Prevalence and risk factors of toxigenic Clostridioides difficile asymptomatic carriage in 11 French hospitals

Clostridioides difficile infection (CDI) incidence has increased over the last 20 years. Studies suggest that asymptomatic carriers may be an important reservoir of C. difficile in healthcare settings. We conducted a point prevalence study to estimate the toxigenic C. difficile asymptomatic carriage rate and the associated risk factors in patients >3 years old. Between September 16, 2019 and January 15, 2020, all patients hospitalized in 11 healthcare facilities in the Paris urban area were included in the study. They were screened on the day of the survey for toxigenic C. difficile carriage by rectal swab and interviewed. Isolates were characterized by PCR ribotyping and multiplex PCR targeting toxin genes. A logistic regression model was used to determine the risk factors associated with toxigenic C. difficile asymptomatic carriage using uni- and multivariate analysis in the subpopulation of patients >3 years old. During the study period, 2,389 patients were included and screened. The median age was 62 years (interquartile range 35–78 years) and 1,153 were male (48.3%). Nineteen patients had a previous CDI (0.9%). Overall, 185/2389 patients were positive for C. difficile (7.7%), including 93 toxigenic strains (3.9%): 77 (82.8%) were asymptomatic (prevalence 3.2%) whereas 12 (12.9%) were diarrheic. Prevalences of toxigenic C. difficile were 3.5% in patients >3 years old and 7.0% in ≤3 years old subjects, respectively. Toxigenic strains mainly belonged to PCR ribotypes 106 (n = 14, 15.0%), 014 (n = 12, 12.9%), and 020 (n = 10, 10.8%). Among toxigenic strains, 6 (6.4%) produced the binary toxin. In multivariate analysis, two factors were positively associated with toxigenic C. difficile asymptomatic carriage in patients >3 years old: multidrug-resistant organisms co-carriage [adjusted Odd Ratio (aOR) 2.3, CI 95% 1.2–4.7, p = 0.02] and previous CDI (aOR 5.8, CI 95% 1.2–28.6, p = 0.03). Conversely, consumption of raw milk products were associated with reduced risk of toxigenic C. difficile colonization (aOR 0.5, CI 95% 0.2–0.9, p = 0.01). We showed that there was a low prevalence of asymptomatic toxigenic C. difficile carriage in hospitalized patients. Consumption of raw milk prevents toxigenic C. difficile colonization, probably due to the barrier effect of milk-associated bacteria.

[1]  E. Kuijper,et al.  European survey on the current surveillance practices, management guidelines, treatment pathways, and heterogeneity of testing of Clostridioides difficile, 2018-2019: results from The Combatting Bacterial Resistance in Europe CDI (COMBACTE-CDI). , 2022, The Journal of hospital infection.

[2]  P. Frange,et al.  Faecal carriage of multidrug-resistant bacteria and associated risk factors: results from a point prevalence study. , 2022, The Journal of antimicrobial chemotherapy.

[3]  Alberto Maria Segre,et al.  Risk for Asymptomatic Household Transmission of Clostridioides difficile Infection Associated with Recently Hospitalized Family Members , 2022, Emerging infectious diseases.

[4]  E. Bille,et al.  One-day prevalence of asymptomatic carriage of toxigenic and non-toxigenic Clostridioides difficile in 10 French hospitals. , 2022, The Journal of hospital infection.

[5]  C. Donskey,et al.  Risk factors for Clostridioides difficile colonization among hospitalized adults: A meta-analysis and systematic review , 2020, Infection Control & Hospital Epidemiology.

[6]  L. Bry,et al.  Genomic determination of relative risks for Clostridioides difficile infection from asymptomatic carriage in ICU patients. , 2020, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[7]  G. Rahav,et al.  Environmental shedding of toxigenic Clostridioides difficile by asymptomatic carriers: A prospective observational study , 2020, bioRxiv.

[8]  M. Colomb-Cotinat,et al.  Epidemiology of Clostridioides difficile infections, France, 2010 to 2017 , 2019, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[9]  N. Thomson,et al.  Whole genome sequencing of toxigenic Clostridium difficile in asymptomatic carriers: insights into possible role in transmission. , 2019, The Journal of hospital infection.

[10]  J. Couturier,et al.  Toxigenic Clostridium difficile carriage in general practice: results of a laboratory-based cohort study. , 2019, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[11]  C. Suetens,et al.  Prevalence of healthcare-associated infections, estimated incidence and composite antimicrobial resistance index in acute care hospitals and long-term care facilities: results from two European point prevalence surveys, 2016 to 2017 , 2018, Eurosurveillance.

[12]  J. Weese,et al.  Examining the epidemiology and microbiology of Clostridium difficile carriage in elderly patients and residents of a healthcare facility in southern Ontario, Canada. , 2018, The Journal of hospital infection.

