Hello this is Donald Trump (laughing) Hi, so this is Charlie Krasner we got Mike Stanton here, coming out of retirement to join us today. First of all you guys have any cases you want to talk about or issues you want to, where you’re going? Uh and who do we have joining us by phone? Hi, this is Vicky Kolar with Healthinsight. Okay, alright thanks for joining us. Can you guys all hear me in there everybody? There’s another one by phone. Uh and who else just joined us by phone can you hear us? No? Oh okay. So you know I’ve been ragging for the last year or so about urinary tract infections and how, you know, you treat the patient and you don’t treat the test, okay the test or the culture results. If the patient has symptoms we go ahead and treat it and you ignore their discolored urine or smelly urine, all that kind of stuff. So urinary tract infection is getting to treat the patient not the test and so that whole principle of treating the patient and not the test is really applicable with C. diff. And because there’s these new tests, the PCR testing come out for C. diff and there’s a lot of confusion about about C. diff. How do you diagnosis this and when do you treat these patients and so I’m going to try to help straighten that up. C. diff is, you know we had this, five years ago we’d be talking about MRSA taking over the world and now we’re just happy to see and MRSA patient. C. diff is really, it’s really just climbing in the hospital you know, we just had everybody has C. diff and it’s really, it’s really become the major nosocomial problem that we’re dealing with. And I think I’m sure you guys would agree it’s just in the hospital it’s just, it’s a very big problem and so. But it’s also been over treated okay. So the whole talk today is real about treating the patient and not the test so.. do you have a little control for that? So let’s review some stuff and then see if we can get this to go here. Okay this is just the background you know they estimate, the CDC estimates that C. diff infection costs us about six billion dollars a year. There’s about half a million infections twenty-nine thousand deaths and then as of a few years ago it passed the number of deaths of MRSA in the hospital so it’s a big problem. Probably as, you know we have antibiotic stewardship programs, probably the number one cause is overuse of antibiotics, number two cause which I’m going to review for you is that there’s a new virulent strain let’s come back that’s really a nastier C. diff, it’s like a super C. diff it causes high mortality increased relapse. But the third reason that we’re seeing so much C. diff is probably over diagnosis okay and that’s what I really want to emphasize today. How do you make that diagnosis of C. diff and when do you treat it? Okay it’s not a test result it’s a clinical call okay and that’s what’s been so important okay. So just review, C. diff it’s called a two hit the two-hit disease. First you gotta be put in the hospital, you know, if you have x-ray glasses you could see C. diff spores everywhere. So you get them into the hospital they get colonized with C. diff and then, the first thing is you get colonize the second you get exposed to an antibiotic. The antibiotic wipes out your gut flora and the C. diff does it’s thing okay. But not all the time that you get C. diff and take antibiotics much of the time you just have colonization. The C. diff is sitting there not doing anything, we call that colonization it’s not causing any problems. On the other hand you can get exposed to C. diff taking antibiotics and then you can get the horrendous C. diff diarrhea colitis, megacolon, the toxic megacolon and death. So when you get c. diff and you get exposed to antibiotics it doesn’t mean that you’re going to get a severe disease. You may just become colonized with it and that’s what the tests are very helpful in differentiating between when do you treat somebody who has C. diff colitis and when do you just say they’re colonized but leave them alone don’t treat them. And so C. diff infection it’s not a lab test it’s a clinical diagnosis okay. So C. diff infection it’s always symptomatic it’s basically defined as watery diarrhea associated with the least bowel movements watery diarrhea 24 hours oftentimes associated with abdominal pain, cramping, fever, nausea, lack of appetite and leukocytosis. So the diagnosis of C. diff infection is a clinical diagnosis and then it’s complemented by lab tests. It’s not a lab test diagnosis it’s a clinical diagnosis okay. If somebody has a positive lab test for C. diff but has none of these symptoms, they don’t have C. diff infection okay they’re just colonized and they don’t need treatment. And so that’s what we’re going to talk a lot about today. So this colorful picture, up in the upper left you see the intestines under the stomach. So somebody gets C. diff on their hands gets exposed to it and they have two forms one