Multi-Donor Fecal Microbial Transplantation for Critically Ill Patients: Rationale and Standard Operating Procedure

Abstract

Patients in the intensive care unit often lose a considerable fraction of their gut microbiome due to exposure to broad-spectrum antibiotics and other reasons. Dysbiosis often results in prolonged diarrhea and increase occurrence of multi-drug resistant pathogens in the colon with clinical consequences not yet well understood. Restoring the microbiome by fecal microbial transplantation (FMT) is a plausible therapeutic possibility, so far only documented in case reports and case series using very heterogeneous methodologies. Before FMT with critically ill patients can be tested in randomized controlled trials, there is a burning need to describe a standardized operating procedure (SOP) of the whole process, respecting the specifics of the critically ill population, such as the risk of the disrupted intestinal barrier and time-critical nature of the procedure. We describe the SOP that has been developed for experimental use in critically ill patients by a multidisciplinary team of intensivists, gastroenterologists, and microbiologists based on feedback from regulatory authority (State Institute for Drug Control of the Czech Republic). The hallmarks of these SOPs are multi-donor freshly frozen transplants guaranteed for 2 months consisting of seven aliquots from seven unrelated healthy donors and administered by a rectal tube. In this paper we discuss the rationale for this SOP and the process of its development in detail and release the full proposed SOP is in the form of an online appendix.