Tag Archives: fidaxomicin

Study Investigators Find Combination of Vancomycin and FMT Superior In Treating Recurrent C.difficile Infection (rCDI)

The combination of vancomycin and fecal microbiota transplantation was found to be superior to fidaxomicin or vancomycin in the treatment of patients with recurrent Clostridium difficile infection (rCDI), according to a study published in Gastroenterology.

This randomized, single-center trial was designed to compare the efficacy of fecal microbiota transplantation with that of fidaxomicin and vancomycin.

Sixty-four adults with recurrent CDI seen at a gastroenterology clinic in Denmark between April 5, 2016 and June 10, 2018 were randomly assigned to a group receiving fecal microbiota transplantation applied by colonoscopy or nasojejunal tube after 4 to 10 days of 125 mg vancomycin 4 times daily (n=24), or 10 days of 200 mg fidaxomicin 2 times daily (n=24), or 10 days of 125 mg vancomycin 4 times daily (n=16).

Patients experiencing a CDI recurrence after this course of treatment, and those who could not be randomly assigned were provided rescue fecal microbiota transplantation. The primary study outcome was combined clinical resolution and negative polymerase chain reaction test for C difficile toxin at 8 weeks post-treatment, and secondary end points included week 8 clinical resolution.

The combination of negative C difficile test results and clinical resolution was observed in 71% of the 24 participants who received fecal microbiota transplantation (95% CI, 49-87%; n=17), 33% of the 24 participants who received fidaxomicin (95% CI, 16-55%; n=8), and 19% of the 16 participants (95% CI, 5-46%; n=3) who received vancomycin (fecal microbiota transplantation vs fidaxomicinP=.009; fecal microbiota transplantation vs vancomycin, P=.001; fidaxomicin vs vancomycin, P=.31). Clinical resolution was observed in 92% of participants who received fecal microbiota transplantation (n=22; P=.0002), 42% of participants who were treated with fidaxomicin (n=10; <.0001), and 19% of participants who were treated with vancomycin (n=3; P=.13). No significant differences in results were seen between patients receiving initial fecal microbiota transplantation therapy and those who received rescue treatment with such a transplant.

Of note, adverse events (transient abdominal pain, constipation, bloating and diarrhea) were observed in 10 of the participants who received a fecal microbiota transplant, 1 of which was classified as severe.

Researchers noted limitation of a lack of patients with C difficile ribotype 027, such that results may not be generalizable to settings with a high ribotype 027 frequency. Study interventions were also unblinded, introducing the possibility of observer bias, although the C difficile toxin test was applied to all patients at all time points in an effort to obtain objective outcome measures.

Study investigators concluded, “[fecal microbiota transplantation] was superior to both fidaxomicin and vancomycin monotherapies for [recurrent] CDI, with regard to both combined clinical and microbiological resolution and clinical resolution alone.”

Reference

https://www.infectiousdiseaseadvisor.com/respiratory/new-powder-formulation-tuberculosis-vaccine-candidate-is-in-human-trial/article/829508/

Hvas CL, Jørgensen SMD, Jørgensen SP, et al. Fecal microbiota transplantation is superior to fidaxomicin for treatment of recurrent Clostridium difficile infection [published online January 2, 2019]. Gastroenterology. doi: 10.1053/j.gastro.2018.12.019

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

Extended-pulsed fidaxomicin Found Superior to Standard-dose vancomycin To Treat C.difficile Infection In Older Adults

In a randomized, controlled, open label phase 3b/4 trial (ClinicalTrials.gov identifier: NCT02254967), hospitalized patients age 60 years and older with confirmed C difficile infection were recruited from 86 European hospitals. Patients were randomly assigned to receive extended-pulsed fidaxomicin (200-mg oral tablets, twice daily on days 1–5, then once daily on alternate days on days 7-25) or vancomycin (125-mg oral capsules, 4 times daily on days 1-10).

Of the 177 patients receiving fidaxomicin, 124 (70%) achieved the primary end point of sustained clinical cure 30 days posttreatment, compared with 106 (59%) of 179 who received vancomycin (odds ratio 1.62; 95% CI 1.04-2.54, P =.03).

Multivariate analysis, which included treatment arm and baseline stratification factors (infection severity, cancer presence, age, and number of previous C difficile infection occurrences) as covariates, also indicated fidaxomicin to be superior (P =.035). A subanalysis of microbiota diversity concluded that microbiota recovery was greater in the fidaxomicin group, and a Cox proportional hazards model suggested that the hazard of infection recurrence in the vancomycin group was 3.8 times greater.

