Donor Efficacy in Fecal Microbiota Transplantation for Recurrent Clostridium difficile: Evidence From a 1,999-Patient Cohort
Bibliographic record
Abstract
Background. Recurrent Clostridium difficile infection (CDI) is a public health challenge and fecal microbiota transplantation (FMT) has emerged as an effective therapeutic option. Although FMT is used for treating recurrent CDI, there is no robust evidence evaluating if different donors have an impact on the clinical cure rate. We aim to evaluate if there are differences in FMT efficacy for CDI between donors from a public stool bank. Methods. Donors were selected using a 178-point clinical assessment and 30 laboratory investigations for infectious and microbiome-mediated diseases where only 2.8% of candidate donors qualify. Among selected donors, fecal microbiota preparations (FMPs) were produced according to standard FMP manufacturing practices. Donor-specific units were tracked by a quality assurance (QA) system that linked to de-identified individual patient outcomes. QA data was consecutively collected from 482 healthcare facilities across 50 states and 7 countries between January 16, 2014 and April 12, 2016. Donors were included if their material was used in over 10 reported patients over the study period. The primary outcome was physician reported clinical cure as per standard of care follow-up. Descriptive statistics and chi-square analysis was conducted. Results. Overall, 28 donors (Figure 1) were used in 1,999 patients. Overall, the clinical cure rate from physician-reported data across all 28 donors was 84.4% with a range of 69.2–95.2% (Figure 2). One outlier donor was found to have a statistically significant lower clinical cure rate (70.9%, p = 0.05). However, upon sensitivity analysis, the lower efficacy was driven by one site (overall clinical cure for all donors at site of 50.7%, p < 0.05) and the reduced clinical cure rate was not seen across other hospitals that the donor's material was used. Otherwise, there was no statistically significant differences between donor FMT material and clinical cure for CDI not responsive to standard therapy. Figure 1: Donor characteristics Figure 2: Clinical efficacy reported by donor Conclusion. To our knowledge, this is the largest study assessing clinical efficacy for FMT in CDI by donor and suggests it is unlikely that different donors have an impact on efficacy. Disclosures. M. Osman, OpenBiome: Employee, Salary; Z. Stoltzner, OpenBiome: Employee, Salary; K. O'Brien, OpenBiome: Employee, Salary; K. Ling, OpenBiome: Employee, Salary; E. Koelsch, OpenBiome: Employee, Salary; N. Dubois, OpenBiome: Employee, Salary; M. Smith, OpenBiome: Employee, Salary. Finch Therapeutic: Board Member, Employee and Shareholder, Equity and Salary; Z. Kassam, OpenBiome: Employee, Salary. Finch Therapeutic: Consultant and Shareholder, Equity and Research support
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.010 | 0.015 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".