Evidence map›Paper›PMID 41830216›Full record

ArticleThe Journal of infectious diseases2026

Antibiotic and Nonantibiotic Drugs Associated With Clostridioides difficile Infection Risk: a Pharmacopoeia-Wide Case-Cohort Study.

Kevin A Brown, Bryan Coburn, Alejandro Hernandez, Bradley J Langford, Valerie Leung, Derek MacFadden, Ashley M Rooney, Kevin L Schwartz, Nick Daneman

Abstract read
In one paragraph

Article in The Journal of infectious diseases, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Burden and Mortality Outcomes ofJournal of clinical medicine · 2026
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Kevin A BrownPublic Health Ontario, Toronto, Ontario, Canada.ORCID 0000-0002-1483-2188
Bryan CoburnDepartment of Medicine, University of Toronto, Toronto, Ontario, Canada.ORCID 0000-0003-0150-4510
Alejandro HernandezICES, Toronto, Ontario, Canada.ORCID 0000-0002-1261-9340
Bradley J LangfordPublic Health Ontario, Toronto, Ontario, Canada.ORCID 0000-0001-5467-6776
Valerie LeungPublic Health Ontario, Toronto, Ontario, Canada.ORCID 0000-0002-6780-5378
Derek MacFaddenOttawa Hospital Research Institute, Ottawa, Ontario, Canada.
Ashley M RooneyInstitute of Medical Microbiology, University of Zurich, Zurich, Switzerland.
Kevin L SchwartzPublic Health Ontario, Toronto, Ontario, Canada.
Nick DanemanPublic Health Ontario, Toronto, Ontario, Canada.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundClostridioides difficile infection (CDI) is principally precipitated by antibiotics, due to their disruption of gut commensal bacteria. The comparative role of nonantibiotic drugs is poorly characterized.

methodsWe examined the contribution of antibiotic and nonantibiotic drugs to CDI risk among residents age >65 years old and not hospitalized in the prior 30 days, between 2018 and 2023. The study used a case-cohort study design, with logistic regression analysis. The case definition consisted of first incident CDI, identified using comprehensive C. difficile testing, hospitalization, and treatment data. Outpatient oral drug exposures were measured in a 1-90-day window prior to case and control days. Adjusted regression models included covariates for age, sex, year and quarter, region, comorbid conditions, healthcare exposures, and drug exposures.

resultsAmong 16 196 CDI case patients and 549 831 controls, 335 drugs were included. After adjustment, the antibiotics amoxicillin-clavulanate (odds ratio [OR], 6.05 [95% confidence interval (CI), 5.69-6.43]), clindamycin (16.83 [15.53-18.24]), ciprofloxacin (3.83 [3.59-4.09]), and cephalexin (3.05 [2.86-3.25]), were the largest contributors to CDI risk. Nonantibiotic drugs pantoprazole (OR, 1.33 [95% CI, 1.27-1.39]) and ferrous fumarate (1.71 [1.61-1.82]) were the next largest. Metformin had a protective association (OR, 0.67 [95% CI, .63-.72]). In a meta-regression on a subset of 182 drugs, in vitro anticommensal activity was positively associated with CDI risk (P < .001).

conclusionsThis study provides insights into CDI etiology and avenues for stewardship and drug repurposing to combat CDI and antimicrobial resistance.

Indexed as

Anti-Bacterial AgentsClostridioides difficileClostridium InfectionsAgedAged, 80 and overCase-Control StudiesCohort StudiesFemaleHumansMaleRisk FactorsAnti-Bacterial Agentsantibiotic-associated diarrheaClostridium difficiledrug surveillancemicrobiome

Identifiers

PMID41830216
PMCPMC13175627

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.