Clinical Correlation of a Clostridium difficile Testing Algorithm Reflexing PCR Positive Specimens to Toxin Enzyme Immunoassay (EIA)

BACKGROUND: An algorithm promoted in the United Kingdom reflexes specimens positive for C. difficile by a nucleic acid amplification test (NAAT) to toxin EIA. Samples positive by NAAT and negative by toxin EIA are reported as “C. difficile could be present (ie, potential C. difficile excretor).” We explored the potential utility of this algorithm to distinguish C. difficile infection (CDI) from colonization compared with retrospective clinical assessment. METHODS: Liquid stool specimens (n = 300) from inpatients (or the Emergency Department) submitted to the Cleveland Clinic Microbiology laboratory for C. difficile PCR testing (Cepheid Xpert C. difficile/Epi) with positive results were included in the study. The CDIFF QUICK CHEK COMPLETE GDH/toxin EIA assay (Alere) was performed according to manufacturer’s instructions. The charts of all patients were reviewed by Infectious Diseases physicians blinded to the EIA results. Using the American College of Gastroenterology (ACG) classification system, CDI status was determined to be mild, moderate, severe, or complicated. Patients without significant diarrhea (<3 unformed stools / 24 hours) were considered colonized. Those without documentation of stools were classified as indeterminate. Correlation of clinical assessment with EIA results was assessed. RESULTS: Most of the PCR positive specimens (75%) were toxin EIA negative. Correlation of clinical assessment with toxin EIA is summarized in the table below. Among patients colonized vs. those with CDI, the percentages with negative toxin EIA results were 80% and 73%, respectively. GDH antigen results were negative for 25 specimens—17 were from patients considered to have CDI. CONCLUSION: Toxin EIA performed on samples positive for C. difficile by PCR does not reliably identify patients considered to have CDI with ACG criteria applied. GDH as an initial screen would not have detected 6.8% of patients with CDI. DISCLOSURES: S. S. Richter, bioMerieux: Investigator, Research support; BD Diagnostics: Investigator, Research support; Roche: Investigator, Research support; BioFire: Investigator, Research support; OpGen: Investigator, Research support