Burden of Clostridium difficile Infection in the United States

Lessa, Fernanda C.; Mu, Yi; Bamberg, Wendy M.; Beldavs, Zintars G.; Dumyati, Ghinwa K.; Dunn, John R.; Farley, Monica M.; Holzbauer, Stacy M.; Meek, James I.; Phipps, Erin C.; Wilson, Lucy E.; Winston, Lisa G.; Cohen, Jessica A.; Limbago, Brandi M.; Fridkin, Scott K.; Gerding, Dale N.; McDonald, L. Clifford

doi:10.1056/nejmoa1408913

Cited by 2,641Clostridium difficile and Clostridium perfringens researchInfection Control in HealthcareAntimicrobial Resistance in Staphylococcus

Burden of Clostridium difficile Infection in the United States

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Lessa, Fernanda C., Mu, Yi, Bamberg, Wendy M., Beldavs, Zintars G., Dumyati, Ghinwa K., Dunn, John R., Farley, Monica M., Holzbauer, Stacy M. +9 more·2015·New England Journal of Medicine

DOI 10.1056/nejmoa1408913PMC PMC10966662

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Abstract

BACKGROUND: The magnitude and scope of Clostridium difficile infection in the United States continue to evolve. METHODS: In 2011, we performed active population- and laboratory-based surveillance across 10 geographic areas in the United States to identify cases of C. difficile infection (stool specimens positive for C. difficile on either toxin or molecular assay in residents ≥ 1 year of age). Cases were classified as community-associated or health care-associated. In a sample of cases of C. difficile infection, specimens were cultured and isolates underwent molecular typing. We used regression models to calculate estimates of national incidence and total number of infections, first recurrences, and deaths within 30 days after the diagnosis of C. difficile infection. RESULTS: A total of 15,461 cases of C. difficile infection were identified in the 10 geographic areas; 65.8% were health care-associated, but only 24.2% had onset during hospitalization. After adjustment for predictors of disease incidence, the estimated number of incident C. difficile infections in the United States was 453,000 (95% confidence interval [CI], 397,100 to 508,500). The incidence was estimated to be higher among females (rate ratio, 1.26; 95% CI, 1.25 to 1.27), whites (rate ratio, 1.72; 95% CI, 1.56 to 2.0), and persons 65 years of age or older (rate ratio, 8.65; 95% CI, 8.16 to 9.31). The estimated number of first recurrences of C. difficile infection was 83,000 (95% CI, 57,000 to 108,900), and the estimated number of deaths was 29,300 (95% CI, 16,500 to 42,100). The North American pulsed-field gel electrophoresis type 1 (NAP1) strain was more prevalent among health care-associated infections than among community-associated infections (30.7% vs. 18.8%, P<0.001). CONCLUSIONS: C. difficile was responsible for almost half a million infections and was associated with approximately 29,000 deaths in 2011. (Funded by the Centers for Disease Control and Prevention.).

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Because the populations under surveillance in the 9 EIP sites are diverse, EIP findings can and have been used to extrapolate to national estimates of other infections.
“Furthermore, because the populations under surveillance in the 9 sites are diverse (by age distribution, race, urban/rural, and other factors), EIP findings can and have been used to extrapolate to national estimates of other infections [33,34].”
From Burden of Candidemia in the United States, 2017 (2020) · cites this paper as [34]
The Methods (Surveillance Population and Definition; Statistical Analysis) describe geographically varied EIP surveillance areas and use EIP data to estimate the national burden of C. difficile infection, accounting for demographic factors. This supports the cited paper as an example of national extrapolation. It studied 10 EIP sites, however, not the nine sites named in the citing sentence, and does not establish that site diversity was the reason extrapolation was possible. (LLM, conf=0.85)
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Desai, K., Gupta, S. B., Dubberke, E. R., Prabhu, V. S., Browne, C., & Mast, T. C. (2016) · BMC Infectious Diseases · doi:10.1186/s12879-016-1610-3 · Cited by 158 · see citing works

