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INTRODUCTION

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Clostridium difficile Infection (CDI) is the most common cause of infectious nosocomial diarrhea in adults in developed countries. Currently, it is considered an important transmissible nosocomial disease causes often appear in outbreaks within healthcare facilities. Prior to 1977, the clostridial disease most commonly described was a form of skin and soft-tissue gangrene caused by a strain named Clostridium perfringens, with fatal outcomes often reported. Once the antibiotic era started, an antibiotic-associated colitis was first described in animal models caused by Clostridium difficile (C. difficile). Shortly after, C. difficile associated colitis became the most common clostridial infection among humans in the hospital setting.14

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Currently, CDI is not a reportable disease in the United States. For this reason, the exact incidence in the United Statesis difficult to establish. Nonetheless, it has been reported that there are at least 500,000 cases in US hospitals and long-term care facilities per year that result in 30,000 deaths. Surveys conducted in different Canadian hospitals between 1997 and 2005 suggest rates ranging from 3.4 to 8.4 cases per 1,000 admissions.5,6 The annual cost spent on patients with CDI in the United States exceeds 1 billion dollars, which is expected to trend up in the next few years given the high burden of recurrent disease.7 The number of patients discharged from the hospital and transferred to long-term care facilities with the diagnosis of CDI doubled between 2000 and 2003.

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It is well known that the vast majority of patients diagnosed with CDI had previous exposure to antibiotics, especially within the 28 days prior to the onset of symptoms—hence, the name antibiotic-associated colitis, which has been proven to be sufficient to support the current effort to restrict the indiscriminate use of antibiotics as part of infection control interventions.

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MICROBIOLOGY AND PATHOGENESIS

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The genus Clostridium includes more than 200 species of anaerobic, gram-positive, rod-shaped bacteria, capable of forming spores and responsible for toxin-mediated pathogenic processes, which can cause a broad spectrum of invasive diseases. The name Clostridium difficile comes from the Greek word Kloster, meaning spindle. When C. difficile was first described, it was particularly difficult to isolate the bacillus, which is the reason why it was initially named Bacillus difficilis. However, posterior ribosomal DNA analysis proved morphologic similarities with some strains from the genus Clostridium, such as Clostridium sordellii; then, it was renamed Clostridium difficile.8

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Clostridia produce an important number of biologically active proteins, such as hemolysins, proteolytic enzymes, an—most important—toxin proteins. Toxin production, which is controlled at the transcriptional level by a sigma factor, includes neurotoxins, enterotoxins, necrotoxins, collagenases, proteases, and neuroaminidases. These toxin molecules account for most of the pathogenic and lethal potential in humans.1

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Clostridium species are usually found in soils and are part of the intestinal microbiome in healthy humans. By the ...

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