C Dff

WARNING: this post contains extensive and graphic discussion of feces. Not for gratuitous purposes, but rather to help out other CFer's who want to prevent or who suffer from C Diff. You are warned. 


Maybe it's just my lack of exposure to the CF community, but I haven't heard many talk about struggles with C Diff (Clostridium difficile). 

So when I was diagnosed with this a week and a half ago, after my second hospital admission in 2 months (I was admitted the 2nd time for sinus surgery and we agreed more IV abx would set me up for a good chance of recovery), I searched the web feverishly for answers for how to treat this potentially deadly condition.

PWCF are no strangers to life-threatening conditions, this is true. But I've mostly been a pulmonary CF type gal for the 31 years I've been on the planet - no real weight problems, despite being PI. I take digestive enzymes, and as of 8 months ago I do have CFRD, but other than that, I don't give my digestive system much attention.

I've always taken probiotics off and on, mostly to either prevent a yeast infection while on IV abx or more recently to boost my immune system (thanks to smart Cyster Mandy). But that was really the extent to which I knew about these little heroes that live in our bodies.

So I'm sure you're absolutely shocked to hear that I went on a whirlwind of research upon being diagnosed with C Diff. I'll give you my research and actions in a few paragraphs - first I'll describe my symptoms. 

I was constipated without a BM for 72 hours - finally had a BM in the early morning of my 1st Friday in the hospital, and I ended up having 7 more that day that were pretty explosive diarrhea . I don't typically get diarrhea with IV abx, but sometimes loose stools. A quick C Diff culture showed I did in fact have the affliction. 

I felt slightly nauseated that Friday, and a bit distended, but nothing too horrendous other than frequent trips to the bathroom. Saturday, however, brought some of the worst pain I have felt since I passed gallstones. I was put on Simethicon and given a small dose or morphine to make me comfortable. I've never been on anything stronger than Tylenol + codeine, so I was pretty afraid of taking a strong pain killer. But the pain was too great and wasn't going away.

I was put on Oral Flagyl and Vanco (in addition to the other 3 IV abx I was on to treat the PA in my lungs) to treat the C Diff - very standard therapy. I was also given packets of lactobacillus to hopefully build up the good bacteria in my gut to combat the C Diff. The lactobacillus was refrigerated by the hospital, but I wasn't sure what the brand was or what the quality was.

Luckily the pain of Saturday never came back - thanks to lots of praying and I think the Flagyl and Vanco (and maybe even Simethicon) were doing their job. The diarrhea, however, did not go away until well over a week later. More on that later. 

As I was healing from my 1st sinus surgery and cranky lungs, I shook my head at myself for not proactively taking probiotics after my hospitalization discharge in October and prior to my admission in November. I knew in the back of my mind this was important, but with all the fevers, lethargy, blah blah blah I was dealing with I just didn't get it done. I asked my doc why he didn't put me on probiotics - he said the studies were mixed on whether probiotics really helped  prevent C Diff. There you go.

So back to the research - I first wanted to understand the exact mechanism of C Diff. Essentially, one can acquire C diff in two different ways - either getting it from someone else (not washing your hands....most commonly in hospital or long term care facilities) or through over use of abx. The abx CFer's normally use are "broad spectrum" - meaning the abx kill the PA we want dead, but the abx also kill some of the good bacteria in our intestines. 

As any of us who have had a yeast infection can attest, the balance between bacteria species, bacteria and fungus, etc etc is very fragile. And when the balance is disrupted, yeast infections and C Diff can result, to name a few afflictions. C Diff is particularly worrisome because the overgrowth of the bacteria releases toxins from the bacteria, causing inflammation of the colon or even damage to the intestines. Scary scary stuff.

So, what I'm hoping to pass on to my fellow CFer's are a few foods for thought on treating and preventing C Diff. This is my research thus far, what has worked for me, and what else I have in my tool box in case things get worse.

• Not all probiotics are made the same. Most notably, good bacteria can be destroyed in your probiotic quite quickly

1. Ask the store where you are purchasing the probiotic if the item arrives to the store refrigerated. Often, probiotics need to be refrigerated, otherwise the bacteria die off. So if you're purchasing a probiotic from a refrigerator in the store, but the probiotic was transported by truck at room temp for 3 days just to get there, are you really getting your money's worth? Or more importantly, what your digestive tract needs? I was shocked that my favorite brand of probiotics didn't arrive at my store refrigerated. So I chose a different brand
2. Read packaging to determine how the probiotics are created. Some yogurt products are infused with the good bacteria, then fermented. This can destroy the bacteria
3. Location of the manufacturer is important as well. I chose a manufacturer just a few dozen miles from the store - I figure the refrigeration transport will have more integrity and the product is fresh

• If things escalated, I was ready to visit a local doctor for a fecal transplant. Not the most glamorous, but scientifically and logically it makes sense. I have no desire to lose my colon over this C Diff infection http://fecalmicrobiotatransplantation.com/FMT/home.html. Things have not escalated and I haven't resorted to this method - but I just want to throw it out there in case anyone needs it/ wants to research it. C Diff is serious.

