Rescue Therapy With Fecal Microbiota Transplantation in Hospitalized Patients With Severe and Severe-Complicated Clostridium difficile Infection

Abstract

Introduction: Severe Clostridium difficile infection (CDI) is often complicated by fulminant colitis and multiorgan failure. Urgent subtotal colectomy can be lifesaving, but it is associated with 50% mortality. Fecal microbiota transplantation (FMT) is widely used to treat recurrent CDI; however, only a few case reports describe its use in hospitalized patients who are critically ill. Methods: Patients with severe and severe/complicated CDI (defined as per 2013 ACG guidelines) who were considered for urgent subtotal colectomy between July 2013 and April 2014 were offered the option of FMT at our institution. Patient variables and outcomes were prospectively collected using an IRB study protocol. FMT was performed using a colonoscope and CO2 insufflation with delivery either proximal or distal to the splenic flexure at the discretion of the endoscopist. Fresh stool was obtained from either a patient-selected donor or universal donor for FMT. After initial FMT, oral vancomycin (125 mg q 6 hrs) was started within 24-72 hours and continued until second FMT (range: 5-14 days). If pseudomembranous colitis was present at the time of the second FMT, oral vancomycin was resumed and a third FMT was offered (range: 5-14 days). Results: Seventeen patients (8 with severe and 9 with severe-complicated CDI) with mean age of 68±14.74 years (53% were females; 100% were white; 12% on immunosuppression) underwent FMT. All patients had failed to respond to prior antibiotic therapy (vancomycin or fidaxomicin) and had pseudomembranous colitis on the first FMT. The mean serum albumin level was 2.4±0.42 g/dL and the mean WBC count was 17.4±19.1 k/mm3. Eleven (65%) patients underwent bowel preparation prior to FMT. Stool was delivered proximal to the splenic flexure in 60% and distal to the splenic flexure in the remaining. Ten patients (59%) received a second FMT with median time to repeat FMT of 7.5 days. Three (18%) patients received a third FMT. Fifteen patients (88%) were cured and avoided colectomy within 3 months of initial FMT. Of the 2 patients who died of multiorgan failure, one was under immunosuppression (recent liver transplantation) and the other had septic shock with a pH of 7.09 at the time of initial FMT. No SAEs related to colonoscopy or FMT were observed. Conclusion: Response-guided FMT in combination with vancomycin is a promising treatment alternative to surgery for severe and severe-complicated CDI, a condition that is typically associated with high mortality.