Morbidity and mortality associated with Clostridium difficile ribotype 078: a case–case study

Patterson, Lynsey; Wilcox, Mark H.; Fawley, Warren N.; Verlander, Neville Q.; Geoghegan, Lourda; Patel, Bhavika B.; Wyatt, T. D.; Smyth, B.

doi:10.1016/j.jhin.2012.07.011

Cited by 20 publications

(16 citation statements)

References 8 publications

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“…In contrast, other studies have found no association between the presence of binary toxin genes (in strains including 078) and more severe disease (Goldenberg & French, 2011;Hensgens & Kuijper, 2013), or between ribotype and disease severity, even for ribotype 027 strains (Walk et al, 2012). A case-comparison study comparing a range of patient characteristics for C. difficile infection cases with ribotypes 001, 027 and 078 in Northern Ireland has been published (Patterson et al, 2012). These authors found that ribotype 078 was community associated, and mortality for 078 cases was not significantly different from 001 or 027 cases, although the relatively small number of 078 cases (n529) may have influenced the outcome.…”

Section: Resultsmentioning

confidence: 99%

Association of Clostridium difficile ribotype 078 with detectable toxin in human stool specimens

Fairley

McKenna

Stevenson

et al. 2015

Journal of Medical Microbiology

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Using a Clostridium difficile glutamate dehydrogenase (GDH) immunoassay and a sensitive C. difficile toxin A/B immunoassay, human stool specimens from patients with diarrhoea (n51085) were classified as either GDH positive/toxin negative, or GDH positive/toxin positive. Overall, 528/725 (73%) of the GDH-positive/toxin-negative specimens contained viable C. difficile, and 433/528 (82%) of these C. difficile isolates were PCR positive for the toxin gene pathogenicity locus. Overall, 867/1078 (80%) of the GDH-positive specimens contained viable C. difficile, and 433/725 (60%) of the GDH-positive/toxin-negative specimens contained a toxigenic C. difficile strain. The diversity of toxigenic C. difficile ribotypes isolated from toxin-negative specimens (n5433) and toxin-positive specimens (n5339) was significantly different (P,0.0001). Specifically, the presence of ribotype 078 strains was very strongly associated (P,0.0001) with detection of toxin in clinical specimens using a sensitive toxin immunoassay. Specimens positive for ribotype 078 were almost twice as likely to be toxin positive as opposed to toxin negative (risk ratio51.90, 95% confidence interval 1.64-2.19). In contrast, other circulating ribotypes were seen with similar frequency in specimens with and without detectable toxin. This supports the view that ribotype 078 strains may be more virulent than other common ribotypes in terms of toxin production. INTRODUCTIONHospital laboratories commonly diagnose Clostridium difficile infection by detection of toxin A and/or B in stool specimens using enzyme immunoassay (EIA) tests, although these tests have unacceptably low sensitivity when they are used alone. Depending on the toxin EIA used, positive predictive values are as low as 15-56% when testing patient populations with low prevalence (Eastwood et al., 2009). UK guidance now recommends dual testing using two different tests to improve diagnostic accuracy for C. difficile infection (Robotham & Wilcox, 2012). Immunoassays to detect the glutamate dehydrogenase (GDH) antigen are more sensitive than toxin EIA tests for detection of C. difficile, and many clinical laboratories have adopted GDH tests for screening, with secondary or parallel testing using a toxin EIA test. Dual testing using two assays with different sensitivities generates a significant number of discrepant GDH-positive/toxin-negative results, in addition to definitive GDH-positive/toxin-positive results that confirm a diagnosis of C. difficile infection. Because GDH tests are not specific for toxigenic strains of C. difficile, interpreting these discrepant results can be difficult.The emergence of virulent C. difficile strains is of concern because a highly virulent epidemic C. difficile clone (ribotype 027/NAP1/toxinotype III) has spread globally during the last decade (He et al., 2013). Ribotype 027 strains have been reported to produce significantly more toxin than other strains in vitro. One study reported that 027 strains produced peak titres of toxin A and B that were 16 and 23 times hi...

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Section: Resultsmentioning

confidence: 99%

Association of Clostridium difficile ribotype 078 with detectable toxin in human stool specimens

Fairley

McKenna

Stevenson

et al. 2015

Journal of Medical Microbiology

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“…The spread of these RTs into mainland China could lead to further dissemination within South East Asia. RT 078 is more commonly associated with community-acquired C. difficile infection; hence hospital-based studies, as most of the studies in this region have been, might miss cases caused by this RT [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Clostridium difficile infection in the Lao People’s Democratic Republic: first isolation and review of the literature

et al. 2017

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BackgroundCurrent knowledge of the epidemiology of Clostridium difficile infection in Asia, and in particular the Greater Mekong Subregion, is very limited. Only a few studies from Thailand and Vietnam have been reported from the region with variable testing methods and results, and no studies from Lao People’s Democratic Republic (PDR). Therefore we investigated the presence of C. difficile in a single centre in the Lao PDR and determined the ribotypes present.MethodSeventy unformed stool samples from hospital inpatients at Mahosot Hospital, Vientiane, were tested for the presence of C. difficile using selective differential agar and confirmed by latex agglutination. C. difficile isolates were further characterised by ribotyping and toxin gene detection.Results C. difficile was isolated from five of the 70 patients, and five different ribotypes were identified (014, 017, 020, QX 107 and QX 574).ConclusionThis is the first isolation of C. difficile from human stool samples in the Lao PDR. These results will add to the limited amount of data on C. difficile in the region. In addition, we hope this information will alert clinicians to the presence of C. difficile in the country and will help inform future investigations into the epidemiology and diagnosis of C. difficile in Lao PDR.

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“…Indeed, current studies indicate that changes may already be taking place. The number of NAP1/BI/027 cases is starting to wane, and new strains, such as the 078 ribotype, are starting to emerge (200). A study from the Netherlands found that the number of CDI cases caused by C. difficile 078 ribotypes increased from 3% to 13% in just 3 years (201).…”

Section: Additional Emerging Hypervirulent Strains Of C Difficilementioning

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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Morbidity and mortality associated with Clostridium difficile ribotype 078: a case–case study

Cited by 20 publications

References 8 publications

Association of Clostridium difficile ribotype 078 with detectable toxin in human stool specimens

Association of Clostridium difficile ribotype 078 with detectable toxin in human stool specimens

Clostridium difficile infection in the Lao People’s Democratic Republic: first isolation and review of the literature

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

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