Characterization of Healthcare-Associated and Community-Associated Clostridioides Difficile Infections Among Adults, Canada, 2015–2019

Tim Du; Kelly B. Choi; Anada Silva; George R. Golding; Linda Pelude; Romeo Hizon; Ghada N. Al-Rawahi; James Brooks; Blanda Chow; Jun C. Collet; Jeannette L. Comeau; Ian Davis; Gerald A. Evans; Charles Frenette; Guanghong Han; Jennie Johnstone; Pamela Kibsey; Kevin C. Katz; Joanne M. Langley; Bonita E. Lee; Yves Longtin; Dominik Mertz; Jessica Minion; Michelle Science; Jocelyn A. Srigley; Paula Stagg; Kathryn N. Suh; Nisha Thampi; Alice Wong; Susy S. Hota

Disclosures

Emerging Infectious Diseases. 2022;28(6):1128-1136.

Abstract and Introduction

Abstract

We investigated epidemiologic and molecular characteristics of healthcare-associated (HA) and community-associated (CA) Clostridioides difficile infection (CDI) among adult patients in Canadian Nosocomial Infection Surveillance Program hospitals during 2015–2019. The study encompassed 18,455 CDI cases, 13,735 (74.4%) HA and 4,720 (25.6%) CA. During 2015–2019, HA CDI rates decreased by 23.8%, whereas CA decreased by 18.8%. HA CDI was significantly associated with increased 30-day all-cause mortality as compared with CA CDI (p<0.01). Of 2,506 isolates analyzed, the most common ribotypes (RTs) were RT027, RT106, RT014, and RT020. RT027 was more often associated with CDI-attributable death than was non-RT027, regardless of acquisition type. Overall resistance C. difficile rates were similar for all drugs tested except moxifloxacin. Adult HA and CA CDI rates have declined, coinciding with changes in prevalence of RT027 and RT106. Infection prevention and control and continued national surveillance are integral to clarifying CDI epidemiology, investigation, and control.

Introduction

Clostridioides difficile is a major cause of infectious nosocomial diarrhea in high-income countries.^[1] Disease severity ranges from asymptomatic colonization to fulminant colitis, sometimes leading to colectomy and death.^[2] Healthcare costs attributed to C. difficile infection (CDI) are estimated to be $4.8 billion in the United States and €3 billion in Europe.^[3] A study in Canada estimated 38,000 annual CDI cases and conservative estimated costs of CDN $280 million resulting from extended hospital stays and rehospitalization.^[4]

The epidemiology of C. difficile has evolved markedly in the past decade.^[1] Whereas CDI was once believed to be mostly healthcare-associated (HA), increased evidence points to transmission in community settings.^[5,6] An estimated 40% of patients with community-associated (CA) CDI require hospitalization; 20% experience treatment failure, and 28% have recurrent CDI episodes.^[7]

Several international studies have reported changes in molecular and epidemiologic characteristics of CDI in healthcare and community settings;^[8–13] we investigated changes in adult CA CDI epidemiology in Canada. The Canadian Nosocomial Infection Surveillance Program (CNISP) collects standardized epidemiologic and laboratory-linked data from sentinel hospitals across Canada, currently representing 30% of all acute care beds. We previously reported a decrease in HA CDI rates during 2009–2015, associated with a reduction in ribotype (RT) 027.^[1] Here, we describe findings of a multicenter study evaluating incidence, patient characteristics, outcomes, RT prevalence, and antimicrobial resistance rates for HA and CA CDI identified during 2015–2019 in hospitals participating in CNISP. We also assessed associations between predominant RTs and all-cause and CDI-attributable deaths.

