Meeta Desai1,2, Kristin Knight1, James M Gray1, Vu Nguyen1, James Boone3, Dario Sorrentino1,4. 1. Division of Gastroenterology, IBD Center, Virginia Tech Carilion School of Medicine, Roanoke, Virginia. 2. Penn State Health, Department of Medicine, Division of Gastroenterology and Hepatology, Hershey, Pennsylvania. 3. Research and Development, TechLab Inc., Blacksburg, Virginia, USA. 4. Department of Clinical and Experimental Medical Sciences, University of Udine, School of Medicine, Udine, Italy.
Abstract
BACKGROUND/AIMS: Clostridioides difficile infection (CDI) remains a diagnostic challenge in patients with inflammatory bowel disease (IBD). We tested novel biomarkers to differentiate CDI from colonization in patients without (CDI-only) and with IBD (IBD-CDI). METHODS: Samples were enzyme immunoassay (EIA)-tested for glutamate dehydrogenase (GDH) and toxin, followed by reflex PCR. Quantitative GDH [(qGDH) - a novel indicator of Clostridium difficile load] and stool lactoferrin were tested at days 0, 3 and 10 during antibiotic treatment. Samples were also analyzed for toxin B cytotoxicity neutralization assay (CNA) and toxigenic culture, gold standards to detect free toxin and virulent bacteria, respectively. RESULTS: Forty-five symptomatic patients (28 CDI-only, 13 with Crohn's disease, 4 with ulcerative colitis) were recruited with 3 sequential samples available for 36 (21 CDI-only, 15 IBD-CDI). Thirty-nine of 45 (87%) cases were toxigenic culture-positive. In the CDI-only group, 78.6% were positive for EIA-toxin, 21.4% were PCR-positive while 82.1% were CNA-positive. In the IBD-CDI group, only one patient (6%) was EIA-toxin positive and 17.6% CNA-positive. The median qGDH level at day 0 was higher in CNA-positive patients compared to CNA-negative patients (1111 vs. 146 ng/g, P = 0.004) and dropped together with lactoferrin from day 0 to 10. CDI eradication improved symptoms in 72.2% of patients with CDI-only. In 60% of patients with IBD-CDI, eradication was ineffective, with symptoms improving in 89% of them after IBD therapy intensification. CONCLUSION: In patients with IBD-CDI, PCR-only positivity might mainly reflect colonization rather than disease. C. difficile load by qGDH correlates with CNA-detected toxin and together with stool lactoferrin might differentiate CDI from colonization in patients with IBD.
BACKGROUND/AIMS: Clostridioides difficileinfection (CDI) remains a diagnostic challenge in patients with inflammatory bowel disease (IBD). We tested novel biomarkers to differentiate CDI from colonization in patients without (CDI-only) and with IBD (IBD-CDI). METHODS: Samples were enzyme immunoassay (EIA)-tested for glutamate dehydrogenase (GDH) and toxin, followed by reflex PCR. Quantitative GDH [(qGDH) - a novel indicator of Clostridium difficile load] and stool lactoferrin were tested at days 0, 3 and 10 during antibiotic treatment. Samples were also analyzed for toxin B cytotoxicity neutralization assay (CNA) and toxigenic culture, gold standards to detect free toxin and virulent bacteria, respectively. RESULTS: Forty-five symptomatic patients (28 CDI-only, 13 with Crohn's disease, 4 with ulcerative colitis) were recruited with 3 sequential samples available for 36 (21 CDI-only, 15 IBD-CDI). Thirty-nine of 45 (87%) cases were toxigenic culture-positive. In the CDI-only group, 78.6% were positive for EIA-toxin, 21.4% were PCR-positive while 82.1% were CNA-positive. In the IBD-CDI group, only one patient (6%) was EIA-toxin positive and 17.6% CNA-positive. The median qGDH level at day 0 was higher in CNA-positive patients compared to CNA-negative patients (1111 vs. 146 ng/g, P = 0.004) and dropped together with lactoferrin from day 0 to 10. CDI eradication improved symptoms in 72.2% of patients with CDI-only. In 60% of patients with IBD-CDI, eradication was ineffective, with symptoms improving in 89% of them after IBD therapy intensification. CONCLUSION: In patients with IBD-CDI, PCR-only positivity might mainly reflect colonization rather than disease. C. difficile load by qGDH correlates with CNA-detected toxin and together with stool lactoferrin might differentiate CDI from colonization in patients with IBD.