Hospitalization With Clostridioides difficile in Pediatric Inflammatory Bowel Disease: a Population-Based Study

M Ellen Kuenzig^{1

2}, Eric I Benchimol^{1

2

3

4

5

6

7}, Charles N Bernstein^{8

9}, Alain Bitton¹⁰, Matthew W Carroll¹¹, Anne M Griffiths^{1

2

4}, Gilaad G Kaplan¹², Geoffrey C Nguyen^{3

13

14}, Anthony R Otley¹⁵, Therese A Stukel^{3

14}, Trevor J B Dummer¹⁶, Wael El-Matary¹⁷, Kevan Jacobson¹⁸, Jennifer L Jones¹⁹, Lisa M Lix^{20

21}, David R Mack^{5

6

7}, Sanjay K Murthy^{22

23

24

25}, Juan-Nicolás Peña-Sánchez²⁵, Laura E Targownik¹³, Stephen G Fung^{3

6

7}, Sarah Spruin^{3

23}, Stephanie Coward¹², Yunsong Cui¹⁹, Christopher Filliter²⁶, Zoann Nugent⁸, Shabnaz Siddiq^{3

6

7}, Harminder Singh^{8

9

27}; Canadian Gastro-Intestinal Epidemiology Consortium (CanGIEC)

Affiliations

¹ From the SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada.
² the Child Health Evaluative Sciences, SickKids Research Institute, Toronto, Ontario, Canada.
³ the ICES, Toronto, Ontario, Canada.
⁴ the Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.
⁵ the Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada.
⁶ the CHEO Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, CHEO, Ottawa, Ontario, Canada.
⁷ the CHEO Research Institute, Ottawa, Ontario, Canada.
⁸ the Univeristy of Manitoba IBD Clinical and Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada.
⁹ the Department of Internal Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
¹⁰ the McGill University Health Centre, Division of Gastroenterology and Hepatology, Montreal, Québec, Canada.
¹¹ the Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
¹² the Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.
¹³ the Mount Sinai Hospital Centre for Inflammatory Bowel Disease, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
¹⁴ the Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada.
¹⁵ the Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada.
¹⁶ the School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.
¹⁷ the Department of Pediatrics, University of Manitoba, Winnipeg, Manitoba, Canada.
¹⁸ the Department of Pediatrics, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
¹⁹ the Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
²⁰ the Department of Community Health Sciences, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
²¹ the George & Fay Yee Centre for Healthcare Innovation, University of Manitoba, Manitoba, Winnipeg, Manitoba, Canada.
²² the Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
²³ the Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
²⁴ the Division of Gastroenterology, The Ottawa Hospital IBD Centre, Ottawa, Ontario, Canada.
²⁵ the School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada.
²⁶ the Lady Davis Institute of Medical Research, Jewish General Hospital, Montreal, Québec, Canada.
²⁷ the Research Institute at CancerCare Manitoba, Winnipeg, Manitoba, Canada.

PMID: 35675701
PMCID: PMC9278713
DOI: 10.1097/MPG.0000000000003489

Hospitalization With Clostridioides difficile in Pediatric Inflammatory Bowel Disease: a Population-Based Study

M Ellen Kuenzig et al. J Pediatr Gastroenterol Nutr. 2022.

. 2022 Aug 1;75(2):173-180.

doi: 10.1097/MPG.0000000000003489. Epub 2022 Jun 7.

Authors

Affiliations

¹ From the SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada.
² the Child Health Evaluative Sciences, SickKids Research Institute, Toronto, Ontario, Canada.
³ the ICES, Toronto, Ontario, Canada.
⁴ the Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.
⁵ the Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada.
⁶ the CHEO Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, CHEO, Ottawa, Ontario, Canada.
⁷ the CHEO Research Institute, Ottawa, Ontario, Canada.
⁸ the Univeristy of Manitoba IBD Clinical and Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada.
⁹ the Department of Internal Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
¹⁰ the McGill University Health Centre, Division of Gastroenterology and Hepatology, Montreal, Québec, Canada.
¹¹ the Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
¹² the Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.
¹³ the Mount Sinai Hospital Centre for Inflammatory Bowel Disease, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
¹⁴ the Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada.
¹⁵ the Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada.
¹⁶ the School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.
¹⁷ the Department of Pediatrics, University of Manitoba, Winnipeg, Manitoba, Canada.
¹⁸ the Department of Pediatrics, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
¹⁹ the Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
²⁰ the Department of Community Health Sciences, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
²¹ the George & Fay Yee Centre for Healthcare Innovation, University of Manitoba, Manitoba, Winnipeg, Manitoba, Canada.
²² the Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
²³ the Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
²⁴ the Division of Gastroenterology, The Ottawa Hospital IBD Centre, Ottawa, Ontario, Canada.
²⁵ the School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada.
²⁶ the Lady Davis Institute of Medical Research, Jewish General Hospital, Montreal, Québec, Canada.
²⁷ the Research Institute at CancerCare Manitoba, Winnipeg, Manitoba, Canada.

