Ultrasensitive Clostridioides difficile Toxin Testing for Higher Diagnostic Accuracy

Sandlund, Johanna; Davies, Kerrie A.; Wilcox, Mark H.

doi:10.1128/jcm.01913-19

Cited by 9 publications

(4 citation statements)

References 45 publications

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“…Unfortunately, the company decided not to pursue commercial application of the Clarity assay. However, these studies demonstrated the enhanced sensitivity of single-molecule counting technology for detection of free toxin in patient stool samples compared with standard EIAs [54,55 ▪ ,56].…”

Section: Future Diagnostic Approachesmentioning

confidence: 99%

The future of Clostridioides difficile diagnostics

Mizusawa

Carroll

2021

Current Opinion in Infectious Diseases

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Purpose of review Although the epidemiology of Clostridioides difficile has changed, this organism continues to cause significant morbidity and mortality. This review addresses current and future approaches to the diagnosis of C. difficile disease. Recent findings Over the last several years, large prospective studies have confirmed that there is no single optimal test for the diagnosis of C. difficile disease. The pendulum has swung from a focus on rapid molecular diagnosis during the years of the ribotype 027 epidemic, to a call for use of algorithmic approaches that include a test for toxin detection. In addition, diagnostic stewardship has been shown to improve test utilization, especially with molecular methods. Advances in testing include development of ultrasensitive toxin tests and an expansion of biomarkers that may be more C. difficile specific. Microbiome research may be leveraged to inform novel diagnostic approaches based on measurements of volatile and nonvolatile organic compounds in stool. Summary As rates of C. difficile infection decline, emphasis is now on improving test utilization and a quest for improved diagnostic approaches. These approaches may involve implementation of technologies that improve toxin testing, predict patients likely to have disease and/or a severe outcome, and harnessing research on changes in the microbiome to advance metabolomics.

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Section: Future Diagnostic Approachesmentioning

confidence: 99%

The future of Clostridioides difficile diagnostics

Mizusawa

Carroll

2021

Current Opinion in Infectious Diseases

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“…One of the challenges in diagnosing CDI is that of being able to distinguish between patients with true CDI and those who are colonized ( Planche and Wilcox, 2015 ). The search for new methods for the detection of C. difficile and for distinguishing true infection from colonization in diarrhea of other causes is ongoing ( Kelly et al., 2020 ; Sandlund et al., 2020 ; Ng et al., 2021 ). Profiling the microbiome and identifying possible microbiome biomarkers could help us differentiate between infection and colonization by C. difficile and diarrhea of other causes (NOCDI) ( Planche and Wilcox, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Characterization of the gut microbiome of patients with Clostridioides difficile infection, patients with non–C. difficile diarrhea, and C. difficile–colonized patients

Vázquez-Cuesta

Villar

García

et al. 2023

Front. Cell. Infect. Microbiol.

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IntroductionClostridioides difficile infection (CDI) is the main cause of nosocomial diarrhea in developed countries. A key challenge in CDI is the lack of objective methods to ensure more accurate diagnosis, especially when differentiating between true infection and colonization/diarrhea of other causes. The main objective of this study was to explore the role of the microbiome as a predictive biomarker of CDI.MethodsBetween 2018 and 2021, we prospectively included patients with CDI, recurrent CDI (R-CDI), non-CDI diarrhea (NO-CDI), colonization by C. difficile, and healthy individuals. Clinical data and fecal samples were collected. The microbiome was analyzed by sequencing the hypervariable V4 region of the 16S rRNA gene on an Illumina Miseq platform. The mothur bioinformatic pipeline was followed for pre-processing of raw data, and mothur and R were used for data analysis.ResultsDuring the study period, 753 samples from 657 patients were analyzed. Of these, 247 were from patients with CDI, 43 were from patients colonized with C. difficile, 63 were from healthy individuals, 324 were from NOCDI, and 76 were from R-CDI. We found significant differences across the groups in alpha and beta diversity and in taxonomic abundance. We identified various genera as the most significant biomarkers for CDI (Bacteroides, Proteus, Paraprevotella, Robinsoniella), R-CDI (Veillonella, Fusobacterium, Lactobacillus, Clostridium sensu stricto I), and colonization by C. difficile (Parabacteroides, Faecalicoccus, Flavonifractor, Clostridium XVIII).DiscussionWe observed differences in microbiome patterns between healthy individuals, colonized patients, CDI, R-CDI, and NOCDI diarrhea. We identified possible microbiome biomarkers that could prove useful in the diagnosis of true CDI infections. Further studies are warranted.

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“…Those assays can detect disease-specific markers at extremely low concentrations with good accuracy. 89 However, these ultrasensitive immunoassays require further validation. 8,89 Glutamate dehydrogenase immunoassays identify a metabolic enzyme that is highly conserved and abundant in all C. difficile isolates.…”

mentioning

confidence: 99%

“…89 However, these ultrasensitive immunoassays require further validation. 8,89 Glutamate dehydrogenase immunoassays identify a metabolic enzyme that is highly conserved and abundant in all C. difficile isolates. Since GDH is found in both toxigenic and nontoxigenic isolates, this test lacks specificity and should be combined with another method (namely, toxin detection test).…”

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confidence: 99%

Clostridioides (Clostridium) difficile

Al-Zahrani

2023

SMJ

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Clostridioides difficile (C. difficile) infection is still a threat to many healthcare settings worldwide. Clostridioides difficile epidemiology has changed over the last 20 years, largely due to the emergence of hypervirulent and antimicrobial-resistant C. difficile strains. The excessive use of antimicrobials, the absence of optimal antibiotic policies, and suboptimal infection control practices have fueled the development of this pressing health issue. The prudent use of antimicrobials, particularly broad-spectrum agents, and simple infection control measures, such as hand hygiene, can significantly reduce C. difficile infection rates. Moreover, the early detection of these infections and understanding their epidemiological behavior using accurate laboratory methods are the cornerstone to decreasing the incidence of C. difficile infection and preventing further spread. Although there is no consensus on the single best laboratory method for the diagnosis of C. difficile infection, the use of 2 or more techniques can improve diagnostic accuracy, and it is recommended.

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Ultrasensitive Clostridioides difficile Toxin Testing for Higher Diagnostic Accuracy

Cited by 9 publications

References 45 publications

The future of Clostridioides difficile diagnostics

The future of Clostridioides difficile diagnostics

Characterization of the gut microbiome of patients with Clostridioides difficile infection, patients with non–C. difficile diarrhea, and C. difficile–colonized patients

Clostridioides (Clostridium) difficile

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