Posted on 09/03/2013 7:11:20 PM PDT by neverdem
VAIL, COLO. The strategy of a short course of probiotics prescribed to prevent development of Clostridium difficileassociated diarrhea in patients on antibiotic therapy for any of myriad indications is attracting serious attention in both pediatrics and adult medicine.
Interest in this low-cost and demonstrably low-risk preventive strategy has been driven by a recent favorable meta-analysis by the Cochrane Collaboration.
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The Cochrane analysis included all 23 randomized controlled trials of probiotics for the prevention of C. difficileassociated diarrhea in adults or children taking antibiotics. The trials, three of which were conducted in children, included 4,213 subjects, none of whom were immunocompromised, severely ill, or had an underlying gastrointestinal disorder.
The incidence of C. difficileassociated diarrhea was 2.0% in patients randomized to probiotics, compared with 5.5% in controls, for a highly significant 64% reduction in risk. Moreover, the risk of adverse GI events such as abdominal cramping, nausea, fever, taste disturbance, or flatulence was reduced by 20% in the probiotics group (Cochrane Database Syst. Rev. 2013 May 31 [doi: 10.1002/14651858.CD006095.pub3]).
The benefit of prophylactic probiotics was similar in magnitude in children and adults.
"Moderate-quality evidence suggests that probiotics are both safe and effective for preventing C. difficileassociated diarrhea when used along with antibiotics in patients who are not immunocompromised or severely debilitated," the Cochrane investigators concluded.
Neither the current American College of Gastroenterology practice guidelines on C. difficileassociated diarrhea (Am. J. Gastroenterol. 2013;108:478-98) nor the Infectious Diseases Society of America guidelines (Infect. Control Hosp. Epidemiol. 2010;31:431-55) recommend using prophylactic probiotics. However, both guidelines were published before the Cochrane meta-analysis was released, Dr. Samuel R. Dominguez pointed out at a conference on pediatric infectious diseases sponsored by the Childrens Hospital Colorado.
"Interestingly, a larger effect size was seen in studies of probiotics that contained multiple species compared to a single species, although the data set wasnt large enough for investigators to be able to look at different specific formulations," added Dr. Dominguez, a pediatric infectious diseases specialist at the University of Colorado, Denver.
He noted that the incidence, severity, and mortality of C. difficile infections have increased dramatically since 2000. Even in children, a population traditionally considered at low risk, a recent population-based study conducted in Olmsted County, Minn., by investigators at the Mayo Clinic concluded that the age- and gender-adjusted incidence of C. difficile infection jumped nearly 13-fold from 1991 to 2009, when it reached 32.6 per 100,000 persons. Three-quarters of the 92 cases were community acquired. Prior studies of C. difficile disease in children may have underestimated the incidence because they were largely based on hospital-acquired cases (Clin. Infect. Dis. 2013;56:1401-6).
Another recent study highlights the serious nature of C. difficile in children, Dr. Dominguez continued. This retrospective cohort study conducted at 41 childrens hospitals included 4,474 patients hospitalized with C. difficile infection and 8,821 matched controls. The in-hospital mortality rate was 1.43% in children with C. difficile infection, compared with 0.66% in controls. In the subgroup of children with hospital-onset C. difficile infection, the mortality risk was an adjusted 6.7-fold higher than in matched controls.
Patients with community-onset C. difficile infection had a mean hospital length of stay that was 5.6 days longer and total hospital costs that were $18,900 greater than those of controls. In patients with hospital-onset C. difficile infection, the differences were even more dramatic: a mean 21.6-day longer length of stay than for controls, and a $93,600 greater hospital cost (Clin. Infect. Dis. 2013;57:1-8).
Dr. Dominguez said that although there is no set policy at Childrens Hospital, his own practice is to recommend probiotics to healthy children who are going to be taking antibiotics.
At a separate conference devoted to adult medicine, Dr. Mel L. Anderson cited both the Cochrane Collaboration meta-analysis and a separate one led by investigators at Torontos Hospital for Sick Children that concluded probiotics reduced the incidence of C. difficileassociated diarrhea by 66% (Ann. Intern. Med. 2012;157:878-88).
"If you look at these randomized controlled trials, I think the evidence is fairly convincing. And its not an expensive treatment. We use a lot of it in our inpatient service to reduce the risk of antibiotic-associated diarrhea, and C. difficile in particular," said Dr. Anderson, chief of the hospital medicine section at the Denver VA Medical Center.