PMID: 35675701
PMCID: PMC9278713
DOI: 10.1097/MPG.0000000000003489

Abstract

Objectives: Several studies have demonstrated higher rates of Clostridioides difficile infection (CDI) in adults with inflammatory bowel disease (IBD). We conducted a population-based study comparing the risk of hospitalization with CDI in children with and without IBD.

Methods: Using health administrative data and validated algorithms, we identified all children (<16 years) diagnosed with IBD in 5 Canadian provinces, then age and sex matched to 5 children without IBD. Province-specific 5-year incidence rates of hospitalization with CDI were pooled and generalized linear mixed-effects models were used to estimate the crude incidence rate ratio (IRR) comparing (1) children with and without IBD and (2) children with Crohn disease and ulcerative colitis. Hazard ratios (HR) from Cox proportional hazards models adjusting for age, sex, rural/urban household, and income were pooled using fixed-effects models.

Results: The incidence rate of CDI identified during hospitalization was 49.06 [95% confidence interval (CI), 39.40-61.08] per 10,000 person-years (PY) in 3593 children with IBD compared to 0.39 (95% CI, 0.13-1.21) per 10,000 PY in 16,284 children without IBD (crude IRR, 133.4, 95% CI, 42.1-422.7; adjusted HR, 68.2, 95% CI, 24.4-190.4). CDI was identified less often in children with Crohn disease than ulcerative colitis (crude IRR, 0.51, 95% CI, 0.32-0.82; adjusted HR, 0.69, 95% CI, 0.46-1.05).

Conclusions: Children with IBD have a markedly higher incidence of CDI identified during a hospitalization relative to children without IBD. Consequently, symptomatic children with IBD who are hospitalized should be screened for CDI.

Copyright © 2022 The Author(s). Published by Wolters Kluwer on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

PubMed Disclaimer

Conflict of interest statement

E.I.B. has acted as a legal consultant for Hoffman La-Roche Limited and Peabody & Arnold LLP for matters unrelated to a medication used to treat inflammatory bowel disease or C. difficile infection. He has also acted as a consultant for McKesson Canada. G.G.K. has received honoraria for speaking or consultancy from Abbvie, Janssen, Pfizer, Amgen, and Takeda. He has received research support from Ferring, Janssen, Abbvie, GlaxoSmith Kline, Merck, and Shire. He shares ownership of a patent: TREATMENT OF INFLAMMATORY DISORDERS, AUTOIMMUNE DISEASE, AND PBC. UTI Limited Partnership, assignee. Patent 62/ 555,397. A.R.O. has been on advisory boards of AbbVie Canada, Janssen Canada, and Nestle. He has received unrestricted educational grants from AbbVie Canada and Janssen Canada. His site is involved with clinical trials for AbbVie, Pfizer, Takeda, Eli Lily, and Celgene. A.M.G. has been a consultant for Abbvie, Amgen, BristolMyersSquibb, Janssen, Lilly, Pfizer, Roche; has received speaker fees from Abbvie, Janssen, Nestle, and investigator-initiated grant support from Abbvie. L.E.T. has received investigator initiated funding from Janssen Canada, and served on advisory boards for AbbVie Canada, Sandoz Canada, Takeda Canada, Merck Canada, Pfizer Canada, Janssen Canada, and Roche Canada. C.N.B. has been on the advisory boards of Abbvie Canada, Amgen Canada, Bristol Myers Squibb Canada, Janssen Canada, Pfizer Canada, Sandoz Canada, Takeda Canada, Roche Canada, and consulted to Takeda and Mylan Pharmaceuticals. He has been on the speaker’s bureau for Abbvie Canada, Janssen Canada, Takeda Canada and Medtronic Canada. He has received unrestricted educational grants from Abbvie Canada, Janssen Canada, Pfizer Canada, and Takeda Canada and has done contract research with Abbvie, Janssen, Pfizer, Celgene, Boeringher Ingelheim, and Roche. K.J. has been on Advisory boards of Abbvie Canada, Janssen Canada, Merck Canada, and Mylan Pharmaceuticals. He has been on the speaker’s bureau of Abbvie Canada and Janssen Canada. He has received investigator-initiated research support from Abbvie Canada and Janssen Canada. W.E.M. has received honoraria for speaking or consultancy from Abbvie and MERCK. H.S. has consulted to Amgen Canada, Bristol-Myers Squibb Canada, Sandoz Canada, Roche Canada, Takeda Canada, and Guardant Health. The remaining authors report no conflicts of interest.

Figures

**Figure 1.**
Incidence per 10,000 person-years (PY) of hospitalization with *Clostridioides difficile* infection among children with inflammatory bowel disease (IBD) in (A) the first year following diagnosis and (B) the first 5 y following diagnosis. CI = confidence interval.

**Figure 2.**
Hazard ratios (HRs) comparing the risk of hospitalization with *Clostridioides difficile* infection in children with Crohn disease relative to ulcerative colitis. CI = confidence interval.

See this image and copyright information in PMC

References

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Hospitalization With Clostridioides difficile in Pediatric Inflammatory Bowel Disease: a Population-Based Study

Affiliations

Hospitalization With Clostridioides difficile in Pediatric Inflammatory Bowel Disease: a Population-Based Study

Authors

Affiliations

Abstract

Conflict of interest statement

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References

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Medical