During this 20-25 minute pre-recorded lecture, Dr. Ari Grinspan discusses the topic of clostridioides difficile infection. This in-depth review will provide an update on this topic for your clinical practice as well as supplement your learning for the ABIM Gastroenterology and Hepatology boards.
My name is Ari Greenspan. I am the director of fecal microbiota transplant at the Mount Sinai health system. I'm here today to talk to you about Clostridium difficile infection. This will be a case based lecture will go through a number of questions and get at the underpinnings of C. Diff through these questions and answers. Question number one. A 45 year old man comes to your office with diarrhea for three days. He had a recent cellulitis from a skin wound which was treated with antibiotics. He reports 7-10 episodes of watery diarrhea, poor appetite and a low grade fever to 37.5 On exam. His heart rate is 90 blood pressure 1 10/80. His abdomen is soft, non tender with bowel sounds. No rebound or guarding. His labs are notable for white blood cells kind of 12,000 Creating of 1.0 and albumin of 3.7 which of the following statement is true for this condition. Okay, Seed of PCR or NA 80 is the most specific test. B. Vancomycin is recommended. First line therapy C. C. T scan is required for diagnosis. D. Ciprofloxacin and Metro nights are appropriate treatments or e anti diarrheal. Our standard of care The correct answer is B. Vanco mason is recommended. First line therapy C. Difficile is a clinical diagnosis and stool tests are only there to confirm your diagnosis and the most important thing about that answer about CDF PcR or N. A. T. Is that that is one of the most sensitive ways to diagnose C. Diff but it is certainly not the most specific and we'll get into testing and a couple of slides. Vancomycin is now first line recommendation as treatment for CDF Metro night is all is only to be used as an adjunct to follow eminent C. Diff infection. CT scan is not indicated nor warranted as there is no evidence of toxicity and ciprofloxacin does not treat C diff infection while anti diarrheal is can be used to treat patients who have gastroenteritis. Uh This is not routinely recommended to patients who have c diff infection In terms of treatment of seed. If these are the new guidelines that were published from the I. D. Society of America in 2017 2018. And they have re categorized C. Diff into non severe, severe and fulfillment. The treatment for non severe and severe is vancomycin or redox emission as you will see. Metro nasal is no longer part of the guidelines for routine treatment of non severe or severe. C. Diff patients who have full minutes CDF are used. We used vancomycin. Higher doses recommended plus Metro not result ivy with or without vancomycin enemas. If there is any concern for alias again how do we administer Vanco miss into patients? It's pio it's by mouth. If there is an alias and you give somebody a by mouth medication it is not going to get to the colon. C. Diff causes the infection in the colon so you have to get the antibiotic there. That's why we add Metro nine is all. And that's why you can consider using vancomycin enemas for recurrent disease which will get to first recurrence is treated with a bank of mice and taper versus a 10 day course of redox emission and a second recurrence. You can consider fecal transplant in terms of epidemiology of see Edith As we all know it's unfortunately a very common infection. About 450,000 new infections every year with almost 30,000 deaths per year attributed to c. diff. The majority of these cases are related to healthcare exposures inpatient or outpatient. The risk factors for C diff include exposures then that would be via hospitalization or some sort of health care exposure or people who were living in a long term care facility. And then there are host factors antibiotic use older age co morbid IBD pregnancy, any immuno compromised condition, kidney or liver disease or P. P. And H. Two blocker use which has been shown to increase the rates of recurrent C. Diff. In terms of testing for patients it's important to know that there is a fair amount of carriers of C. Diff out there and what that means is that their gut their microbiome is colonized with C. Diff and so therefore you can detect it Using some very sensitive testing modalities but that does not mean that they are having an active C. Diff infection In healthy neonatal up to one year. It can be very commonly found up to 70% of healthy neonatal will test positive for Steve it will be in their colon but it's not causing disease In healthy adults. Up to 5%. If not more of healthy adults will have a positive will test positive for c. Death meaning it's colonized as part of their microbiome but it is not leading to infection. And if you look at hospitalized patients, 10-30% of them can be colonized with c. diff. So it's important to notice. So you do not send stool inappropriately. So we don't send stool for C diff on patients who have formed stool for those who had recent lacks of diffuse. For example, if they're going for a colonoscopy to give them bowel prep in the report diarrhea. That's not