ZINPLAVA (bezlotoxumab) is now available for prescription.
Ordering information is available on the brand website:
What is Zinplava™ ?
ZINPLAVA™ is indicated to reduce recurrence of Clostridium difficile infection (CDI) in patients 18 years of age or older who are receiving antibacterial drug treatment of CDI and are at a high risk for CDI recurrence.
ZINPLAVA is not indicated for the treatment of CDI.
ZINPLAVA is not an antibacterial drug.
ZINPLAVA should only be used in conjunction with antibacterial drug treatment of CDI.
Full prescribing information can be read at
The Merck Access Program can help answer physician’s questions about:
Insurance coverage for patients
Prior Authorizations and Appeals
Coding and Billing
Potential financial assistance options for eligible patients
Full program details can be found at:
Also, Information about co-pay assistance for eligible, privately insured patients
Information about available independent assistance foundation support.
*PLEASE NOTE – The C Diff Foundation does not endorse any product, medication, and/or clinical study in progress and available. All website postings are strictly for informational purposes only.
Early Diagnosis, Prevention, and Treatment of Clostridium difficile: Update
Clostridium difficile is a gram-positive, anaerobic bacterium generally associated through ingestion. Various strains of the bacteria may produce disease generating toxins
and TedA and TedB, as well as the lesser understood binary toxin.
Our use of the term indicates this review’s focus is the presence of clinical disease rather than asymptomatic carriage of C. difficile CDI symptoms can range from mild diarrhea to severe cases including pseudomembranous colitis and toxic megacolon and death.
Estimated U.S. health care associated CDI incidence in 2011 was 95.3 per 100,000, or about
293,000 cases nationally. Incidence is higher among females, whites, and persons 65 years of
age or older. (1)
About one third to one half of health-care onset CDI cases begin in long term care,thus residents in these facilities are at high risk. Incidence rates may increase by four or five-fold during outbreaks.
Community associated CDI, where CDI occurs outside the institutional setting,
is also on the rise, though still generally lower than institution associated rates and may be in part due to increased surveillance. Estimated community associated CDI was 51.9 per 100,000, or 159,700 cases in 2011. (1)
Community-associated CDI complicates measuring the effectiveness of prevention within an institutional setting. 3 Additionally, the pathogenesis of CDI is complex and not
completely understood, and onset may occur as late as several months after hospitalization or antibiotic use
The estimated mortality rate for health -care associated CDI ranged from 2.4 to 8.9 deaths per
was 55.1 deaths per 100,000; (1)
CDI was the 17th leading cause of death in this age group (4)
Hypervirulent C. difficile strains have emerged since 2000 . These affect a wider population
adults, many of whom lack standard risk profiles such as previous hospitalization or antibiotic use.(5)
The hypervirulent strains account for 51 percent of CDI, compared to only 17 percent
of historical isolates. (6)
Time from symptom development to septic shock may be reduced in the hypervirulent strains, making quick diagnosis and proactive treatment regimens critical for positive outcomes.
To read more on TREATMENT, PREVENTION, KEY QUESTIONS ——
Early Diagnosis, Prevention, and Treatment of Clostridium difficile: Update
We are pleased to welcome Dr. Caterina Oneto, MD to the
C Diff Foundation.
Dr. Oneto presides as a Medical Advocate for the
C. diff. Nationwide Community Support Program teleconferencing sessions.
Dr. Caterina Oneto is a Clinical Assistant Professor within the NYU Division of Gastroenterology, Board Certified in Gastroenterology and Internal Medicine.
Fluent in Spanish, she graduated with a degree in Medicine and Surgery from the
Universidad de Valparaiso in Chile. She completed her residency in
Internal Medicine at Cabrini Medical Center, where she served also as Chief Resident, and later completed her Fellowship in Gastroenterology at Montefiore Medical Center, Albert Einstein College of Medicine.
With expertise in endoscopy, colonoscopy, capsule endoscopy, liver and pancreatic diseases, Dr. Oneto’s special interests include IBD (Crohn’s disease and Ulcerative Colitis), IBS (irritable bowel syndrome), microbiota modification, treatment of Clostridium Difficile and FMT (Fecal Microbiota Transplantation).
Fecal microbiota transplantation
The process of delivering stool bacteria from a healthy donor to a patient suffering from intestinal infection with the bacterium Clostridium difficile works by restoring healthy bacteria and functioning to the recipient’s gut, according to a study published this week in mBio®, the online open-access journal of the American Society for Microbiology.
