1. Management of Clostridium Difficile Infection
UC Irvine Medical Center
Department of Internal Medicine
05/2018
Mitch Edwards, D.O.

2. Objectives
Define the severity of Clostridium Difficile Infection (CDI)
Learn how to treat CDI by degree of severity
Learn how to treat recurrent CDI

3. Approach to treatment How severe is the disease?
Non-severe disease
Severe disease
Fulminant disease (previously known as severe complicated CDI)
Is this the first episode, or is it recurrent infection?
Initial
First recurrence
Second or subsequent recurrence

4. CDI Disease Severity: Nonsevere vs severe/fulminant
Does that patient have any of the following:
WBC ≥ 15,000
Creatinine ≥1.5
Guideline parameters for severe CDI include white blood cell count of >15,000 cells/microL, and/or a serum creatinine level ≥1.5 times the premorbid level
Nonsevere disease No
Yes
Severe or Fulminant Disease

5. Severe vs Fulminant No Yes Does the patient have any of the following?
Hypotension/shock
Ileus
Toxic Megacolon
Severe disease No
Yes
Fulminant Disease

6. Management of First Time CDI
Nonsevere disease:
Vancomycin 125 mg orally four times a day for a total of 10 days, OR
Fidaxomicin 200mg twice a day for 10 days
If above agents are unavailable: Metronidazole 500mg three times a day for 10 days
Severe disease:
Vancomycin 125 mg orally four times a day for 10 days, OR
Fidaxomicin 200 mg orally twice a day for 10 days
Notice how metronidazole is NOT first line for non-severe disease

7. Management of Fulminant CDI
Vancomycin 500mg PO or via NG tube QID, PLUS
Metronidazole 500mg IV TID
If ileus is present (or if oral antibiotics are not expected to reach a segment of the colon):
Rectal vancomycin may be administered as a retention enema (500mg in 100 mL normal saline per rectum; retained as long as possible, and readministered every 6 hours)
Examples of when oral antibiotics may not reach a segment of the colon: ileus, megacolon, Hartman’s pouch, ileostomy, colon diversion

8. Recurrent CDI First recurrence:
If vancomycin was used for the initial episode:
Vancomycin oral pulsed-taper for 6 weeks, OR
Fidaxomicin 200mg BID for 10 days
If fidaxomicin or flagyl was used for the initial episode: Vancomycin 125mg PO QID for 10 days
Second recurrence or subsequent recurrence:
Tapering and pulsed oral vancomycin, OR
Fidaxomicin 200mg BID for 10 days, OR
Vancomycin followed by Rifaximin
Vancomycin 125mg PO QID for 10 days, then Rifaximin 400mg TID for 20 days, OR
Fecal microbiota transplantation
Vancomycin pulsed taper is as follows: 125 mg orally QID daily for 10 to 14 days, then BID for 7 days, then QD for 7 days, then q48h-q72h for 2-8 weeks
Despite appropriate initial therapy, CDI recurs in approximately 20% of patients
The choice of therapy for the 1st recurrence does not decrease the probability of a 2nd recurrence

10. Case- Part A
A 42 year-old man is evaluated for diarrhea in the emergency department. He has been having 6-8 episodes of watery diarrhea associated with crampy abdominal pain and occasional fevers at home for the past week. He feels fatigued. He has never had anything like this before. Vitals are noted to be: BP 125/82, HR 94, RR 20, T F, SaO2 98% on room air. Physical exam shows a soft and mildly tender to palpation abdomen diffusely without peritoneal signs. Labs are significant for a WBC of 12.1K, Hgb 14.6, Na 129, K 3.8, BUN 24, and Cr 1.0. His stool C. diff PCR is positive.
What is the most appropriate treatment for this patients CDI?
Metronidazole 500mg TID for 14 days
Vancomycin 125mg QID for 10 days
Vancomycin pulse-tapered regimen for 6 weeks
Vancomycin 500mg PO QID plus IV metronidazole 500mg TID

