Lack of Association between Clinical Outcome of Clostridium difficile Infections, Strain Type, and Virulence-Associated Phenotypes

Sirard, Stéphanie; Valiquette, Louis; Fortier, Louis‐Charles

doi:10.1128/jcm.05053-11

Cited by 80 publications

(84 citation statements)

References 44 publications

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“…The common occurrence of toxinotype V in the present study underscores a potential concern, as this type has been associated with community-associated disease and increasing prevalence in CDI in humans (6,21,26,27). Further investigation is necessary, as some recent reports have found toxinotype V in asymptomatic people (21), and others found that there was no association between virulence attributes and clinical outcomes (28).…”

Section: Discussionmentioning

confidence: 83%

Antimicrobial Resistance, Toxinotype, and Genotypic Profiling of Clostridium difficile Isolates of Swine Origin

et al. 2012

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bThe occurrence of Clostridium difficile infections in patients that do not fulfill the classical risk factors prompted us to investigate new risk factors of disease. The goal of this study was to characterize strains and associated antimicrobial resistance determinants of C. difficile isolated from swine raised in Ohio and North Carolina. Genotypic approaches used include PCR detection, toxinotyping, DNA sequencing, and pulsed-field gel electrophoresis (PFGE) DNA fingerprinting. Thirty-one percent (37/119) of isolates carried both tetM and tetW genes. The ermB gene was found in 91% of isolates that were resistant to erythromycin (68/75). Eighty-five percent (521/609) of isolates were toxin gene tcdB and tcdA positive. A total of 81% (494/609) of isolates were positive for cdtB and carry a tcdC gene (a toxin gene negative regulator) with a 39-bp deletion. Overall, 88% (196/223) of pigs carry a single C. difficile strain, while 12% (27/223) of pigs carried multiple strains. To the best of our knowledge, this is the first report of individual pigs found to carry more than one strain type of C. difficile. A significant difference in toxinotype profiles in the two geographic locations was noted, with a significantly (P < 0.001) higher prevalence of toxinotype V found in North Carolina (84%; 189/224) than in Ohio (55%; 99/181). Overall, the study findings indicate that significant proportions of C. difficile in swine are toxigenic and often are associated with antimicrobial resistance genes, although they are not resistant to drugs that are used to treat C. difficile infections.

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Section: Discussionmentioning

confidence: 83%

Antimicrobial Resistance, Toxinotype, and Genotypic Profiling of Clostridium difficile Isolates of Swine Origin

et al. 2012

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“…These strains are associated with both community-acquired and health care-associated CDI. However, a preliminary review of patients with or without the 027/NAP1/BI strain did not show any significant differences in disease severity (21). Thus, this issue requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

Detection of Toxigenic Clostridium difficile: Comparison of the Cell Culture Neutralization, Xpert C. difficile, Xpert C. difficile/Epi, and Illumigene C. difficile Assays

et al. 2012

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Clostridium difficile is the most important cause of nosocomial diarrhea. Several laboratory techniques are available to detect C. difficile toxins or the genes that encode them in fecal samples. We evaluated the Xpert C. difficile and Xpert C. difficile/Epi (Cepheid, CA) that detect the toxin B gene (tcdB) and tcdB, cdt, and a deletion in tcdC associated with the 027/NAP1/BI strain, respectively, by real-time PCR, and the Illumigene C. difficile (Meridian Bioscience, Inc.) that detects the toxin A gene (tcdA) by loop-mediated isothermal amplification in stool specimens. Toxigenic culture was used as the reference method for discrepant stool specimens. Two hundred prospective and fifty retrospective diarrheal stool specimens were tested simultaneously by the cell cytotoxin neutralization assay (CCNA) and the Xpert C. difficile, Xpert C. difficile/Epi, and Illumigene C. difficile assays. Of the 200 prospective stools tested, 10.5% (n ‫؍‬ 23) were determined to be positive by CCNA, 17.5% (n ‫؍‬ 35) were determined to be positive by Illumigene C. difficile, and 21.5% (n ‫؍‬ 43) were determined to be positive by Xpert C. difficile and Xpert C. difficile/ Epi. Of the 50 retrospective stools, previously determined to be positive by CCNA, 94% (n ‫؍‬ 47) were determined to be positive by Illumigene C. difficile and 100% (n ‫؍‬ 50) were determined to be positive by Xpert C. difficile and Xpert C. difficile/Epi. Of the 11 discrepant results (i.e., negative by Illumigene C. difficile but positive by Xpert C. difficile and Xpert C. difficile/Epi), all were determined to be positive by the toxigenic culture. A total of 21% of the isolates were presumptively identified by the Xpert C. difficile/Epi as the 027/NAP1/BI strain. The Xpert C. difficile and Xpert C. difficile/Epi assays were the most sensitive, rapid, and easy-to use assays for the detection of toxigenic C. difficile in stool specimens.

