A Predominantly Clonal Multi-Institutional Outbreak of Clostridium difficile –Associated Diarrhea with High Morbidity and Mortality

Department of Microbiology, McGill University Health Center, Montreal, Que., Canada.
New England Journal of Medicine (Impact Factor: 55.87). 01/2006; 353(23):2442-9. DOI: 10.1056/NEJMoa051639
Source: PubMed


In March 2003, several hospitals in Quebec, Canada, noted a marked increase in the incidence of Clostridium difficile-associated diarrhea.
In 2004 we conducted a prospective study at 12 Quebec hospitals to determine the incidence of nosocomial C. difficile-associated diarrhea and its complications and a case-control study to identify risk factors for the disease. Isolates of C. difficile were typed by pulsed-field gel electrophoresis and analyzed for binary toxin genes and partial deletions in the toxin A and B repressor gene tcdC. Antimicrobial susceptibility was evaluated in a subgroup of isolates.
A total of 1703 patients with 1719 episodes of nosocomial C. difficile-associated diarrhea were identified. The incidence was 22.5 per 1000 admissions. The 30-day attributable mortality rate was 6.9 percent. Case patients were more likely than matched controls to have received fluoroquinolones (odds ratio, 3.9; 95 percent confidence interval, 2.3 to 6.6) or cephalosporins (odds ratio, 3.8; 95 percent confidence interval, 2.2 to 6.6). A predominant strain, resistant to fluoroquinolones, was found in 129 of 157 isolates (82.2 percent), and the binary toxin genes and partial deletions in the tcdC gene were present in 132 isolates (84.1 percent).
A strain of C. difficile that was resistant to fluoroquinolones and had binary toxin and a partial deletion of the tcdC gene was responsible for this outbreak of C. difficile-associated diarrhea. Exposure to fluoroquinolones or cephalosporins was a risk factor.

