Division of GIM Lecture Series Case Presentation David A. Erickson, M.D October 9th, 2013

Transcription

1 Division of GIM Lecture Series Case Presentation David A. Erickson, M.D October 9th, 2013

2 Financial Disclosures No financial disclosures

3 Objectives Review a case of recurrent Clostridium difficile infection Basic review of Clostridium difficile Review treatment options for Clostridium difficile infections

4 The Case GL is a 36 y/o female with a history of hypertension, hyperlipidemia, diabetes mellitus, morbid obesity and obstructive sleep apnea Medications: Carvedilol 25 mg BID Lisinopril 10 mg daily Rosuvastatin 10 mg daily Glargine 38 units daily Aspart per carb count ratio & sliding scale Metformin XR 2000 mg daily

5 The Case Surgical history: No prior surgeries Allergies: No known drug allergies Social history: Hospital employee with frequent direct patient contact

6 The Case Encounter #1: September 29 th (PCP) Cellulitis of the left breast Treatment with Clindamycin 300 mg TID x7 days Encounter #2: November 10 th (Urgent Care) Severe diarrhea x1 week Positive testing for Clostridium difficile toxin B by PCR. Negative NAP1 testing Treatment with Metronidazole 500 mg TID x14 days

7 The Case Encounter #3: November 28 th (PCP) Follow up clinic visit. Diarrhea stopped ~1 week prior to the appointment but returned two days after the appointment Empiric treatment with Vancomycin 125 mg QID x10 days Encounter #4: December 14 th (PCP) Diarrhea did not resolve. Stool testing was again positive for Clostridium difficile Treatment with Metronidazole 500 mg TID x21 days

8 The Case Encounter #5: December 28 th (Hospitalization) Pancreatitis after being on Metronidazole for 14 days. Metronidazole was stopped as it was felt to be the cause of her pancreatitis (Class IA Drug) Negative testing for Clostridium difficile while in the hospital and no further treatment for Clostridium difficile was prescribed Encounter #6: January 13 th (PCP) Hospital follow up appointment. Abdominal pain & diarrhea had resolved but Enterococcus urinary tract infection was noted Treatment with Ciprofloxacin 250 BID x7 days

9 The Case Encounter #7: January 20 th (PCP) Profuse diarrhea x1 day (cystitis had resolved) Positive testing for Clostridium difficile Treatment with pulse dose Vancomycin (125 mg QID x14 days, then stop x5 days, then 125 mg QID x5 days, then stop x5 days, then 125 mg QID x5 days) Encounter #8: February 24 th (PCP) Diarrhea briefly resolved but then returned Testing was again positive for Clostridium difficile. Vancomycin increased to 250 mg TID and infectious disease consulted

10 The Case Encounter #9: February 27 th (Infectious Disease) Fidaxomicin 200 mg BID x10 days followed by an extended Vancomycin taper (125 mg TID for 2 weeks, then 125 mg BID x2 weeks then 125 mg daily for 2 months, then stop) Encounter #10: June 3 rd (Infectious Disease) Diarrhea returned after antibiotics were completed Testing positive for Clostridium difficile Treatment with IVIG 400 mg/kg x1 infusion. Then Fidaxomicin 200 mg BID x10 days. Then Vancomycin 125 mg QID pending fecal microbiota transplantation

11 The Case Encounter #11: July 17 th (Meriter) Fecal microbiota transplant #1 (two separate enemas in the same day, each held for one hour) Encounter #12: August 21 st (Meriter) Diarrhea transiently resolved but then returned Positive testing for Clostridium difficile Fecal microbiota transplant #2 was performed with a bowel prep (Polyethylene Glycol) prior to the fecal enemas. No antibiotic treatment for Clostridium difficile immediately prior to transplantation

12 The Case Encounter #13: September 27 (Infectious Disease) No improvement following the 2 nd fecal microbiota transplant Stool positive for Clostridium difficile Treatment with Vancomycin 125 mg QID for 2 months (9/27 11/28), followed by Vancomycin 125 mg every other day for one week, then Vancomycin every third day for one week Encounter #14: October 15 th (Colonoscopy) No overt colitis. No pseudomembranous colitis

13 The Case Encounter #15: December 12 th (Infectious Disease) Complete resolution of symptoms and negative testing for Clostridium difficile

14 Clostridium difficile Clostridium difficile Anaerobic, gram positive, spore forming bacillus NAP1 is a specific strain of Clostridium difficile that has increased virulence and resistance Colonization/Infection occurs via the fecal oral route and is most common after disruption of the normal colonic flora by antibiotics. Most implicated antibiotics: Clindamycin, Fluoroquinolones, Penicillins and Cephalosporins Safest antibiotics: Macrolides, Sulfonamides & Tetracycline

15 Clostridium difficile Clostridium difficile Additional risk factors for colonization/infection include advanced age, hospitalization, enteric feeding, gastrointestinal surgery and gastric acid suppression Approximately 3% of healthy adults are colonized with Clostridium difficile (high levels of serum antitoxin antibodies in asymptomatic individuals) Clostridium difficile produces two exotoxins that are responsible for colonic inflammation, intestinal fluid secretion and mucosal injury Testing for Clostridium difficile is performed by stool culture or detections of exotoxin in the stool (EIA or PCR testing)