The study provides insight into the structural and potential metabolic changes that occur following fecal transplant, says senior author Vincent B. Young, MD, PhD, an associate professor in the Department of Internal Medicine/Infectious Diseases and the Department of Microbiology & Immunology at the University of Michigan in Ann Arbor. The transplants, which have been successful at curing more than 90 percent of recipients, have been used successfully since the 1950s, he says, though it hasn’t been clear how they work to recover gut function.
“The bottom line is fecal transplants work, and not by just supplying a missing bug but a missing function being carried out by multiple organisms in the transplanted feces,” Young says. “By restoring this function, C. difficile isn’t allowed to grow unchecked, and the whole ecosystem is able to recover.”
Young and colleagues used DNA sequencing to study the composition and structure of fecal microbiota (bacteria) in stool samples from 14 patients before and two to four weeks after fecal transplant. In 10 of the patients, researchers also compared stool samples before and after transplant to samples from their donors.
All transplant patients, treated at the Essentia Health Duluth Clinic in Minnesota, had a history of at least two recurrent C. difficile infections following an initial infection and failed antibiotic therapy.
Studying families of bacteria in the samples, investigators found marked differences among donor, pre-transplant and post-transplant samples. However, those from the donors and post-transplant patients were most similar to each other, indicating that the transplants at least partially returned a diverse community of healthy gut bacteria to the recipients. While not as robust as their donors, the bacterial communities in patients after transplant showed a reduced amount of Proteobacteria, which include a variety of infectious agents, and an increased amount of Firmicutes and Bacteroidetes bacteria typically found in healthy individuals, compared to their pre-transplant status.
Then, using a predictive software tool, researchers analyzed the relationship between the community structure of the micoorganisms and their function, presumably involved in maintaining resistance against CDI.
They identified 75 metabolic/functional pathways prevalent in the samples. The samples taken from patients before transplant had decreased levels of several modules related to basic metabolism and production of chemicals like amino acids and carbohydrates, but were enriched in pathways associated with stress response, compared to donor samples or post-transplant samples.
CDI has significantly increased during the past decade, Young says, with previous studies estimating there are more than 500,000 cases of CDI in the United States annually, with health care costs ranging from $1.3 billion to $3.4 billion. Up to 40 percent of patients suffer from recurrence of disease following standard antibiotic treatment. In a healthy person, gut microorganisms limit infections but antibiotics are believed to disrupt the normal structure of these microoganisms, rendering the gut less able to prevent infection with C. difficile.
Further identification of the specific microorganisms and functions that promote resistance of bacterial colonization, or growth, may aid in the development of improved CDI treatments, Young says: “If we can understand the functions that are missing, we can identify supplemental bacteria or chemicals that could be given therapeutically to help restore proper gut function.”
For article in its entirety click on the link below:
The study was supported by the National Institutes of Health, the Michigan Gastrointestinal Peptide Research Center, and the Essentia Health Foundation in Duluth, Minn.
mBio® is an open access online journal published by the American Society for Microbiology to make microbiology research broadly accessible. The focus of the journal is on rapid publication of cutting-edge research spanning the entire spectrum of microbiology and related fields. It can be found online at http://mbio.asm.org.
The American Society for Microbiology is the largest single life science society, composed of over 39,000 scientists and health professionals. ASM’s mission is to advance the microbiological sciences as a vehicle for understanding life processes and to apply and communicate this knowledge for the improvement of health and environmental and economic well-being worldwide.
Join us at the second annual
“Raising C Diff Awareness” Conference
The C Diff Foundation is proud to host this conference at
the University of Illinois at Chicago – Chicago, IL, USA on November 4th, 2014
Registration is OPEN. Click on the link below to view conference details, guest speakers confirmed to date, while taking advantage of the early-bird registration savings in effect before August 16th.
In The News May 20, 2014 *
Editor’s Note: Dr. John Bartlett, MD, gave an update on Clostridium difficile infection (CDI) at the April 2014 meeting of the American College of Physicians. He provided Medscape with this synopsis.
We are going to talk about CDI. It is a disease that seemed like it was well covered a decade or two ago, but all of a sudden there is a rush of new information that is clinically important. I would like to review the more recent information.