This study demonstrates the superiority of extended-pulsed fidaxomicin treatment over standard treatment with vancomycin. The researchers note the absence of blinding and racial diversity in the study group as limitations and recommend that future investigations should study this treatment course in patients age 60 years and younger and should compare this treatment course with standard fidaxomicin treatment protocols.

Disclosure

The study was funded by Astellas Pharma Inc, who were involved in all stages of the study, including manuscript preparation.

Reference

Guery B, Menichetti F, Anttila V-J, et al.; for the EXTEND Clinical Study Group. Extended-pulsed fidaxomicin versus vancomycin for Clostridium difficile infection in patients 60 years and older (EXTEND): a randomised, controlled, open-label, phase 3b/4 trial. [published online December 19, 2017]. Lancet Infect Dis. doi: 10.1016/S1473-3099(17)30751-X

 

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

https://www.infectiousdiseaseadvisor.com/clostridium-difficile/extended-pulsed-fidaxomicin-vs-vancomycin-sustained-clostridium-difficile-infection-cure/article/738757/

Clostridium difficile Treatment Strategies

laboratorytests

Authors: Teena Chopra, Ellie J.C. Goldstein, Sherwood L. Gorbach

  • First published: 20 December 2016 Full publication history
  • DOI: 10.1002/phar.1863View/save citation
  • Funding: This work was supported by Merck & Co., Inc., Kenilworth, New Jersey.
  • Disclosures: T.C. served as a speaker for Pfizer Inc., Merck & Co., Inc., Cubist Pharmaceuticals, Inc., and Actavis, plc. E.J.C.G. has participated in advisory boards sponsored by Merck & Co., Inc., Cubist Pharmaceuticals, Inc., Optimer Pharmaceuticals, Inc., Bayer AG, Bio-K Plus International, Inc., Summit Therapeutics, plc, Kindred Healthcare, Inc., Novartis Pharmaceuticals Corporation, Daiichi Sankyo Company, Ltd., and Rempex Pharmaceuticals, Inc. He has served as a speaker for Bayer AG, Merck & Co., Inc., Forest Laboratories, Inc., Optimer Pharmaceuticals, Inc., and Cubist Pharmaceuticals, Inc.; he has received research grants from Merck and Co., Inc., Schering-Plough Pharmaceuticals, LLC, Optimer Pharmaceuticals, Inc., Theravance Biopharma, Cubist Pharmaceuticals, Inc., Pfizer, Inc., Astellas Pharma US, Inc., Cerexa, Inc., Forest Laboratories, Inc., Impax Laboratories, Inc., Novartis Pharmaceuticals Corporation, Clinical Microbiology Institute, Genzyme Corporation, a Sanofi company, Nano Pacific Holdings, Inc., Romark Laboratories, LC, ViroXis Corp., Warner Chilcott, plc, AvidBiotics Corp., GLSynthesis, Inc., Immunome, Inc., Salix Pharmaceuticals, Inc., Summit Therapeutics, plc, GlaxoSmithKline plc, Rempex Pharmaceuticals, Inc., Symbiomix Therapeutics, Gynuity Health Projects, Durata Therapeutics, Inc., and Toltec Pharmaceuticals, LLC. S.L.G. has served as a consultant for Seres Therapeutics, Inc., Medimmune, LLC, and Cempra Pharmaceuticals. He was also a consultant for Cubist Pharmaceuticals, now Merck & Co, Inc., at the time that the manuscript was written.

Abstract

In recent years, Clostridium difficile infection (CDI) has become a global public health threat associated with increased morbidity, mortality, and economic burden, all of which are exacerbated with disease recurrence. Current guidelines informing treatment decisions are largely based on definitions of disease severity at diagnosis, with subjective components not well delineated across treatment algorithms and clinical trials. Furthermore, there is little evidence linking severity at onset to outcome. However, reducing the risk of recurrence may offer both a better outcome for the individual and decreased downstream economic impact.

The authors present data supporting the opinion that patients deemed at low risk for recurrence should receive vancomycin (or metronidazole when cost is an issue), while those at higher risk of recurrence would benefit from fidaxomicin treatment.

Although further prospective studies are needed, choosing treatment with the goal of preventing recurrent CDI may offer a better guide than disease severity.

