Re: C-Diff info...long but worth it...several responses

[Guest guest]

This is very educational, and useful. I have gained a wealth of knowledge.

My understanding was so simple and almost childish. But, I hadn't researched

it, and knew only what the big boys wanted me to know in a very simplified

form.

It will be pursued even more fully, though. I guess I am a skeptic when it

comes to the medical world.

I noticed that the writer of these two pieces have Dr. in front of their

names. That is what we see in front of Chiropractor's names, or health food

advocates names. Our Physicians use M.D. I said well, " I am not being told

about

anything that is sold in the health food Stores, so I read on. "

The first article was very good.

But, the second article started giving names of products, and by whom.

Natren's

Healthy Trinity. The other 2 are Lactobacillus GG and " Acidophilus Plus " ,

This bothers me.

Imogene

In a message dated 1/2/2007 9:13:18 PM Central Standard Time,

cheeps4u@... writes:

INFECTION WITH CLOSTRIDIUM DIFFICILE

By Dr. Borody

( with references/credits at the end of the article)

Human infection with Clostridium difficile (CD) can take many forms.

Those reading this section are probably interested in this topic

because they, or perhaps a friend, may be suffering with the more

severe effects of CD infection. However, there is a whole spectrum of

CD infections ranging from mild forms through to life threatening

clinical CD infections (1,14,25,31). These will now be described.

CD infection can exist in patients who can be clinically relatively

well – eg carriers of very mildly pathogenic bacteria. Some may have

recurrent mild to moderate diarrhea resembling Irritable Bowel

Syndrome (IBS) and may not be at all concerned with these symptoms. In

fact they may consider themselves to be perhaps part of the normal

spectrum of bowel behavior. Still others may have recurrent bouts of

severe cramps, diarrhea with or without `wind' and other symptoms.

Unless CD is diagnosed and causes these symptoms such patients could

well be labeled with a diagnosis of IBS.

Still other patients may have a condition indistinguishable from

colitis, with cramps, diarrhea, urgency, mucus and variable amounts of

blood (33). At sigmoidoscopy typical inflammation is seen and may

initially be diagnosed as `idiopathic' colitis(colitis of unknown

cause). This disorder can also be recurrent with red patches visible

on colonoscopy in some areas of the bowel or indeed throughout the

colon. This kind of colitis can respond to prednisone, Asacol and

other anti-colitis drugs because the steroids and anti-inflammatory

drugs non-specifically inhibit many types of inflammation.

Furthermore, drugs such as Asacol (5-ASA compounds) have their own

anti-CD activity.

Lastly the most severe and even devastating CD infection can develop

into `pseudomembranous enterocolitis' with specific type of

inflammation visible at colonoscopy. It may lead to fulminant colitis,

megacolon and even to death from colon perforation and peritonitis.

However, these latter conditions are generally uncommon (35).

Chronic CD infection is estimated to occur in perhaps 15-30% of those

infected. In some, re-infection can occur with same or different

strain. Also, the small bowel may act as reservoir of spores, entering

the colon. Risk factors for relapse are said to include the number of

previous episodes, the need to use antibiotics recurrently, female

sex, and older age groups. (3,34)

C difficile is acquired from contact with humans or objects harboring

these bacteria. It can be commonly acquired during hospitalization

with up to 30% of those who have spent a prolonged period in hospital

leaving the hospital carrying these bacteria in the bowel flora.

(12,13) This is particularly so if antibiotics had been administered

so disturbing the protection of the natural bowel flora. Non-hospital

acquisition of CD also occurs and again a course of antibiotics may

permit the growth of CD and `awake' a clinical condition.

Human infection occurs through ingestion (via the mouth) and if the

bacterium survives acid and bile on its passage into the bowel it may

be eradicated by the normal bowel flora. However, if the bowel flora

is suppressed because of concomitant use of antibiotics, CD can

colonize the flora and remain with the patient – generally for life.

