Fulminant Clostridioides difficile infection (CDI) carries high mortality in patients with hematologic malignancies who develop chemotherapy-induced aplasia. Treatment options are limited for patients who fail standard antimicrobial therapy. This pilot study assessed whether fecal filtrate transplantation (FFT) could serve as a salvage therapy in this high-risk population and explored whether donor–recipient phage dynamics might contribute to clinical responses.
This was a single-center, prospective, protocol-defined pilot case series. Consecutive adult patients were included if they had a hematologic malignancy, chemotherapy-induced grade-4 aplasia, and fulminant CDI that was refractory to at least five days of high-dose oral vancomycin plus intravenous metronidazole and tigecycline. The study enrolled three patients, each with adverse-risk acute myeloid leukemia and fulminant CDI due to genetically distinct C. difficile strains.
FFT material was prepared from a single unrelated donor. Preparation included sequential centrifugation and filtration to produce a sterile filtrate (stool supernatant) rather than whole-stool suspension. Administration was performed via a nasogastric tube in two doses according to the protocol-defined schedule.
The primary outcome was sustained clinical cure. Secondary outcomes included survival and adverse events, assessed at +14 and +30 days after FFT. Microbiome composition was monitored using 16S rRNA gene sequencing. Viral metagenomics combined with in vitro propagation assays were employed to characterize donor–recipient phageome interactions and to probe possible mechanistic signals associated with CDI resolution.
Microbiome profiling used 16S rRNA gene sequencing to detect shifts in bacterial community composition after FFT. Viral metagenomics and propagation assays allowed detection and comparison of bacteriophages present in donor filtrate and recipient samples, and provided information on whether donor-derived phages engrafted or whether recipient-resident prophages were induced. The analyses were designed to probe whether phage transfer or activation correlated with clinical outcomes.
All three patients experienced clinical resolution of fulminant CDI by day +14. Clinical improvement included reduced abdominal distension and favorable changes in inflammatory markers. At the +30-day assessment, two patients remained in remission; one patient died from Pseudomonas aeruginosa septic shock. The report indicates this death occurred despite prior CDI resolution and does not attribute it to FFT.
FFT was reported to be well tolerated in these aplastic patients. There were no immediate procedure-related complications or adverse events attributed to the FFT itself within the observation window reported.
Microbiome and phage profiling revealed heterogeneous responses across recipients. Bacterial community composition shifted after FFT, but there was no clear or consistent evidence that donor-derived phages were responsible for CDI resolution in this small series. Instead, the investigators observed induction of prophages harbored by recipient-associated Clostridium species. The authors suggest that stress-induced entry of these prophages into the lytic cycle may have contributed to decolonization of pathogenic Clostridioides in some cases.
As a pilot case series with three patients, the study provides feasibility and proof-of-concept data but is limited in size and generalizability. The heterogeneous microbiome and phageome responses underscore the need for larger studies to determine reproducibility, to clarify mechanisms, and to define safety more broadly. Details beyond the 30-day follow-up window and broader clinical applicability were not reported in this source.
In this prospective single-center pilot series, fecal filtrate transplantation (FFT) was feasible and well tolerated in adults with hematologic malignancies experiencing chemotherapy-induced aplasia and fulminant, treatment-refractory CDI. All three patients achieved rapid clinical cure by day +14; two remained in remission at day +30 while one patient later died from Pseudomonas aeruginosa septic shock. Microbiome and phageome analyses produced heterogeneous findings and did not demonstrate a consistent role for donor-derived phages in CDI resolution, though induction of recipient-associated prophages was observed and may warrant further mechanistic study.
The study is registered at ClinicalTrials.gov (NCT07172191). These pilot data support further investigation of FFT in larger cohorts to evaluate efficacy, mechanisms, and safety in immunocompromised aplastic patients.