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Available from: Paul Brassard, Sep 15, 2015
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    • "The intestinal pathogen Clostridium difficile is a strictly anaerobic, Gram-positive bacterium. In recent years it has become a huge burden both economically and to human health due to its global spread throughout health care environments, where it causes disease ranging from mild diarrhoea to life threatening pseudomembranous colitis (Loo et al., 2005; Goorhuis et al., 2007; Kuijper et al., 2007). Its ability to differentiate into endospores, a metabolically dormant and highly robust cell form, is essential in its transmission as this allows it to survive external stresses such as desiccation, osmotic shock, and contact with chemicals such as disinfectants (Lawley et al., 2010; Deakin et al., 2012). "
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    ABSTRACT: Clostridium difficile is a prominent nosocomial pathogen, proliferating and causing enteric disease in individuals with a compromised gut microflora. We characterised the post-translational modification of flagellin in C. difficile 630. The structure of the modification was solved by nuclear magnetic resonance and shown to contain an N-acetylglucosamine substituted with a phosphorylated N-methyl-L-threonine. A reverse genetics approach investigated the function of the putative four-gene modification locus. All mutants were found to have truncated glycan structures by LC-MS/MS, taking into account bioinformatic analysis, we propose that the open reading frame CD0241 encodes a kinase involved in the transfer of the phosphate to the threonine, the CD0242 protein catalyses the addition of the phosphothreonine to the N-acetylglucosamine moiety and CD0243 transfers the methyl group to the threonine. Some mutations affected motility and caused cells to aggregate to each other and abiotic surfaces. Altering the structure of the flagellin modification impacted on colonisation and disease recurrence in a murine model of infection, showing that alterations in the surface architecture of C. difficile vegetative cells can play a significant role in disease. We show that motility is not a requirement for colonisation, but that colonisation was compromised when the glycan structure was incomplete.
    Molecular Microbiology 08/2014; 94(2). DOI:10.1111/mmi.12755 · 4.42 Impact Factor
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    • "Clostridium species can infect a host but without any clinical signs and symptoms [7]. Despite this in some patients, symptoms may range from uncomplicated watery diarrhea, to bloody diarrhea and life threatening complications such as stiff and flaccid muscles [3] [13] [24]. "
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    ABSTRACT: Clostridium species cause diseases in humans that result from consumption of undercooked beef. The objectives of this study were to isolate Clostridium species from beef then the detection of the presence of tpi housekeeping gene as well as determination of the antibiotic resistant profile of the isolates. Twenty six (26) beef samples were bought from butcheries, supermarkets and street vendors. The samples were analyzed for the characteristics of Clostridium species and a total of 78 presumptive isolates were subjected to Gram-staining, catalase test, API 20A sugar fermentation profiles 16S rRNA and tpi species specific PCR analysis. Susceptibility profiles to 8 antibiotics were determined and antibiotic resistance patterns were compiled. Large proportions (93.3%-100%) of the isolates were penicillin, vancomycin and erythromycin resistant. PCR were performed to amplify species-specific 16S rRNA gene to confirm the identity of the isolates and 44.7% of the isolates were positively identified as Clostridium species. PCR were performed to amplify tpi housekeeping gene fragments. The tpi housekeeping gene produced amplicons of 501bp after PCR amplification and 19% of the isolates possess tpi housekeeping gene which confirmed the presence of Clostridium species in beef.
    Journal of food and nutrition research 05/2014; 2(5):236-243. DOI:10.12691/jfnr-2-5-5 · 0.80 Impact Factor
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    • "This is not surprising as these two ribotypes have been identified as the most prevalent among C. difficile isolates from Ontario diagnostic laboratories [33]. Ribotype 027 has been responsible for various outbreaks of CDI with increased severity, high relapse rates, and significant mortality in Canada [34,35] and internationally [36,37]. Overall, 50% of C. difficile isolates in this study were identified containing the gene for the binary toxin. "
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    ABSTRACT: Background In hospitals, Clostridium difficile infection (CDI) surveillance relies on unvalidated guidelines or threshold criteria to identify outbreaks. This can result in false-positive and -negative cluster alarms. The application of statistical methods to identify and understand CDI clusters may be a useful alternative or complement to standard surveillance techniques. The objectives of this study were to investigate the utility of the temporal scan statistic for detecting CDI clusters and determine if there are significant differences in the rate of CDI cases by month, season, and year in a community hospital. Methods Bacteriology reports of patients identified with a CDI from August 2006 to February 2011 were collected. For patients detected with CDI from March 2010 to February 2011, stool specimens were obtained. Clostridium difficile isolates were characterized by ribotyping and investigated for the presence of toxin genes by PCR. CDI clusters were investigated using a retrospective temporal scan test statistic. Statistically significant clusters were compared to known CDI outbreaks within the hospital. A negative binomial regression model was used to identify associations between year, season, month and the rate of CDI cases. Results Overall, 86 CDI cases were identified. Eighteen specimens were analyzed and nine ribotypes were classified with ribotype 027 (n = 6) the most prevalent. The temporal scan statistic identified significant CDI clusters at the hospital (n = 5), service (n = 6), and ward (n = 4) levels (P ≤ 0.05). Three clusters were concordant with the one C. difficile outbreak identified by hospital personnel. Two clusters were identified as potential outbreaks. The negative binomial model indicated years 2007–2010 (P ≤ 0.05) had decreased CDI rates compared to 2006 and spring had an increased CDI rate compared to the fall (P = 0.023). Conclusions Application of the temporal scan statistic identified several clusters, including potential outbreaks not detected by hospital personnel. The identification of time periods with decreased or increased CDI rates may have been a result of specific hospital events. Understanding the clustering of CDIs can aid in the interpretation of surveillance data and lead to the development of better early detection systems.
    BMC Infectious Diseases 05/2014; 14(1):254. DOI:10.1186/1471-2334-14-254 · 2.61 Impact Factor
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