Fecal Microbiota Therapy as Rescue Therapy for Life-Threatening Clostridium difficile Infection in the Critically Ill: A Small Case Series

To the Editor—A retrospective review of anonymous data obtained from patients treated with fecal microbiota therapy (FMT) was conducted as part of an antibiotic stewardship program in a Bavarian regional medical center that is part of the Network of the German Consulting Center for Infection Control and Prevention. Data handling was perfomed in accordance with German Federal Data Protection Law (Bundesdatenschutzgesetz); the analysis of anonymous routine quality assurance data does not constitute human research requiring institutional review board approval. Table 1 summarizes the descriptions of each case based on point prevalence data from antibiotic stewardship rounds.

TABLE 1 Case Descriptions in Study of Fecal Microbiota Therapy as Rescue Therapy for Life-Threatening CDI

NOTE. ?, no data available; CDI, Clostridium difficile infection diagnosed by clinical signs and positive glutamate dehydrogenase test and C. difficile toxin production by polymerase chain reaction; COPD, chronic obstructive pulmonary disease; FMT, fecal microbiota therapy; GI, gastrointestinal; ICU, intensive care unit; PPI, proton-pump inhibitor.

^a FMT was performed with an abbreviated donor screening program consisting of history and physical exam, no known chronic gastrointestinal disease, negative glutamate dehydrogenase screen, and negative human immunodeficiency virus screen by discretion of the critical care attending in charge after progression of severe CDI to septic shock despite intravenous metronidazole (3×500 mg) and enteral vancomycin (4×250 mg). In 1 case enteral vancomycin treatment was continued after FMT for 2 more days after resolution of symptoms but did not seem to interfere with the effectiveness of FMT.

All patients were recovering well from their underlying illness at the time of Clostridium difficile infection (CDI) onset and deteriorated rapidly in septic shock, so that the attending physicians opted for an emergency FMT as rescue therapy. Our patients met criteria for septic shock with multiple organ failure unresponsive to fluids, specific antibiotics, and increasing vasopressor demand. Informed consent from the patient or guardian was obtained and relatives volunteered as stool donors after an abbreviated medical screen. FMT was performed as soon as possible, at least within 24 hours after the therapeutic decision. One patient died during the preparation period. All treated patients started to respond within 12–24 hours after FMT with clinical improvement including a change of consistency and odor of stools within 12 h, resolution of shock symptoms, significantly reduced vasopressor support after 48 hours, and resolution of inflammatory markers. No immediate procedure-specific complications were observed; however, no long-term follow up was possible owing to the nature of the data source, highlighting the importance of registry projects like the one by the German Society of Gastroenterology and the University of Jena (https://service.zks.med.uni-jena.de/STReg).

Disturbance of the intestinal microbiome by multiple antibiotics, particularly third-generation cephalosporins, fluoroquinolones, and clindamycin ¹ and likely proton-pump inhibitors, especially in combination with high-risk antibiotics, ² plays an important role for the development of symptomatic CDI. Several definitions of CDI severity of illness make comparative studies of treatment difficult. There are increasing positive experiences with FMT in cases of recurrent illness; despite methodological limitations FMT has become a part of the treatment algorithm for recurrent CDI. ³ In a recent meta-analysis the great majority of adverse events of FMT appeared to be mild and self-limiting. In some cases, a credible association was not established owing to the lack of controlled data. ⁴

On the basis of our experiences, FMT can be considered as rescue therapy in life-threatening CDI unresponsive to conventional treatment, using an abbreviated donor screening protocol and informed consent stressing the potential risks and nature of the treatment. We recommend participation in existing registries and future studies including critically ill patients and using prescreened volunteer stool or capsules ⁵ in order to resolve the problem of minimally screened emergency donors.