage microbiome company focused
on harnessing the power of the human microbiome to treat challenging diseases, today announced that three posters highlighting RBX2660 clinical and microbiome data will be featured at ID Week™ 2017 in San Diego, Oct. 4th to the 8th.

The posters describe clinical findings that highlight the key changes to
the human microbiome profiles of patients who received RBX2660, Rebotix’s Phase 3 drug candidate.

For the first time, researchers will discuss findings from the open-label Phase 2 trial of RBX2660 for the prevention of recurrent Clostridium difficile (C. diff.) infection. Data indicated that RBX2660 was well tolerated and achieved the primary efficacy endpoint of preventing C. diff. recurrence; patients treated with RBX2660 exhibited a treatment success rate of 78.8% compared with a historical control of 51.8% (p<0.0001, N=242). These results demonstrate a 55% reduction in recurrence for those patients treated with RBX2660 compared to the historical controls reflecting standard-of-care antibiotics today.

RBX2660 is currently being evaluated in a multinational Phase 3 clinical trial for the prevention of recurrent C. diff.  Researchers will also be presenting two posters on the microbiome analyses of the Phase 2B  randomized, placebo-controlled, double-blind clinical trial of RBX2660. The analyses, utilizing leading  edge genomic sequencing technology to measure the patient’s microbiome, provide measurable  evidence of RBX2660’s rehabilitative effect on human microbiome profiles of patients who were successfully treated with Rebiotix’s microbiota drug technology.

“The clinical potential of RBX2660 has been highlighted in multiple trials, including our recently
completed open-label Phase 2 study, and the data being presented at ID Week enables us to more fully understand RBX2660’s ability to rehabilitate a dysbiotic intestinal microbiome,” commented Lee Jones, president and CEO of Rebiotix. “These findings are important in that not only can we observe the clinical 2 effect of RB X2660, such as in the open-label Phase 2 study, but by analyzing the microbiota of RBX2660-treated patients, we can see how the microbiome changes in response to RBX2660 treatment and how those changes correlate to treatment success and to the microbiomes of healthy individuals.”

The first poster (#1863; to be presented Friday, Oct. 6th), titled RBX2660 is Safe, Superior to Antibiotic- Treated Controls for Preventing Recurrent Clostridium difficile, and May Rehabilitate Patient Microbiomes:  Open Label Trial Results, reported data from an open-label Phase 2 study of RBX2660 that included 242 subjects. Data from the study indicated that RBX2660’s efficacy in preventing recurrent Clostridium difficile infection (rCDI) was higher (78.8%) than CDI-free rates in the Historical Control Group (51.8%, p<0.0001). The reduction in recurrence of C. diff between these two arms is approximately 55%. Moreover, the safety profile of RBX2660 was consistent with results from previous clinical trials, and microbiota analysis suggested that RBX2660 may rehabilitate patient microbiota as RBX2660-treated subjects’ microbiomes were significantly altered compared to baseline and more closely resembled the RBX2660 microbiome profile than at baseline (p<0.05 by Dirichlet multinomial Wald-type pairwise hypothesis test).

The second poster (#1267; to be presented Saturday, Oct, 7th), titled Successful Response to
Microbiota-Based Drug RBX2660 in Patients with Recurrent Clostridium Difficile Infection is Associated with More Pronounced Alterations in Microbiome Profile, involved an analysis of 58 patients whose stool samples were collected in the randomized Phase 2B clinical trial to determine the effect of RBX2660 on rCDI patient microbiomes. 16s RNA sequencing analyses of patients’ microbiomes indicated that RBX2660 treatment shifted the relative microbiome densities, with taxa-specific increase in Bacteroidia, Clostridia, and decrease in Gamma-proteobacteria abundance. Importantly, a larger shift from baseline microbiome was seen in responders to RBX2600 compared to non-responders, and RBX2660 treatment appears to increase microbiome diversity.