the person to send a C. Diff sample on. And we never send C diff as a test of cure. You had see there for a couple of weeks ago. Let's just make sure it's gone. We do not do that is not recommended again, there are high rates of colonization and we do not treat it. So a positive C diff test result without the clinical scenario of active C diff infection is a meaningless test results and it should be disregarded now in terms of what we're sending. Uh we look at the bristol stool chart and we're looking at type 56 or seven. It really should be more like type six or seven. That's the stuff we're looking forward to be what we see with a true C. Diff infection. Now. In terms of CDF tests there are three tests that are currently available. There's a G. D. H. The toxin enzyme immuno assay And then the toxin b. PCR or an 80 nucleic acid amplification test. Those are synonymous. The G. D. H. Is the most is a very sensitive marker for C. Diff. It's found on all C. Diff bacteria but it does not distinguish between toxic genic versus non toxic genetic strains of CDF. So by itself it is clinically useless. The toxin enzyme immuno assay is the most specific test for C. Diff of all the commercially available tests. It looks specifically for the toxin itself. And again this is a toxin mediated kel itis. So it's a toxin that causes the problems. It's not the bacteria it's the toxin that the bacteria produces a toxin ends. I mean you know I say is the most specific test. The problem is it is not the most sensitive. It can degrade in a few short hours when it sits at room temperature. So using this by itself as a screening test is not the best because it doesn't have the highest sensitivity. But it is the most important to confirm that your patient has a C. Diff infection. And then there's toxin B. Pcr or an A. 80 nucleic acid amplification test and these are incredibly sensitive tests for C. Diff and what it is, it's detecting the gene that encodes for the toxin. The problem with this test is by itself it does not distinguish colonization from infection, meaning it detects the gene that encodes for the toxin but it's not actually detecting if toxin is present or not. So while the G. D. H. At the top of your screen and the toxin B. P. C. R. Or N A. 80 at the bottom of your screen are the most sensitive tests. Those should be viewed as in my opinion as screening tests for C. Diff if they come back positive, I am recommending that my patients undergo toxin testing to confirm whether or not that is what is causing their diarrhea or not. Commercial labs frequently use this algorithm where they send if you look on the right hand side they send an E. I A. For the G. D. H. As well as the enzyme immuno asset for toxin and they send those at the same time. If you get a concordant result meaning both of those are positive then the testing is consistent with the C. Diff infection. If they are both negative and then you've got a concordant negative result. That testing is consistent with us with that testing is not consistent with the C. Diff infection. If you get a discordant result and a discordant results is almost always going to be G. D. H. Positive. But toxin negative Then most of these labs will reflex to PcR testing. And they are using the PcR testing as the tie breaker. So if the PcR is positive overall this is viewed as a positive result for C. Diff. But as I spoke with you about the prior slide this is probably flawed thinking because the most useful test to determine whether or not you truly think your patient has a C. Diff infection or not is actually going to be the toxin E. A. The actual study that looks specifically for the toxin itself. And so testing for see death can be incredibly confusing because you're sending multi you're getting multiple results back and you have to interpret what these results mean. Again the toxin enzyme amino S. A. Look that looks specifically for the toxin itself. That is the most important test in my opinion. Question two, The same 45 year old male presents to the emergency department. Two weeks after finishing the course of vancomycin presenting with diarrhea. He had responded well to vancomycin but symptoms rickard soon after stopping the antibiotic, He complained of diary up to 10 times a day exam is notable for a heart rate of 100 blood pressure 1 20/70 T max 37.8 and abdominal tenderness Labs are notable for a white blood cell count of 18,000 creating a 1.5 and albumin of 3.0 C. Diff toxin is positive in the emergency room which is the next best treatment option for this patient, a Metro night is R. P. O. Be fecal transplant. C. Metro night is all ivy and vancomycin pl d intravenous immunoglobulin or e ven commission pl. The correct answer is e. Vancomycin pio. And the objective of this question was to select the appropriate treatment strategy for recurrent and severe. So again, in terms of severity of C. Diff we're talking about non severe versus severe versus full minute. The clinical parameters for non severe are those who don't meet parameters of severe C. Diff which is a white count greater than 15,000 or a creating greater than 1.5 full minutes. Edith is any of the