is the spores which is the blue one or the vegetative cells okay up here. And they pass through the intestines, if you’re not on an acid blocker, not even, there’s no inhibition of pro. So it goes into the small bowels but it’s not causing any trouble and then on the next thing, on the right side, it goes into the colon again it’s not causing any trouble it’s in the colon it’s just colonizing the colon, the spores and the vegetative spores the cells, but it’s not causing any trouble it’s just minding its own business. Then on the, on the bottom you get exposed to antibiotics, there’s a vacuum you don’t have these healthy bacteria inhibiting the growth of the C. diff. So also the healthy bacteria are gone the C. diff are not being inhibited by bacterial other healthy bacteria in the microbiome and they start producing toxins. These toxins are called A and B toxins and so if you have the healthy bacteria in the intestines most of the time the C. diff is just going to sit there colonizing, not causing any problems okay. But it has that potential to cause these toxins production. So you wipe out the gut flora there’s no inhibition the C. diff starts producing the toxins. The toxins and A and B, they cause inflammation of the lining of the intestines, the whole body of the intestines gets inflamed and actually comes up off and you see this what’s called pseudo membranes okay. See this next slide. These pseudo membranes are are the result of the toxins A and B attacking the lining of intestines. The whole mucosal lining gets lifted off, you see when you do a colonoscopy you see these what are called pseudo membranes, this is called pseudomembranous colitis which is the clinical manifestation of C. difficile colitis with the watery diarrhea, the mucus, the green stuff, the smell, the white count okay. So this is clinical disease it’s not because the patient has C. diff in their intestines is because these C. diff are now producing toxins. So the real bent and the cause of this infection is the toxin A and B toxin. Most of the time when you have C. diff in your colon it’s being inhibited by healthy bacteria and it’s not causing any infection, okay so just colonization. So how do we, this whole talk is about how you differentiate between colonization that you don’t need to treat and actual toxic disease so this is the manifestation of C. diff infection caused by these toxins. So why are we having more C. diff infection? One of the major reasons is that it’s, about 15 years ago C. diff mutated itself instead of being inhibited by antibiotics we used the quinolones clindamycin and stuff, it mutated itself so it was no longer inhibited by these antibiotics we’re using. So we’re using a lot of quinolones we’re using a lot of drugs that would wipe out the healthy flora but this C. difficile was not being killed by it okay. So one it was becoming resistant to the antibiotics we’re using, so it wasn’t getting wiped out. And two it had mutations instead of producing just like normal levels of toxin A and B these mutations totally blocked the ability to inhibit the growth of these toxins. So now we have these C. diff producing 10-20x more toxin then we traditionally saw. So we had a C. diff that was resistant to antibiotics and two was producing such amazing amounts of toxin they’re sort of overwhelming the ability of the antibiotics like vano and flagyl to inhibit their growth. It can also cause, there’s so much toxin that’s causing such severe colitis and increase incidence of death okay. And this C. diff, does anybody know the name of this C. diff? The fancy term for this this virulent strain? It’s the NAP1 strain… NAP1 Yeah exactly. So that one is a marker of this C. diff that’s sort of taken over the world that produces high levels of virulents and it’s not inhibited by the traditional antibiotics. And so as of a few years ago we had no cases in Nevada and now approximately half of all cases in Nevada people are hospitalized are NAP1 positive. So this is like a nasty super bug it’s sort of like MRSA how it sort of took over the world. So half of all cases in Nevada are NAP1 positive, which means; one that they’re producing high levels of toxins, two that they’re very likely to cause severe complications much greater incidence of death and other problems and two because there’s so much toxin produced and it, you get greater complications and it’s also much more likely to relapse okay. So it’s resistant to the antibiotics, high toxin levels, fulminant disease and death. And if you’re lab does what’s a micro, if your micro lab does what’s called a PCR test, the PCR test will also test at the same time for the NAP1 strain. So they should be able to tell you if you’re doing PCR testing whether or not you have NAP1 strain It’s just, it’s sort of like a red flag, that this patient’s more likely to have a very severe disease much more likely to relapse on this disease. So this NAP1 