 

The third poster (#1870; to be presented Saturday, Oct. 7th), titled Microbiome Profile is Distinct in Patients with Successful Response to Microbiota-Based Drug RBX2660 Relative to Placebo Responders involved a sub-analysis of 57 patients who participated in the randomized Phase 2B clinical trial of RBX2660. 16s rRNA sequencing analysis was used to compare the microbiome changes from baseline of patients classified as responders to RBX2660 vs placebo. Investigators determined that RBX2660 treatment for rCDI is associated with greater changes in patient microbiomes than placebo treatment. Notably, at 7, 30 and 60 days, microbiomes from RBX2660-treated patients had high Kullback-Leibler divergence from baseline and significantly different means from baseline (p<0.001). Further, active responders trended toward higher Bacteroides and lower Gamma-proteobacteria and Bacilli after treatment, both of which are characteristic of a healthier microbiome. According to the 3 researchers, these changes are consistent with the hypothesis that RBX2660 can restore a healthier microbiome in rCDI patients.

Rebiotix, Inc. funded all three studies.

For More Information About Rebiotix Please

Click On the Following Link:

http://www.rebiotix.com

SYN-004 (ribaxamase) For C. difficile Prevention Advances; U.S. Food and Drug Administration (FDA) Has Granted A Breakthrough Therapy Designation

On May 11, 2017 Synthetic Biologics, Inc. a late-stage clinical company developing therapeutics that preserve the microbiome to protect and restore the health of patients, announced that the U.S. Food and Drug Administration (FDA) has granted a Breakthrough Therapy Designation for SYN-004 (ribaxamase) for the prevention of Clostridium difficile infection.

SYN-004 (ribaxamase) is the Company’s first-in-class oral enzyme designed to protect the gut microbiome from disruption caused by certain intravenous (IV) beta-lactam antibiotics.

The Breakthrough Therapy Designation is based on data from the successful Phase 2b clinical trial of ribaxamase, which met its primary endpoint of significantly reducing CDI. FDA Breakthrough Therapy Designation is intended to expedite development and review timelines when preliminary clinical evidence indicates that a drug may demonstrate substantial improvement on one or more clinically significant endpoints over available therapies for serious or life threatening diseases. If approved by the FDA, SYN-004 (ribaxamase) would be the first available drug designed to prevent Clostridium difficile infection by protecting the gut microbiome from antibiotic-mediated dysbiosis.

“We are delighted by the FDA’s recognition of ribaxamase’s potential to prevent CDI, and the dire need to fill the current void of an approved intervention,” said Jeffrey Riley, President and Chief Executive Officer. “Following this announcement, we have been asked and anticipate requesting a Type-B multidisciplinary meeting with the Agency for a comprehensive discussion on the overarching, high-level drug development plan and pathway to licensure for ribaxamase. We look forward to working closely with the FDA throughout the development and review process and remain dedicated to bringing this potentially paradigm-shifting approach to antibiotic therapy to patients in critical need.”

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C. diff. Spores and More Global Broadcasting Network 

www.cdiffradio.com

Protecting the Gut Microbiome: A Paradigm Shift in Managing GI Disorders

Live Broadcast On Tuesday, May 16th Join us with our guest, Dr. Joseph Sliman, MD, MPH, Chief Medical Officer of Synthetic Biologics.  Dr. Sliman will be discussing  the protection of the natural gut microbiome from the unintended consequences of intravenous (IV) antibiotics which are excreted into the gut is expected to protect against opportunistic enteric infections. Synthetic Biologics is developing two microbiome-focused drug candidates in Phase 3 development including, SYN-004 (ribaxamase) which is designed to protect the gut microbiome by degrading certain IV beta-lactam antibiotics for the prevention of Clostridium difficile infection (CDI), pathogenic
overgrowth and the emergence of antimicrobial resistance, and SYN-010 which is intended to reduce the impact of methane producing organisms in the gut microbiome to treat an underlying cause of irritable bowel syndrome with constipation (IBS-C).

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To learn more about Synthetic Biologics, please click on the link provided below

.http://www.syntheticbiologics.com/about/overview

Source:  Synthetic Biologics

Synthetic Biologics – Protecting the Gut Microbiome: A Paradigm Shift in Managing GI Disorders

Research Seeks Greater Insight Into Whether Changes In the Composition and Function Of the Gut Microbiota Are Associated With Disease

 

 

 

 

Health and Disease Imprinted in the Time Variability of the Human Microbiome

Abstract

The animal microbiota (including the human microbiota) plays an important role in keeping the physiological status of the host healthy.

Research seeks greater insight into whether changes in the composition and function of the microbiota are associated with disease.

