Globally, the overall rate of healthcare-associated Clostridioides difficile infection has been reported to be 2.24 cases per 1000 admissions per year and 3.54 cases per 10,000 patient days per year. The rate in intensive care units and internal medicine wards was 11.08 and 10.8 cases per 1000 admissions per year, respectively. The rate for community-acquired infection is much lower (0.55 cases per 1000 admissions per year). Higher rates of infection have been reported in the US compared with Europe and the Western Pacific region.[4]Balsells E, Shi T, Leese C, et al. Global burden of Clostridium difficile infections: a systematic review and meta-analysis. J Glob Health. 2019 Jun;9(1):010407.
http://jogh.org/documents/issue201901/jogh-09-010407.pdf
http://www.ncbi.nlm.nih.gov/pubmed/30603078?tool=bestpractice.com
An increasing proportion of infections treated by hospitals are community-acquired; however, the reason for this remains unclear.[5]Turner NA, Grambow SC, Woods CW, et al. Epidemiologic trends in Clostridioides difficile infections in a regional community hospital network. JAMA Netw Open. 2019 Oct 2;2(10):e1914149.
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2753662
http://www.ncbi.nlm.nih.gov/pubmed/31664443?tool=bestpractice.com
C difficile infection has become the most common cause of healthcare-associated infections in US hospitals, with estimates of 500,000 infections and 29,000 deaths (within 30 days of the initial diagnosis) among patients in the US in one year. Approximately 65% of cases were healthcare-associated (including nursing homes and patients who have visited outpatient settings), but only 24% of cases had onset while in hospital. The incidence of healthcare-associated infection was 92.8 per 100,000 persons, while the incidence of community-associated infection was 48.2 per 100,000 persons. White people, females, and patients aged 65 years and older had a higher incidence of infection.[6]Lessa FC, Mu Y, Bamberg WM, et al. Burden of Clostridium difficile infection in the United States. N Engl J Med. 2015 Feb 26;372(9):825-34.
http://www.nejm.org/doi/pdf/10.1056/NEJMoa1408913
http://www.ncbi.nlm.nih.gov/pubmed/25714160?tool=bestpractice.com
In terms of patient-days, the incidence rates of hospital-onset infection were 8 and 2 cases per 10,000 patient-days for healthcare-associated and community-associated infection, respectively, in the US.[7]Finn E, Andersson FL, Madin-Warburton M. Burden of Clostridioides difficile infection (CDI) - a systematic review of the epidemiology of primary and recurrent CDI. BMC Infect Dis. 2021 May 19;21(1):456.
https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06147-y
http://www.ncbi.nlm.nih.gov/pubmed/34016040?tool=bestpractice.com
A prospective study found that C difficile infection accounted for approximately 10% of patients presenting to the emergency department with diarrhoea and no vomiting, and more than one third of these patients lacked traditional risk factors for infection.[8]Abrahamian FM, Talan DA, Krishnadasan A, et al; EMERGEncy ID NET Study Group. Clostridium difficile infection among US emergency department patients with diarrhea and no vomiting. Ann Emerg Med. 2017 Jul;70(1):19-27;e4.
http://www.ncbi.nlm.nih.gov/pubmed/28242058?tool=bestpractice.com
The epidemiology changed in the 2000s due to the emergence of the more toxic North American pulsed-field gel electrophoresis type 1 (NAP1) strain (also known as PCR ribotype 027 [RT027] epidemic strain).[9]Bartlett JG, Perl TM. The new Clostridium difficile - what does it mean? N Engl J Med. 2005 Dec 8;353(23):2503-5.
http://www.ncbi.nlm.nih.gov/pubmed/16322604?tool=bestpractice.com
[10]Loo VG, Poirier L, Miller MA, et al. A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N Engl J Med. 2005 Dec 8;353(23):2442-9.
http://www.nejm.org/doi/full/10.1056/NEJMoa051639#t=article
http://www.ncbi.nlm.nih.gov/pubmed/16322602?tool=bestpractice.com
[11]McDonald LC, Killgore GE, Thompson A, et al. An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med. 2005 Dec 8;353(23):2433-41.
http://www.nejm.org/doi/full/10.1056/NEJMoa051590#t=article
http://www.ncbi.nlm.nih.gov/pubmed/16322603?tool=bestpractice.com
Outbreaks occurred in North America, the UK, Europe, and Asia. The NAP1 strain has been decreasing in prevalence since it was first isolated, but remains a significant problem in the US. The emergence of this strain may be the result of widespread use of fluoroquinolones.[12]Bartlett JG. Narrative review: the new epidemic of Clostridium difficile-associated enteric disease. Ann Intern Med. 2006 Nov 21;145(10):758-64.
http://www.ncbi.nlm.nih.gov/pubmed/17116920?tool=bestpractice.com
The NAP1 strain is more prevalent in healthcare-associated infections.[6]Lessa FC, Mu Y, Bamberg WM, et al. Burden of Clostridium difficile infection in the United States. N Engl J Med. 2015 Feb 26;372(9):825-34.
