Alternative Causes of Infectious Diarrhea in Patients with Negative Tests for Clostridoides Difficile

Background Hospitalized patients with diarrhea who have a negative Clostridoides difficile (C. difficile) test are not routinely evaluated for alternative causes of infectious diarrhea. This study assessed for potential infectious causes of diarrhea in hospitalized patients with an order for repeat C. difficile toxin enzyme immunoassay (tEIA) testing after an initial tEIA test was negative. Methods For patients age ≥18 years who had a second C. difficile tEIA test ordered within 96 h after a negative tEIA test, remnant fecal specimens from the first (negative) tEIA test were evaluated using the BioFire FilmArray Gastrointestinal Panel PCR, C. difficile toxigenic culture, and culture on a blood agar plate (BAP) to identify other potential causes of infectious diarrhea. Growth of organisms on the BAP was also used to assess potential disruptions in the gastrointestinal microbiota. Results Among 84 remnant specimens, toxigenic C. difficile was identified in 9 (11%) by culture or PCR, while potential alternative causes of infectious diarrhea, including norovirus, rotavirus, enteropathogenic Escherichia coli, and Salmonella, were identified in 11 specimens (13%) by PCR. For the majority of patients, no infectious cause of diarrhea was identified, but 84% exhibited disrupted gastrointestinal microbiota, which may contribute to diarrhea. Conclusions When a hospitalized patient has a negative C. difficile tEIA test but continues to have diarrhea, alternative infectious and noninfectious causes of diarrhea should be considered. If the patient has clinical signs and symptoms suggestive of infection or risk factors for gastrointestinal infection, laboratory testing for other etiologic agents may be appropriate.

Multiplatform assessment of saliva for SARS-CoV-2 molecular detection in symptomatic healthcare personnel and patients presenting to the emergency department

Background Saliva has garnered great interest as an alternative specimen type for molecular detection of SARS-CoV-2. Data are limited on the relative performance of different molecular methods using saliva specimens and the relative sensitivity of saliva to NP swabs. Methods To address the gap in knowledge, we enrolled symptomatic healthcare personnel (n = 250) from Barnes-Jewish Hospital/Washington University Medical Center and patients presenting to the Emergency Department with clinical symptoms compatible with COVID-19 (n = 292). We collected paired saliva specimens and NP swabs. The Lyra SARS-CoV-2 assay (Quidel, San Diego, CA) was evaluated on paired saliva and NP samples. Subsequently we compared the Simplexa COVID-19 Direct Kit (Diasorin, Cypress, CA) and a modified SalivaDirect (Yale) assay on a subset of positive and negative saliva specimens. Results The positive percent agreement between saliva and NP samples using the Lyra SARS-CoV-2 assay was 63.2%. Saliva samples had higher SARS-CoV-2 cycle threshold values compared to NP swabs (p < 0.0001). We found a 76.47% (26/34) positive percent agreement for Simplexa COVID-19 Direct Kit on saliva and a 67.6% (23/34) positive percent agreement for SalivaDirect compared to NP swab results. Conclusion These data demonstrate molecular assays have variability in performance for detection of SARS-CoV-2 in saliva.

Multi-Inflammatory Syndrome in Children: A View into Immune Pathogenesis from a Laboratory Perspective

Background Multi-inflammatory syndrome in children (MIS-C) is a novel and rare inflammatory disorder associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in school-age children. Reports in the past year have suggested a multi-system pathophysiology characterized by hyperinflammation, gastrointestinal distress, and cardiovascular complications. Clinical laboratory investigations, including routine blood testing for inflammatory (e.g., CRP, ferritin) and cardiac (e.g., troponin, brain natriuretic peptides) markers have provided insight into potential drivers of disease pathogenesis, highlighting the role of the laboratory in the differential diagnosis of patients presenting with similar conditions (e.g., Kawasaki Disease, Macrophage Activating Syndrome). Content While few studies have applied high-dimensional immune profiling to further characterize underlying MIS-C pathophysiology, much remains unknown regarding predisposing risk factors, etiology, and long-term impact of disease onset. The extent of autoimmune involvement is also unclear. In the current review, we summarize and critically evaluate available literature on potential pathogenic mechanisms underlying MIS-C onset and discuss the current and anticipated value of various laboratory testing paradigms in MIS-C diagnosis and monitoring. Summary From initial reports, it is clear that MIS-C has unique inflammatory signatures involving both adaptive and innate systems. Certain cytokines, inflammatory markers, and cardiac markers assist in the differentiation of MIS-C from other hyperinflammatory conditions. However, there are still major gaps in our understanding of MIS-C pathogenesis, including T cell, B cell, and innate response. It is essential that researchers not only continue to decipher initial pathogenesis but also monitor long-term health outcomes, particularly given observed presence of circulating autoantibodies with unknown impact.