strain is this is the marker for C. diff that’s very nasty. And again it’s about half the cases came out of nowhere the last few years. So I want to present the case I’m have in the hospital right now. This is a NAP1 C. diff case alright. So in spring of 2016 this 84 year old male he was given ciprofloxacin for bacteriuria, he developed C. diff colitis. So the PCR test tells us that he has C. diff, the NAP1 strain tells us that this C. diff is high toxin producing. Again he could be colonized with this but he was actually symptomatic because he had diarrhea, so we’d say this is a clinical case of C. diff. He was put on flagyl subsequently over the next few months he had four C. diff infection relapses. Again treated with oral flagyl and oral vancomycin. And so after the fifth relapse in October he received a stool transplant where they stick a tube down him and gave him a stool infusion and he did very well. About two weeks ago he had a fall at home, he was admitted to the hospital he had a hematoma they told us possibly cellulitis. They gave him ampicillin few days in his hospitalization he developed watery diarrhea, hypotension lactic acidosis, renal failure, his white count went up to 35,000, his abdomen got distended, the stool again showed C. diff, PCR, NAP1 positive, again this nasty C. diff. On the day three of the diarrhea underwent subtotal colectomy when they took out his colon. He’s presently on pressors, dialysis and a respirator. This is a nasty C. diff okay this is not a joke. So this guy had C. diff he has NAP1 strain and he was clinically very sick with the diarrhea and all the other symptoms. So we’d call this a C. diff infection. On the other end of the spectrum we have C. diff carriers so these are people who have C. diff, the PCR will be positive because they have the C. diff. But they’re not sick at all and so that would tell me that they’re carriers but the C. diff is being controlled, it’s not producing toxin, so just having C. diff in your stool doesn’t mean you have C. diff infection just means you’re a carrier. Those are pictures of the spores you can see the picture down there. So there’s a whole spectrum of disease severe C. diff colitis, toxic megacolon, to carriers. And so what I want to emphasize now is don’t treat C. diff carriers because they’re not infected okay. Again both these patients have C. diff PCR positive, one who almost dies and the other patients who are carriers, but only one had the clinical disease. So you don’t want to treat somebody who doesn’t have a clinical disease which is the watery diarrhea multiple bowel movements associated with GI complaints. So the question is are we over diagnosing and over treating C. diff infection. Okay how’s C. diff diagnosed? Traditionally up to a few years ago, we don’t do cultures because they just tell you C. diff is there it doesn’t really help it takes a long time. Traditionally we were doing the ELISA test. The ELISA test was the C. diff quick check and what it does is there’s two parts to the ELISA test. One, would tell you if there’s a thing called the gloomy dehydrogenase which is a enzyme found in C diff and so you get a positive GBH. Tells you that there’s C. diff present and it would then also have a test to look for toxins A and B. So you would get a GDH positive, plus or minus a toxin test okay. So that was how we diagnosed C. diff okay. Sometimes we’d say oh the GDH is positive but we have no toxins so we think maybe the test isn’t that sensitive. But probably what they were doing was they were finding out C. diff that was not producing a toxin. So now everybody’s moved to PCR testing so the PCR is a molecular test that actually looks for C. diff and to see whether or not it has the gene that can produce these toxins. But just because C. diff has that gene that can produce toxin doesn’t mean it’s producing disease. Okay so we’re getting all these positive PCR tests all it tells us is that that patient has C. diff in their stool it doesn’t tell us if they’re producing the toxin and so what’s happening, a lot of people are getting treated for C. diff because their PCR is positive but they don’t have clinical disease, they don’t meet that criteria. They may have diarrhea because they’re on lactulose because they have other things from their feedings and stuff like that but C. diff is not should not, treating C. diff should not be based on your PCR results okay. So let’s talk about the drawbacks to the PCR test okay. A positive PCR test tells us that you have C. diff, but does not mean active infection because the C. diff is not the cause of the problem, the problem is the toxins it produces. So only a test that looks for active toxin A and B production can help you determine if a patient really has active infection. So if somebody, a colonized patient will have a PCR positive but their toxin will be negative and these are patients that are carriers are 5-10 times