Abstract
Clostridium difficile infection (CDI) is gradually being recognised as a cause of morbidity in the community. We investigated the incidence and clinical characteristics of CDI in a community setting and characterised the C. difficile strains by toxin gene profiling and polymerase chain reaction (PCR) ribotyping. Patients included in the study had attended general practice, primarily because of diarrhoea; CDI patients (259 patients; 121 <2 years of age) had positive cultures for toxigenic C. difficile and non-CDI patients (455 patients) were culture-negative. Outcome variables included the frequency and duration of diarrhoea, vomiting, stomach ache, fever >38 °C, weight loss and sick leave. Data were analysed by logistic regression. CDI patients <2 and ≥2 years of age with C. difficile as the only enteropathogen in the faecal sample reported slimy stools (65 % vs. 62 %), stomach ache (60 % vs. 75 %), weight loss (50 % vs. 76 %) and duration of diarrhoea >15 days (59 % vs. 73 %) as the predominant symptoms. CDI patients ≥2 years old reported duration of diarrhoea >15 days more often compared to non-CDI patients (73 % vs. 27 %, p < 0.0001). The annual incidence of CDI was 518 and 23/100,000 for patients <2 and ≥2 years of age, respectively, and 46/100,000 in the subgroup of patients ≥60 years of age. CDI was characterised by stomach ache and persistent diarrhoea, often leading to weight loss. This emphasises the importance of diagnosing CDI not only in hospitalised patients, but also in individuals ≥2 years of age attending general practice because of gastrointestinal symptoms, especially in the elderly, where the incidence of CDI is high.
Similar content being viewed by others
References
Bartlett JG (2008) Historical perspectives on studies of Clostridium difficile and C. difficile infection. Clin Infect Dis 46(Suppl 1):S4–S11
Norén T, Akerlund T, Bäck E, Sjöberg L, Persson I, Alriksson I et al (2004) Molecular epidemiology of hospital-associated and community-acquired Clostridium difficile infection in a Swedish county. J Clin Microbiol 42:3635–3643
Khanna S, Pardi DS, Aronson SL, Kammer PP, Orenstein R, St Sauver JL et al (2012) The epidemiology of community-acquired Clostridium difficile infection: a population-based study. Am J Gastroenterol 107:89–95
Søes LM, Brock I, Persson S, Simonsen J, Pribil Olsen KE, Kemp M (2012) Clinical features of Clostridium difficile infection and molecular characterization of the isolated strains in a cohort of Danish hospitalized patients. Eur J Clin Microbiol Infect Dis 31:185–192. doi:10.1007/s10096-011-1292-0
Barbut F, Gariazzo B, Bonné L, Lalande V, Burghoffer B, Luiuz R et al (2007) Clinical features of Clostridium difficile-associated infections and molecular characterization of strains: results of a retrospective study, 2000–2004. Infect Control Hosp Epidemiol 28:131–139
Bauer MP, Notermans DW, van Benthem BHB, Brazier JS, Wilcox MH, Rupnik M et al (2011) Clostridium difficile infection in Europe: a hospital-based survey. Lancet 377(9759):63–73. doi:10.1016/S0140-6736(10)61266-4
Bauer MP, Veenendaal D, Verhoef L, Bloembergen P, van Dissel JT, Kuijper EJ (2009) Clinical and microbiological characteristics of community-onset Clostridium difficile infection in The Netherlands. Clin Microbiol Infect 15:1087–1092. doi:10.1111/j.1469-0691.2009.02853.x
Jangi S, Lamont JT (2010) Asymptomatic colonization by Clostridium difficile in infants: implications for disease in later life. J Pediatr Gastroenterol Nutr 51:2–7. doi:10.1097/MPG.0b013e3181d29767
Viscidi R, Willey S, Bartlett JG (1981) Isolation rates and toxigenic potential of Clostridium difficile isolates from various patient populations. Gastroenterology 81:5–9
McFarland LV, Brandmarker SA, Guandalini S (2000) Pediatric Clostridium difficile: a phantom menace or clinical reality? J Pediatr Gastroenterol Nutr 31:220–231