16 Table 1 (IDSA/SHEA) Strength of recommendation A Good evidence to support a recommendation for or against use B Moderate evidence to support a recommendation for or against C Poor evidence to support a recommendation Quality of evidence I Evidence from at least 1 properly randomized, controlled trial II Evidence from at least 1 well-designed clinical trial without randomization, from cohort or case-controlled analytic studies (preferably from more than 1 center), from multiple time-series, or from dramatic results from uncontrolled experiments III Evidence from opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees

17 Treatment Cessation of the inciting antibiotic as soon as possible (A-II). Transition to an antibiotic that is less frequently implicated in Clostridium difficile infection Frequent hand washing with soap and water (A-II) and contact precautions for the duration of the diarrhea (C-III) Avoidance of antimotility agents such as Loperamide (C-III)

18 Treatment Antibiotics are indicated for symptomatic patients with positive testing for Clostridium difficile or if there is high clinical suspicion for Clostridium difficile infection Initial therapy (mild to moderate disease) Metronidazole 500 mg TID days (A-I) Initial therapy (severe disease): Vancomycin 125 mg QID x days (B-I)

19 Treatment Test of cure is not necessary for asymptomatic patients. Up to 50% of patients will have positive testing for Clostridium difficile for up to 6 weeks after completion of therapy Recurrent disease is defined as, complete abatement of CDI symptoms while on appropriate therapy, followed by subsequent reappearance of diarrhea and other symptoms after treatment has been stopped

20 Treatment Recurrence occurs in 10 to 25 percent of patients who are treated with Metronidazole or Vancomycin Most recurrences occur within 1-3 weeks of stopping treatment although they can occur up to 2-3 months later Patients with one episode of recurrent Clostridium difficile have a percent chance of having another recurrent episode

21 Treatment Potential causes of recurrence include persistence of spores from the initial infection, poor host immune response or alterations in the colonic microenvironment Other causes of diarrhea should be considered when recurrence is suspected (positive stool toxin test does not rule out asymptomatic carriage)

22 Treatment Treatment for the initial recurrence is typically the same as for the initial episode unless the severity has changed (A-II) Metronidazole 500 mg TID x days Vancomycin 125 mg QID x10-14 days Fidaxomicin 200 mg BID (approved by Food & Drug Administration in May 2011)

23 Treatment Treatment options for second recurrence Pulse dose Vancomycin (B-III) Fidaxomicin 200 mg BID Treatment options for subsequent recurrences (limited evidence): Fidaxomicin or Vancomycin followed by Rifampin Fecal microbiota transplantation Intravenous Immunoglobulin

24 Treatment Other Considerations: Probiotics Administration of probiotics is not recommended to prevent primary Clostridium difficile infection (C-III) Probiotics are not recommended for routine treatment of Clostridium difficile infection. Probiotics may be reasonable in patients with recurrent disease that is not severe Proton Pump Inhibitors The Food & Drug Administration issued a safety advisory in February 2012 that warned of a positive correlation between the use of proton pump inhibitors and Clostridium difficile infection

25 Treatment Other Considerations: Fecal microbiota transplantation Cure rates of 81 to 94 percent. Response usually occurs within 1-12 days. Response is durable (donor fecal microbiota remains largely stable in composition over a 24 week period) Can be administered via enema, via colonoscope or via nasogastric tube (Clostridium difficile can reside in the distal small bowel in addition to the colon)

26 Treatment Fecal microbiota transplantation Safe procedure as long as screening for infection is performed (most common side effect is intestinal gurgling) Recommended Screening: Stool Culture, O&P, Clostridium difficile, Giardia, Cryptosporidium, Cyclospora, Isospora, H pylori antigen, CBC, Hepatitis A/B/C, HIV & Syphilis

27 Treatment Fecal microbiota transplantation Recommended protocol (rectal administration): Vancomycin 500 mg twice daily x7 days before the procedure. Bowel prep with 3-4 liters of Polyethylene Glycol immediately prior to the procedure grams of donor stool suspended in 200 to 300 ml of sterile saline. Homogenized in kitchen blender and administered within 10 minutes of preparation Repeat daily enemas x5 days. Hold each enema for 6 hours

28 Follow Up & Questions The patient has been asymptomatic for the past 10 months Questions?????

29 References Cohen S, Gerding D, Johnson S et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults: 2010 Update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infection control and hospital epidemiology May 2010, Vol. 31, No. 5 LaMont JT. Up to Date. Clostridium difficile in adults: Clinical manifestations and diagnosis. Last updated 9/19/2013 LaMont JT. Up to Date. Clostridium difficile in adults: Epidemiology, microbiology, and pathophysiology. Last updated 9/26/2013 LaMont J and Kelly C. Up to Date. Clostridium difficile in adults: Treatment. Last updated 3/26/2013 Borody TJ et al. Up to Date. Fecal microbiota transplantation in the treatment of recurrent Clostridium difficile infection. Last updated 8/29/2013