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Abstract and Introduction
Methods
Results
Discussion
References

Table 1. Clinical and molecular characteristics of healthcare-associated and community-associated *Clostridioides difficile* infection among adults, Canada, 2015–2019*
Characteristics	Healthcare-associated	Community-associated	All cases	p value
Routine surveillance, no. (%)†	13,735 (74.4)	4,720 (25.6)	18,455
Patient characteristics
Age, y
Mean (SD)	68.3 (16.9)	64.4 (18.4)	67.3 (17.4)	<0.001
Median (IQR)	70.0 (59.0–81.0)	67.0 (54.0–79.0)	70.0 (58.0–80.0)	<0.001
Sex, no. (%)
F	6,747 (49.1)	2,645 (56.0)	9,392 (50.9)	<0.001
M	6,988 (50.9)	2,075 (44.0)	9,063 (49.1)
Targeted surveillance, no. (%)‡	2,350 (76.2)	734 (23.8)	3,084
Clinical results and outcomes
Median (IQR) leukocyte count, × 10⁹ cells/L	10.9 (23.0–33.0)	10.6 (6.9–15.7)	10.8 (7.1–16.0)	NS
Median (IQR) albumin, g/L	26.0 (22.0–31.0)	28.0 (23.0–33.0)	27.0 (22.0–32.0)	0.0232
FMT, no. positive/no. tested (%)§	11/3,645 (0.3)	4/1,557 (0.3)	15/5,202 (0.3)	NS
Colectomy, no. positive/no. tested (%)	30/2,255 (1.3)	15/725 (2.1)	45/2,980 (1.5)	NS
Loop ileostomy, no. positive/no. tested (%)	2/798 (0.3)	3/270 (1.1)	5/1,068 (0.5)	NS
ICU admission, no. (%)	n = 2,340	n = 733	n = 3,073
All cause	156 (6.7)	51 (7.0)	207 (6.8)	NS
Due to complications of CDI	46 (2.0)	11 (1.5)	57 (1.9)	NS
30-d mortality, no. (%)	n = 2,302	n = 731
Death, all causes	263 (11.4)	53 (7.3)	316/3,033 (10.4)	0.0001
Death, attributable to CDI	69 (3.0)	17 (2.3)	86/3,019 (2.9)	NS

*Missing or unknown values were excluded from the analysis. χ² test was used to assess statistical significance for categorical variables; Student t test, or the Wilcoxon rank sum test was used for continuous variables. CDI, Clostridiodes difficile infection; FMT, fecal microbiota transplantation; ICU, intensive care unit; IQR, interquartile range; NS, not significant.
†Patient characeristics data collected year-round.
‡Clinical results and outcome data are collected during a 2-month targeted surveillance period (March–April) each year except FMT where the data were collected year-around.
§FMT data collection started in 2018.

Table 2. Univariable and multivariable analysis of 30-day all-cause and *Clostridioides difficile*–attributable mortality, Canada, 2015–2019*
Characteristics	Univariable analysis		Multivariable analysis
Characteristics	Odds ratio (95% CI)	p value	Adjusted odds ratio (95% CI)	p value
All-cause mortality
Sex
M	Referent		Referent
F	1.15 (0.91–1.45)	0.2484	1.26 (0.93–1.70)	NS
Age group, y
<65	Referent		Referent
≥65	2.66 (2.00–3.53)	<0.0001	3.63 (2.45–5.39)	<0.0001
Severe CDI†	2.53 (1.90–3.36)	<0.0001	2.66 (1.90–3.73)	<0.0001
CDI case type
Community-associated	Referent		Referent
Healthcare-associated	1.65 (1.21–2.24)	0.0014	1.83 (1.23–2.72)	0.0028
RT027 vs. non-RT027	1.48 (1.04–2.10)	0.0289	1.10 (0.74–1.63)	NS
RT106 vs. non-RT106	1.09 (0.73–1.63)	0.6804	NA
CDI-attributable mortality
Sex
M	Referent		Referent
F	1.22 (0.79–1.87)	0.3776	1.33 (0.81–1.19)	NS
Age group, y
<65	Referent		Referent
≥65	3.28 (1.84–5.85)	<0.0001	3.44 (1.73–6.82)	0.0004
Severe CDI†	2.40 (1.45–4.0)	0.0006	2.25 (1.28–3.94)	0.0050
CDI case type
Community-associated	Referent		Referent
Healthcare-associated	1.29 (0.76–2.22)	0.3476	1.25 (0.67–2.35)	NS
RT027 vs. non-RT027	3.17 (1.89–5.29)	<0.0001	2.85 (1.64–5.00)	0.0002
RT106 vs. non-RT106	0.95 (0.45–2.00)	0.8830	NA

*Bold text indicates statistical significance. CDI, Clostridioides difficile infection; NA, not applicable; NS, not significant; RT, ribotype.
†Severe CDI defined as albumin level <30 g/L, leukocyte count ≥15 × 10⁹ cells/L, or both.