Prophylactic probiotics are not for the surgical patient who is merely getting a dose or two of perioperative antibiotic coverage. But the preventive therapy is worth at least considering in pretty much everybody else getting a prescription for antibiotics. The randomized trials included in the two meta-analyses basically included patients receiving 3 days or more of antibiotics. Classes of antibiotics identified in previous work as posing an increased risk of C. difficileassociated diarrhea included the beta-lactams, cephalosporins, fluoroquinolones, and clindamycin "pretty much everything you prescribe" Dr. Anderson observed in Estes Park, Colo., at a conference on internal medicine sponsored by the University of Colorado.
"I have to say, if someone comes in with uncomplicated community-acquired pneumonia, I oftentimes dont prescribe prophylactic probiotics unless theyve had C. difficileassociated diarrhea before or theyre very fragile. But if something is even a little bit wrong with you, bad diarrheal illness can be the straw that breaks the camels back. And I strongly think about prophylactic probiotics in folks on long-term antibiotics, like for a diabetic foot ulcer," he noted.
Dr. Anderson said his typical prescription is for two Lactobacillus acidophilus capsules twice daily.
"The randomized studies done to date dont let us know the optimal mix of critters or how much is enough," according to the hospitalist.
While preventive probiotic therapy is low cost, Dr. Dominguez noted that a more high-tech therapy for secondary prevention of C. difficile infection is in the developmental pipeline.
A pair of neutralizing, fully human monoclonal antibodies against C. difficile toxins A and B administered together in a single infusion in a randomized, double-blind, placebo-controlled, phase II clinical trial in patients with C. difficileassociated diarrhea didnt have any effect on duration of hospitalization for that episode. However, it did result in a highly significant 72% reduction in recurrence, according to investigators at Medarex in Princeton, N.J., and the University of Massachusetts, Boston (N. Engl. J. Med. 2010;362:197-205).
"This may be a useful tool in the future for preventing recurrences," Dr. Dominguez commented.
Dr. Dominguez and Dr. Anderson reported having no financial conflicts of interest.
We are huge probiotic fans. The more they are finally accepted by the medical community the more I worry about our unfettered access to them. I know how to naturally incorporate them into my family’s diet, but I also like the convenience of a multi-billion packed pill or chewable.
FReepmail me if you want on or off my combined microbiology/immunology ping list.
Or a fecal transplant...
I’ve been taking probiotics for years. And certainly I’ve known about taking them to counteract the bad effects of antibiotics on the intestines for many years.
I’m surprised that all doctors aren’t already aware of this.
Maybe apple cider vinegar too?? And of course, Kim Chi.
chicory root tea, a little baking soda, then common acidophilus pearls.
Cheap as heck, and works.
Don’t do that megaBuck fecal transplant stuff.
If it doesn’t work after 3 or 4 times, also throw in the dilute psyllium husk/bentonite clay shakes —so easy, and cheap.
REALLY WORKS, though gradually.
almost all drs are aware of the connection...but ours is a system where you need study after study to get something approved and then accepted as routine....READ...to get the insurance companies to pay....
Konbucha works, also. Lot of people ferment their own, after getting the grains.
But I love keifir.
Yes, raw yogurt is great, but not everyone has easy access to it.
Well after taking a fairly potent antibiotic dose for a substantial duration I can say I am none the worse for it and my thrice daily intake of kefir and yogurt certainly didn’t hurt. I believe in it. No fecal transplants in my future, thank you very much. Who would want a leftist grafted into them anyway— to what end?
I love Kim Chi and it is easy to make your own. However, don’t make the mistake of eating too much on an empty stomach or a violent “eruption’ may occur. Thanks.
It's a staple in my house. I do wish, however, we could get good yogurt like the Europeans have.
One of the really best is Japanese fermented beans, “NATTO”.
ALL of Japan either LOVES it or loathes it —there is little “in-between”.
It is sticky, and to me it smells like a fart. I’m serious.
I loathe it, but there are TONS of people in Japan who are nuts about it.
It is a very, very concentrated form of probiotics.
Some people stir a special MUSTARD into it.
Sounds gross, huh? But Japanese gastroenterologists say it’s the bomb.
However, dont make the mistake of eating too much on an empty stomach or a violent eruption may occur. Thanks.
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Ah the voice of experience. Once again the collective wisdom of FR rears its head.
It is easy to make your own; recipes are all over the internet. If Free Republic would like mine, I will post it.
You are too kind!
I guess that’s right. I use a number of dietary supplements, and my medical insurance doesn’t pay for any of them.
On the other hand, I used to get flu and/or stomach bugs fairly regularly, and now, knock on wood, I hardly ever do. So, I guess it’s worth it.
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