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Clinical pathology selected abstracts

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Correlation of clinical severity with stool microbiome changes in Clostridioides difficile infection

Clostridioides difficile infection is the most common cause of infectious diarrhea and pseudomembranous colitis worldwide. Its symptoms can range from mild diarrhea to life-threatening complications. Risk factors for this infection include age older than 65 years, hospitalization in an intensive care unit, clinical history of inflammatory bowel disease, use of proton pump inhibitors, and exposure to antibiotics. Treatment guidelines include targeted antimicrobial therapy and rely on the susceptibility of C. difficile to specific antibiotics, despite the emergence of antibiotic-resistant strains. Other treatment alternatives, such as fecal microbiome transplant, focus on restoring the stool microbiome. More data are needed to correlate clinical variables and 16S rRNA microbiome profiles in C. difficile-infected patients. The authors conducted a study to determine the relationship between a patient’s clinical factors and the stool bacteriome in C. difficile infection (CDI)-positive patients versus CDI-negative patients who have concurrent diarrheal symptoms. They used stool samples and clinical data from 358 hospitalized patients with nosocomial diarrhea. Of these patients, 180 were CDI negative and 178 were CDI positive. Of the 358 hospitalized patients, 24.86 percent were lost to follow-up and 11.52 percent died within the medical facility. Patients’ stool bacteriomes were profiled by amplicon deep sequencing of the 16S rRNA gene and the clinical data were correlated. The data showed that the stool bacteriome in each patient was significantly different. The results indicated that severity alone, regardless of CDI diagnosis, plays an important role in the stool bacteriome. Phyla and species varied based on CDI diagnosis. Furthermore, blood tests were run on hospitalized patients to assess the levels of white blood cells, creatinine, albumin, and C-reactive protein, which play a role in defining the severity of CDI. Severity, defined as a serum WBC count greater than 15 cells/mL or creatinine level greater than 1.5 mg/dL, or both, correlated significantly with dysbiosis of the stool bacteriome profile of CDI-positive versus CDI-negative patients. The serum WBC count was significantly higher in patients with bacterial dysbiosis, and high levels of creatinine were associated with lower microbiome diversity. C-reactive protein was significantly lower in the CDI-negative versus CDI-positive cohort, which suggests a higher level of inflammation in the latter group. The authors concluded that the stool microbiome was less diverse in CDI-positive patients than in those with diarrhea caused by other etiologic agents. They reported that their study is one of the first to investigate both the stool microbiome and clinical variables of symptomatic hospital patients.

Castaneda-Mogollon D, Doolan CP, Toppings NB, et al. Correlation of clinical severity with stool microbiome changes in Clostridioides difficile infection. Arch Pathol Lab Med. 2023;147:774–785.

Correspondence: Dr. Dylan R. Pillai at drpillai@ucalgary.ca

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