Authors and Disclosures

Tim Du¹, Kelly B. Choi¹, Anada Silva, George R. Golding, Linda Pelude, Romeo Hizon, Ghada N. Al-Rawahi, James Brooks, Blanda Chow, Jun C. Collet, Jeannette L. Comeau, Ian Davis, Gerald A. Evans, Charles Frenette, Guanghong Han, Jennie Johnstone, Pamela Kibsey, Kevin C. Katz, Joanne M. Langley, Bonita E. Lee, Yves Longtin, Dominik Mertz, Jessica Minion, Michelle Science, Jocelyn A. Srigley, Paula Stagg, Kathryn N. Suh, Nisha Thampi, Alice Wong and Susy S. Hota

National Microbiology Laboratory, Winnipeg, Manitoba, Canada (T. Du, G.R. Golding, R. Hizon); Public Health Agency of Canada, Ottawa, Ontario, Canada (K.B. Choi, A. Silva, L. Pelude, J. Brooks); British Columbia Children's Hospital, Vancouver, British Columbia, Canada (G.N. Al-Rawahi); Alberta Health Services, Calgary, Alberta, Canada (B. Chow); BC Children's & Women's Hospitals, Vancouver (J.C. Collet, J.A. Srigley); Dalhousie University, Halifax, Nova Scotia, Canada (J.L. Comeau); Queen Elizabeth II Health Sciences Centre, Halifax (I. Davis); Kingston Health Sciences Centre, Kingston, Ontario, Canada (G.A. Evans); McGill University Health Centre, Montréal, Quebec, Canada (C. Frenette); Provincial Infection Control Network, Vancouver (G. Han); Sinai Health, Toronto, Ontario, Canada (J. Johnstone); Royal Jubilee Hospital, Victoria, British Columbia, Canada (P. Kibsey); North York General Hospital, Toronto (K.C. Katz); IWK Health Centre, Halifax (J.M. Langley); Stollery Children's Hospital, Edmonton, Alberta, Canada (B.E. Lee); Jewish General Hospital, Montréal (Y. Longtin); Hamilton Health Sciences, Hamilton, Ontario, Canada (D. Mertz); Regina General Hospital, Regina, Saskatchewan, Canada (J. Minion); The Hospital for Sick Children, Toronto (M. Science); Western Memorial Regional Hospital, Corner Brook, Newfoundland and Labrador, Canada (P. Stagg); The Ottawa Hospital, Ottawa (K.N. Suh); Childrens Hospital of Eastern Ontario, Ottawa (N. Thampi); Royal University Hospital, Saskatoon, Saskatchewan, Canada (A. Wong); University Health Network, Toronto (S.S. Hota)

Address for correspondence
George Golding, Surveillance, Reference and Science Directorate of the National Microbiology Laboratory Branch, One Health Division, Antimicrobial Resistance and Nosocomial Infections, National Microbiology Laboratory, 1015 Arlington St, Winnipeg, MB R3E 3R2, Canada; email: george.golding@phac-aspc.gc.ca

¹These authors contributed equally to this article.

About the Authors
Dr. Du is a biologist with the Public Health Agency of Canada in Winnipeg, Manitoba, Canada. His primary research interests include the epidemiology of Clostridioides difficile in addition to antimicrobial resistance in hospital acquired infections. Dr. Choi is an epidemiologist with Canadian Nosocomian Infection Surveillance Program, Public Health Agency of Canada, Ottawa, Ontario, Canada. Her primary research interest is antimicrobial-resistant infections, including C. difficile infection and surgical site infections.