Clostridium difficile Ribotype Does Not Predict Severe Infection

Walk, Seth T.; Micić, Dejan; Jain, Ruchika; Lo, Edward C M; Trivedi, Itishree; Liu, Eugene; Almassalha, Luay M.; Ewing, Sarah; Ring, Cathrin; Gałecki, Andrzej T.; Rogers, Mary A.M.; Washer, Laraine; Newton, Duane W.; Malani, Preeti N.; Young, Vincent B.; Aronoff, David M.

doi:10.1093/cid/cis786

Cited by 175 publications

(179 citation statements)

References 41 publications

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“…The finding also suggests that C. difficile ribotypes may not be determinants of the development of symptomatic infection but, rather, that the development of symptoms may be mainly driven by host factors, such as immune state and disruption of the gut microbiome by exposure to antimicrobials or underlying conditions affecting the gastrointestinal tract (17)(18)(19). Our findings differ from those of a previous study in which a binary toxin-producing C. difficile strain (i.e., ribotype 027) was more likely than other strains to cause symptomatic disease (6).…”

Section: Discussionmentioning

confidence: 99%

Comparison of Clostridium difficile Ribotypes Circulating in Australian Hospitals and Communities

et al. 2017

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Clostridium difficile infection (CDI) is becoming less exclusively a health care-associated CDI (HA-CDI). The incidence of community-associated CDI (CA-CDI) has increased over the past few decades. It has been postulated that asymptomatic toxigenic C. difficile (TCD)-colonized patients may play a role in the transfer of C. difficile between the hospital setting and the community. Thus, to investigate the relatedness of C. difficile across the hospital and community settings, we compared the characteristics of symptomatic and asymptomatic host patients and the pathogens from these patients in these two settings over a 3-year period. Two studies were simultaneously conducted; the first study enrolled symptomatic CDI patients from two tertiary care hospitals and the community in two Australian states, while the second study enrolled asymptomatic TCD-colonized patients from the same tertiary care hospitals. A total of 324 patients (96 with HA-CDI, 152 with CA-CDI, and 76 colonized with TCD) were enrolled. The predominant C. difficile ribotypes isolated in the hospital setting corresponded with those isolated in the community, as it was found that for 79% of the C. difficile isolates from hospitals, an isolate with a matching ribotype was isolated in the community, suggesting that transmission between these two settings is occurring. The toxigenic C. difficile strains causing symptomatic infection were similar to those causing asymptomatic infection, and patients exposed to antimicrobials prior to admission were more likely to develop a symptomatic infection (odds ratio, 2.94; 95% confidence interval, 1.20 to 7.14). Our findings suggest that the development of CDI symptoms in a setting without establishment of hospital epidemics with binary toxin-producing C. difficile strains may be driven mainly by host susceptibility and exposure to antimicrobials, rather than by C. difficile strain characteristics.

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Section: Discussionmentioning

confidence: 99%

Comparison of Clostridium difficile Ribotypes Circulating in Australian Hospitals and Communities

et al. 2017

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“…While some studies have demonstrated more severe disease and increased mortality associated with ribotype 027 (16,19), more recent studies have challenged this observation (21,22). In the latter studies, when other covariates were considered, the ribotype of the infecting organism was not found to be a significant predictor of severe CDI (21). Currently, there are no recommendations to alter infection control practices based upon ribotype.…”