http://www.nejm.org/doi/pdf/10.1056/NEJMoa1408913
http://www.ncbi.nlm.nih.gov/pubmed/25714160?tool=bestpractice.com
Ribotype 106 (RT106) is found globally, and became more prevalent in the 2010s (it became the most prevalent strain in the US in 2016). It is thought to cause less severe disease compared with RT027.[13]Carlson TJ, Blasingame D, Gonzales-Luna AJ, et al. Clostridioides difficile ribotype 106: a systematic review of the antimicrobial susceptibility, genetics, and clinical outcomes of this common worldwide strain. Anaerobe. 2020 Apr;62:102142.
http://www.ncbi.nlm.nih.gov/pubmed/32007682?tool=bestpractice.com
Recurrence rates have been reported to vary from 5% to 50%, although one study found at least one recurrence in 21% of healthcare-associated infections and 14% of community-associated infections.[6]Lessa FC, Mu Y, Bamberg WM, et al. Burden of Clostridium difficile infection in the United States. N Engl J Med. 2015 Feb 26;372(9):825-34.
http://www.nejm.org/doi/pdf/10.1056/NEJMoa1408913
http://www.ncbi.nlm.nih.gov/pubmed/25714160?tool=bestpractice.com
The risk of developing a first recurrent episode after an initial episode is 25%, with a risk of 38% for a second, 29% for a third, and 27% of a fourth episode. The risk of severe infection decreased with each subsequent recurrence.[14]Sheitoyan-Pesant C, Abou Chakra CN, Pépin J, et al. Clinical and healthcare burden of multiple recurrences of Clostridium difficile infection. Clin Infect Dis. 2016 Mar 1;62(5):574-80.
https://academic.oup.com/cid/article/62/5/574/2462831
http://www.ncbi.nlm.nih.gov/pubmed/26582748?tool=bestpractice.com
The annual incidence of multiply-recurrent infection has increased in recent years. Risk factors for recurrent infection include female sex, increasing age, chronic kidney disease, diagnosis in a nursing home, healthcare-associated infection, prior hospitalisation, previous recurrent infection, and recent use of corticosteroids or proton-pump inhibitors.[15]Ma GK, Brensinger CM, Wu Q, et al. Increasing incidence of multiply recurrent Clostridium difficile infection in the United States: a cohort study. Ann Intern Med. 2017 Aug 1;167(3):152-8.
http://www.ncbi.nlm.nih.gov/pubmed/28672282?tool=bestpractice.com
[16]van Rossen TM, Ooijevaar RE, Vandenbroucke-Grauls CMJE, et al. Prognostic factors for severe and recurrent Clostridioides difficile infection: a systematic review. Clin Microbiol Infect. 2022 Mar;28(3):321-31.
https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(21)00552-8/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/34655745?tool=bestpractice.com
Patients on acid-suppressing drugs were 64% more likely to develop recurrent C difficile infection compared to patients not on acid-suppressing drugs, and the association was greater with PPIs.[17]Mehta P, Nahass RG, Brunetti L. Acid suppression medications during hospitalization as a risk factor for recurrence of clostridioides difficile Infection: systematic review and meta-analysis. Clin Infect Dis. 2021 Jul 1;73(1):e62-8.
https://academic.oup.com/cid/article/73/1/e62/5835316
http://www.ncbi.nlm.nih.gov/pubmed/32386313?tool=bestpractice.com
In the UK, approximately 20,000 cases were reported between November 2023 to November 2024 (trust-apportioned cases only).[18]UK Health Security Agency. C. difficile infection: monthly data by prior trust exposure. Dec 2024 [internet publication].
https://www.gov.uk/government/statistics/c-difficile-infection-monthly-data-by-prior-trust-exposure
Approximately 86,000 cases were reported in 26 countries across Europe in 2018-2020, approximately 61% of which were healthcare associated.[19]European Centre for Disease Prevention and Control. Healthcare-associated infections: Clostridium difficile infections - annual epidemiological report for 2018-2020. May 2024 [internet publication].
https://www.ecdc.europa.eu/en/publications-data/clostridioides-difficile-infections-annual-epidemiological-report-2018-2020
In terms of patient-days, the incidence rates of hospital-onset infection were highest in Poland (6.2 and 1.4 cases per 10,000 patient-days for healthcare-associated and community-associated infection, respectively) and lowest in the UK (2 and 0.6 cases per 10,000 patient-days for healthcare-associated and community-associated infection, respectively).[7]Finn E, Andersson FL, Madin-Warburton M. Burden of Clostridioides difficile infection (CDI) - a systematic review of the epidemiology of primary and recurrent CDI. BMC Infect Dis. 2021 May 19;21(1):456.
https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06147-y
http://www.ncbi.nlm.nih.gov/pubmed/34016040?tool=bestpractice.com
Incidence rates in Asia are reported to be similar to rates in Europe and North America.[20]Borren NZ, Ghadermarzi S, Hutfless S, et al. The emergence of Clostridium difficile infection in Asia: a systematic review and meta-analysis of incidence and impact. PLoS One. 2017 May 2;12(5):e0176797.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5413003
http://www.ncbi.nlm.nih.gov/pubmed/28463987?tool=bestpractice.com