In some individuals it seems that antibiotics are not required for

colonization to take place. This may be perhaps due to inadequate

defense of the naturally occurring flora within the bowel. CD is a

very hardy organism probably because it contains spores. Spores are

unable to be eradicated by any known antibiotic. One way of

eradicating spores is to autoclave the spore-containing specimen using

a sterilizer. Of course a patient cannot be placed in a sterilizer.

However some bacteria appear to be capable of inhibiting the growth of

CD and even eradicating the spores and this characteristic has been

used to develop `bacteriotherapy' which will be described below.

There are a number of therapies for C difficile-associated disorders:

Withdrawal of antibiotics

In many situations when antibiotics are stopped the normal flora

re-grows and the patient can actually lose the presence of the CD and

its toxins. In this situation the normal indigenous flora has not been

damaged enough by the antibiotics to lose its protective bacteria,

especially Bacteroides, the friendly Clostridia species and other

bacteria which are antagonistic to CD. This may be the mechanism by

which many recover spontaneously and indeed lose the CD. However, in

many situations even withdrawal of antibiotics does not lead to the

disappearance of CD which then may persist lifelong.

Metronidazole(Flagyl)

This is a first-line medication for treatment of CD infection but on

its own it is unlikely to eradicate CD and can cause nausea in higher

doses. From clinical experience it appears that if the bowel flora is

adequate then metronidazole together with the existing bowel flora may

at least terminate the clinical infection. (4,5,6)

Vancomycin

Equally powerful if not a better though more expensive anti-microbial

agent. Vancomycin's advantage is that it is not absorbed into the

blood stream and very rarely causes side effects. Some specialists

prefer a combination of metronidazole and vancomycin. Whereas

metronidazole has some theoretical problems such as peripheral nerve

damage with long term usage vancomycin does not have significant

complications when used orally long term. (4,5,7)

Rifampicin

Yet another anti-clostridial antibiotic which has been found to be

useful in CD infection and can be used for longer periods but may have

side effects. We know it can be used for 1-2 years continuously since

rifampicin was part of the standard drug for treatment in tuberculosis

giving us experience in long-term usage .

Teichoplanin

This is a newer glycopeptide antibiotic related to vancomycin and is

not readily available. It has probably little advantage over

vancomycin unless resistance has developed and resistance is said to

be rare. (5,7)

With antibiotics as a group various methods such as `pulsing',

combinations, tapering and combination with probiotics – listed below

– have been advocated by some – and indeed useful in some individuals.

Such combinations should not be discarded as `anecdotal' and we should

collect reports from individual successes and cures, for in this way

we may be able to design trials and test better treatments. (9,10,25,26)

Cholestyramine(Questran) and Colestid granules

These are adsorbing agents to which CD toxins attach so as not to

cause diarrhea and cramping. They do not eradicate CD but can reduce

the effects of the toxins. The powders can be difficult to mix with

fluids and may cause nausea. Helpful clinically to many, and also

lower cholesterol as a beneficial `side effect'. (8)

Antagonistic bacteria - Lactobacillus GG (Culturelle – in the US)

This lactobacillus is a probiotic which was isolated by Drs Sherwood

Gorbach and Barry Goldin (hence LGG) is available in many countries

for treatment of chronic CD infection symptoms. On its own LGG may

suppress CD. When combined or preceded with vancomycin and

metronidazole it may be curative in some situations. In our experience

it is probably required in high doses and for longer periods of time.

The major advantage of LGG is its lack of side effects and potential

for cure in some patients. (11,15,27)

Saccharomyces boulardii

This is a friendly fungus which has activity against the C. difficile

toxins A and B. It colonizes the bowel transiently, has been proven to

give relief better than placebo but has never been able to eradicate

CD. It is useful especially in combinations to control symptoms

initially. (2,16,28)

Clostridium butyricum (Myiari 588 Strain)

This is a friendly Clostridium which can live normally in the human

flora, is quite safe and is available commercially in Japan, Korea and

China. It interferes with the growth of CD antagonizing its

multiplication. It is commonly used in Japanese hospitals to

successfully prevent CD being acquired And is given to patients on

admission to hospital. Little western literature is available on this

probiotic.

i) Immune Anti-C difficile Globulin

This is normal pooled human gammaglobulin which generally contains

antibodies to C difficile toxins and can be used in severe cases.