We analyzed published 16S rRNA and shotgun metagenomic sequencing (SMS) data pertaining to the gut microbiotas of 99 subjects monitored over time.

Temporal fluctuations in the microbial composition revealed significant differences due to factors such as dietary changes, antibiotic intake, age, and disease.

This article shows that a fluctuation scaling law can describe the temporal changes in the gut microbiota. This law estimates the temporal variability of the microbial population and quantitatively characterizes the path toward disease via a noise-induced phase transition. Estimation of the systemic parameters may be of clinical utility in follow-up studies and have more general applications in fields where it is important to know whether a given community is stable or not. IMPORTANCE The human microbiota correlates closely with the health status of its host. This article analyzes the microbial composition of several subjects under different conditions over time spans that ranged from days to months. Using the Langevin equation as the basis of our mathematical framework to evaluate microbial temporal stability, we proved that stable microbiotas can be distinguished from unstable microbiotas. This initial step will help us to determine how temporal microbiota stability is related to a subject’s health status and to develop a more comprehensive framework that will provide greater insight into this complex system.

To review article/abstract please click on the following link:

https://www.ncbi.nlm.nih.gov/pubmed/28345059?dopt=Abstract&utm_source=dlvr.it&utm_medium=twitter

Seres Therapeutics Announces a New SER-109 Phase 2 Clinical Study (ECOSPOR III) For Patients With Multiple Recurrent C. diff. Infections (CDI’s)

Seres Therapeutics Inc. a leading microbiome therapeutics platform company, announced on March 16th, 2017 plans to initiate a new SER-109 Phase 2 clinical study (ECOSPOR III) in patients with multiply recurrent Clostridium difficile (C. difficile) infection. The ECOSPOR III study design was finalized following a positive Type B meeting with the U.S. Food and Drug Administration (FDA). In a separate announcement today, Seres reported fourth quarter and full year 2016 financial results and provided an update on multiple ongoing microbiome clinical programs.

Seres plans to initiate a new SER-109 clinical study in approximately 320 patients with multiply recurrent C. difficile infection. Study participants will be randomized 1:1 between SER-109 and placebo. To ensure accurate measurement of C. difficile infection, diagnosis of recurrent C. difficile infection for both study entry and for endpoint analysis will be confirmed by C. difficile cytotoxin assay. Patients in the SER-109 arm will receive a total SER-109 dose, administered over three days, approximately 10-fold higher than the dose used in the prior ECOSPOR study. ECOSPOR III will evaluate patients for 24 weeks and the primary endpoint will compare the C. difficile recurrence rate in subjects who receive SER-109 verses placebo at up to eight weeks after dosing. The FDA has agreed that this new trial may qualify as a pivotal study with achievement of a persuasive clinical effect and addressing FDA requirements, including clinical and statistical factors, an adequately sized safety database, and certain CMC parameters.

“We are pleased to have received highly constructive guidance from the FDA regarding further SER-109 clinical development and we plan to initiate a new clinical study as soon as possible,” said Roger J. Pomerantz, M.D., President, CEO and Chairman of Seres. “Our prior SER-109 studies provided important new biological and clinical data that have advanced our pioneering microbiome therapeutic efforts. Based on our learnings and dialogue with the FDA, we believe that we are now positioned to initiate a robust clinical study that may provide the basis for SER-109 approval. There is an urgent need for improved treatments for C. difficile infection, and we believe SER-109 has great potential to address the underlying cause of the disease and become the first approved microbiome therapeutic in this new field of medicine.”

About SER-109

SER-109, an oral capsule, is Seres’ lead Ecobiotic® microbiome therapeutic for the treatment of multiply recurrent C. difficile infection. SER-109 is a biologically sourced consortium of bacterial spores designed to catalyze a shift in a dysbiotic gastrointestinal microbiome to a healthier state.

About Seres Therapeutics

Seres Therapeutics, Inc. is a leading microbiome therapeutics platform company developing a novel class of biological drugs that are designed to treat disease by restoring the function of a dysbiotic microbiome, where the natural state of bacterial diversity and function is imbalanced. The Phase 2 study of Seres’ program SER-109 has been completed in multiply recurrent Clostridium difficile infection. Seres’ second clinical candidate, SER-287, is being evaluated in a Phase 1b study in patients with mild-to-moderate ulcerative colitis (UC). Seres is also developing SER-262, the first ever synthetic microbiome therapeutic candidate, in a Phase 1b study in patients with primary CDI. For more information, please visit www.serestherapeutics.com. Follow us on Twitter @SeresTx.