To access entire article – click on the following link:

http://onlinelibrary.wiley.com/doi/10.1002/phar.1863/full

AccessDIFICID (fidaxomicin) Is A Support Program For Patients Prescribed DIFICID®

Dificid (fidaxomicin)  Product Access and Support Information:

AccessDIFICID is a support program for patients who have been prescribed DIFICID® (fidaxomicin) tablets.

Case managers are available M-F, 8 am – 8 pm; SAT, 9 am – 1 pm, ET, to provide the following information and support:

  • Research your insurance benefits
  • Obtain information about your out-of-pocket costs
  • Provide information on co-pay assistance options
  • Provide a referral to the Patient Assistance Program (PAP)
  • Provide information about local pharmacies that stock DIFICID and/or options for overnight deliveries of DIFICID, where available, to the location of your choice
  • Answer questions about filling out the AccessDIFICID Enrollment Form

Getting started is simple

  • Download and complete the appropriate sections of the AccessDIFICID Enrollment Form with your health care provider
  • You or your health care provider can fax the completed form to 1-888-997-9329
  • A program representative will then contact you and your health care provider’s office
After your intake form has been processed, you will receive a phone call from an AccessDIFICID case manager, who will work with you throughout the process. You may also contact a case manager at 1-844-282-4782 (M-F, 8 am – 8 pm; SAT, 9 am – 1 pm, ET).

 For continued information for AccessDIFICID please click on the following link:

http://www.accessdificid.com/

 

*The C Diff Foundation does not endorse this or any medical and non-medical treatment available for the
treatment of a C. difficile infection.  All possible treatment options are strictly information
based and for the general public and for general knowledge.   Discuss all treatment options
with the physician/s providing care for and and all diagnosis.  *

C. difficile Data Analyst Appointed For NHS Highland UK

cdiffmicro

Highland health bosses have appointed an analyst in an attempt to halt the march of a potentially deadly hospital infection.

NHS Highland heard yesterday that it was now “very unlikely” that national targets set for cases of Clostridium difficile (C.diff) would be met this year.

The board’s nurse director Heidi May confirmed yesterday that the board had already recorded 66 patient cases of the infection as of November 1.

To meet their target the board cannot exceed 78 cases by the end of March.

Ms May told the board that they did not have an “outbreak situation” but said the reasons for the number of cases were “not clear”.

She said a data analyst had been taken on to study the cases of patients with C.diff to try and identify trends.

So far 44 cases occurred in patients over 65-years-old, with the remaining 22 in people from 15 to 65-years-old.

Nine cases were acquired in hospital, 18 community acquired, 33 linked to other healthcare and the remaining six currently under investigation.

Ms May said: “We don’t have an outbreak situation but we have no one single group of people and there’s no single area affected.

“It’s not clear why the situation is the way it is and that’s a big issue for us.”

Ms May confirmed the appointment of a data analyst, while adding that cleaning policies will be reviewed and confirming that NHS Highland is part of a nationwide project to introduce a new antibiotic Fidaxomicin which could help reduce relapses of the condition.

She added: “There is a huge amount of work being undertaken to reduce the amount of C.diff and everyone remains fully committed to this.”

C.diff is a type of bacterial infection that can affect the digestive system and can lead to potentially life-threatening complications such as severe swelling of the bowel from a build-up of gas.

It most commonly affects people who have been treated with antibiotics.

NHS Highland chairman Garry Coutts said: “It’s a very complex bug and all very complicated and there are various things we can do which might or might not work.

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

https://www.pressandjournal.co.uk/fp/news/highlands/767402/nhs-highland-hire-analyst-in-attempt-to-understand-c-diff-cases/

Dr. Nicholas Kartsonis Discusses Merck’s History In Infectious Disease and Their Ongoing Research Plus Some Of The Company’s Current Treatments, Including Dificid, To Address C. diff. Infections (CDI)

cdiffRadioLogoMarch2015                What’s new in the C Diff Foundation?

Let us introduce you to the first internet radio talk show dedicated to C. diff. and more……

C. diff. Spores and More”

 

UPCOMING SHOW:  TODAY ~ Tuesday, May 26th: 

 Dr. Nicholas Kartsonis;  Merck Research Laboratories (MRL)

Join us today, Tuesday, May 26th,  as our guest Dr. Nicholas Kartsonis , Associate Vice President of Clinical Research for Infectious Diseases for Merck Research Laboratories (MRL) and Section Head within MRL for antibiotics, antibacterials and cytomegalovirus  shares his time and discusses the past, present, and future contributions of Merck Research Laboratories.  