Generally not curative. (29,30,32)

Surgery

In severe cases of fulminant colitis or toxic megacolon removal of the

colon may be required, otherwise perforation, septic shock and death

may follow. Even surgery in these very severe cases may be too late to

save lives.

Restoration of Human Bowel Flora

Two methods have been used. Infusion into the bowel of freshly

cultured mix of bowel bacteria, or infusion of filtered, complete,

healthy human fecal bacteria. The first form has been reported by

Tvede et al in 1989 but is no longer available. A two-bacterial

per-enteroscope infusion has been available in Kansas City for several

patients and has been of help. It uses Bacteroides bacteria (the most

common bacterium in the bowel) plus healthy or beneficial E.coli as

two antagonistic bugs to CD. It can rid the patient of CD and spores.

Success rate is not known. (21)

The other method is the infusion of all the bacteria originating from

a healthy donor. This is the standard therapy of last resort for

relapsing, severe CD infection where other therapies are failing and

the patient continues to have marked symptoms. The treatment uses

bowel flora (feces) homogenized in sterile saline, often filtered, and

the slurry containing the total living protective bacteria is infused

into the bowel of the patient. This can be done through a colonoscope

under sedation, via enema, or through a naso-jejunal tube to take care

of the small bowel reservoir of CD.

Though perhaps aesthetically not very attractive this therapy is the

most reliable method to kill the CD and its spores and if we count up

all published anecdotal reports the therapy has a documented cure rate

of well over 80%. (17,18,19,20,22,23,24) It is carried out on a

routine basis as a clinical service in Sydney, Australia for patients

with documented, chronic CD infection. All methods described above can

be used and success rate in CD eradication is > 90%. A site for North

America may soon be available.

Probiotics: What Are They and Do They Really Help C. diff?

Common definitions for probiotics say something like this: probiotics

are live microorganisms that may provide health benefits when

ingested. Sound disgusting? It's not really.

Think about all the foods that you choose to eat that intentionally

use microorganisms because of their fermentation properties: yogurt,

cheese, miso, sauerkraut…to name a few.

Granted, not all of these foods still contain live microorganisms by

the time they reach your refrigerator. Pasteurization often sees to

that. But, maybe we should consider eating more unpasteurized foods

and making our own fermented dairy and vegetable products. After all,

our ancestors did and they didn't suffer from the same type of

illnesses that we have today. Numerous medical conditions that plague

us were unheard of by our great-grandparents. And many of these

conditions have been associated with too few " healthy "

gastrointestinal species and too many " bad guys. "

C. difficile is no exception. It is an opportunistic bacteria that

does no harm as long as there are enough " healthy " bacteria to keep

its growth in check. However, when given the opportunity to overgrow

in the intestines, it will! So, if the problem is not C diff per se,

but rather too few of the " good guys, " probiotics offer a wonderful

way to replace some of the " healthy " bacteria.

How do they target C. diff?

Let's explore how probiotics may be effective treatments for C. diff

infections. First, many probiotic strains are known to secrete toxins

--toxins that are selectively toxic to C. difficile spores. Now,

that's a good thing, because none of the antibiotics currently in our

armamentarium are capable of eliminating C. difficile spores.

Second, many strains of probiotic bacteria are capable of secreting

acidic substances (i.e. short chain fatty acids and peroxides). Normal

conditions in the colon are not very acidic. However, if we can create

acidic conditions in the colon, it is helpful in our fight because C

difficile is not a happy camper when conditions are acidic.

Additionally, some of the acidic substances secreted by probiotic

bacteria (especially butyric acid) also possess anti-inflammatory

properties. This property may help heal the damaged intestinal wall.