11. Case- Part A
A 42 year-old man is evaluated for diarrhea in the emergency department. He has been having 6-8 episodes of watery diarrhea associated with crampy abdominal pain and occasional fevers at home for the past week. He feels fatigued. He has never had anything like this before. Vitals are noted to be: BP 125/82, HR 94, RR 20, T F, SaO2 98% on room air. Physical exam shows a soft and mildly tender to palpation abdomen diffusely without peritoneal signs. Labs are significant for a WBC of 12.1K, Hgb 14.6, Na 129, K 3.8, BUN 24, and Cr 1.0. His stool C. diff PCR is positive.
What is the most appropriate treatment for this patients CDI?
Metronidazole 500mg TID for 14 days
Vancomycin 125mg QID for 10 days
Vancomycin pulse-tapered regimen for 6 weeks
Vancomycin 500mg PO QID plus IV metronidazole 500mg TID
The patient has a first time CDI, that is non-severe (WBC <15,000 and Cr <1.5 without evidence of shock or ileus). Treatment of this is now either with vancomycin 125mg QID for 10 days or fidaxomicin 200mg BID for 10 days. If one of those agents is not available, then you can use metronidazole 500mg TID for 10 days. Vancomycin in a pulse-tapaered fashion is only used for recurrent C. diff, and vancomycin plus IV flagyl is used for fulminant C. diff.

12. Case- Part B
The same patient visits you in your office 4 weeks after completing his 10 day course of vancomycin. He is now complaining of similar symptoms, with 3 watery bowel movements a day, abdominal pain, and fevers at home for the past 2 days. His vitals in the office are: BP 126/80, HR 72, RR 18, T He overall feels ok, and agrees to getting labs today in the office and going home. A CBC is significant for a WBC of 13k, and his serum Cr is 1.1. Stool C. diff PCR is again positive. You call him to let him know he has C. diff again, and that you are sending a prescription to his pharmacy to treat it. What antibiotic(s) are you sending to his pharmacy?
Vancomycin 125mg QID for 10 days
Metronidazole 500mg QID for 10 days
Vancomycin pulse-taper for 6 weeks
Vancomycin 125mg QID for 10 days then Rifaximin 400mg TID for 20 days
Fecal transplant

13. Case- Part B
The same patient visits you in your office 4 weeks after completing his 10 day course of vancomycin. He is now complaining of similar symptoms, with 3 watery bowel movements a day, abdominal pain, and fevers at home for the past 2 days. His vitals in the office are: BP 126/80, HR 72, RR 18, T He overall feels ok, and agrees to getting labs today in the office and going home. A CBC is significant for a WBC of 13k, and his serum Cr is 1.1. Stool C. diff PCR is again positive. You call him to let him know he has C. diff again, and that you are sending a prescription to his pharmacy to treat it. What antibiotic(s) are you sending to his pharmacy?
Vancomycin 125mg QID for 10 days
Metronidazole 500mg QID for 10 days
Vancomycin pulse-taper for 6 weeks
Vancomycin 125mg QID for 10 days then Rifaximin 400mg TID for 20 days
Fecal transplant
The patient has a 1st time recurrence of a CDI. It again is a non-severe infection. Because vancomycin was used the for the first infection, you could either use a vancomycin pulse-tapered regimen for 6 weeks, or you could use fidaxomicin 200mg BID for 10 days. Metronidazole PO is not used for a first time recurrence. Vancomycin PO for 10 days then PO rifaxmin for 20 days can be used for a second or subsequent recurrence, but this is his first recurrence. Fecal transplant is also only used in a second or subsequent recurrence.

14. Key Points
Treatment is based on severity of infection (nonsevere, severe, fulminant) and recurrence
For non-severe or severe, initial treatment is vancomycin or fidaxomicin for 10 days
Treatment of fulminant CDI is with oral vancomycin plus IV flagyl, and can add rectal vancomycin if ileus is present
Treat 1st recurrence with pulse tapered vancomycin or fidaxomicin
Treat second or subsequent recurrences with either pulse-tapered vancomycin, fidaxomicin, vancomycin followed by rifaximin, and/or fecal microbiota transplantation

15. The End

16. References
Up-to-date Article: Clostridium difficile in adults: Treatment: