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

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

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

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

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

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

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

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

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-100.4 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

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-100.4 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.

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- 98.6. 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

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- 98.6. 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.

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

The End

References Up-to-date Article: Clostridium difficile in adults: Treatment: https://www.uptodate.com/contents/clostridium-difficile-infection-in-adults-treatment-and-prevention?search=C.%20diff&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#H1525206458