#117 Clostridium Difficile Infection: IDSA Guidelines, Bad Puns, and Random Pearls

October 1, 2018 | By Carolyn Chan

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!

Credits

Written by: Carolyn Chan MD
Produced by: Matthew Watto MD
Hosts: Carolyn Chan MD, Matthew Watto MD, Paul Williams MD
Editor: Matthew Watto MD
Guest: Curtis Donskey, MD

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.

In-depth Show Notes

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.

Treating Clostridium difficile Infections

1. The first line treatment for initial CDI is vancomycin or fidaxomicin. Metronidazole is NO longer first line treatment for an initial episode of CDI.
2. Why was metronidazole dropped as first line? Metronidazole is almost entirely absorbed in the small intestine. It works less quickly, and less consistently. Studies have demonstrated that metronidazole is inferior to vancomycin for mild-moderate cases of CDI.  (Siegfried et al. Initial therapy for mild to moderate Clostridium).

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.

Fecal Microbiota Transplant Pearls (FMT)

1. The 2017 IDSA C.diff guidelines currently recommend a trial of treatment with either a vancomycin or fidaxomicin taper before pursuing a fecal transplant.
2. Counseling patients prior to FMT: Patients should stop vancomycin or metronidazole two days prior to FMT. Otherwise, these antibiotics will kill the transplanted stool! Note: fidaxomicin has a much narrower spectrum and can be given up to the date of transplant.
3. FMT by colonoscopy: Patients should anticipate a full bowel prep prior to the transplant if delivering via colonoscopy. Check out episode #9 for detailed discussion
4. FMT by freeze dried or frozen capsules: Dr. Donskey gives patients 30 freeze dried (or frozen) capsules to be taken over 1-2 days! He notes that newer data suggests as few as four frozen capsules may be adequate in some situations. Stay tuned!
5. “Dr. Donseky’s Expert Opinion”: Consider a trial of FMT in patients who are acutely ill with fulminant CDI and not improving on standard therapy. They might be able to avoid surgery.

Infection Control

1. Counselling patients and family members: There is a very low risk of giving Clostridium difficile to others unless your family member is taking antibiotics or immunocompromised. Decrease the risk of spreading CDI by encouraging general precautions like frequent hand-washing, changing clothes and taking showers. Hospital visitors should wear a gown and gloves in patient rooms.
2. Dr. Donskey notes that patients with CDI are “covered from head to toe with C. diff”. Gross!!!
3. We can’t say for sure whether washing with soap and water is superior to alcohol based hand wash. Dr. Donskey recommends hand washing with soap and water after all encounters with active CDI.

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.

Goals and Learning Objectives

Goals

Listeners will learn how to diagnose and treat clostridium difficile infections per the recent 2017 IDSA CDI guidelines.

Learning objectives

After listening to this episode listeners will…

1. Describe clinical criteria to test for c.diff infections (CDI).
2. Interpret different laboratory methods to test for CDI infections.
3. Describe changes in the recent IDSA CDI treatment guidelines.
4. Discuss infection control methods to prevent c.diff.
5. Choose the appropriate agent, modality and regimen to treat Clostridium difficile infection

Disclosures

Dr. Donskey reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures.

Time Stamps

• 00:00 Intro, disclaimer, guest bio
• 02:19 Getting to know our guest, recommendations for reading, career advice
• 06:40 Clinical case and CDI testing
• 09:30 Testing for CDI: PCR and Two step testing
• 16:30 Testing after treatment
• 20:00 Treatment of initial CDI episodes, metronidazole pharmacokinetics
• 24:15 Classification of CDI severity
• 29:30 Fidaxomicin pearls: when to use, cost, and tapers
• 34:10 Vancomycin tapers
• 36:05 Fecal transplant pearls: freeze dried capsules, c-scopes, treating fulminant CDI
• 44:44 Infection control: counseling homegoing patients, hand washing, and baths
• 47:50 Social media questions: immodium and toxic megacolon, antibiotics less likely to promote CDI, probiotics, and more!
• 59:14 Best CDI joke in the history of time
• 60:00 Take home points
• 62:42 Outro

Links from the show

1. Dr. Donskey’s Book Pick: Being Mortal by Atul Gawande
2. Updated 2017 IDSA Guidelines (published in 2018): McDonald, L. C., Gerding, D. N., Johnson, S., Bakken, J. S., Carroll, K. C., Coffin, S. E., … & Loo, V. (2018). Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of Am
3. Metronidazole inferior to Vancomycin for mild CDI: Siegfried J, Dubrovskaya Y, Flagiello T, et al. Initial therapy for mild to moderate Clostridium difficile infection. Infect Dis Clin Pract 2016; 24:210–6
4. Vancomycin vs Fidaxomicin: Louie TJ, Miller MA, Mullane KM, Weiss K, Lentnek A, Golan Y, et al. Fidaxomicin versus vancomycin for Clostridium difficile infection. New England Journal of Medicine 2011;364(5):422‐3
5. Healthcare workers and CDI: Dorn, Spencer D. “Clostridium Difficile Colitis in a Health Care Worker: Case Report and Review of the Literature.” Digestive Diseases and Sciences, vol. 54, no. 1, 2008, pp. 178–180., doi:10.1007/s10620-008-0330-y
6. Fidaxomicin tapers: Soriano, Melinda M., et al. “Novel fidaxomicin treatment regimens for patients with multiple Clostridium difficile infection recurrences that are refractory to standard therapies.” Open forum infectious diseases. Vol. 1. No. 2. Oxford University Press, 2014.
7. Fidaxomicin Tapers: Guery, Benoit, et al. “Extended-pulsed fidaxomicin versus vancomycin for Clostridium difficile infection in patients 60 years and older (EXTEND): a randomised, controlled, open-label, phase 3b/4 trial.” The Lancet Infectious Diseases 18.3 (2018): 296-307.
8. Fecal transplant for primary CDI infections: Juul, Frederik E., et al. “Fecal Microbiota Transplantation for Primary Clostridium difficile Infection.” New England Journal of Medicine(2018).
9. Antibiotics and CDI risk: Owens Jr, Robert C., et al. “Antimicrobial-associated risk factors for Clostridium difficile infection.” Clinical Infectious Diseases46.Supplement_1 (2008): S19-S31.

Pre-Show Reading

1. FOAMiD: Clostridium difficile (aka C.Diff).
2. Leffler, Daniel A., and J. Thomas Lamont. “Clostridium difficile infection.” New England Journal of Medicine 372.16 (2015): 1539-1548.
3. Louie, Thomas J., et al. “Fidaxomicin versus vancomycin for Clostridium difficile infection.” New England Journal of Medicine 364.5 (2011): 422-431.
4. Beinortas, T., Burr, N. E., Wilcox, M. H., & Subramanian, V. (2018). Comparative efficacy of treatments for Clostridium difficile infection: a systematic review and network meta-analysis. The Lancet Infectious Diseases.