The Patients’ Voice in Clostridioides difficile Infection: Large Language Model-Assisted Thematic Analysis of Patient Testimonials

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ID: 331858
2026
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Abstract
Abstract Background Clostridioides difficile infection (CDI) imposes a burden that extends well beyond the gastrointestinal tract, yet existing outcome measures only partially capture the patient experience. We used frontier large language models (LLMs) on patient and caregiver narratives at scale to describe how burden shifts with disease course. Methods We analyzed 189 testimonials from the Peggy Lillis Foundation corpus, sorted into four cohorts with recurrence (r) and fulminant (f) severity as axes (rfCDI, fCDI, rCDI, non-rfCDI). Two independent LLMs coded eight thematic domains, four fulminant flags, thirteen emerging semantic fields, the dominant dimension, and narrative arcs. Two physicians independently coded a subset for inter-rater reliability (PABAK, Gwet's AC1). Results Treatment trajectory was the dominant theme in recurrent disease, whereas death and near-death dominated non-recurrent fulminant narratives. Psychological burden was near-universal in fulminant disease (98.0% in rfCDI, 97.2% in fCDI). Caregiver and bereavement content concentrated in fCDI (66.7%). Diagnostic failure was frequent across recurrent cohorts (47.6 - 56.1%). Mentions of bacteriotherapy (fecal microbiota transplantation) concentrated in recurrent cohorts (60.2% rfCDI versus 5.6% fCDI). Financial, mental-health, and caregiver burdens were prominent and remain largely unaddressed by guidelines. Human-human reliability was substantial (PABAK 0.79 for semantic fields, 0.76 for domains); arc coding was least reliable. Conclusions Patient narratives reveal a course-dependent, multidimensional burden in CDI. Concrete gaps exist between what patients prioritize, what guidelines recommend, and what therapy access provides. Frontier-LLM coding, validated against clinicians, offers a reproducible route to translate these priorities into research, care, and policy.
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Authors Javier Villafuerte-Gálvez, Marco A. Noriega, Sena Cakir Colak, Carl V. Crawford
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Journal Open forum infectious diseases
Year 2026
DOI
10.1093/ofid/ofag650
URL
https://doi.org/10.1093/ofid/ofag650
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