prevention of Clostridium difficile infection

micrograph of Clostridium difficile

Clostridium difficile infection is caused by antibiotics which kill off the ordinary good bacteria allowing the C. diff to flourish in the gut.

C. diff causes inflammation of the large intestine and CDAD (C. diff associated diarrhea); CDAD is caused by toxins that cause bloating, diarrhea and abdominal pain.

That doesn't sound so terrible, rather like the flu, except C. diff is really hard to get rid of. An infection can go on for months or years, preventing people from leaving the house. And as the ability to absorb nutirion is impeded. they can waste away and die.

So when I was in the ICU on two types of IV antibiotics and overheard the doctor ask my nurse if I had diarrhea, I knew why he was asking and was not a happy camper.

Image credit: Clostridium difficile 01 by CDC/Lois S. Wiggs [public domain], via Wikimedia Commons.

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about CDAD

Approximately 8 in 100,000 people in the US get CDAD every year. When people are hospitalized, that rate jumps to 4-8 in 1000.

For mild cases, often stopping the antibiotics is sufficient to clear up the problem.

The next intervention is targeted antibiotics, meds that specifically kill C. diff. When it works, 20% of the patients suffer a relapse of infection. If you've already had a relapse and do targeted antibiotics again after a relapse, your odds of another relapse are 40-60%.

The final intervention is fecal transplant. This is 85-90% effective, but... gross. And it's also not commonly available, meaning you might have to travel to have it done by a physician or figure out how to do it yourself. But gross and inconvenient, it beats dying.

In 2011, there were half a million C. diff infections in the US and 29,000 deaths. It really kills people and the best way to get it is to be hospitalized on antibiotics as I was.

This is why my ears perked up when I overheard the doctor ask if I had diarrhea.

preventing CDAD

I had cellulitis in my leg. As a diabetic, any infection in an extremity can be very dangerous, and I knew this and absolutely agreed this was not an inappropriate use of antibiotics. I am rather attached to my leg and want to keep it that way.

I was on two IV antibiotics in the hospital. When I left the hospital, my regular doctor prescribed 3 weeks of Clindamycin, which I also agreed with as the leg was still very red, obviously inflamed.

I also developed an open sore on top of the cellulitis, so he referred me to a place that specializes in wound care. I joked with the doctor there that we'd save my leg, but I'd wind up dying of C. diff and she recommended probiotics.

Well, I know something about probiotics - namely that we don't know squat about them. We know general things about them, but the specific details of what is good or bad about the hundreds of species of bacteria that live in us is sometimes sketchy.

(And sometimes useless. Akkermansia muciniphila apparently cures T2 diabetes, but you can't buy it. It only grows in tissue culture in an anaerobic environment, so isn't particularly amenable to production.)

I didn't think yogurt would kill C. diff and though I had 3 probiotic products here, when my stool situation began heading in the direction of CDAD, I decided it was time to Google.

The last reference below is a review of the literature regarding prevention (there is a more recent review, but this article was free). While many bugs may or may not be useful, only a few have been tested thoroughly.

Saccharomyces boulardii

S. boulardii is a yeast commonly used as a probiotic to treat acute diarrhea, recurrent C. diff infection, Candida overgrowth, IBS and IBD, and diarrhea associated with travel, antibiotics, and HIV.

The review noted that all studies did not show it was effective in preventing CDAD; the issue seemed to be dose-dependent. Studies that used between 5-40 CFU (colony forming units) were effective in preventing CDAD from developing.

S. boulardii is commonly available from many manufacturers and is cheap.

Lactobacillus rhamnosus GG

The specific GG strain of L. rhamnosus has been thoroughly studied and shows a similar dose-dependent effect, requiring 5-40 CFUs to be effective in preventing CDAD.

Unfortunately, this strain only seems to exist in a product called Culturelle, which is relatively expensive. Other strains may or may not be equally or even more effective, but the research has been done on this stuff.

my experience

I did not actively have diarrhea when I decided to take action. But my stools had become much looser and more frequent and I feared I was heading that way.

By this time, I was on a second three-week course of Clindamycin, and it didn't seem that quitting that was a good idea, given I still wanted to keep the leg and all. So I quit most of my other medications; at least one, metformin, can have similar side effects.

Quitting everything else was to determine if the change in bathroom habits was from the antibiotics. Symptoms persisted several days, indicating to me it was definitly an issue with the antibiotics. So I ordered the two products shown.

The S. boulardii arrived first and I began taking one daily immediately. The frequency of bowel movements decreased in a day or two.

It was several more days before the Culturelle arrived and things firmed up after almost the first dose; but that could be from either of the probiotics or a combination of the two.

I am pretty confident I am not going to develop CDAD.

References

Ryan KJ, Ray CG. (editors) Sherris Medical Microbiology (4th ed.). McGraw Hill. 2004 pp. 322-4. PDF: http://cdn.intechopen.com/pdfs-wm/25640.pdf, ISBN 0-8385-8529-9 (accessed Dec 2015).

Lessa, Fernanda C.; Mu, Yi; Bamberg, Wendy M.; Beldavs, Zintars G.; Dumyati, Ghinwa K.; Dunn, John R.; Farley, Monica M.; Holzbauer, Stacy M.; Meek, James I.; Phipps, Erin C.; Wilson, Lucy E.; Winston, Lisa G.; Cohen, Jessica A.; Limbago, Brandi M.; Fridkin, Scott K.; Gerding, Dale N.; McDonald, L. Clifford. Burden of Infection in the United States. N Engl J Med. 2015 372(9):825-834. PubMed http://www.ncbi.nlm.nih.gov/PubMed/, PMID=25714160 (accessed Dec 2015).

Kelly CP; LaMont JT. Clostridium difficile - more difficult than ever. N Engl J Med. 2008 359(18):1932-40; PubMed http://www.ncbi.nlm.nih.gov/PubMed/, PMID=18971494 (accessed Dec 2015).

Burke KE; Lamont JT. Fecal Transplantation for Recurrent Clostridium difficile Infection in Older Adults: A Review. J Am Geriatr Soc. 2013 61(8):1394-8; PubMed http://www.ncbi.nlm.nih.gov/PubMed/, PMID=23869970 (accessed Dec 2015).

Drekonja, D; Reich, J; Gezahegn, S; Greer, N; Shaukat, A; MacDonald, R; Rutks, I; Wilt, TJ. Fecal Microbiota Transplantation for Clostridium difficile Infection: A Systematic Review. Ann Intern Med. 2015 162(9):630-8; PubMed http://www.ncbi.nlm.nih.gov/PubMed/, PMID=25938992 (accessed Dec 2015).

Mary Hickson. Probiotics in the prevention of antibiotic-associated diarrhoea and Clostridium difficile infection. Therap Adv Gastroenterol. 2011 4(3):185-197.; PubMed Central http://http://www.ncbi.nlm.nih.gov/pmc/, PMCID=PMC3105609 (accessed Dec 2015).