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[Dr. Handy] Hi, welcome to Harrison's Podclass, where we discuss important concepts in internal medicine. I'm Cathy Handy. [Dr. Wiener] And I'm Charlie Wiener and we're coming to you from the Johns Hopkins School of Medicine. [Dr. Handy] Welcome to episode 55, a 78-year-old with diarrhea. [Dr. Wiener] Hi Cathy, today's case is a 78-year-old woman who presents to the hospital from a nursing home with complaints of diarrhea.
She's been in the nursing home for the past five years, following a stroke, which left her with a residual right sided hemiplegia. Earlier this month, she had presumed pyelonephritis due to E. coli growing in her urine, and she was treated with ceftriaxone for 10 days. She completed the treatment about four days ago. Yesterday, she developed diffuse abdominal pain and over the past 24 hours she has had worsening abdominal pain and abdominal distension.
Despite only tolerating minimal liquid intake, she has had eight bowel movements in the last day. The staff noted the bowel movements are loose and they've become a little bit blood-tinged. So any thoughts at this point? [Dr. Handy] A nursing home patient with functional limitations is at risk of a host of disorders ranging from infections to vascular events. So in this case, I'd be worried about a recurrent urinary tract infection because you mentioned she had a history of that.
I'm also thinking about acute abdomen due to a vascular cause, remember that you mentioned she's already had a stroke. And I also am thinking about C. diff infection given her most recent course of antibiotics, which would put her at risk of that. Can you give me more history? [Dr. Wiener] Sure. Her past medical history is significant for cerebrovascular disease, intermittent atrial fibrillation, coronary artery disease requiring an angioplasty five years ago, hypertension and hyperlipidemia.
Six months ago, she was treated with oral metronidazole for a documented C. difficile infection. Her medications include warfarin, atorvastatin and losartan. [Dr. Handy] Okay, well now with the bloody diarrhea and the abdominal complaints of the possibilities that I mentioned, I would move C. diff and an abdominal vascular event higher on my differential.
C. diff moves up higher because of her prior history as well as antibiotic exposure and the vascular event moves higher given her history of significant vascular disease and atrial fibrillation that you mentioned she has now. What about her physical exam? What does that show? Is she febrile or do you have any recent labs? [Dr. Wiener] Okay. So on physical examination, she appears uncomfortable and has a temperature of 101.2 degrees Fahrenheit.
Her blood pressure is 98 over 60, her heart rate is irregularly irregular at 115 per minute. Her abdomen appears distended and tympanitic with diffuse tenderness to palpation. There are no new neurologic defects and no new skin rashes. An abdominal X-ray shows distension of the colon with ileus. Her initial lab exam shows a white cell count of 27,200 with 92% neutrophils and 3% band forms. Her hemoglobin is 11.5, one month ago her hemoglobin was 10.1.
Her urinalysis shows no white blood cells or bacteria. [Dr. Handy] The fever and leukocytosis is pushing me more towards C. difficile infection. Her urine has no white blood cells and no bacteria, so recurrent pyelonephritis would be less likely. [Dr. Wiener] Okay, so let's get to the question. The question asks, which of the following findings is least likely to be found in C. difficile infection?
And the options are, A. bloody diarrhea; B. fever; C. ileus; D. leukocytosis; and E. recurrence after therapy. Remember, she has all of these, but which one is the least likely if this truly is C. difficile infection? [Dr. Handy] I just mentioned that fever and leukocytosis are what's making me lean towards C. difficile infection. Both of those symptoms are quite common.
Leukocytosis is probably the most common and is seen in about 50% of cases, fever is seen in about 28% of cases, and then abdominal pain is seen in about 22% of cases. Of the symptoms mentioned, bloody diarrhea is actually not common in C. difficile infection. In this case, I don't think she's had much blood loss, in fact, she seems hemo-concentrated, likely due to volume depletion, and the blood-tinged stools I would suspect are more likely related to her warfarin.
[Dr. Wiener] Okay, well let's talk a little bit more about C. difficile infection. How does one get it? [Dr. Handy] Well, the current thinking is that it takes three steps to develop the infection. First, one must acquire the bacterium in the GI tract. This most frequently occurs in hospitalized or institutionalized patients because of the frequency of C. difficile.
