Emergence of Clostridium difficile-associated disease in North America and Europe

Abstract

The clinical spectrum of Clostridium difficile-associated disease (CDAD) ranges from diarrhoea to severe life-threatening pseudomembranous colitis. Although not always associated with previous antibiotic exposure, it is in the majority of cases. CDAD is recognised increasingly in a variety of animal species and in individuals previously not considered to be predisposed. C. difficile can be transmitted via personal contact or environmentally. The role of patients and healthcare workers who are symptom-free but colonised with C. difficile in the intestinal tract is unclear. C. difficile, with more than 150 PCR ribotypes and 24 toxinotypes, has a pathogenicity locus (PaLoc) with genes encoding enterotoxin A (tcdA) and cytotoxin B (tcdB). Genes for the binary toxin are located outside the PaLoc, but the role of this toxin is unclear. The recently completed genome sequence of C. difficile 630 revealed a large proportion of 11% of mobile genetic elements, mainly in the form of conjugative transposons. Diagnostic assays include tests for the detection of C. difficile products or genes and culture methods for isolation of a toxin-producing bacterium. Enzyme immunoassays to detect toxin in faeces are widely available, with varying sensitivities and specificities. Despite practical drawbacks and sensitivity less than 100%, the cell cytototoxicity assay is still considered to be the standard. Rapid diagnostic assays are available on a limited scale and require much improvement. Molecular tests enable the detection of carriers of toxigenic and non-toxigenic strains, as does culture. It is highly recommended to culture C. difficile from toxin-positive faeces samples and to store isolates for future characterisation and typing. The financial impact of CDAD on the healthcare system is substantial (5-15,000 euro/case in England and $1.1 billion/year in the USA). Assuming a European Union population of 457 million, the potential cost of CDAD can be estimated to be 3000 million euro/year, and is expected to almost double over the next four decades. In North America, increasing rates of CDAD have been reported in Canada and the USA since March 2003, involving a more severe course, higher mortality, increased risk of relapse and more complications. This increased virulence is presumably associated with higher levels of toxin production by fluoroquinolone-resistant strains belonging to PCR ribotype 027, pulsed-field gel electrophoresis (PFGE) type NAP1, REA (restriction endonuclease analysis) type BI and toxinotype III. In Europe, outbreaks of CDAD due to the new, highly virulent strain of C. difficile PCR ribotype 027, toxinotype III have been recognised in 75 hospitals in England, 16 hospitals in The Netherlands, 13 healthcare facilities in Belgium and nine healthcare facilities in France. These outbreaks are very difficult to control, and preliminary results from case-control studies indicate a correlation with fluoroquinolones and cephalosporins. Information concerning community-acquired cases of ribotype 027 is lacking, and data...

Strategies to Prevent Clostridium difficile Infections in Acute Care Hospitals

“…1 CDI incidence has also increased in Canada and Europe. [2][3][4] b. There have been numerous reports of an increase in CDI severity.…”

Hand Hygiene

“…The increasing morbidity and mortality of C. difficile-associated disease in the USA, Canada, and some European countries since 2001 has been especially attributed to more frequent outbreaks and the emergence of a new, more virulent strain (ribotype 027). 408 Epidemic strains differ among countries: for instance, while in Canada and the Netherlands ribotype 027 is predominant, the United Kingdom detected three different strains (ribotype 001, 027 and 106) responsible for 70% of C. difficile-associated diarrhoea. [409][410][411][412][413][414][415][416][417] Apart from iodophors, but at a concentration remarkably higher than the one used in antiseptics, 373 none of the agents (including alcohols, chlorhexidine, hexachlorophene, chloroxylenol, and triclosan) used in antiseptic handwash or antiseptic handrub preparations is reliably sporicidal against Clostridium spp.…”

Esporas de Clostridium difficile y su relevancia en la persistencia y transmisión de la infección

“…Durante la última década, el número de casos reportados de IACD ha experimentado un dramático incremento en la incidencia, con mayores tasas de mortalidad, recurrencia y de casos graves [9][10][11] . Estos cambios epidemiológicos se deberían, en parte, a la aparición de cepas epidémicas pertenecientes al ribotipo 027 12,13 .…”

“…Estos cambios epidemiológicos se deberían, en parte, a la aparición de cepas epidémicas pertenecientes al ribotipo 027 12,13 . Se han descrito brotes de IACD causados por estas cepas con tasas de mortalidad y recurrencia cercanas a 15 y 30%, respectivamente [9][10][11] . Otros estudios han sugerido un aumento de la gravedad de las IACD y de la frecuencia de colectomía 14 .…”