Zilberberg MD, Tillotson GS, McDonald C (2010) Clostridium difficile infections among hospitalized children, United States, 1997–2006. Emerg Infect Dis 16:604–609
Kim J, Smathers SA, Prasad P, Leckerman KH, Coffin S, Zaoutis T (2008) Epidemiological features of Clostridium difficile-associated disease among inpatients at children’s hospitals in the United States, 2001–2006. Pediatrics 122:1266–1270
Blom M, Meyer A, Gerner-Smidt P, Gaarslev K, Espersen F (1999) Evaluation of Statens Serum Institut enteric medium for detection of enteric pathogens. J Clin Microbiol 37:2312–2316
Hutchinson DN, Bolton FJ (1984) Improved blood free selective medium for the isolation of Campylobacter jejuni from faecal specimens. J Clin Pathol 37:956–957
Persson S, Olsen KEP, Scheutz F, Krogfelt KA, Gerner-Smidt P (2007) A method for fast and simple detection of major diarrhoeagenic Escherichia coli in the routine diagnostic laboratory. Clin Microbiol Infect 13:516–524. doi:10.1111/j.1469-0691.2007.01692.x
Kageyama T, Kojima S, Shinohara M, Uchida K, Fukushi S, Hoshino FB et al (2003) Broadly reactive and highly sensitive assay for Norwalk-like viruses based on real-time quantitative reverse transcription-PCR. J Clin Microbiol 41:1548–1557
Johnsen CK, Midgley S, Böttiger B (2009) Genetic diversity of sapovirus infections in Danish children 2005–2007. J Clin Virol 46:265–269. doi:10.1016/j.jcv.2009.07.008
Pang XL, Lee B, Boroumand N, Leblanc B, Preiksaitis JK, Yu Ip CC (2004) Increased detection of rotavirus using a real time reverse transcription-polymerase chain reaction (RT-PCR) assay in stool specimens from children with diarrhea. J Med Virol 72:496–501. doi:10.1002/jmv.20009
Logan C, O’Leary JJ, O’Sullivan N (2006) Real-time reverse transcription-PCR for detection of rotavirus and adenovirus as causative agents of acute viral gastroenteritis in children. J Clin Microbiol 44:3189–3195. doi:10.1128/JCM.00915-06
Logan C, O’Leary JJ, O’Sullivan N (2007) Real-time reverse transcription PCR detection of norovirus, sapovirus and astrovirus as causative agents of acute viral gastroenteritis. J Virol Methods 146:36–44. doi:10.1016/j.jviromet.2007.05.031
Stensvold CR, Nielsen HV (2012) Comparison of microscopy and PCR for detection of intestinal parasites in Danish patients supports an incentive for molecular screening platforms. J Clin Microbiol 50:540–541. doi:10.1128/JCM.06012-11
Persson S, Torpdahl M, Olsen KE (2008) New multiplex PCR method for the detection of Clostridium difficile toxin A (tcdA) and toxin B (tcdB) and the binary toxin (cdtA/cdtB) genes applied to a Danish strain collection. Clin Microbiol Infect 14:1057–1064
O’Neill GL, Ogunsola FT, Brazier JS, Duerden BI (1996) Modification of a PCR ribotyping method for application as a routine typing scheme for Clostridium difficile. Anaerobe 2:205–209. doi:10.1006/anae.1996.0028
Stubbs SL, Brazier JS, O’Neill GL, Duerden BI (1999) PCR targeted to the 16S-23S rRNA gene intergenic spacer region of Clostridium difficile and construction of a library consisting of 116 different PCR ribotypes. J Clin Microbiol 37:461–463
Kuijper EJ, Coignard B, Tüll P; ESCMID Study Group for Clostridium difficile; EU Member States; European Centre for Disease Prevention and Control (2006) Emergence of Clostridium difficile-associated disease in North America and Europe. Clin Microbiol Infect 12(Suppl 6):2–18
McDonald LC, Coignard B, Dubberke E, Song X, Horan T, Kutty PK; Ad Hoc Clostridium difficile Surveillance Working Group (2007) Recommendations for surveillance of Clostridium difficile-associated disease. Infect Control Hosp Epidemiol 28:140–145
Statistics Denmark. Home page at: http://www.dst.dk/en.aspx
Pedersen CB, Gøtzsche H, Møller JO, Mortensen PB (2006) The Danish Civil Registration System. A cohort of eight million persons. Dan Med Bull 53:441–449
