Elsevier

The Lancet

Volume 377, Issue 9759, 1–7 January 2011, Pages 63-73
The Lancet

Articles
Clostridium difficile infection in Europe: a hospital-based survey

https://doi.org/10.1016/S0140-6736(10)61266-4Get rights and content

Summary

Background

Little is known about the extent of Clostridium difficile infection in Europe. Our aim was to obtain a more complete overview of C difficile infection in Europe and build capacity for diagnosis and surveillance.

Methods

We set up a network of 106 laboratories in 34 European countries. In November, 2008, one to six hospitals per country, relative to population size, tested stool samples of patients with suspected C difficile infection or diarrhoea that developed 3 or more days after hospital admission. A case was defined when, subsequently, toxins were identified in stool samples. Detailed clinical data and stool isolates were collected for the first ten cases per hospital. After 3 months, clinical data were followed up.

Findings

The incidence of C difficile infection varied across hospitals (weighted mean 4·1 per 10 000 patient-days per hospital, range 0·0–36·3). Detailed information was obtained for 509 patients. For 389 of these patients, isolates were available for characterisation. 65 different PCR ribotypes were identified, of which 014/020 (61 patients [16%]), 001 (37 [9%]), and 078 (31 [8%]) were the most prevalent. The prevalence of PCR-ribotype 027 was 5%. Most patients had a previously identified risk profile of old age, comorbidity, and recent antibiotic use. At follow up, 101 (22%) of 455 patients had died, and C difficile infection played a part in 40 (40%) of deaths. After adjustment for potential confounders, an age of 65 years or older (adjusted odds ratio 3·26, 95% CI 1·08–9·78; p=0·026), and infection by PCR-ribotypes 018 (6·19, 1·28–29·81; p=0·023) and 056 (13·01; 1·14–148·26; p=0·039) were significantly associated with complicated disease outcome.

Interpretation

PCR ribotypes other than 027 are prevalent in European hospitals. The data emphasise the importance of multicountry surveillance to detect and control C difficile infection in Europe.

Funding

European Centre for Disease Prevention and Control.

Introduction

Clostridium difficile infection is prevalent in health-care facilities throughout the developed world, but also presents as large outbreaks. Less often, it is acquired in the community from an unknown source. It characteristically occurs in elderly patients with comorbidity in whom the intestinal flora has been disrupted by previous use of antibiotics.1, 2 Since early 2003, increasing rates of C difficile infection have been reported in Canada and the USA, with a larger proportion of severe and recurrent cases occuring in these countries than previously reported. The raised incidence and virulence of such infection have partly been explained by the spread of fluoroquinolone-resistant strains belonging to the PCR-ribotype 027.3, 4, 5 In addition to the usual toxins A and B, these fluoroquinolone-resistant strains produce a binary toxin, with a hitherto uncertain pathogenic significance.1, 2, 3, 4, 5, 6 In Europe, PCR-ribotype 027 was first reported in 2005 in England and shortly thereafter in the Netherlands.7, 8 Subsequently, epidemics of C difficile infection caused by PCR-ribotype 027 have been recognised in hospitals in many European countries.9

The attention given to this infection, diagnostic procedures in hospitals, presence and methodology of national surveillance, and availability of typing vary widely across Europe, which hampers comparisons between countries.9, 10 We did this study to obtain a more complete overview of the situation in Europe and build capacity for diagnosis and surveillance of C difficile infection both nationally and Europe-wide.

Section snippets

Study design and patients

With support from the European Centre for Disease Prevention and Control, we appointed national coordinators for 34 European countries (including 27 member states, three candidate states, and four European-Free-Trade-Association countries) who selected hospitals in each country, relative to the country's population size. No randomisation was used for this selection. The aim was to include one hospital for countries with fewer than two million inhabitants, three for those with between two and 20

Results

In total, 97 hospitals provided patients or epidemiological data, or both. Because some hospitals were unable to supply denominator data, we could not calculate incidences for all hospitals (table 1). Most hospitals were large, as judged by the number of patient-days and admissions (median number of admissions per month 2645; IQR 1808–4257); 62 hospitals (67%) were academic hospitals. The estimated incidence of health-care-associated infection varied widely between hospitals. We calculated the

Discussion

We have shown that the incidence of C difficile infection and the distribution of causative PCR ribotypes differed greatly between hospitals in Europe; overall and attributable mortality were strikingly high. The strengths of this pan-European study are the large number of participating countries and hospitals, and a study design with a fixed 3-month follow-up. The high follow-up rate and the fact that patients with missing follow-up were younger, were more likely to be outpatients, and had

References (39)

  • LV McFarland et al.

    Breaking the cycle: treatment strategies for 163 cases of recurrent Clostridium difficile disease

    Am J Gastroenterol

    (2002)
  • CP Kelly et al.

    Clostridium difficile–more difficult than ever

    N Engl J Med

    (2008)
  • LC McDonald et al.

    An epidemic, toxin gene-variant strain of Clostridium difficile

    N Engl J Med

    (2005)
  • VG Loo et al.

    A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality

    N Engl J Med

    (2005)
  • M Rupnik et al.

    Clostridium difficile infection: new developments in epidemiology and pathogenesis

    Nat Rev Microbiol

    (2009)
  • A Smith

    Outbreak of Clostridium difficile infection in an English hospital linked to hypertoxin-producing strains in Canada and the US

    Euro Surveill

    (2005)
  • EJ Kuijper et al.

    Clostridium difficile ribotype 027, toxinotype III, the Netherlands

    Emerg Infect Dis

    (2006)
  • EJ Kuijper et al.

    Update of Clostridium difficile infection due to PCR ribotype 027 in Europe, 2008

    Euro Surveill

    (2008)
  • P Bidet et al.

    Comparison of PCR-ribotyping, arbitrarily primed PCR, and pulsed-field gel electrophoresis for typing Clostridium difficile

    J Clin Microbiol

    (2000)
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