Links To And Excerpts From The Curbsiders’ #117 Clostridium Difficile Infection With Links To Additional Resources

Consider and review the dangers that we all should think about in every diarrhea patient – toxic colitis (toxic megacolon) overview and etiology [Links are to pages of the article]; as well as dehydration, and septic shock*.

Note to myself: I had some trouble understanding the two step C. difficile testing algorithm described in the Curbsiders post. So I accessed Quest Diagnostics Test Directory: Clostridium difficile Toxin/GDH with Reflex to PCR*

Test Summary Clostridium difficile Toxin/GDH with Reflex to PCR, Test Code: 91664CPT Code(s)
87449, 87324

I’ve also included the Quest Test FAQ on Clostridium difficile Diagnostic Testing resource:

The American College of Gastroenterology3 and the American Society for Microbiology4 guidelines recommend utilizing 2 different testing options for the detection of C difficile infection:

  • Nucleic acid amplification tests (NAAT) for C difficile toxin genes (test code 16377)
  • 2- or 3-step algorithm that includes assessment of C difficile toxin and glutamate dehydrogenase (GDH), as well as detection of the C difficile toxin B gene (test code 91664)

The Infectious Disease Society of America/The Society for Healthcare Epidemiology of America (IDSA/SHEA) guidelines, which are posted on the CDC website, recommend gene detection for confirmation when the GDH test is positive and toxin is not detected. They also recommend gene detection when the GDH test is negative and toxin is detected. PCR or another nucleic acid amplification test (NAAT) can be used.1,5

And here is the Quest flow chart:

In this post, I link to and excerpt from The Curbsiders#117 Clostridium Difficile Infection: IDSA Guidelines, Bad Puns, and Random Pearls

All that follows is from the above outstanding resource.

Conquer Clostridium difficile (Clostridioides difficile) with this “spore-tacular” episode featuring infectious diseases expert, Dr. Curtis Donskey, Professor at Case Western Reserve University and clinician at the Louis Stokes VA Hospital. We discuss the updates in the 2017 IDSA C. difficile guidelines, plus a bunch of random pearls. If you have ever laid awake at night wondering how many pills are needed for a fecal transplant, then this is the episode for you!  We discuss why metronidazole was dropped as the first line therapy for Clostridium difficile infection (CDI) along with other hot topics such as two-step testing, loperamide use, which antibiotics are the least likely to cause CDI, and a bunch more random facts. Do not miss this episode!

Clinical Pearls

  1. Test for Clostridium difficile (CDI) only if there is clinically significant diarrhea; defined as more than three unformed stools in 24 hours.
    Ask your patient: What do they mean by diarrhea? Quantify and characterize.
    Ask yourself: Is there any other reason for the diarrhea, ie laxative?
  2. Best performing method for CDI testing: A two-step algorithm utilizing GDH assay plus toxin EIA assay is recommended since it can identify asymptomatic carriers, and those with non-toxigenic strains of CDI. This can help avoid overtreatment. The most SENSITIVE CDI test is a NAAT (PCR assay targeting the B toxin gene, tcdB) alone or as part of a multistep algorithm.
  3. Repeat testing for Clostridium difficile infection is not recommended within 7 days during the same episode of diarrhea. In those recently treated for CDI, testing can remain positive even if symptoms have resolved.
  4. Treat with vancomycin or fidaxomicin for initial CDI infections. Metronidazole is NO longer first line therapy, unless the patient is intolerant of first line options.
  5. Try to treat patients at high risk for CDI with low risk antibiotic such as doxycycline, TMP-SMX, pip/tazo (instead of cephalosporins) or cefepime (in place of ceftriaxone).

Dr. Donskey’s Take Home Points

Clostridium difficile colonization is very common. This complicates everything we do for diagnostic testing in suspected CDI. Therefore, it leads to both over and under treatment. There’s probably more CDI out there that is not causing disease. Thus, order and interpret your tests cautiously.

Testing for Clostridium difficile

  1. Don’t test for CDI unless a patient has had at least three unformed stools in 24 hours.
  2. Nucleic Acid Amplification Test (NAAT/ PCR): This tests for the tcdB gene (toxin B). Pros: It’s a very SENSITIVE test. Cons: It can pick up asymptomatic carriers who do not need treatment.
  3. Two Step Approach: Step One: Check for GDH stool antigen (glutamate dehydrogenase). GDH detects the presence of C.diff organisms in the GI tract with a high sensitivity (NOT specificity). Step 2: Check the toxin EIA Assay. This determines if the patient has a toxigenic CDI versus being an asymptomatic carrier.
  4. Interpreting a two step approach:Case 1: GDH Pos / Toxin Pos: Treat! Your patient has a toxigenic strain of CDI. Case 2: GDH Pos / Toxin Neg: Patient is a carrier of CDI (not producing enough toxin to create symptoms). Alternatively, this may be a false negative toxin assay. Dr. Donskey’s expert opinion: Observe the patient clinically before determining whether to treat or not treat.
  5. Repeat testing for CDI is not recommended since a test can remain positive even if their symptoms have resolved.

Classification of CDI infections

The criteria for severe CDI are as follows: WBC above 15,000, or Cr above 1.5. Infections are considered mild-moderate if not meeting these criteria. The guideline does not distinguish between a Cr elevation from AKI or CKD. Dr. Donskey notes that clinical judgement can also be used to classify a CDI as severe.

Fulminant CDI is present if the patient has any of the following: hypotension, ileus or shock (ICU level sick). Dr. Donskey recommends a surgery consult for patients with fulminant CDI. Add IV metronidazole and increase the dose of vancomycin to 500 mg four times daily in fulminant CDI, especially if an ileus is present.

Fidaxomicin Pearls

  1. High costs limit its use. In practice, fidaxomicin is used for recurrent CDI, or as a bridge to fecal microbiota transplant. Its narrow spectrum is ideal because it does not kill off as many good bacteria as vancomycin. Dr. Donskey notes that fidaxomicin has equal efficacy and lower risk of recurrent CDI when compared to Vancomycin (See Louie, et al)
  2. There are some studies looking at fidaxomicin taper regimens to improve cure rates or decrease recurrences, but these are not standards of practice at this time (see Guerty, et al, and Soriano et al)

Vancomycin Pearls

  1. How do you taper vancomycin? The guidelines provide a wide range of options. Vancomycin can be tapered over 3-4 months. Dr Donskey notes that, in theory, a pulse and taper allows more time to kill the spores that remain in the colon, which theoretically could improve cure rates. Lower doses of vancomycin during the taper allow repopulation of normal flora.
  2. The CDI guidelines suggest a vancomycin taper for first recurrence as follows:

Vancomycin 125 mg po four times per day for 10–14 days, two times per day for a week, once per day for a week, and then every two or three days for two to eight weeks.

Social Media questions

  1. Can loperamide cause toxic megacolon? Case studies suggest it can! If a patient has an uncontrolled acute diarrheal illness, then avoid antimotility agents. Dr. Donskey’s Expert Opinion:  It can be OK to give loperamide for persistent diarrhea if a patient has been on therapy for 5-7 days and shows signs of clinical improvement. BUT use it judiciously!
  2. CDI and antibiotic triggers: Avoid clindamycin. Choose antibiotics with a lower risk for CDI if possible. For example, doxycycline has a lower risk of CDI than moxifloxacin. TMP-SMX has a low risk of CDI. Penicillins such as Pip/tazo have a lower CDI risk than cephalosporins. Ceftriaxone is a strong promoter of C.diff so consider utilizing cefazolin or cefepime as they are less likely to promote C.diff (Owens, et al).
  3. Probiotics: Some evidence evidence suggests that probiotics may prevent antibiotic associated diarrhea, and may prevent CDI recurrence. BUT, the evidence is conflicting/weak. Dr Donskey’s expert opinion: It’s OK for patients to try probiotics if they want, but he doesn’t routinely prescribe them.
  4. Is there any utility in placing patients on “prophylactic low dose oral vancomycin”, when treating with broad spectrum antibiotics? Dr Donskey’s expert opinion: This is an area of debate and active research. In the future, giving a low dose of oral vancomycin for prophylaxis may prove beneficial in select patients.
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