Assessing Risk of Infectious Episodes in Patients Post Hematopoietic Stem Cell Transplantation Using Pre-Transplant Baseline Colonization Screening
Bibliographic record
Abstract
INTRODUCTION Infection is a major cause of mortality following hematopoietic stem cell transplant (HCT). The primary source of bacterial infections are gut-derived bacteria from the patient's own microbial flora. Understanding patient specific colonizing organisms may inform downstream infections. This study aims to establish feasibility of identifying baseline colonization of antimicrobial resistant organisms (AROs), such as methicillin-resistant S. aureus (MRSA), vancomycin-resistant enterococci (VRE), extended-spectrum beta-lactamase (ESBL), and fluoroquinolone-resistant (FQR) enterobacterales and Clostridioides difficile (C. difficile), to assess the association between pre-transplant colonization and subsequent post-transplant infection. METHODS This prospective cohort study followed 60 HCT patients (34 autologous and 26 allogenic) for 6 months. Primary hematologic diagnoses were multiple myeloma (30%), leukemia (AML, ALL; 27%) and myelodysplastic syndrome (15%). Stool samples were collected pre-transplant and twice weekly for 3 weeks post-transplant. Culture-based stool samples were processed using selective media to detect colonization with AROs harbouring resistance mechanisms and antibiotic class resistance in Gram-negative organisms. C. difficile colonization was assessed using routine glutamine dehydrogenase (GDH) assay and toxin B gene PCR. Clinical data collected included infectious complications, neutropenia, disease relapse, and mortality. Infectious episodes were identified using positive culture results and patients' clinical history, classified by pathogen and ARO type. RESULTS Baseline colonization with C. difficile and/or AROs was identified in 27% (16/60) of patients. The median length of neutropenia was 11 (IQR 7-32) days, with 72% (43/60) of patients developing febrile neutropenia. C. difficile colonization was identified in 10% (6/60) of patients. All colonized patients were asymptomatic at baseline. Ten (17%) patients developed a C. difficile infection (CDI) within 6 months of transplant, with 3 individuals having recurrent CDIs. Of these 10 patients, 50% were amongst those colonized at baseline. Of all colonized patients, 83% (5/6) developed CDI over the course of their follow up period. ARO colonization was found in 18% (11/60) of patients, including VRE (4/11), ESBL and FQRE (4/11), and FQRE alone (3/11). Of the 7 patients colonized with ESBL or FQRE, 1 (14%) patient developed a bloodstream infection with an ESBL K. pneumonaie. An additional 16 (27%) patients were found to be colonized with other Gram-negative organisms, the majority of which harboured inducible beta-lactamases (AMP-C). In the overall cohort, 50% of patients experienced at least 1 culture-positive infection within the first 6 months post-HCT. The majority (45%) of infections were viral in nature. Bloodstream infections accounted for 23% (16/71) of all infections, of which there were 13 episodes of bacteremia amongst 10 participants. Of these, 4/10 participants were diagnosed with resistant Gram-negative bacteremia including 3 with ESBL K. pneumonaie. Furthermore, 2/10 participants were diagnosed with VRE bacteremia. Of the 26 individuals who underwent an allogenic HCT, data pertaining to graft-vs-host disease (GVHD) was available for 23 participants at the 6-month follow-up. Nine (39%) individuals developed GVHD, with most cases presenting as skin GVHD. Among these, there was 1 severe case of gastrointestinal GVHD which resulted in death. Complete 6-month follow-up data regarding disease relapse and mortality was available for 47 of the 60 participants. Six (13%) individuals relapsed within the follow-up period and 4 of the patients underwent further treatment (e.g., chimeric antigen receptor T-cell (CART) therapy, subsequent allogenic HCT). The remaining 2 individuals' relapse resulted in death. In total, there were 6/47 (13%) reported deaths by the 6-month follow-up, including 2 secondary to infection. CONCLUSION This study highlights the significant burden of infections post-HCT and demonstrates the feasibility of establishing pre-transplant baseline colonization to identify resistant organisms that may inform downstream infection risk. Future studies are needed to evaluate use of colonization data for predicting post-transplant infection and assess the role of targeted prophylaxis or treatment based on patient's flora.
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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 | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".