The first thing to acknowledge is that we got a thrust of new cases in the early 2000s in Europe and in North America, including Canada and the United States, reflecting the NAP-1 strain. NAP-1 wasn’t a particularly virulent strain, but it was resistant to fluoroquinolones, and that drove its epidemiology. The slide shows the rush of cases in the United States, a 4- or 5-fold increase over that rather short 8-year period of time.
More recently, we received guidelines from the European Society of Clinical Microbiology and Infectious Diseases. I think these are really good. They are similar to the Infectious Diseases Society of America (IDSA) guidelines but much newer — 3 years newer. They said that for mild or not severe disease, metronidazole would be the preferred drug 500 mg 3 times/day, and for severe disease, vancomycin 125 mg 4 times/day. No change there. A helpful hint for the treatment of patients who can’t take oral drugs is intravenous metronidazole combined with vancomycin enemas. For relapse, they like the taper and pulse, which was recommended earlier. It has never been studied but seems to work. The new drug on the block, fidaxomicin, also seems to do well in relapsing disease. Stool transplant is hot, and I will talk more about that. Interestingly, probiotics were not recommended, which is highly controversial. I won’t say much about it except that I don’t personally recommend them, but I don’t mind if my patients take it.
The next slide is about a trial comparing vancomycin with fidaxomicin in patients who have relapsing CDI. Fidaxomicin works just as well as vancomycin for primary disease. It is less likely to prompt a relapse, probably because it has a less profound effect on the colonic microbiome. It re-establishes the pathophysiology that was intended. What it shows here is a difference in relapse rate of 36% vs 20%, which is substantial. That is for relapsing disease.
Next is an interesting slide about the epidemiology, which has really changed our concept of epidemiology completely. Most people have always thought that CDI was a hospital-acquired infection, but this great study from the Centers for Disease Control and Prevention (CDC) reviewed 10,000 cases and showed that only about 25% of patients with CDI acquired the disease in the hospital where it was expressed. Therefore, the majority of patients came into the hospital with CDI, which obviously has big implications in regard to infection control. The patient who comes in with it has to be protected from getting it with antibiotic control and also has to protect others from contagion, which is not the way it has been advocated.
The next slide is the British system. They are running away with this disease especially in terms of the epidemiology of the disease. The UK had a lot of CDI with the NAP1 strain, and the hospitals were told to get rid of it. They were very aggressive in dealing with their epidemic of CDI and, in fact, managed to accomplish a 61% decrease in CDI rates. They did that largely by the control of antibiotics, primarily fluoroquinolones. They essentially stopped fluoroquinolones and also had a major reduction in the use of cephalosporins, the 2 big contenders. Of course, clindamycin is in that mix, but it was not prominently used at the time, so that didn’t make a big difference. But they achieved a decrease in CDI rates, and the reason was that they controlled antibiotics.
One of the things they have done magnificently is chain sequencing to show epidemiologic patterns. The next slide shows that they were able to demonstrate patient-to-patient transmission within a ward in only 23% of the cases. Chain sequencing is probably the ultimate infection control tool. This has contributed to our changing concepts of the epidemiology of C difficile. Many patients are already colonized when they are hospitalized. That reverses the standard teaching that you get CDI when you go to a ward that has the disease.
The next slide is not clinically important, but it’s fun to talk about The Netherlands beagle. Of course, dogs have an incredible sense of smell. The dog was trained to smell p-cresol so that it can make an identification of CDI. Its performance was essentially 100% in detecting positives and negatives. I contacted the author to find out what they were doing now with the dog, and they said that they only take the dog on the ward, but they do it regularly. The reason they don’t do it in individual cases is that they simply don’t have enough cases in the lab. So they screen wards, not individual patients, with the dog test, but they still use it. Interestingly, they wanted to bring it to the United States because we have a lot of CDI and it would be a good way to test the dog in the lab, but the requirements for quarantine and so forth were too tough.
The next slide has to do with polymerase chain reaction (PCR). PCR is probably the most commonly used test. It is a molecular test, so it is essentially 100% sensitive but not very specific. There will be many more carriers than there are cases, so you have to make clinical correlations in order to properly understand that test. The other test, of course, is the enzyme immunoassay (EIA), which is commonly used in about 30% of laboratories. It has the opposite lesion, which is that it is more specific but less sensitive. It is not a molecular test and is probably not adequately sensitive to detect about a third of cases.