I realize this post is all over the place, but I want to get out as much info as possible. 2 days ago, Friday, I was released from the hospital, PICC line pulled, no more abx except for the Flagyl and Vanco. I immediately went to the store to pick out a probiotic. After looking at the criteria above, I chose http://www.biokplus.com/en-us   Strawberry probiotic (yes, it has a little added sugar Mandy, I know, I know....) with 50 billion live and active cultures for my struggling belly. Now I'm just telling you what I chose and what was best for me - it's important that you do your research for which probiotic is best for your situation.

Friday night I drank my 1st 1/2 jar of the probiotic (I didn't want to start off too aggressively... too many good bacteria can be disruptive as well) and I drank the other 1/2 Saturday morning. Saturday evening (last night) I have my first formed BM and much more appetite than I had had in over a week. This morning, Sunday, another formed BM. 

To be fair, I was taken off IV abx 36 hours before this solid BM. So it's possible that being off the IV abx helped the good bacteria start to grow. But I am convinced that the probiotic certainly helped the good bacteria and of course implanted more good bacteria for my digestive system to work and the C Diff to settle down a bit.

I will keep you guys posted, as I'm certainly not out of the woods yet. C Diff can re-occur after my Flagyl/Vanco cycle ends, or of course with my next round of abx. But I feel more confident with the right probiotic in hand I can try to PREVENT the infection in the future, and treat it if it comes back. 

Oh yes, and my sinuses and lungs are doing fine too. 

Hoping this info can help other CFer's out there who are need of help - C Diff is certainly a nightmare. FIGHT ON!

Positive Results from Optimer Pharmaceuticals' Second Phase 3 Study of Fidaxomicin for the Treatment of Clostridium difficile

Press Release Source: Optimer Pharmaceuticals, Inc. On Saturday April 10, 2010, 9:30 am EDT
SAN DIEGO, April 10 /PRNewswire-FirstCall/ -- Optimer Pharmaceuticals, Inc.

(Nasdaq:OPTR - News) announced that the top-line results from its second fidaxomicin Phase 3 clinical study in patients with Clostridium difficile infection (CDI) were presented today at the 20th Annual European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) in Vienna, Austria.


Clinical investigator Derrick Crook, M.D. presented the positive top-line results that the Company had previously announced in February 2010. In the trial, fidaxomicin met the primary endpoint of non-inferiority in clinical cure compared to Vancocin®. Importantly, fidaxomicin also had significantly lower recurrence rates compared to Vancocin (p = 0.002), and significantly higher global cure rates (defined as cure with no recurrence within four weeks of completing therapy) compared to Vancocin (p < 0.001). The robust results from this second fidaxomicin Phase 3 trial confirm the results from the first fidaxomicin Phase 3 trial. Together these trials enrolled more than 1,100 subjects thus making them the two largest comparative studies ever conducted against Vancocin in CDI.

"Fidaxomicin offers potential advantages over existing therapies as a single agent that can provide a high cure rate and fewer recurrences for Clostridium difficile infection," said Dr. Crook, M.D., Consultant Microbiologist/Infectious Diseases and Professor of Infectious Diseases and Microbiology, Experimental Medicine Division, Nuffield Department of Clinical Medicine (NDM), University of Oxford. "Moreover, we found that even in patients with the hypervirulent BI/NAP1/027 subtype, fidaxomicin provided an improvement in recurrence rates compared to the currently approved treatment."

Additional data presented for the first time by Dr. Crook included a subgroup analysis of the BI/NAP1/027 strain and the non-BI/NAP1/027 strain showing clinical cure, recurrence and global cure rates for fidaxomicin compared to Vancocin®. Most notably, Fidaxomicin showed a clinically meaningful reduction in recurrence rates and higher global cure rates compared to Vancocin in both strain type subgroups. Clinical cure rates for fidaxomicin and Vancocin were similar in these two strain type subgroups.

Dr. Crook also presented baseline demographic and disease characteristics of study participants which were similar between the fidaxomicin and Vancocin arms. The BI/NAP1/027 strain was identified in 32% of subjects in the second Phase 3 study. 54% of the study participants were over the age of 65, 68% were in-patients, and 15% had a prior episode of CDI. An average of 7.5 bowel movements per day was observed among all subjects. The incidence of adverse events and serious adverse events was similar in the fidaxomicin and Vancocin arms.

In a separate poster presentation, Mark A. Miller, M.D., head of the Division of Infectious Diseases, Chair of the Infection Prevention and Control Unit at the Jewish General Hospital in Montreal, Quebec, Canada, presented analyses from the first fidaxomicin Phase 3 clinical study in patients with CDI regarding three of the 14 severity criteria specified in the CDI treatment guidelines recently published by The European Society of Clinical Microbiology and Infectious Diseases (ESCMID). Three of ESCMID's 14 severity criteria (temperature, leukocyte count and serum creatinine) had been routinely collected from all subjects in this study and were examined in relationship to clinical cure, recurrence, global cure, and time to resolution of diarrhea (TTROD). According to the ESCMID guidelines, patients with one or more of the criteria could be classified as a severe CDI patient. Out of 596 subjects from this study, 155, or 26%, had one or more of the three ESCMID severity criteria monitored in the study. A validated severity index, score, or categorization system does not exist at the present time for predicting CDI outcomes based on risk factors. The analyses indicated that the three ESCMID criteria monitored in the study were useful in predicting CDI treatment outcomes.

Fidaxomicin Clinical Study Design

The second Phase 3 trial was a multi-center, randomized, double-blind clinical trial, which enrolled 535 adult subjects. Subjects with confirmed CDI received either fidaxomicin (200 mg q12h) or Vancocin (125 mg q6h). This study was conducted in approximately 100 clinical sites throughout North America and Europe. The study was designed to evaluate safety and compare the response to treatment in subjects during and after a 10-day course of therapy. Non-inferiority in clinical cure (defined as patients requiring no further CDI therapy two days after completion of study medication, as determined by the investigator) compared to Vancocin was the primary endpoint. If cured, subjects were monitored for a subsequent four-week period to evaluate recurrence, which was a secondary endpoint. Global cure, also a secondary endpoint, was defined as patients who were cured and did not have a recurrence during this subsequent four-week period.

About Clostridium difficile Infection

CDI has become a significant medical problem in hospitals, long-term care facilities, and in the community. It is a serious illness caused by infection of the inner lining of the colon by C. difficile bacteria, which produces toxins that cause inflammation of the colon, severe diarrhea and, in the most serious cases, death. Patients typically develop CDI from the use of broad-spectrum antibiotics that disrupt normal gastrointestinal (gut) flora, and thus allowing C. difficile bacteria to flourish.

Current therapeutic options for CDI include the off-label use of metronidazole and oral vancomycin, the only FDA-approved treatment. However, approximately 20% to 30% of CDI patients who initially respond to these treatments experience a clinical recurrence following cessation of antibiotic administration.

Primary risk factors for CDI include broad-spectrum antibiotic use (such as cephalosporins and fluoroquinolones), advanced age (over 65) and emerging hyper-virulent strains (BI/NAP1/027, 078, 001) of C. difficile. Increasing incidence, higher treatment failures and recurrence with current therapies have resulted in greater awareness and concern of CDI among medical professionals and public health officials.

About Fidaxomicin

Fidaxomicin is the first in a new class of antibiotics called macrocycles, which inhibit the bacterial enzyme RNA polymerase, resulting in the death of C. difficile. The narrow-spectrum profile of fidaxomicin may eradicate C. difficile selectively with minimal disruption to the normal intestinal flora, while most broad-spectrum antibiotics, including metronidazole and vancomycin, disrupt these flora. Fidaxomicin may facilitate the return of the normal physiological conditions in the colon and reduce the probability of CDI recurrence.

About Optimer Pharmaceuticals

Optimer Pharmaceuticals, Inc. is a biopharmaceutical company focused on discovering, developing and commercializing innovative anti-infectives to treat serious infections and address unmet medical needs. Optimer has two late-stage anti-infective product candidates under development. Fidaxomicin is a narrow spectrum antibiotic being developed for the treatment of Clostridium difficile infection. Optimer has reported positive top-line results from two Phase 3 trials of fidaxomicin. Pruvel™ is a prodrug in the fluoroquinolone class of antibiotics being developed as a treatment for infectious diarrhea. Optimer has also successfully completed two Phase 3 trials with Pruvel. Additional information can be found at http://www.optimerpharma.com.