following including hypertension shock alias in terms of again, treatment of seed if it really will depend on how you classify their severity. Vancomycin and paradox emissions are approved. First line treatments for both non severe and severe. Well when it comes to full moment, that's when we'll be using bank of Meyssan plus metronomic. Again with or without vancomycin enemas and its recurrent disease that you will consider vancomycin, taper versus Madox emission and the second recurrence or later you can consider fecal transplant. The reason why Metro night is all is no longer part of guidelines is that if you look at the clinical trials after the year 2000 Metro nasal has been inferior to vancomycin. Whereas there has been a recent trial which showed bank for doc's emission and vancomycin are essentially equivalent that they are non documents is not inferior to vancomycin. So that's why Fedex mission is in the guidelines. And Metro nasal is out of the guidelines. When it comes to recurrence see death. About 20% of patients will recur after a first treatment. 40% will recur after a second treatment and nearly two thirds of patients will have a recurrent episode after a third or subsequent treatment. And the mechanism for recurrent C. Diff is a combination of the alterations in the host immune response as well as altered colonic microbiota. When it comes to treating recurrent C. Diff. There is limited evidence for the use of probiotics. Uh sacrifices Belardi was effective in the prevention of C. D. I. In some small trials, Ivy League has absolutely no role as a sole treatment but may be helpful nose with hypo gimmick Lobell anemia and again, F empty isn't indicated after a third episode or recurrence of C. Diff F. M. T. This was the landmarks trial back in 2013 which randomized patients who had recurrent C. Diff to receiving F. M. T. Vs. Vanco mason versus vancomycin with bowel lavage. Those who received fecal transplant had a 94% Curate at 10 weeks compared to vancomycin who had 30% curate and victimized with alibaba's who had 23%. So that's where the that's when FM T. Really hit mainstream. That this was a remarkably effective treatment for C. D. And now has become an established treatment. Um Study after study has shown that F. M. T. Is an effective treatment for CDF And really no matter how you give it whether it is an enema, colonoscopy, nasal gastric tube or upper gi delivery or in capsule preparation and that is where the field is currently moving to. There are a number of clinical trials which have just recently come out that have shown that F. M. T. V. A capsule formulation is better than placebo. Uh There are a number of pharmaceutical companies that will hopefully have some drugs out there. But again for the purpose of the board, F. M. T. Is absolutely an established treatment for a currency death. It's an all of the guidelines. Both I. D. And G. I. Uh So empty can be used after a third episode or recurrence of C. Diff questions. The same 45 year old male returns to your office for follow up three months later he reports having mildly altered bowel habits with 1-2 semi formed bowel movements daily without abdominal pain. He denies fever chills, nausea, vomiting, blood per rectum or changes in weight. He has not required any antibiotics in the past three months which is the appropriate management for this patient proceed with F. M. T to reduce his chance of future recurrence council to empirically treat with vancomycin If he should be prescribed any antibiotics in the future conservative management, repeat seat of testing now to confirm eradication or should we start suppressive vancomycin. The answer is conservative management and the objective of this question was to select the appropriate management strategy for patients who have been successfully treated for C. Diff. So monitoring patients after seeded. Remember there is no such thing as test of cure. It is not recommended. The only time you should send repeat ct of testing on a patient is if the patient reports diarrhea and typically we're looking for at least three or more episodes of true diarrhea per day. That is a patient that you should be thinking about testing again As this patient is asymptomatic and more than eight weeks out. There is no indication for performing a fecal transplant at this time. It's important to know that altered bowel movements After a C. Diff infection is common. This entity which is referred to as post infection. Irritable bowel syndrome occurs in about 30% of patients after a C. Diff infection. There is no defined role for vancomycin prophylaxis. So if your patient has a history of C. Diff and there are several months ago and they are to get an antibiotic for some reason. Profile. Axing profile accident with. Thank you. Mrs Not part of any recommendation. And again there's no defined role for chronic suppressive vancomycin for patients who have a history of recurrent C. Diff question for A 27 year old woman with all sort of colitis presents to your office with Diarrhea. Her symptoms had been well controlled and muscle main and as a pipeline for the past year, However, she now reports four days of Diarrhea. She