more likely be found.. People who are PCR positive 5-10 times more are toxin negative then they are toxin positive in the hospital. And we see diarrhea is very common the hospital due to laxatives, dietary supplements, medication side effects, not just colitis. So don’t assume a positive PCR test means active disease that needs treatment, it has the potential negative consequences for your hospital. You’re going to treat somebody who doesn’t need it, you’ll put them in isolation. Your infection rates are going to go up okay if you really want to be able to tell if somebody is just a carrier or he is actually infected. Okay and so what a lot of places are doing, that we talked about, negative consequences of only treating CDI it affects your infection control rates, get to isolate somebody, exposing them to unnecessary antibiotics and the patient who’s in isolation gets anxious is depressed okay. So we’ve basically moved into the PCR generation now but we’re seeing that we’re picking up a lot of patients that have diarrhea but are not producing the toxin okay, are not sick with the disease. So what a lot of places are going based on a study I’ll tell you about, you’re doing the PCR as a screening test. That just means you’re a carrier but then let’s actually look for the toxin itself and a lot of people are going back to the test which is back to the future. We’re using the C. diff quick chek that’s a test made by I think… And what it does, you see that test in the bottom can test for the GDH so the antigen is positive and then on the right side of that test you see a toxin. If that’s not there it tells you that person’s a carrier but they’re not producing toxin okay. So this test allows us to say yes they’re a carrier but no you’re not producing toxin and if you’re not producing the toxin they’re just carriers. So these are the patients you don’t want to treat okay. So this was the study from JAMA for the University UC Davis and you can see there’s three lines here. They wanted to see how people who had, who are on these were all, these are patients who had PCR so they were carriers and some of them produce toxins and some do not. They want to know how do these patients diarrhea? So if you look at the highest one, the first, this one up here the these people have dreadfully long diarrhea. And so these were patients, if you go up to the corner they were toxin positive, PCR positive. So these are patients that were just carriers of C. diff but they are actually producing the toxin. So toxin test was positive the screening tests showed that they were carriers okay. The next group is PCR positive but toxin negative, the see the line the yellow, and they compare those with people who are PCR negative and toxin negative. So there was no difference in people who had diarrhea that were not carriers versus those who had carriers if they weren’t producing the toxin. So definitely what you’re differentiating from is between people who produce the toxin very sick versus people who just have diarrhea for whatever reason but aren’t producing toxins, so there’s no difference. And so the PCR test picks up C. diff but the toxin test actually picks up patients who are producing toxins are very likely to have their colitis So are we over-diagnosing C. diff? Up to 50% of tested patients don’t have diarrhea or significant diarrhea, I’ll show you this funny thing that tells you what the diarrhea is supposed to look like okay. So half these patients who are being tested either don’t have diarrhea at all or have just loose stool, they don’t have three or more stools, watery stools. Up to 40% of the patients who have been tested, or PCR positive turn out to be on laxatives. So the PCR test is 100% sensetive it tells you if there’s C. diff in their stool but it only has a 45% predictive value that they actually have the disease. So this is a this is the Bristol stool scale which I just recently learned about. And this is, if you have C. diff you’re supposed to be, look at the child’s one, you’re supposed to have gravy for diarrhea alright. So unless they have gravy for diarrhea they should not be tested for C. diff okay. So these are called stage 7, it goes from porridge, chicken nuggets, sausage, corn-on-the-cob, a bunch of grapes, or rabbit droppings. (laughing) Alright so C. diff, if you have C. diff that’s toxin producing it should look like gravy or type 7 on the adult scale okay. It should look like three or four alright or even six right. Really should have diarrhea as we said the clinical diagnosis of C. diff is watery type 7 diarrhea, multiple movements associated abdominal pain and discomfort. So antibiotic stewardship role treat the symptom not the test result just because somebody has a positive PCR it doesn’t mean they have infection okay. If they have a positive C. diff PCR which means they’re the least colonized; do they have symptoms, are they having watery diarrhea, do