Dr. Kartsonis joined Merck Research Laboratories in February 2000 and has been actively involved in programs for new antibacterials, antifungals, anti-HIV, anti-CMV, and agents targeted against C. difficile infection.  Most recently, he has led the efforts to ensure the integration of the Cubist Pharmaceuticals clinical research portfolio within Merck. 

 Dr. Kartsonis will provide an overview of Merck’s current efforts to address the worldwide public health crisis posed by antimicrobial resistance, as well as the company’s history in infectious disease and antimicrobial stewardship. In addition, he will talk about the company’s current treatment for C. difficile and ongoing research efforts to address C. difficile infections (CDI).

http://www.voiceamerica.com/show/2441/c-diff-spores-and-more

 

We invite you to join us in listening to this exciting, new internet talk show that broadcasts live every Tuesday at the following times:

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 Click Image Above to Listen to Archived Shows

 


PT 11a,  MT 12p, CT 1p, ET  2 p

 

We are pleased to share C. diff. Spores and More” with you because, as advocates of C. diff., we know how important this cutting-edge new weekly radio show means for our Foundation’s community worldwide.

Hard Facts: Deaths and illnesses are much higher than reports have shown. Nearly half a million Americans suffered from Clostridium difficile (C. diff.) infections in a single year according to a study released today, February 25, 2015, by the Centers for Disease Control and Prevention (CDC).

• More than 100,000 of these infections developed among residents of U.S. nursing homes.

Approximately 29,000 patients died within 30 days of the initial diagnosis of a C. diff. infection. Of these 29,000 – 15,000 deaths were estimated to be directly related to a
C. diff. infection. Therefore; C. diff. is an important cause of infectious disease death in the U.S.
Previous studies indicate that C. diff. has become the most common microbial cause of Healthcare-Associated Infections found in U.S. hospitals driving up costs to $4.8 billion each year in excess health care costs in acute care facilities alone. Approximately
two-thirds of C. diff. infections were found to be associated with an inpatient stay in a health care facility, only 24% of the total cases occurred in patients while they were hospitalized. The study also revealed that almost as many cases occurred in nursing homes as in hospitals and the remainder of individuals acquired the
Healthcare-Associated infection, C. diff., recently discharged from a health care facility.

This new study finds that 1 out of every 5 patients with the Healthcare-Associated Infection (HAI), C. diff., experience a recurrence of the infection and 1 out of every 9 patients over the age of 65 diagnosed with a HAI – C. diff. infection died within 30 days of being diagnosed. Older Americans are quite vulnerable to this life-threatening diarrhea infection. The CDC study also found that women and Caucasian individuals are at an increased risk of acquiring a C. diff. infection. The CDC Director, Dr. Tom Frieden, MD, MPH said, “C. difficile infections cause immense suffering and death for thousands of Americans each year.” “These infections can be prevented by improving antibiotic prescribing and by improving infection control in the health care system. CDC hopes to ramp up prevention of this deadly infection by supporting State Antibiotic Resistance Prevention Programs in all 50 states.”

“This does not include the number of C. diff. infections taking place and being treated in other countries.”  “The  CDF supports hundreds of communities by sharing the CDF mission and    raising C. diff. awareness to healthcare professionals, individuals, patients, families,  and communities working towards a shared goal ~  witnessing a reduction of newly diagnosed            C. diff. cases by 2020 .”   ” The CDF Volunteers are greatly appreciated as they create positive changes sharing their time so generously worldwide aiding in the success of our mission and raising C. diff. awareness.”

C. diff. Spores and More” spotlights world renown topic experts, research scientists, healthcare professionals, organization representatives, C. diff. survivors, board members, and their volunteers who are all creating positive changes in the C. diff. community and more.

Through their interviews, the CDF mission will connect, educate, and empower many worldwide.

 

Questions received through the show page portal will be reviewed and addressed  by the show’s Medical Correspondent, Dr. Fred Zar, MD, FACP,  Dr. Fred Zar is a Professor of Clinical Medicine, Vice HeZarPhotoWebsiteTop (2)ad for Education in the Department of Medicine, and Program Director of the Internal Medicine Residency at the University of Illinois at Chicago.  Over the last two decades he has been a pioneer in the study of the treatment of Clostridium difficile disease and the need to stratify patients by disease severity.

 

Please join us Tuesdays in listening to the educational episodes of C. diff. Spores and More”

View the programs and radio information and access previous episodes available as a podcast by clicking on the link below:

www.voiceamerica.com/show/2441/c-diff-spores-and-more

 

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