Prevalence of diagnostically-discrepant Clostridioides difficile clinical specimens: insights from longitudinal surveillance
BackgroundClostridioides difficile Infection (CDI) is a healthcare-associated diarrheal disease prevalent worldwide. A common diagnostic algorithm relies on a two-step protocol that employs stool enzyme immunoassays (EIAs) to detect the pathogen, and its toxins, respectively. Active CDI is deemed le...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2023.1238159/full |
| _version_ | 1797657477772214272 |
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| author | Farhan Anwar Marielle Clark Jason Lindsey Rachel Claus-Walker Asad Mansoor Evy Nguyen Justin Billy William Lainhart Kareem Shehab V. K. Viswanathan V. K. Viswanathan Gayatri Vedantam Gayatri Vedantam Gayatri Vedantam |
| author_facet | Farhan Anwar Marielle Clark Jason Lindsey Rachel Claus-Walker Asad Mansoor Evy Nguyen Justin Billy William Lainhart Kareem Shehab V. K. Viswanathan V. K. Viswanathan Gayatri Vedantam Gayatri Vedantam Gayatri Vedantam |
| author_sort | Farhan Anwar |
| collection | DOAJ |
| description | BackgroundClostridioides difficile Infection (CDI) is a healthcare-associated diarrheal disease prevalent worldwide. A common diagnostic algorithm relies on a two-step protocol that employs stool enzyme immunoassays (EIAs) to detect the pathogen, and its toxins, respectively. Active CDI is deemed less likely when the Toxin EIA result is negative, even if the pathogen-specific EIA is positive for C. difficile. We recently reported, however, that low-toxin-producing C. difficile strains recovered from Toxin-negative (‘discrepant’) clinical stool specimens can be fully pathogenic, and cause lethality in a rodent CDI model. To document frequency of discrepant CDI specimens, and evaluate C. difficile strain diversity, we performed longitudinal surveillance at a Southern Arizona tertiary-care hospital.MethodsDiarrheic stool specimens from patients with clinical suspicion of CDI were obtained over an eight-year period (2015–2022) from all inpatient and outpatient Units of a > 600-bed Medical Center in Southern Arizona. Clinical laboratory EIA testing identified C. difficile-containing specimens, and classified them as Toxin-positive or Toxin-negative. C. difficile isolates recovered from the stool specimens were DNA fingerprinted using an international phylogenetic lineage assignment system (“ribotyping”). For select isolates, toxin abundance in stationary phase supernatants of pure cultures was quantified via EIA.ResultsOf 8,910 diarrheic specimens that underwent diagnostic testing, 1733 (19.4%) harbored C. difficile. Our major findings were that: (1) C. difficile prevalence and phylogenetic diversity was stable over the 8-year period; (2) toxigenic C. difficile was recovered from 69% of clinically Tox-neg (‘discrepant’) specimens; (3) the six most prevalent USA ribotypes were recovered in significant proportions (>60%) from Tox-neg specimens; and (4) toxin–producing C. difficile recovered from discrepant specimens produced less toxin than strains of the same ribotype isolated from non-discrepant specimens.ConclusionOur study highlights the dominance of Toxin EIA-negative CDI specimens in a clinical setting and the high frequency of known virulent ribotypes in these specimens. Therefore, a careful reevaluation of the clinical relevance of diagnostically-discrepant specimens particularly in the context of missed CDI diagnoses and C. difficile persistence, is warranted. |
| first_indexed | 2024-03-11T17:45:04Z |
| format | Article |
| id | doaj.art-a5d52939eab24928a9218ce0c859a840 |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-03-11T17:45:04Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Medicine |
| spelling | doaj.art-a5d52939eab24928a9218ce0c859a8402023-10-18T08:32:19ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2023-10-011010.3389/fmed.2023.12381591238159Prevalence of diagnostically-discrepant Clostridioides difficile clinical specimens: insights from longitudinal surveillanceFarhan Anwar0Marielle Clark1Jason Lindsey2Rachel Claus-Walker3Asad Mansoor4Evy Nguyen5Justin Billy6William Lainhart7Kareem Shehab8V. K. Viswanathan9V. K. Viswanathan10Gayatri Vedantam11Gayatri Vedantam12Gayatri Vedantam13School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ, United StatesSchool of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ, United StatesSchool of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ, United StatesSchool of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ, United StatesSchool of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ, United StatesSchool of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ, United StatesSchool