Forward-looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding SER-109 development plans, the timing, design, and results of the ECOSPOR III study , the potential for ECOSPOR III to provide different results than the previous ECOSPOR study, the impact analysis of prior clinical studies may have on clinical outcomes, the potential for ECOSPOR III to qualify as a Pivotal Study, dysbiosis as an underlying cause of C. difficile and other diseases.

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

http://finance.yahoo.com/news/seres-therapeutics-initiate-ser-109-110000650.html;_ylt=AwrBT.EHTNBYMRUAv3hXNyoA;_ylu=X3oDMTEzbjcwdjAxBGNvbG8DYmYxBHBvcwM4BHZ0aWQDVUkwMkM0XzEEc2VjA3Ny

 

 

Highlights Of the Latest Advances In the Battle Against the Deadly Pathogen – Dale Gerding, MD

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http://www.mdmag.com/medical-news/c-diff-foundation-highlights-latest-advances-in-the-battle-against-the-deadly-pathogen

In September, researchers, health care workers, and industry and patient advocates convened for the 4th Annual International Raising C. diff Awareness Conference and Health Expo in Atlanta.

Clifford McDonald, MD, Associate Director for Science in the Division of Healthcare Quality Promotion at the Centers for Disease Control and Prevention (CDC), chaired the conference. In his role at the CDC, McDonald’s at the forefront of efforts to prevent and treat the infection – one the CDC has declared among the most urgent drug-resistant threats that we currently face.

“It’s my firm belief that we are on the threshold of a new era in better diagnosis, treatment, and prevention approaches. At the CDC, we deal with statistics, but there are faces behind those numbers. At the heart of every infection is a patient who deserves our competence, our empathy, and our passion,” said McDonald.

One of those faces, Roy Poole, is a volunteer patient advocate for the  C Diff Foundation. After retiring from a career in the Air Force, Poole led a healthy, active lifestyle as an avid outdoors-man in Colorado before antibiotics prescribed for a routine dental procedure set the stage for CDI. In the medical community, his symptoms were met with disbelief and inappropriate treatment.

“Three weeks after leaving the hospital, I walked into my (previous) primary care physician, and asked for an order to have a stool sample taken to determine if Toxins A or B were present. His response was, ‘Are you still having problems with that?’ Clearly, there is a need for more education about C. diff among physicians,” said Poole.

CDI is a formidable opponent. However, with the newly focused attention on discovering ways to disable the bacteria and cohesive public health approaches aimed at prevention, presenters from government, academia and industry offered five key reasons we can win the battle against C. diff:

Antibiotic stewardship efforts are gaining a foothold.
Statistics present a chilling picture: 453,000 new cases and an estimated 30,000 deaths each year. It’s likely that those numbers grossly underestimate the true impact of CDI, since it’s what we know from death certificate reporting.

However, we are seeing that rates may have peaked after a long plateau. Mark Wilcox, MD, Head of Microbiology at Leeds Teaching Hospital, Professor of Medical Microbiology at University of Leeds, and the lead on Clostridium difficile for Public Health England in the United Kingdom, has demonstrated a 70% reduction in cases in England in just 7 years. This was after a concerted effort that Wilcox spearheaded surrounding antibiotic stewardship, specifically addressing a reduction in unnecessary prescribing of fluoroquinolones and cephalosporin antibiotics.

Commonly prescribed antibiotics disrupt the protective microbiota (the normal bacteria of the gut) and leave it vulnerable for C. diff colonization. “There was a concerted effort that went beyond lip service and truly embraced the principles of improved surveillance, more accurate diagnostics, enhanced infection prevention measures to use antibiotics more wisely and to limit transmission and careful treatment,” said Wilcox.

High rates of CDI are always associated with the use of certain antibiotics: clindamycin, cephalosporin, and fluoroquinolones. Research has shown that lower respiratory tract infections and urinary tract infections account for more than 50% of all in-patient antibiotics use. But are these really necessary?

