title: Underdiagnosis of Clostridium difficile across Europe: the European, multicentre, prospective, biannual, point-prevalence study of Clostridium difficile infection in hospitalised patients with diarrhoea (EUCLID).
abstract: BACKGROUND
  Variations in testing for Clostridium difficile infection can hinder patients' care, increase the risk of transmission, and skew epidemiological data. We aimed to measure the underdiagnosis of C difficile infection across Europe.
  
  
  METHODS
  We did a questionnaire-based study at 482 participating hospitals across 20 European countries. Hospitals were questioned about their methods and testing policy for C difficile infection during the periods September, 2011, to August, 2012, and September, 2012, to August, 2013. On one day in winter, 2012-13 (December, 2012, or January, 2013), and summer, 2013 (July or August), every hospital sent all diarrhoeal samples submitted to their microbiology laboratory to a national coordinating laboratory for standardised testing of C difficile infection. Our primary outcome measures were the rates of testing for and cases of C difficile infection per 10 000 patient bed-days. Results of local and national C difficile infection testing were compared with each other. If the result was positive at the national laboratory but negative at the local hospital, the result was classified as undiagnosed C difficile infection. We compared differences in proportions with the Mann-Whitney test, or McNemar's test if data were matched.
  
  
  RESULTS
  During the study period, participating hospitals reported a mean of 65·8 tests (country range 4·6-223·3) for C difficile infection per 10 000 patient-bed days and a mean of 7·0 cases (country range 0·7-28·7) of C difficile infection per 10 000 patient-bed days. Only two-fifths of hospitals reported using optimum methods for testing of C difficile infection (defined by European guidelines), although the number of participating hospitals using optimum methods increased during the study period, from 152 (32%) of 468 in 2011-12 to 205 (48%) of 428 in 2012-13. Across all 482 European hospitals on the two sampling days, 148 (23%) of 641 samples positive for C difficile infection (as determined by the national laboratory) were not diagnosed by participating hospitals because of an absence of clinical suspicion, equating to about 74 missed diagnoses per day.
  
  
  CONCLUSIONS
  A wide variety of testing strategies for C difficile infection are used across Europe. Absence of clinical suspicion and suboptimum laboratory diagnostic methods mean that an estimated 40 000 inpatients with C difficile infection are potentially undiagnosed every year in 482 European hospitals.
  
  
  BACKGROUND
  Astellas Pharmaceuticals Europe.
authors.affiliation: EUCLID European Coordinators, University of Leeds, Leeds, UK.
authors.forename: Kerrie A
authors.initials: KA
authors.lastname: Davies
authors.affiliation: Astellas Pharma Europe, Chertsey, UK.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Longshaw
authors.affiliation: EUCLID European Coordinators, University of Leeds, Leeds, UK.
authors.forename: Georgina L
authors.initials: GL
authors.lastname: Davis
authors.affiliation: Catedrático-Jefe de Servicio, Microbiologica Clinica E Infecciosas, Hospital General Universitario 'Gregorio Marañón', Madrid, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Bouza
authors.affiliation: National Reference Laboratory for Clostridium difficile, Université Pierre et Marie Curie, Paris, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Barbut
authors.affiliation: Department of Bacteriology, National Centre for Epidemiology, Budapest, Hungary.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Barna
authors.affiliation: Univerisité Catholique de Louvain, Institut de Recherché Expérimentale et Clinique (IREC), Brussels, Belgium.
authors.forename: Michel
authors.initials: M
authors.lastname: Delmée
authors.affiliation: Health Protection Surveillance Centre and Beaumont Hospital, Dublin, Ireland.
authors.forename: Fidelma
authors.initials: F
authors.lastname: Fitzpatrick
authors.affiliation: National Centre of Infectious and Parasitic Diseases, Sofia, Bulgaria.
authors.forename: Kate
authors.initials: K
authors.lastname: Ivanova
authors.affiliation: Department of Medical Microbiology, Leiden University Medical Centre, Leiden, Netherlands.
authors.forename: Ed
authors.initials: E
authors.lastname: Kuijper
authors.affiliation: 'Cantacuzino' National Institute of Research and Development for Microbiology and Immunology, Bucharest, Romania.
authors.forename: Ioana S
authors.initials: IS
authors.lastname: Macovei
authors.affiliation: Bacteriology Unit, National Institute for Health and Welfare (THL), Helsinki, Finland.
authors.forename: Silja
authors.initials: S
authors.lastname: Mentula
authors.affiliation: Istituto Superiore di Sanità, Department of Infectious Diseases, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Mastrantonio
authors.affiliation: Institute of Medical Microbiology and Hygiene, University of Saarland Medical Centre, Homburg/Saar, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: von Müller
authors.affiliation: Department of Infectious Diseases, National Institute for Health 'Dr Ricardo Jorge', Lisbon, Portugal.
authors.forename: Mónica
authors.initials: M
authors.lastname: Oleastro
authors.affiliation: University Hospital, Medical School, University of Thessalia, Larissa, Greece.
authors.forename: Efthymia
authors.initials: E
authors.lastname: Petinaki
authors.affiliation: Department of Medical Microbiology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Pituch
authors.affiliation: Örebro University Hospital, Örebro, Sweden.
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Norén
authors.affiliation: Jessenius Faculty of Medicine in Martin, Comenius University, Bratislava, Martin, Slovakia.
authors.forename: Elena
authors.initials: E
authors.lastname: Nováková
authors.affiliation: Department of Medical Microbiology, University Hospital in Motol, Prague, Czech Republic.
authors.forename: Otakar
authors.initials: O
authors.lastname: Nyč
authors.affiliation: National Laboratory for Health, Environment and Food (NLZOH), and University of Maribor, Faculty of Medicine, Maribor, Slovenia.
authors.forename: Maja
authors.initials: M
authors.lastname: Rupnik
authors.affiliation: Austrian Agency for Health and Food Safety, Institute for Medical Microbiology and Hygiene, Vienna, Austria.
authors.forename: Daniela
authors.initials: D
authors.lastname: Schmid
authors.affiliation: EUCLID European Coordinators, University of Leeds, Leeds, UK. Electronic address: mark.wilcox@leedsth.nhs.uk.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Wilcox
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016360:Clostridioides difficile / Q000302:isolation & purification*; D003015:Clostridium Infections / Q000175:diagnosis* / Q000453:epidemiology*; D003951:Diagnostic Errors / Q000706:statistics & numerical data*; D005060:Europe / Q000453:epidemiology; D005188:False Negative Reactions; D005260:Female; D006302:Health Services Research; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011795:Surveys and Questionnaires; D055815:Young Adult