they have a white count or not a white count their belly pain. If they don’t have any of those clinical signs and symptoms they’re almost certainly just colonized, okay. Do, don’t treat the test result and what we’re doing at your Nevada or where I work is we’re going back, we’re now adding the, we’re now adding back the C. diff toxin test. So we’re doing PCR as a screening test and and then the microbiology lab is immediately switching over to the ELISA test to see if there’s toxins present. If the C. diff PCR is positive for either carriers, and then the PCR test, I mean the ELISA test for toxins positive we’re saying this patient has C. diff if they have clinical indications go ahead and treat them. But the patient is PCR positive for being a carrier but the toxins negative we’re writing a note saying that you know this patient just may be a carrier it’s important to use your clinical judgment to decide whether or not this patient needs treatment okay So the other thing is you guys if you if you work in a hospital you know how the nursing home torches you okay. They say we won’t take our patient back until we have a test of cure. They want to test of cure PCR test and you should just refuse because up to 60% of the patients will remain positive after successful C. diff treatment. Which means that they’re no longer producing Bristol type 7, they’re now just in carrier state they are not infected with disease. So there’s zero role for retesting C. diff, don’t do it. The Micro Lab should refuse to test any stool except Bristol 7, watery diarrhea. If you get one were, because I’ve had this a number of times where we’re trying to get a patient out that had C. diff, trying to send them to a nursing home and they’re telling the nurse – No we can’t take them until they have tested cured. I would end up calling them and usually I could convince them but the other option is you can tell Washoe County Health to call them and they’ll call the nursing home and explain they can’t, they cannot do a test of cured. Yeah because the PCR test is just it’s a carrier, doesn’t mean anything. What you want to know is how they’re clinically doing. Alright this is some things just to review. Increased virulence in the NAP1 strain which is that nasty strain, is a result of which of the following: lower rates of germination. Yes or no? No Highly resistant to anti-fungal agents (inaudible) A gene mutation leading to reduced toxin production.. Right, right. So the ability to produce large amounts of toxin A and B that overwhelm treatment attempts. Yes a really nasty bacteria. So this is a case that was just written up in JAMA, it was really interesting. A 28 year old male presented with abdominal pain and diarrhea, it was greater than 10 Bristol type seven, so type 7 stools about watery stuff. After a course of augmentin for pneumonia. So he was diagnosed with C. diff infection by the PCR test. So the PCR test just to review looks for the presence of the gene that makes the toxin, doesn’t tell you whether or not it’s producing. You could, you have the diagnosis right there but if you wanted to you could also do a ELISA test to look for the toxin itself. The PCR test tells you that it’s a C. diff that has the gene capable of doing it, but you have clinically you have a diagnosis though, so ten watery stools he took augmentin. So he was treated with a 10 day course of flagyl with resolution of his symptoms. He returns to baseline two to three Bristol type four stools, let me go back… Type four are sausage okay. Infectious disease is fun. (laughing) Okay so he returns to baseline two to three Bristol type four stools per day. Starting six weeks later, again has abdominal discomfort for the next three weeks relieved by bowel movements was increased stool frequency. So he has four to five type four stools per day so he has this increasing of the bowel movements with type four stools. Physical exam shows a soft abdomen, white count is normal repeat stool test for C. diff toxin PCR again showing that he’s colonized at least colonized with C. diff. What would you do next with this patient? This is a very common presentation. One would you diagnose the current C. diff infection to prescribe another course of metronidazole? Why not? Anybody.. Well one he didn’t have the type of stool and also PCR, I mean that’s just showing that he’s colonized likely not infected. Right, so he doesn’t fit the criteria, he has four to five bowl movements but it’s not the watery type he just has loose stools okay. So he has a normal white count, his belly is soft he doesn’t have, he doesn’t have that Bristol’s type seven stool. So he’s again the PCR is picking up the guy who’s colonized with C. diff but not cause infection. Would you diagnose as a severe C. diff infection and prescribe oral vancomycin? No. Again No. Oral vancomycin would be used if somebody’s very sick and their white count is over 15,000 etc. How