Tu1715 Candida Albicans Colonization and Anti-Glycan Antibodies in Active and Quiescent Crohn's Disease

Abstract

Severe Clostridium difficile infection (CDI) is associated with high mortality even with surgical intervention. Fecal microbiota transplantation (FMT) is a potential alternative treatment approach, but one that has not yet been mechanistically investigated. The primary aim of this study was to measure changes in the bacterial composition of fecal microbiota following FMT in treatment of severe CDI refractory to standard antibiotic therapy. Here we report outcomes of four consecutive cases of severe CDI, refractory to antibiotic therapy, treated with FMT at our institution. Standardized frozen fecal microbiota material we had described previously (Hamilton, et al., Am J Gastroenterol, 2012) was used in three out of four cases. FMT was performed by a colonoscopic route following antibiotic cessation for 12-24 hours and purging intestinal contents with a polyethylene glycol based laxative. Gentle colonoscope insertion technique without loop formation was used in all cases, and CO2 was used for insufflation. Bacterial composition of distal gut microbiota was characterized before and after FMT with frozen material using high throughput 16S rRNA gene sequence analyses . FMT resulted in initial clinical improvement in all four cases. However, the subsequent course was characterized by recurrence of CDI. This was associatedwith instability of the bacterial composition of fecal microbiota, specifically increasing abundance of Enterobacteriaceae and decreasing abundance of Lachnospiraceae and Bacteroidaceae family members. Optimal stabilization of the fecal microbiota composition and clearing of CDI was achieved by use of the second FMT performed on an outpatient basis following an intervening course of antibiotics. In conclusion, FMT is a promising alternative to surgical treatment of severe CDI. However, a single FMT may not achieve sustained protection against recurrence of CDI in this clinical situation. This problem may be solved by a double FMT protocol we describe here. The first FMT allows clinical stabilization of the patient. However, three days after FMT patients are started on another course of antibiotics such as vancomycin or fidaxomicin. The second FMT is performed after completion of the antibiotic course on an outpatient basis. Availability of standardized frozen fecal microbiota material should allow performance of urgent FMT, which is commonly required in the setting of severe CDI. The standardized FMT protocol may simplify future testing of this approach in randomized clinical trials.