Third, successful probiotic therapy may simply be a matter of

competitive exclusion. As a Penn State football fan, I like to use the

football analogy to explain this. If Beaver Stadium has 100,000 seats,

but 200,000 fans show up for Saturday afternoon kick-off, by default,

half the people have to leave.

The same is true in the intestines. There are only so many places for

bacteria to bind on the intestinal wall. Furthermore, there is only so

much food to go around; bacteria living in our colons are largely

living under starvation conditions. If you over-load the body with

enough " good " guys, some of the " bad guys " have to leave.

A fourth, more general mechanism that might explain beneficial actions

of probiotics in C difficile simply may have to do with the ways in

which probiotics stimulate the immune system and increase our body's

production of protective antibodies --antibodies that may react

against C. difficile and its toxins.

Lastly, while the majority of probiotic products are bacteria-based,

one specific strain of a " friendly " probiotic yeast offers a unique

quality in that this yeast probiotic secretes an enzyme that

selectively inactivates C. difficile toxins. Even if C. difficile

microbes are producing their harmful toxins, this yeast enzyme

destroys the toxins before they can be harmful to us.

Where to find probiotics

Unless you are willing to dramatically alter your diet, you probably

need to use some type of probiotic supplement in order to

substantially fix your own gastrointestinal bacteria once they become

disrupted--especially if the " bad guys " have already taken over.

Probiotic supplements are available as powders, capsules, yogurts,

fermented milks, etc. Thousands of products are on the market. A few

have been studied in clinical trials. Some products I recommend

without hesitation. Some products I wouldn't waste my money on. Some

products I run from and wouldn't give to my dog. With many more

products, I simply haven't formed an opinion and would simply have to

say, " I don't know. I haven't seen any published studies and I don't

have any clinical experience with it. "

For the best chance of success

Although some probiotic manufacturers disagree and claim to have

solved this problem, from what I read in the literature, from what the

food bacteriologists tell me, and from independent laboratory

analyses, refrigeration is key for maximal probiotic viability.

Optimally, the products should be refrigerated during shipping from

the manufacturer, refrigerated at the store when purchased, and

refrigerated in your kitchen.

I suspect a common problem that many folks make is simply not

ingesting enough probiotics to do any good. It is estimated that each

gram of fecal matter in the colon contains tens of trillions of

bacteria! Think about that for a minute. If you only add a few million

bacteria to your intestines, those couple-of-million bacteria won't

even make a dent in changing the overall intestinal environment!

Successful clinical studies almost always use tens- or hundred- of

billions of bacteria; I've even seen some studies that have reportedly

used trillions of bacteria ingested each day. My personal rule of

thumb is to recommend products that guarantee a minimum of 10 billion

bacteria per dose. To be able to make that guarantee, these companies

have to over-stuff their capsules initially to account for any

bacteria that might die off between the time of manufacture and the

expiration date. Keep in mind, too, that a single daily dose may not

be enough. Depending upon the medical condition being treated and the

severity of it, I may recommend taking 6 or 8 doses each day until the

situation improves.

This " guarantee " of a minimum number of bacteria per dose brings up

another interesting point. Many companies simply state on their label

" 'x' number of bacteria per dose at time of manufacture " . Here's the

deal on this. I don't care how many bacteria they put in there when

they made the stuff, I want to see a product expiration date that

guarantees me a set amount of bacteria until the product expires.

Having an expiration date also, at least in principle, suggests that

the company is doing some quality control studies on their product.

Its an added plus if the company can provide documentation that an

independent laboratory is providing quality control tests and can

guarantee that there are no harmful bacterial contaminants.

Experts estimate that our intestines are home to approximately 400-500

different types of bacteria. Experts also agree that, when trying to

repopulate the gut with " good guys " , it is wise to select a product

that contains several different strains of bacteria as opposed to only

one. Personally, I also prefer to use probiotics that were initially

identified from healthy humans. At least I know, then, that those

species of bacteria I choose to ingest intentionally are supposed to

be there.

