FMT for the treatment of recurrent and severe CDI in solid organ transplant recipients

Fecal microbiota transplant (FMT) is recommended for Clostridium difficile infection (CDI) treatment; however, use in solid organ transplantation (SOT) patients has theoretical safety concerns. This multicenter, retrospective study evaluated FMT safety, effectiveness, and risk factors for failure in SOT patients. Primary cure and overall cure were defined as resolution of diarrhea or negative C. difficile stool test after a single FMT or after subsequent FMT(s) ± anti‐CDI antibiotics, respectively. Ninety‐four SOT patients underwent FMT, 78% for recurrent CDI and 22% for severe or fulminant CDI. FMT‐related adverse events (AE) occurred in 22.3% of cases, mainly comprising self‐limiting conditions including nausea, abdominal pain, and FMT‐related diarrhea. Severe AEs occurred in 3.2% of cases, with no FMT‐related bacteremia. After FMT, 25% of patients with underlying inflammatory bowel disease had worsening disease activity, while 14% of cytomegalovirus‐seropositive patients had reactivation. At 3 months, primary cure was 58.7%, while overall cure was 91.3%. Predictors of failing a single FMT included inpatient status, severe and fulminant CDI, presence of pseudomembranous colitis, and use of non‐CDI antibiotics at the time of FMT. These data suggest FMT is safe in SOT patients. However, repeated FMT(s) or additional antibiotics may be needed to optimize rates of cure with FMT.



Summary:


The incidence of Clostridium difficile infection (CDI) has increased over the past two decades. Patients who have a history of solid organ transplant (SOT) have a greater chance of getting C. diff infection due to an increase in exposure to risk factors including hospitalization, profound immunosuppression, and frequent antibiotic exposure. CDI is the most frequent cause of diarrhea in SOT patients and are at a higher risk for recurrent CDI. While anti-CDI antibiotics are the recommended first line therapy, it has been suggested that fecal microbiota transplantation (FMT) is superior at inducing a lasting cure. Despite the proven efficacy of FMT in treating CDI, people have been hesitant to embrace FMT in immunocompromised patients. A study of FMT for the treatment of CDI in immunocompromised patients revealed no increase in infectious complications or risk of adverse events. This multicenter, retrospective study evaluated FMT safety, effectiveness, and risk factors for failure in SOT patients.


This study used adult patients with a history of SOT and FMT for the treatment of CDI between May 2012 and February 2017 in 10 academic sites. FMT success was defined as complete resolution of diarrhea and/or negative stool test after a single FMT or after subsequent FTS (with or without anti-CDI antibiotics). FMT-related data that was collected included severity, CDI related complications, type of stool utilized, antibiotic use, and route of FMT administration.


94 SOT patients underwent FMT, 78% for recurrent CDI and 22% for severe or fulminant CDI. The overall cure rate was 91.3%, some after single FMTs, and some after multiple FMTs. FMT‐related adverse events (AE) occurred in 22.3% of cases, mainly comprising self‐limiting conditions including nausea, abdominal pain, and FMT‐related diarrhea. Severe AEs occurred in 3.2% of cases, with no FMT‐related bacteremia. After FMT, 25% of patients with underlying inflammatory bowel disease had worsening disease activity, while 14% of cytomegalovirus‐seropositive patients had reactivation. At 3 months, primary cure was 58.7%, while overall cure was 91.3%.


There were multiple risk factors associated with greater risk for FMT failure, including FMT performed in the hospital setting, use of non-CDI antibiotics at the time of FMT, and having severe or fulminant CDI, receiving a fresh stool FMT (versus a frozen FMT), and the presence of pseudo membranes at the time of FMT.


We found that FMT is a safe option in the SOT population. More than one FMT may be necessary to correct the profound gut dysbiosis associated with SOT status. Rates of cure improved when repeat FMT ± anti-CDI antibiotics are subsequently utilized.


Read the full paper at: https://www.ncbi.nlm.nih.gov/pubmed/30085388