Determinants of Clostridium difficile Infection Incidence Across Diverse United States Geographic Locations
(2016)
Trends in U.S. Burden of Clostridioides difficile Infection and Outcomes
Guh, A. Y., Mu, Y., Winston, L. G., Johnston, H. L., Olson, D. M., Farley, M. M., Wilson, L. E., Holzbauer, S., Phipps, E. C., Dumyati, G. K., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa1910215 · Cited by 863 · see citing works
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524National estimates of incidence, recurrence, hospitalization, and death of nursing home-onset Clostridium difficile infections — United States, 2012
Hunter, J. C., Mu, Y., Dumyati, G. K., Farley, M. M., Winston, L. G., Johnston, H. L., Meek, J. I., Wilson, L. E., Stacy, M., Beldavs, Z. G., et al. (2014) · Open Forum Infectious Diseases · doi:10.1093/ofid/ofu051.43 · Cited by 1 · see citing works
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Epidemiology of community-acquired and recurrent Clostridioides difficile infection
Fu, Y., Luo, Y., & Grinspan, A. M. (2021) · Therapeutic Advances in Gastroenterology · doi:10.1177/17562848211016248 · Cited by 94 · see citing works
Epidemiologic Trends in Clostridioides difficile Infections in a Regional Community Hospital Network
Turner, N., Grambow, S. C., Woods, C. W., Fowler, V. G., Moehring, R. W., Anderson, D. J., & Lewis, S. S. (2019) · JAMA Network Open · doi:10.1001/jamanetworkopen.2019.14149 · Cited by 49 · see citing works

Authors: Lessa, F. C., Mu, Y., Bamberg, W. M., Beldavs, Z. G., Dumyati, G. K., Dunn, J. R., Farley, M. M., Holzbauer, S. M., Meek, J. I., Phipps, E. C., Wilson, L. E., Winston, L. G., Cohen, J. A., Limbago, B. M., Fridkin, S. K., Gerding, D. N., & McDonald, L. C.
Affiliations: National Center for Emerging and Zoonotic Infectious Diseases (US)
Colorado Department of Public Health and Environment (US)
Oregon Health Authority (US)
University of Rochester Medicine (US)
Tennessee Department of Health (US)
Emory University (US)
Office of Readiness and Response (US)
Yale University (US)
University of New Mexico (US)
Maryland Department of Health (US)
University of California, San Francisco (US)
Loyola University Chicago (US)
ORCID: Lessa, Fernanda C.
Mu, Yi
Bamberg, Wendy M.
Dumyati, Ghinwa K.
Dunn, John R.
Farley, Monica M.
Holzbauer, Stacy M.
Meek, James I.
Phipps, Erin C.
Wilson, Lucy E.
Fridkin, Scott K.
Gerding, Dale N.
McDonald, L. Clifford
Venue: New England Journal of Medicine
Publisher: Massachusetts Medical Society
Published: 2015-02-26
Volume: 372
Issue: 9
Pages: 825-834
ISSN: 0028-4793 (ISSN-L)
1533-4406
DOI: 10.1056/nejmoa1408913
PMC: PMC10966662
OpenAlex: W2071054182
Cited by: 2,641
References: 44
Citations by year: 2026: 94 · 2025: 111 · 2024: 120 · 2023: 150 · 2022: 176 · 2021: 225 · 2020: 328 · 2019: 382 · 2018: 356 · 2017: 323 · 2016: 262 · 2015: 108 · 2014: 1
FWCI: 270.42
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: other-oa
Locations: New England Journal of Medicine (publishedVersion, other-oa)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Maryland Shared Open Access Repository (USMAI Consortium) (submittedVersion, public-domain)
eScholarship (California Digital Library) (submittedVersion)
Digital Repository at the University of Maryland (University of Maryland College Park) (public-domain)
Funders: National Institutes of Health (CC999999)
Centers for Disease Control and Prevention
Topics: Health Sciences › Medicine › Infectious Diseases › Clostridium difficile and Clostridium perfringens research
Health Sciences › Medicine › Infectious Diseases › Infection Control in Healthcare
Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
Keywords: Clostridium difficile infection, incidence, nosocomial infections, community-associated infections, recurrence, mortality, NAP1 strain, molecular typing, pulsed-field gel electrophoresis
MeSH terms: Adolescent, Adult, Aged, Child, Child, Preschool, Clostridium Infections, Cross Infection, Female, Humans, Infant, Male, Middle Aged, Population Surveillance, Recurrence, United States, Bacterial Typing Techniques, Incidence, Clostridioides difficile, Electrophoresis, Gel, Pulsed-Field, Age Distribution, Sex Distribution

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