And finally, a few more practical considerations to keep in mind:

-Take your probiotic on an empty stomach. This means one hour before

eating or two-to-three hours after meals.

-Take your probiotic with non-chlorinated water or milk.

-If taking antibiotics simultaneously with probiotics, separate your

probiotic as many hours as possible away from your dose of antibiotic.

By the way, some experts recommend when initiating probiotic therapy

for C. difficile, that it may be wise to overlap your antibiotic (i.e.

metronidazole or vancomycin) and probiotic therapy for 10 days. This

allows your antibiotic to " beat down " the C. diff as much as possible,

while beginning to repopulate your intestines with the " healthy guys. "

-It is common to experience transient flatulence (i.e. gas) when

starting probiotics. Don't stop the product if you experience gas,

burping, or bloating. These symptoms are actually good. They are signs

that the probiotic you are taking is alive and working. Too many

people stop probiotic therapy too soon. The gastrointestinal

discomfort usually subsides in 5-10 days and tends to be worse the

more disrupted your own gastrointestinal bacteria are.

Finally, but unfortunately, there are no guarantees. Probiotics have

helped many. They saved my son's life when he was a toddler.

Probiotics have been shown in clinical studies to both prevent and

treat C. difficile diarrhea, but every body is different. If there was

one " miracle " cure for everyone, we'd already have heard about it. The

" healthy " bacteria that your body is missing may be different than

someone else's. The best thing you can do is stay informed, make

healthy choices, and work together with your physician to find the

cure that works for you!

Written by Dowhower Karpa, PhD, RPh. Additional probiotic

information can be found in her book entitled Bacteria for Breakfast:

Probiotics for Good Health.

Dr. McCann posted the following advice after reading 's case

history, and we thought it might be useful to reproduce it here:

Adding a probiotic empirically to any antibiotic regimen is the

standard of care for C diff disease (and should be for ANY antibiotic

regimen but the latter is futuristic and not standard practice, yet).

One problem with standard oral regimens is that the dose is far too

low if given by mouth unless you use one of the enteric coated to get

enough live bacteria thru the acid stomach. Enemas may be the best way

but standard bacterial regimens of normal flora have yet to be

developed and approved here as opposed to overseas. There are 3 oral

products you may try. The one I am most familiar with is Natren's

Healthy Trinity. The other 2 are Lactobacillus GG and " Acidophilus

Plus " , all of which have been proven to eliminate C diff. If you use

Natren's product, which is an oil matrix specially designed to resist

stomach acid, you should take 5 caps every 4 hours until diarrhea

abates, then gradually reduce to 2 b.i.d. and maintain continuously.

One or two tums beforehand also helps get more live bacteria thru,

especially if you use a product in a normal capsule. Look for the 2

main bacteria on the label; L acidophilus and B bifidum. After 1 to 2

weeks of normal stools and no occult blood you can try to discontinue

the Vanco, but not the probiotic. The rub lies in the cost. We are

lobbying insurance companies that the cost justifies the alternative,

of which your case is classic. Your work-up should include serum

antibody vs. C diff as there are some patients who do not make an

antiIgG antibody to the G diff toxin. These patients still respond

well to Probiotics but are bound to relapse if treatment is

discontinued. Some of my patients have switched over to " Lactobacillus

Plus " or " Acidophilus Plus " after they have been in remission for some

while on GG or " Healthy Trinity " , also known as Trenev Trio. Cost is

about 8 times less.

The keys to success are 1) the large initial doses required (pay no

attention to the labels; I have taken 10 caps of TT with no side

effects and their safety is well proven over span 100 years) and 2)

starting when while also taking vancomycin or whatever antibiotic

regimen puts you into remission, 3) then trying to D/C antibiotic

while maintaining daily probiotics, at least b.i.d. Some of my

patients have learned to make their own cultures by re-incubating a

starter dose in diluted sterile skim milk, which is very cheap.( but

there are some risks to this if you get a contaminant. They have

learned to culture it for purity on blood