Prevalence of diagnostically-discrepant Clostridioides difficile clinical specimens: insights from longitudinal surveillance

Frontiers in Medicine

Medicine

William Lainhart¹  Kareem Shehab²  Farhan Anwar³  Evy Nguyen³  Rachel Claus-Walker³  Justin Billy³  Marielle Clark³  Jason Lindsey³  Asad Mansoor³  V. K. Viswanathan⁴  Gayatri Vedantam⁵ 

[1] Department of Pathology, Clinical Microbiology Laboratories, Banner University Medical Center, Tucson, AZ, United States;Department of Pediatrics, College of Medicine, University of Arizona, Tucson, AZ, United States;School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ, United States;School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ, United States;Bio5 Institute for Collaborative Research, University of Arizona, Tucson, AZ, United States;School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ, United States;Bio5 Institute for Collaborative Research, University of Arizona, Tucson, AZ, United States;Southern Arizona VA Healthcare System, Tucson, AZ, United States;

关键词: Clostridioides difficile;    prevalence;    surveillance;    ribotyping;    discrepant;    longitudinal;   

DOI  :  10.3389/fmed.2023.1238159

 received in 2023-06-10, accepted in 2023-10-03,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2023 Anwar, Clark, Lindsey, Claus-Walker, Mansoor, Nguyen, Billy, Lainhart, Shehab, Viswanathan and Vedantam.