[13]  Mark A. Miller,et al.  Microbial Preparations (Probiotics) for the Prevention of Clostridium difficile Infection in Adults and Children: An Individual Patient Data Meta-analysis of 6,851 Participants , 2018, Infection Control & Hospital Epidemiology.

[14]  E. Kuijper,et al.  Guidance document for prevention of Clostridium difficile infection in acute healthcare settings. , 2018, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[15]  T. Peto,et al.  Epidemiology of Clostridium difficile in infants in Oxfordshire, UK: Risk factors for colonization and carriage, and genetic overlap with regional C. difficile infection strains , 2017, PloS one.

[16]  D. Lecky,et al.  Investigation of community carriage rates of Clostridium difficile and Hungatella hathewayi in healthy volunteers from four regions of England. , 2017, Journal of Hospital Infection.

[17]  T. Peto,et al.  Contribution to Clostridium Difficile Transmission of Symptomatic Patients With Toxigenic Strains Who Are Fecal Toxin Negative , 2017, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[18]  A. Rösler,et al.  Asymptomatic and yet C. difficile-toxin positive? Prevalence and risk factors of carriers of toxigenic Clostridium difficile among geriatric in-patients , 2016, BMC Geriatrics.

[19]  M. Wilcox,et al.  Diversity of Clostridium difficile PCR ribotypes in Europe: results from the European, multicentre, prospective, biannual, point-prevalence study of Clostridium difficile infection in hospitalised patients with diarrhoea (EUCLID), 2012 and 2013. , 2016, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[20]  S. Trottier,et al.  Effect of Detecting and Isolating Clostridium difficile Carriers at Hospital Admission on the Incidence of C difficile Infections: A Quasi-Experimental Controlled Study. , 2016, JAMA internal medicine.

[21]  H. Jacquier,et al.  Hospital cost of Clostridium difficile infection including the contribution of recurrences in French acute-care hospitals. , 2015, The Journal of hospital infection.

[22]  E. Mylonakis,et al.  Colonization With Toxinogenic C. difficile Upon Hospital Admission, and Risk of Infection: A Systematic Review and Meta-Analysis , 2015, The American Journal of Gastroenterology.

[23]  E. Mylonakis,et al.  Asymptomatic Carriers of Toxigenic C. difficile in Long-Term Care Facilities: A Meta-Analysis of Prevalence and Risk Factors , 2015, PloS one.

[24]  C. Burnham,et al.  Prevalence and risk factors for asymptomatic Clostridium difficile carriage. , 2014, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[25]  K. Garey,et al.  Real-Time Polymerase Chain Reaction Detection of Asymptomatic Clostridium difficile Colonization and Rising C. difficile–Associated Disease Rates1 , 2014, Infection Control & Hospital Epidemiology.

[26]  C. Donskey,et al.  Asymptomatic carriage of toxigenic Clostridium difficile by hospitalized patients. , 2013, The Journal of hospital infection.

[27]  C. Vincent,et al.  Reductions in intestinal Clostridiales precede the development of nosocomial Clostridium difficile infection , 2013, Microbiome.

[28]  B. Coignard,et al.  Clinical and microbiological features of Clostridium difficile infections in France: the ICD-RAISIN 2009 national survey. , 2013, Medecine et maladies infectieuses.

[29]  G. Schutze,et al.  Clostridium difficile Infection in Infants and Children , 2013, Pediatrics.

[30]  A. Le Monnier,et al.  Clostridium difficile carriage in healthy infants in the community: a potential reservoir for pathogenic strains. , 2012, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[31]  I. Brukner,et al.  Host and pathogen factors for Clostridium difficile infection and colonization. , 2011, The New England journal of medicine.

[32]  A. Le Monnier,et al.  Prevalence and diversity of Clostridium difficile strains in infants. , 2011, Journal of medical microbiology.

[33]  D. Enoch,et al.  Clostridium difficile in children: colonisation and disease. , 2011, The Journal of infection.

[34]  T. Lamont,et al.  Asymptomatic colonization by Clostridium difficile in infants: implications for disease in later life. , 2010, Journal of pediatric gastroenterology and nutrition.

[35]  P. Bidet,et al.  Development of a new PCR-ribotyping method for Clostridium difficile based on ribosomal RNA gene sequencing. , 1999, FEMS microbiology letters.

[36]  Marta Elena Losa-Iglesias,et al.  Footwear used by older people and a history of hyperkeratotic lesions on the foot , 2017, Medicine.

[37]  藤倉雄二,et al.  わが国における成人市中肺炎の原因微生物の変遷(Meta‐analysis and systematic review) , 2017 .

[38]  E. Kuijper,et al.  Emergence of Clostridium difficile-associated disease in North America and Europe. , 2006, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.