Remember, while we are all diligent about cleaning ourselves with alcohol-based disinfectants, these do not eliminate the spores of C. difficile, that requires rigorous handwashing with soap and water. [Dr. Wiener] So you mentioned it takes three steps. Then what? [Dr. Handy] The second step is usually exposure to antibiotics to make the colon susceptible to the infection. It's thought that the change in the microbiome as a result of antibiotic exposure allows C. difficile to proliferate.
Finally, if the strain of C. difficile is toxigenic and the patient has sufficient IgG response to the toxigenic strain, the patient won't develop a symptomatic infection. This scheme is important to know because it explains how patients may have asymptomatic disease with a toxigenic strain or be colonized with a non-toxigenic strain of C. difficile. [Dr. Wiener] That's interesting. What about the signs and the symptoms mentioned in the question?
You mentioned a couple already, but can you elaborate? [Dr. Handy] Yeah, so C. difficile infection is a common gastrointestinal illness that's most commonly associated with antimicrobial use and subsequent disruption of normal colonic flora. When adynamic ileus, which is seen on X-ray in about 20% of cases, when that results in cessation of stool passage, the diagnosis of C. difficile infection is frequently overlooked.
A clue to the presence of unsuspected C. difficile infection in these patients would be unexplained leukocytosis with over 15,000 white blood cells per microliter. These patients are at high risk for complications of C. diff infection, particularly toxic megacolon and sepsis. [Dr. Wiener] Okay. The question also asks about recurrences, that's common, right?
[Dr. Handy] Yeah. It recurs after treatment in 15 to 30% of cases, susceptibility to recurrence of clinical C. diff infection is likely a result of continued disruption of the normal fecal microbiome, which is caused by the antibiotic used to treat C. diff infection and the aforementioned immune predisposition. I should also mention that it's not recommended that you retest patients. You're really looking for resolution of symptoms as a marker of improvement. [Dr. Wiener] Okay, great.
Well, this is a two part question because it now asks, how would you treat this patient? And the options are, A. oral metronidazole; B. intravenous metronidazole; C. rectal instillation of vancomycin; D. oral vancomycin and IV metronidazole; or E. oral vancomycin. [Dr. Handy] Mild cases of C. diff can be treated with oral medications, either oral metronidazole, vancomycin or fidaxomicin.
Oral metronidazole is less effective than the other options, and may necessitate a longer treatment course for response. Metronidazole is really only recommended now if vancomycin or fidaxomicin is not readily accessible. [Dr. Wiener] But she doesn't have a mild case, does she? [Dr. Handy] No, she would be classified as fulminant infection. [Dr. Wiener] How do you define that?
[Dr. Handy] Fulminant C. diff infection is defined as severe disease, which is leukocytosis with a white blood cell count over 15,000, and a creatinine level 1.5 times the premorbid value, that, plus the presence of hypotension, shock, ileus or toxic megacolon would be how you diagnose fulminant C. diff infections. [Dr. Wiener] Okay, so her white cell count is 27,000. So even though we don't have her serum creatinine, she meets definition by that alone, given her clinical symptoms.
[Dr. Handy] Exactly and she also has ileus, which puts her in the fulminant infection category. [Dr. Wiener] So what would you recommend for treatment then? [Dr. Handy] The medical management of fulminant C. difficile infection is suboptimal because of the difficulty of delivering oral medications to the colon in the presence of ileus.
The combination of vancomycin, which is usually given orally or via nasogastric tube, or even by retention enema plus IV metronidazole has been used with some success in uncontrolled studies. Another option is IV tigecycline in a small-scale uncontrolled study, which also potentially showed some benefit. Surgical colectomy may be life-saving in these cases, if there's no response to medical management, but if possible colectomy should be performed before the serum lactate level reaches 5 mmol/L.
[Dr. Wiener] Okay, so you're recommending option D. enteral vancomycin and IV metronidazole. [Dr. Handy] Yes, that's the correct answer, and I'd also add to that, that she needs close observation to determine if she needs a surgical intervention. [Dr. Wiener] Okay, great. So the teaching points of this case are that C. difficile infection occurs in a susceptible host, and is usually precipitated by prior antibiotics.
The infection may become severe and mimic an acute abdomen when developing fulminant disease. [Dr. Handy] And you can read more about this in Harrison's chapter on C. diff infection and the IDSA guidelines last published in 2018 on the topic. [outro music] [Mr. Shanahan] This is Jim Shanahan, publisher at McGraw Hill. Harrison's Podclass is brought to you by McGraw Hill's Access Medicine, the online medical resource that delivers the latest trusted content from the best minds in medicine.
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