Section: Discussionmentioning

confidence: 99%

Multicenter Evaluation of the Verigene Clostridium difficile Nucleic Acid Assay

et al. 2013

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hThe Verigene Clostridium difficile Nucleic Acid test (Verigene CDF test) (Nanosphere, Northbrook, IL) is a multiplex qualitative PCR assay that utilizes a nanoparticle-based array hybridization method to detect C. difficile tcdA and tcdB in fecal specimens. In addition, the assay detects binary toxin gene sequences and the single base pair deletion at nucleotide 117 (⌬ 117) in tcdC to provide a presumptive identification of the epidemic strain 027/NAP1/BI (referred to here as ribotype 027). This study compared the Verigene CDF test with anaerobic direct and enriched toxigenic culture on stool specimens from symptomatic patients among five geographically diverse laboratories within the United States. The Verigene CDF test was performed according to the manufacturer's instructions, and the reference methods performed by a central laboratory included direct culture onto cycloserine cefoxitin fructose agar (CCFA) and enriched culture using cycloserine cefoxitin mannitol broth with taurocholate and lysozyme. Recovered isolates were identified as C. difficile using gas liquid chromatography and were tested for toxin using a cell culture cytotoxicity neutralization assay. Strains belonging to ribotype 027 were determined by PCR ribotyping and bidirectional sequencing for ⌬ 117 in tcdC. A total of 1,875 specimens were evaluable. Of these, 275 specimens (14.7%) were culture positive by either direct or enriched culture methods. Compared to direct culture alone, the overall sensitivity, specificity, positive predictive value, and negative predictive value for the Verigene CDF test were 98.7%, 87.5%, 42%, and 99.9%, respectively. Compared to combined direct and enriched culture results, the sensitivity, specificity, positive predictive value, and negative predictive values of the Verigene CDF test were 90.9%, 92.5%, 67.6%, and 98.3%, respectively. Of the 250 concordantly culture-positive specimens, 59 (23.6%) were flagged as "hypervirulent"; 53 were confirmed as ribotype 027, and all 59 possessed ⌬ 117 in tcdC. Time to results was approximately 2.5 h per specimen. The Verigene CDF test is a novel nucleic acid microarray that reliably detects both C. difficile toxins A and B in unformed stool specimens and appears to adequately identify ribotype 027 isolates. The optimum testing method for the diagnosis of Clostridium difficile is still a matter of debate. A variety of testing methods are available and include enzyme immunoassays (EIAs) for detection of toxins A and B, cell culture cytotoxicity neutralization assays (CCNAs), anaerobic toxigenic culture, detection of glutamate dehydrogenase, and nucleic acid amplification tests (NAATs). Although EIAs provide same-day results and are relatively inexpensive and easy to perform, there is general agreement in the United States and in some European countries that EIAs should not be performed as stand-alone tests due to their lack of sensitivity (1, 2). CCNAs and anaerobic toxigenic culture do not provide timely results and have never been standardized. Laboratories are beginning...

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“…Some studies suggest that this may not always be the case. A recent study by Walk and colleagues found that while the NAP1/BI/027 strain is associated with severe disease, it is not the sole predictor of disease severity (173). Other factors, such as white blood cell count, may be better clinical indicators of the severity of disease.…”

Section: History and Emergence Of Nap1/027/bi Strainsmentioning

confidence: 99%

Variations in Virulence and Molecular Biology among Emerging Strains of Clostridium difficile

Hunt

Ballard

2013

Microbiol Mol Biol Rev

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SUMMARY Clostridium difficile is a Gram-positive, spore-forming organism which infects and colonizes the large intestine, produces potent toxins, triggers inflammation, and causes significant systemic complications. Treating C. difficile infection (CDI) has always been difficult, because the disease is both caused and resolved by antibiotic treatment. For three and a half decades, C. difficile has presented a treatment challenge to clinicians, and the situation took a turn for the worse about 10 years ago. An increase in epidemic outbreaks related to CDI was first noticed around 2003, and these outbreaks correlated with a sudden increase in the mortality rate of this illness. Further studies discovered that these changes in CDI epidemiology were associated with the rapid emergence of hypervirulent strains of C. difficile , now collectively referred to as NAP1/BI/027 strains. The discovery of new epidemic strains of C. difficile has provided a unique opportunity for retrospective and prospective studies that have sought to understand how these strains have essentially replaced more historical strains as a major cause of CDI. Moreover, detailed studies on the pathogenesis of NAP1/BI/027 strains are leading to new hypotheses on how this emerging strain causes severe disease and is more commonly associated with epidemics. In this review, we provide an overview of CDI, discuss critical mechanisms of C. difficile virulence, and explain how differences in virulence-associated factors between historical and newly emerging strains might explain the hypervirulence exhibited by this pathogen during the past decade.

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Clostridium difficile Ribotype Does Not Predict Severe Infection

Abstract: Ribotype is not a significant predictor of severe CDI when adjusted for the influence of any other variables separately or in combination. White blood cell count and albumin level are the most clinically relevant predictors of severe CDI cases.

Cited by 175 publications

References 41 publications

Comparison of Clostridium difficile Ribotypes Circulating in Australian Hospitals and Communities

Comparison of Clostridium difficile Ribotypes Circulating in Australian Hospitals and Communities

Multicenter Evaluation of the Verigene Clostridium difficile Nucleic Acid Assay

Variations in Virulence and Molecular Biology among Emerging Strains of Clostridium difficile

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