Tag Archives: C. difficile treatment

Raising C Diff Awareness CHICAGO November 4, 2014

CONFERENCE

#RCDAChicago

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.

http://events.r20.constantcontact.com/register/event?oeidk=a07e9h6shhd46356532&llr=6iomnjnab

 

C. difficile – Update From The Expert

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.[1] 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.[2] 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.[3] 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.[4] 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.[5] 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.[6] 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.[7] 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.

 

References

  1. 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.
  2. 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.
  3. 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
  4. 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.
  5. 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.
  6. 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.
  7. 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

C. difficile Infection Treatment; DIFICLIR™ (fidaxomicin) Clinically Effective At Reducing Recurrence and Provides Cost Savings When Used First-Line

* In The News *  14 May 2014

 

DIFICLIR™  (fidaxomicin)

Recurrence has been identified by The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) as the most important problem in the treatment of CDI.[1]

New  data presented at the 24th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) demonstrates that fidaxomicin, when used first-line, is clinically effective and provides cost savings for the treatment of potentially fatal Clostridium difficile infection (CDI).[2] Treatment with fidaxomicin led to a reduction in recurrence for patients with CDI[2] and a saving of over £48,000 to the UK’s NHS versus standard of care treatment (vancomycin or metronidazole).[3]

The study, conducted at St George’s Hospital in London, England, is the first of its kind and looks at a year’s experience using fidaxomicin as a first-line treatment for all adults confirmed to have CDI, including populations not previously studied in randomised controlled Phase III   trials.[2],[4] Data collected from a total of 62 patients treated with fidaxomicin during the 12 month evaluation period were compared with those from a retrospective cohort treated with standard of care (vancomycin or metronidazole) during the previous 12 month period.[5]

Only 6% of patients treated with fidaxomicin had a recurrence of CDI, within 28 days of end of therapy, compared with a 20% recurrence rate with vancomycin/metronidazole in the preceding year.[5] Recurrence is a major challenge in CDI treatment, with previous studies reporting that patients who have already had one recurrence, have a 40% risk of a further episode of CDI.[6]Importantly, in this ‘real world’ study, there were no second recurrences reported in those treated with fidaxomicin. Hence, the observed reduction in recurrence rates and reduced hospital stays since the introduction of fidaxomicin as first-line treatment for CDI has culminated in overall cost savings.[5]

Commenting on the findings, Dr. Tim Planche, lead investigator and Consultant Microbiologist, St George’s Hospital said: “We decided to start using fidaxomicin first-line over a year and a half ago for all cases of Clostridium difficile infection at St George’s, after the exciting data reported in clinical trials showed reduction in recurrence of infection. Having looked at our data we are very pleased to see that we find the same effects occurring in our own “real world” patients. Our team have also looked at the cost-effectiveness of using fidaxomicin and we are assured of the cost benefits of continuing to use this drug. From our experience of using this drug we are very happy to continue using it first-line and that it is worth other hospitals considering as part of their strategy to treat and control Clostridium difficile infection.”

Based on the findings of this landmark study, The Drugs and Therapeutics Committee for the hospital have upheld their recommendation for the use of fidaxomicin as a first-line therapy for all adult patients with CDI.[5]

CDI is one of the most common causes of antibiotic-associated diarrhea and severe cases can lead to bowel surgery and even death.[7] Hospital patients with CDI are up to three times more likely to die in hospital (or within a month of infection) than those without CDI.[8],[9] Recurrence is a major challenge in CDI treatment, 25% of CDI patients suffer a recurrence within one month[10],[11],[12]and patients who have already had one recurrence have a 40% risk of a further episode of CDI.[6]

Commenting on the findings, Professor Oliver Cornely, University Hospital Cologne, Germany said: “One of the biggest challenges to optimal CDI management is recurrence, therefore the significant reduction in disease recurrence by fidaxomicin, compared with vancomycin, is an important step in reducing the morbidity and possibly mortality associated with CDI. The treatment for CDI had remained largely unchanged for 20 years. This real life data demonstrates a treatment advance that can improve patient outcomes and reduce the significant burden of this disease, which will hopefully lead to improved management of CDI in clinical practice.”

These results represent the interim findings of a larger cohort of real world data being collected and analysed from across the UK to assess the effectiveness of fidaxomicin. Data reporting from additional study centres are expected to be presented later in the year.

 

About Astellas Pharma Europe Ltd.

Astellas Pharma Europe Ltd., located in the UK, is the European Headquarters of Tokyo-based Astellas Pharma Inc. Astellas is a pharmaceutical company dedicated to improving the health of people around the world through the provision of innovative and reliable pharmaceuticals. As a global company, Astellas is committed to combining outstanding research and development (R&D) and marketing capabilities to continue to grow in the world pharmaceutical market. Astellas Pharma Europe Ltd. manages 21 affiliate offices located across Europe, the Middle East and Africa. In addition, the Company has an R&D site and three manufacturing plants in Europe. The company employs approximately 4,300 staff across these regions. For more information about Astellas Pharma Europe, please visit http://www.astellas.eu/.

References

1. Bauer MP, et al. European Society of Clinical Microbiology and Infectious Disease (ESCMID): treatment guidance document for Clostridium difficile-infection (CDI). Clin Microbiol Infect. 2009;15:1067-79.
2. Planche T, et al. Cost-effectiveness of fidaxomicin as first-line treatment for Clostridium difficile infection. Abstract presented at ECCMID 2014.
3. Astellas Data on File DIF14036UK.
4. Cornely A, et al. Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: a double-blind, non-inferiority, randomised controlled trial. Lancet Infect Diseases. 2012:12;281-289.
5. Astellas Data on File FDX/13/0090/EUi.
6. Kelly CP, LaMont JT. Clostridium difficile – more difficult than ever. N Engl J Med. 2008;359(18): 1932−1940.
7. Ananthakrishnan AN. Clostridium difficile infection: epidemiology, risk factors and management. Nat Rev Gastroenterol Hepatol. 2011;8:17-26.
8. Oake N, et al. The effect of hospital-acquired Clostridium difficile infection on in-hospital mortality. Arch Intern Med. 2010;170:1804-10.
9. Hensgens MP, et al. All-Cause and disease-specific mortality in hospitalized patients with Clostridium difficile infection: a Multicenter Cohort Study. Clin Infect Dis. 2013;56:1108-16.
10. Lowy I, et al. Treatment with Monoclonal Antibodies against Clostridium difficile Toxins. N Engl J Med. 2010;362;3:197-205.
11. Bouza E, et al. Results of a phase III trial comparing tolevamer, vancomycin and metronidazole in patients with Clostridium difficile-associated diarrhoea. Clin Micro Infect. 2008;14(Suppl 7):S103-4.
12. Louie TJ, et al. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med. 2011;364:422-31.
13. Poutanen SM, et al. Clostridium difficile-associated diarrhoea in adults. CMAJ. 2004;171:51-8.
14. Kelly CP, et al. Clostridium difficile infection. Ann Rev Med. 1998;49:375-390.
15. Crobach MJ, et al. European Society of Clinical Microbiology and Infectious Diseases (ESCMID): Data review and recommendations for diagnosing Clostridium difficile-infection (CDI). Clin Micro Infect. 2009;15:1053-1066.
16. Pepin J, et al. Increasing risk of relapse after treatment of Clostridium difficile colitis in Quebec, Canada. Clin Infect Dis. 2005;40:1591-7.