Stool transplant is hot. It has been done since 1958 and has been in a large number of series. What is important here is the summary of late information with guidelines from the IDSA and the US Food and Drug Administration (FDA), who are now into this in a big way. According to the IDSA, the indications for stool transplant are relapsing CDI 3 times or more. They also advocated for acute disease, but the published experience for that is not very robust — good, but not very robust. The stool that is transplanted can be put in in a hospital, in a clinic, or at the patient’s home. It can be put in by the patient. The method can be by endoscopy, by enema, by nasogastric tube, or by any other way that you can get it there, such as capsules. The important thing is to get the stool into the colon. How you get it there is probably not terribly important. Who selects the donor? We usually have the patient select a donor, but there are other places that use alternative systems. There are several other sources now, including a website operated by medical students called OpenBiome which will send you a stool for $250. You have to be aware that the screening test for a stool transplant costs about $600, and no insurance or third-party payer will pay for this. It is a patient expense that patients need to be warned about.
In terms of clinical management, I’ve summarized a lot of data here. The risks are well known: advanced age, antibiotics (especially fluoroquinolones and cephalosporins), and exposure to the healthcare system. That was the message from before. In other words, the patient acquired the disease not at the current hospital but often from a previous hospitalization, a nursing home where they were previously a resident, or an outpatient clinic. They acquired it in the healthcare system but not necessarily this hospital at this time.
Know the test. The first question to ask when somebody says that there is a positive test for a patient is “which test?” If it’s PCR, worry about false positives. If it’s an EIA, worry about false negatives.
For determining the prognosis, the signs to watch for are shown here. Renal function, white blood cell count, lactate level, and albumin level are all barometers for the severity of disease. Of course, there are also the issues of ileus, toxic megacolon, and so forth.
I’ve talked about epidemiology quite a bit. We call it “hospital-associated C difficile” and not “hospital-acquired” for the reasons that I mentioned. There is no new information about treatment except that fidaxomicin is the new kid on the block. It’s probably the best drug, but it’s also very expensive. For stool transplants, be aware that many of the people watching this will not do stool transplants. What you need to do is know someone in your community to whom you can refer patients if there is an indication, preferably a place that has a fair amount of experience. Also be aware that there are published guidelines on when to do it. For the first time, the FDA has gotten engaged, and now they call stool a drug. You have to jump through some hoops. You have to get a treatment investigational new drug (IND) application. They have some rules about knowing who the donor is or the donor source. All of that can be sorted out at the site of the transplant, but it’s probably a good idea to keep that in mind when you’re communicating with patients.
Those are my highlights for what is going on in the field of C difficile today.
C diff: An Update From the Expert. Medscape. May 20, 2014.
- Steiner C, Barrett M, Terrel L. HCUP Projections: Clostridium Difficile Hospitalizations 2011 to 2012. 2012 HCUP Projections Report # 2012-01 July 10, 2012. U.S. Agency for Healthcare Research and Quality. http://www.hcup-us.ahrq.gov/reports/projections/CDI_Regional_projections_Final.pdf Accessed April 30, 2014.
- Debast SB, Bauer MP, Kuijper EJ; Committee. European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection. Clin Microbiol Infect. 2014;20 Suppl 2:1-26.
- Crook DW, Walker AS, Kean Y, et al; Study 003/004 Teams. Fidaxomicin versus vancomycin for Clostridium difficile infection: meta-analysis of pivotal randomized controlled trials. Clin Infect Dis. 2012;55 Suppl 2:S93-103. Abstract
- Centers for Disease Control and Prevention (CDC). Vital signs: preventing Clostridium difficile infection. MMWR Morb Mortal Wkly Rep. 2012;61:157-162. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6109a3.htm Accessed April 30, 2014.
- Walker AS, Eyre DW, Wyllie, DH, et al; Infections in Oxfordshire Research Database. Characterisation of Clostridium difficile hospital ward-based transmission using extensive epidemiological data and molecular typing, PLoS Medicine. 2012;9:1001172. http://www.plosmedicine.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pmed.1001172&representation=PDF Accessed April 30, 2014.
- Bomers MK, van Agtmael MA, Luik H, van Veen MC, Vandenbroucke-Grauls CM, Smulders YM. Using a dog’s superior olfactory sensitivity to identify Clostridium difficile in stools and patients: proof of principle study. BMJ. 2012;345:e7396.
- Loo VG, Bourgault AM, Poirier L, et al. Host and pathogen factors for Clostridium difficile infection and colonization. N Engl J Med. 2011;365:1693-1703. Abstract