about this would you diagnose refractory C. diff infection and consider a fecal stool transplant? You shouldn’t but they do. Okay, don’t be judgmental (laughing) Sorry Diagnose post infectious alter bowel habits with C. diff colonization and recommend a high-fiber diet. That’s the answer, it turns out at least 25% of people are treated for C. diff and it resolves will at some point, in the next month or two have loose stools etc and it’s not, they’ll be colonized but it’s not the cause the infection they just have you know their gut’s been wiped out and their bowel flora it takes a long time to get back the healthy microbiome okay. So that’s again don’t I see people over treated all the time with flagyl over and over again, and then they’ll do a PCR test that’s positive and they’ll keep on giving them flagyl and after about four times they’ll come see us. But it’s really just it’s sort of like an irritable bowel syndrome thinks your gut flora is upset Alright so that is the right answer Okay so the bottom line: C. diff testing should be restricted to patients suspected of having C. diff infection who have multiple watery stools okay. Don’t test people just because they have loose stools okay, they need to have watery stools okay Asymptomatic C. diff colonization is a common reason for false positive stool PCR test. Again the PCR is very sensitive at picking up the presence of C. diff in the stool but doesn’t tell you anything about whether or not it’s actually causing problems or just sitting there minding it’s own business. So how would you go about, if you have the patient with diarrhea, how would you go about determining whether or not you know it’s clinically suggestive what would you what test would you get next that’s available to you? The ELISA Yes if you get the ELISA test back in your lap you know that’s what we’re doing okay. Stool C. diff testing is not appropriate after the treatment of C. diff infection in the absence of symptoms. Don’t retest okay because it mean nothing, it just means they’re carriers. Post-infection functional abdominal symptoms occur in up to 25% percent of CDI patients they should be differentiated from recurrent CDI with a careful history alright. But you don’t need, you guys work in the hospital everybody gets stool laxatives no matter what, they’re all put on ensheild which gives them diarrhea. They’re given regular antibodies which upset the gut flora so it’s extremely common to find C. diff PCR positive patients who, they don’t don’t have like the watery diarrhea they just have soft stools but have no symptoms and they’re just carries, do not treat those patients okay. And don’t, you may at least put them in isolation or at least you know so that they do have loose stooIs you don’t spread it but do not give those people the diagnosis of C. diff okay. Alright to paraphrase Bill Clinton when it comes to C. diff and UTI, it’s the patient stupid, okay. So don’t, you know, don’t reflexly treat PCR positive okay look at the patient. Why are you doing it? Are they asymptomatic? If they’re symptomatic you don’t even need the ELISA test but if there’s ever a question get that test. As I said it’s very common what we’re seeing in these patients. And then what we’re looking for it you know it’s, I think we’re seeing very frequently that you’re over diagnosing it. Enough people are dying of C. diff we don’t need to over treat the patients that don’t have it. Does it mean that we now do the NAP1 or… Yeah we were very slow with the VA, we just got about a year ago we got the PCR test setting up and now that all this information is coming about that we’re over treating it we’ve now, we’re doing the PCR test and then were going to flip over we’ve got the ELISA test back. But I mean are they doing the NAP1? Yes Oh they are We’re getting a new machine that’s testing for the NAP1 too. Because one thing with the NAP1 they don’t, it doesn’t respond very well to metronidazole at all and it’s offen a slow responder to vancomycin. So if you have that I wouldn’t even mess with flagyl I wouldn’t, I would go right to vanco plus or minus something else. My policy: if anyone’s in the hospital sick enough to be treated for C. diff I don’t go with flagyl in the hospital, I just do oral vancomycin okay. As I said this guy we just had last week, he went from 0 to 60 within you know, the diarrhea onset it was in 48 hours we were taking him to surgery. So this is a, the NAP1 particularly is rapidly progressive severe disease. You got to get a quick grip on that because it is very nasty okay. Yes so if anyone’s in the hospital put them on vanco, vaco orally. Have you guys hadany experience with the C. diff in your hospitals being an issue? Or any questions about our talk? Um yes I have one question. Sure Um I’m sorry to have missed the JAMA article, is there any correlation between the doses of the metronidazole um or to see if there’s relief in symptoms? And