of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ, United StatesDepartment of Pathology, Clinical Microbiology Laboratories, Banner University Medical Center, Tucson, AZ, United StatesDepartment of Pediatrics, College of Medicine, University of Arizona, Tucson, AZ, United StatesSchool of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ, United StatesBio5 Institute for Collaborative Research, University of Arizona, Tucson, AZ, United StatesSchool of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ, United StatesBio5 Institute for Collaborative Research, University of Arizona, Tucson, AZ, United StatesSouthern Arizona VA Healthcare System, Tucson, AZ, United StatesBackgroundClostridioides difficile Infection (CDI) is a healthcare-associated diarrheal disease prevalent worldwide. A common diagnostic algorithm relies on a two-step protocol that employs stool enzyme immunoassays (EIAs) to detect the pathogen, and its toxins, respectively. Active CDI is deemed less likely when the Toxin EIA result is negative, even if the pathogen-specific EIA is positive for C. difficile. We recently reported, however, that low-toxin-producing C. difficile strains recovered from Toxin-negative (‘discrepant’) clinical stool specimens can be fully pathogenic, and cause lethality in a rodent CDI model. To document frequency of discrepant CDI specimens, and evaluate C. difficile strain diversity, we performed longitudinal surveillance at a Southern Arizona tertiary-care hospital.MethodsDiarrheic stool specimens from patients with clinical suspicion of CDI were obtained over an eight-year period (2015–2022) from all inpatient and outpatient Units of a > 600-bed Medical Center in Southern Arizona. Clinical laboratory EIA testing identified C. difficile-containing specimens, and classified them as Toxin-positive or Toxin-negative. C. difficile isolates recovered from the stool specimens were DNA fingerprinted using an international phylogenetic lineage assignment system (“ribotyping”). For select isolates, toxin abundance in stationary phase supernatants of pure cultures was quantified via EIA.ResultsOf 8,910 diarrheic specimens that underwent diagnostic testing, 1733 (19.4%) harbored C. difficile. Our major findings were that: (1) C. difficile prevalence and phylogenetic diversity was stable over the 8-year period; (2) toxigenic C. difficile was recovered from 69% of clinically Tox-neg (‘discrepant’) specimens; (3) the six most prevalent USA ribotypes were recovered in significant proportions (>60%) from Tox-neg specimens; and (4) toxin–producing C. difficile recovered from discrepant specimens produced less toxin than strains of the same ribotype isolated from non-discrepant specimens.ConclusionOur study highlights the dominance of Toxin EIA-negative CDI specimens in a clinical setting and the high frequency of known virulent ribotypes in these specimens. Therefore, a careful reevaluation of the clinical relevance of diagnostically-discrepant specimens particularly in the context of missed CDI diagnoses and C. difficile persistence, is warranted.https://www.frontiersin.org/articles/10.3389/fmed.2023.1238159/fullClostridioides difficileprevalencesurveillanceribotypingdiscrepantlongitudinal |
| spellingShingle | Farhan Anwar Marielle Clark Jason Lindsey Rachel Claus-Walker Asad Mansoor Evy Nguyen Justin Billy William Lainhart Kareem Shehab V. K. Viswanathan V. K. Viswanathan Gayatri Vedantam Gayatri Vedantam Gayatri Vedantam Prevalence of diagnostically-discrepant Clostridioides difficile clinical specimens: insights from longitudinal surveillance Frontiers in Medicine Clostridioides difficile prevalence surveillance ribotyping discrepant longitudinal |
| title | Prevalence of diagnostically-discrepant Clostridioides difficile clinical specimens: insights from longitudinal surveillance |
| title_full | Prevalence of diagnostically-discrepant Clostridioides difficile clinical specimens: insights from longitudinal surveillance |
| title_fullStr | Prevalence of diagnostically-discrepant Clostridioides difficile clinical specimens: insights from longitudinal surveillance |
| title_full_unstemmed | Prevalence of diagnostically-discrepant Clostridioides difficile clinical specimens: insights from longitudinal surveillance |
| title_short | Prevalence of diagnostically-discrepant Clostridioides difficile clinical specimens: insights from longitudinal surveillance |
| title_sort | prevalence of diagnostically discrepant clostridioides difficile clinical specimens insights from longitudinal surveillance |
| topic | Clostridioides difficile prevalence surveillance ribotyping discrepant longitudinal |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2023.1238159/full |
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