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“…Previous reports suggested a poor correlation between the presence of tcdC or binary genes with clinical outcomes in nonepidemic settings (34,35). These studies were based on comparisons of NAP1 strains in different severity groups without a genetic comparison, or the genetic comparison was limited to tcdC and binary toxin genes.…”

Section: Discussionmentioning

confidence: 99%

Phenotypic and Genotypic Analysis of Clostridium difficile Isolates: a Single-Center Study

et al. 2014

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f Clostridium difficile infections (CDI) are a growing concern in North America, because of their increasing incidence and severity. Using integrated approaches, we correlated pathogen genotypes and host clinical characteristics for 46 C. difficile infections in a tertiary care medical center during a 6-month interval from January to June 2010. Multilocus sequence typing (MLST) demonstrated 21 known and 2 novel sequence types (STs), suggesting that the institution's C. difficile strains are genetically diverse. ST-1 (which corresponds to pulsed-field gel electrophoresis strain type NAP1/ribotype 027) was the most prevalent (32.6%); 43.5% of the isolates were binary toxin gene positive, of which 75% were ST-1. All strains were ciprofloxacin resistant and metronidazole susceptible, and 8.3% and 13.0% of the isolates were resistant to clindamycin and tetracycline, respectively. The corresponding resistance loci, including potential novel mutations, were identified from the whole-genome sequencing (WGS) of the resistant strains. Core genome single nucleotide polymorphisms (SNPs) determining the phylogenetic relatedness of the 46 strains recapitulated MLST types and provided greater interstrain differentiation. The disease severity was greatest in patients infected with ST-1 and/or binary gene-positive strains, but genome-wide SNP analysis failed to provide additional associations with CDI severity within the same STs. We conclude that MLST and core genome SNP typing result in the same phylogenetic grouping of the 46 C. difficile strains collected in a single hospital. WGS also has the capacity to differentiate those strains within STs and allows the comparison of strains at the individual gene level and at the whole-genome level. The most common C. difficile strain that has emerged in the past decade in North America and some areas in Europe has been classified as 027 by ribotyping, NAP1 by pulsed-field gel electrophoresis (PFGE), BI by restriction endonuclease analysis, and ST-1 by multilocus sequence typing (MLST). ST-1 strains account for half of the sporadic hospital-associated CDI in some settings (5). Some studies have reported that ST-1 strains elaborate C. difficile toxins (TCDs) at high concentrations; its purported hypervirulence is plausibly related to this trait. This strain has single and 18-bp deletions of tcdC, a negative regulator of tcdA and tcdB. These mutations cause premature stops, and this truncation is believed to cause toxin overproduction (6, 7). However, this assumption was challenged by recent studies showing no significant difference in toxin production between hypervirulent and nonhypervirulent C. difficile strains, and no association of the tcdC genotype and toxin production (8, 9).C. difficile strains containing cdtA and cdtB binary toxin genes are associated with greater mortality in their hosts than strains in which these genes are absent (10). However, it is not clear if the binary toxin genes increase the virulence of ST-1 or if they are simply epidemiologic markers of C. difficile...

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Lack of Association between Clinical Outcome of Clostridium difficile Infections, Strain Type, and Virulence-Associated Phenotypes

Cited by 80 publications

References 44 publications

Antimicrobial Resistance, Toxinotype, and Genotypic Profiling of Clostridium difficile Isolates of Swine Origin

Antimicrobial Resistance, Toxinotype, and Genotypic Profiling of Clostridium difficile Isolates of Swine Origin

Detection of Toxigenic Clostridium difficile: Comparison of the Cell Culture Neutralization, Xpert C. difficile, Xpert C. difficile/Epi, and Illumigene C. difficile Assays

Phenotypic and Genotypic Analysis of Clostridium difficile Isolates: a Single-Center Study

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