Reexamining Novel Risk Factors for Community-Acquired Clostridioides difficile: A Multimodal Approach

Geospatial surveys have identified livestock operations as potential sources for community-acquired Clostridioides difficile infection. Confirmatory studies integrating individual-level risk factors, geospatial data, and environmental surveys are limited.

We conducted 2 parallel studies: (1) a case-control assessment of C difficile risk associated with livestock and (2) a microbiologic survey of surface waters and wastewater influent for C difficile. For aim 1, adult residents of North Carolina tested for C difficile through the Duke University Health System from March 2020 to December 2025 were included. Tests sent after day 3 of hospitalization (presumed hospital-onset) were excluded. Multivariable logistic regression with generalized estimating equations was used to assess C difficile risk associated with livestock operations while adjusting for age, comorbidities, antibiotic receipt, and hospital contact. For aim 2, samples collected from 3 surface water and 2 municipal wastewater sites in North Carolina from April 2022 to October 2023 were tested for C difficile gene targets by quantitative polymerase chain reaction.

The case-control cohort included 26 195 tests from 21 045 unique subjects, 3835 (14.6%) of which were positive for C difficile by nucleic acid amplification testing. Residence in the same watershed as commercial swine operations was associated with C difficile risk (adjusted odds ratio, 1.11 [95% confidence interval, 1.00-1.23]; P = .04). While C difficile gene targets were ubiquitous in municipal wastewater, they were not detected in 3 regional surface waters.

Swine operations were associated with C difficile risk even after adjustment for individual-level risk factors. Clostridioides difficile detection in water varies by source.