then the other question is are there antibiotics which are more predisposed towards C. diff? Yeah that’s a, the answer is always the quinolones okay. You really have to be real concerned about the quinolones for causing C. diff. They’re probably the biggest risk factor in the hospital and that’s part of one of the reasons that NAP1 took off 15 years ago, is overuse of quinolones because the NAP1 strain are resistant to it and it wipes out your gut flora. Those are very bad clindamycin’s obviously bad and some of the penicillin. Tryacim is bad it’s bad yeah. Yeah, and then there’s some that are not really not inducers like doxycycline to tetracycline bactrim’s not an inducer, aminoglycoside is not an inducer. (inaudible) many times people go ceftriaxone Rocephin and azithro both increase your risk for C. diff and so one other option is to if you’re going to use rocephin, instead of using azithro use doxycycline. Because doxycycline has some activity against C. diff and will reduce the instance of C. diff by 80% compared to most definitely azithro. So we’re trying to encourage people to do that regimen. Cause doxy gives you capable coverage and has activity against C. diff so that’s a real good regimen. If rocephin is being excreted, so it gets right into the intestine so it’s really high concentrations of it wipes out the gut flora. I mean it’s a great drug cause it’s once a day and expensive and works well but it does increase your risk of C. diff. And the dosing, the dosing is standard on the flagyl, and the vancomycin vancomycin 125 sounds like a small dose but if you remember it’s just inside the intestines so even though it stays in the intestines, which is a very small area. So 125 gives an extremely good level you know vancomycin level 100 to 200 so it’s very high.. Actually the MIC of above the vanco is about one mic/ml so it’s very low. The levels in the gut on 125 qid is between 500 and 1000 mic/ml. Yeah so we give them 250 Yeah it doesn’t you don’t even need that much yeah. It’s just the disease is so nasty the toxins are so it just overwhelms it. It’s not that it’s resistant to vanco it’s just the toxins are just so amazingly strong. And the other thing is when you give like vancomycin or metronidazole that screws up the patient’s flora for a long time. So it puts them at risk again because once the ones the antibiotic is gone now their flora is it’s going to take three months or more to get their flora back. That’s when you get that irritable bowel syndrome afterwards. Yeah. Do you have a hard time finding stool donors? Uh down the street (laughing) No there’s I’m happy to volunteer is what I’m saying. Well you know I could participate if you needed some. No they have, there’s a, the GI doctors do it in town. But there’s this there’s this nonprofit group out of Boston and they have this amazing thing where they’ll provide it for you, they’ve already they screen it completely, they ship it to you and it really is great. They’re very dedicated people and so it’s pretty interesting the things they’ll just send it to you. So that’s a that’s pretty neat. It’s a big, the screening test for the stool is pretty elaborate I mean they have to look at HIV, they have to look at hepatitis, they have to look at C. diff, they have to look at a number of things to make sure the patient has none of that. Yeah, what’s that place in Boston called? OpenBiome Yeah it’s interesting just to Google OpenBiome.org or something like that. There’s a whole bunch of young people that are very motivated and they set up this whole program so they provide that’s pretty neat. It comes from a lot of MIT students Yeah just a bunch of motivated students so that’s pretty cool. Yeah your uh patients might get smarter. Yeah cause changing their intestines might make them smart. There you go. So there’s some advantages to getting a stool transfer. S hey we’re in Ely I apologize. We do not carry the vancomycin capsules tablets whatever we just are using the IV orally, mixing it that way. You have any qualms with that or any problems doing that? No that’s what everybody does nobody uses the capsules or tablets Okay You just make it from the IV. How long is it good, if you mix it how long is it good for? I think it, I don’t know exactly but you know it’s good for a couple of weeks anyway. So enough to give, make it for a patient and have them take it for the course. Thank you Yeah we use that, I think they stopped, we used to give them we’d mix the vanco it was so cheap we just say you know here take this home with you when you finish it off. But I think there was a regulation to do with that or something. Yeah (inaudible) So that’s a great way to do it that vanco capsule’s a big ripoff. Yeah a big ripoff. Yeah what a joke. Alright well thank you all. Any other questions? Thanks Thank you Alright so this clinic will meet again next month February 16th same time same place. Thanks everyone!