Riley TV, Wetherall F, Bowman J, Mogyorosy J, Golledge CL (1991) Diarrheal disease due to Clostridium difficile in general practice. Pathology 23:346–349
Bartlett JG (1994) Clostridium difficile: history of its role as an enteric pathogen and the current state of knowledge about the organism. Clin Infect Dis 18(Suppl 4):S265–S272
Bolton RP, Tait SK, Dear PR, Losowsky MS (1984) Asymptomatic neonatal colonisation by Clostridium difficile. Arch Dis Child 59:466–472
Boenning DA, Fleisher GR, Campos JM, Hulkower CW, Quinlan RW (1982) Clostridium difficile in a pediatric outpatient population. Pediatr Infect Dis 1:336–338
Kutty PK, Woods CW, Sena AC, Benoit SR, Naggie S, Frederick J et al (2010) Risk factors for and estimated incidence of community-associated Clostridium difficile infection, North Carolina, USA. Emerg Infect Dis 16:197–204
Karlström O, Fryklund B, Tullus K, Burman LG (1998) A prospective nationwide study of Clostridium difficile-associated diarrhea in Sweden. The Swedish C. difficile Study Group. Clin Infect Dis 26:141–145
Wilcox MH, Mooney L, Bendall R, Settle CD, Fawley WN (2008) A case–control study of community-associated Clostridium difficile infection. J Antimicrob Chemother 62:388–396
Bryant K, McDonald LC (2009) Clostridium difficile infections in children. Pediatr Infect Dis J 28:145–146. doi:10.1097/INF.0b013e318198c984
Rousseau C, Lemée L, Le Monnier A, Poilane I, Pons JL, Collignon A (2011) Prevalence and diversity of Clostridium difficile strains in infants. J Med Microbiol 60:1112–1118
Søes LM, Holt HM, Böttiger B, Nielsen HV, Andreasen V, Kemp M et al (2013) Risk factors for Clostridium difficile infection in the community: a case–control study in patients in general practice, Denmark, 2009–2011. Epidemiol Infect 27:1–12. doi:10.1017/S0950268813002380
Pang XL, Honma S, Nakata S, Vesikari T (2000) Human caliciviruses in acute gastroenteritis of young children in the community. J Infect Dis 181(Suppl 2):S288–S294
Tvede M, Schiøtz PO, Krasilnikoff PA (1990) Incidence of Clostridium difficile in hospitalized children. A prospective study. Acta Paediatr Scand 79:292–299
Klein EJ, Boster DR, Stapp JR, Wells JG, Qin X, Clausen CR et al (2006) Diarrhea etiology in a Children’s Hospital Emergency Department: a prospective cohort study. Clin Infect Dis 43(7):807–813
McFarland LV, Surawicz CM, Stamm WE (1990) Risk factors for Clostridium difficile carriage and C. difficile-associated diarrhea in a cohort of hospitalized patients. J Infect Dis 162:678–684
Crobach MJ, Dekkers OM, Wilcox MH, Kuijper EJ (2009) European Society of Clinical Microbiology and Infectious Diseases (ESCMID): data review and recommendations for diagnosing Clostridium difficile-infection (CDI). Clin Microbiol Infect 15:1053–1066
Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG, McDonald LC et al (2010) Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol 31:431–455. doi:10.1086/651706
Planche TD, Davies KA, Coen PG, Finney JM, Monahan IM, Morris KA et al (2013) Differences in outcome according to Clostridium difficile testing method: a prospective multicentre diagnostic validation study of C difficile infection. Lancet Infect Dis 13:936–945. doi:10.1016/S1473-3099(13)70200-7
Acknowledgements
We thank all the laboratory technicians who participated in the stool sample analyses at Statens Serum Institut, Copenhagen, Denmark and Odense University Hospital, Odense, Denmark.
Conflict of interest
The authors declare that they have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Søes, L.M., Holt, H.M., Böttiger, B. et al. The incidence and clinical symptomatology of Clostridium difficile infections in a community setting in a cohort of Danish patients attending general practice. Eur J Clin Microbiol Infect Dis 33, 957–967 (2014). https://doi.org/10.1007/s10096-013-2033-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10096-013-2033-3