“We know that antibiotics are overused and misused across every healthcare setting. At least 30% of antibiotic prescriptions are unnecessary – and this equates to 47 million unnecessary antibiotic prescriptions per year written in doctors’ offices, hospital outpatient departments, and emergency departments. We have a lot of work to do, and CDC is actively working to reduce unnecessary antibiotic use,” said Arjun Srinivasan, MD at the CDC. “Stopping unnecessary antibiotics is the single most effective thing we can do to curb C. diff infections in the United States. This is something that we can do today.”

Srinivasan acknowledged that telling patients that they can’t have a prescription for an antibiotic might result in some pushback. “Patient satisfaction scores are a very real concern. When someone is sick and takes a day off work, they’re not leaving without a prescription – especially when the last provider wrote one for their same symptoms,” he said. “But this is a new day, and it’s up to the physician to educate their patients and stay strong.”

Hospitalists have access to accurate, inexpensive and quick diagnostic tests that can lead to targeted, effective treatment. This can arm the treating physician and patient with information that can put patients on a path to recovery without feeling like they are being dismissed.

Emerging guidance reflects important advances in research and development.

Most recently published in 2010, the Society for Healthcare Epidemiology of America (SHEA) and Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines for C. diff are currently under review. This is critical because of the number of physicians still treating with metronidazole first, despite the fact that the largest randomized controlled clinical trial has shown that vancomycin is more effective.

“Since 2010, the landscape has changed dramatically,” said Stuart B. Johnson, MD, Professor, Department of Medicine, Loyola University, and Researcher at the Hines VA Hospital in Chicago.

“The past few years have ushered in a new age of understanding how and where C. diff colonizes, and the damaging toxins A and B that it produces.”

Considering that 25-30% of patients experience a CDI recurrence, it’s evident that metronidazole unnecessarily contributes to the failed treatment outcomes for patients. Metronidazole is less expensive, but has more side effects than oral vancomycin and is less effective in treating CDI.

Johnson provided an overview of the dramatic advances this space has seen in just the past few years.

Limitations of current guidelines include:
•       No mention of fidaxomicin, a narrow-spectrum antibiotic, which in 2011 was the first medication approved in 25 years for the treatment of C. diff associated diarrhea
•       Limited evidence for recommendations to treat severe, complicated CDI
•       Limited evidence for recommendations on recurrent CDI
•       Little mention of Fecal Microbiota Transplant (FMT)

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5.  Patient advocacy and awareness efforts can alter the course of CDI.
CDI survivors shared their experiences along their emotional journey – fear, disbelief, isolation, and depression. They also expressed gratitude at the validation, information and support they received from the patient advocacy community. Perhaps the greatest gift they have received is the empowerment to question their physicians about the necessity of antibiotics they have been prescribed in terms of risk of CDI.

“The hospital where I was treated initially seemed eager to have me leave. They offered no additional help. The C diff Foundation has been my greatest source of help. In turn, I feel I help myself cope best, when I help others to cope with the disease,” said Poole.

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Dale Gerding, MD, FACP, FIDSA, is Professor of Medicine at Loyola University Chicago, Research Physician at the Edward Hines Jr. VA Hospital. Additionally, Gerding is an infectious disease specialist and hospital epidemiologist, past president of the Society for Healthcare Epidemiology of America and past chair of the antibiotic resistance committee of SHEA. He is a fellow of the Infectious Diseases Society of America and past chair of the National and Global Public Health Committee and the Antibiotic Resistance Subcommittee of IDSA. His research interests include the epidemiology and prevention of Clostridium difficile, antimicrobial resistance, and antimicrobial distribution and kinetics.

The paper, “Burden of Clostridium difficile Infection in the United States,” was published in the New England Journal of Medicine.

The study, “Changing epidemiology of Clostridium difficile infection following the intriduction of a national ribotyping-based surveillance scheme in England,” was published in the journal Clinical Infectious Diseases.

The study, “Prevalence of antimicrobial use in US acute care hospitals,” was published in JAMA.

The paper, “Vancomycin, metronidazole, or toleyamer for Clostridium difficile infection: results from two multinaionalm randomized, controlled trials,” was published in Clinical Infectious Diseases.

The study, “A Randomized Placebo-controlled Trial of Saccharomyces boulardii in Combination with Standard Antibiotics for Clostridium difficile disease,” was published in JAMA.