denies fever or other symptoms, exam is unremarkable and labs reveal leukocyte count of 18,000 A flex sig reveals the following. Which of the following is the next best step initiate ivy steroids. Check for C. Diff. Start in flex map, colorectal surgery, consultation or await pathology. The next best step is to check foresee death and the objective is to recognize the risk of underlying C. Diff. In the setting of IBD C. Diff occurs 5 to 8 times more likely in IBD patients than non IBD patients. And the problem is that the C. Diff infection frequently resembles an IBD flair. You rarely if ever see pseudo membranes during, during a flex sigur colonoscopy on these patients. It happens reportedly 13 ish percent of the time, but I can tell you my practice I've seen it far less than that. Risk factors include colonic inflammation, severe disease and those who are on immuno suppression specifically steroids. This comes straight from our guidelines for C. Diff all patients with IBD who are hospitalized with a disease flare should undergo C diff testing and ambulatory patients who develop diarrhea in setting of quiescent disease or presence of risk factors should be tested for C. Diff. So this patient who comes to your office with prior history of quiet and disease and is now having symptoms. You should certainly check for seating and C. Diff and IBD again. Vancomycin. It's now first line treatment for anybody but it is always still recommended to use vancomycin for patients with IBD who have C. Diff. It's important that we treat the CDF for at least two or three days if not longer before escalating the therapy. Um In terms of patients who have who are admitted to the hospital this can be a very challenging clinical scenario. They come into the hospital with an IBD flare. They test positive for C. Diff. Is a D. C. Diff that's causing the symptoms. Or is it the underlying IBD treat the CDA first and if after 72 hours or so there is no improvement. Then you can talk about escalating or IBD therapy starting steroids or increasing their immune suppression. Whatever it may be there is this entity of post collect um E. C. Diff. So patients can have enteritis or pouch itis that are caused by city. Uh these rates are less than uh we all potentially think that they are um pouch itis. Uh there's some data that can happen about 10% of these patients but it's something that we should be cognizant of and testing foreign patients to treat appropriately. Question number five you are consulted for a 76 year old gentleman with three prior episodes of C. Diff who developed recurrent watery diarrhea. After receiving I. V. Antibiotics for pneumonia. On exam he is February to 38 5 tachycardic hypertensive. He has significant left lower quadrant tenderness labs show white count of 52,000 album in of 2.7. A rise in the creatinine from 1 to 2.2 and elected a 5.5 abdominal x ray is obtained and you can see on the slide stool testing for C. Diff is pending. He has intubated for respiratory failure, initiated on dopamine and empirically started vancomycin pio and Metro notice all ivy which of the following is true about this condition. A There is no data to support FM. T. In this scenario. Be adding for doc's emission will improve survival. See I? Ve can reduce mortality. D probiotics and bowel rest. Our mainstay of therapy. E-30 day mortality is approximately 40% if he proceeds to surgery. The correct answer is e. The 30 day mortality is approximately 40% if he proceeds to surgery. The objective of this question was to recognize toxic mega colon and its high rate of mortality. Full imminent CDF is characterized. Those who are admitted to iCU hypertension fever greater than 38.5 alias or abdominal distention. patients with mental status changes lactate greater than 2.2 or those with end organ failure. Our patient has a number of these toxic and mega coal and is an entity where the patient is both toxic Number one and have a mega colon. Number two. A mega colon refers to a trans verse colon diameter greater than six centimeters. This correlates with a 40% 30 day mortality if the patients brought for emergency surgery. But surgery Consul should absolutely be called to see this patient as surgery is frequently the most appropriate step in management. There is no data to support adding or changing to fit docks emission frequently. That's done. But there's zero data to support that practice. There's no role for probiotics. There's no defined role for ivy league. And interestingly there is mounting data that suggests that F. M. T. Can be beneficial in these patients. But again, surgery must be on board in terms of conclusions for this talk. It's important to know the guidelines and they're they're new and they're based on the treatment of the based on the severity of the disease that you categorize the patient. Um No what the guidelines are for treatment of recurrent disease. Know what the risk factors are for C. Diff. And they may ask you about endoscopic appearance. So you should have an idea of what pseudo membranes look like. Um And I will add a picture at the end of the slides for you to see. Thank you so much for your time
