title: Performance of Clostridium difficile toxin enzyme immunoassay and nucleic acid amplification tests stratified by patient disease severity.
abstract: Many clinical laboratories in the United States are transitioning from toxin enzyme immunoassays (EIA) to nucleic acid amplification tests (NAATs) as the primary diagnostic test for Clostridium difficile infection (CDI). While it is known that the analytical sensitivity of the toxin EIA is poor, there are limited clinical data on the performance of these assays for patients with mild or severe CDI. Two hundred ninety-six hospital inpatients with diarrhea and clinical suspicion for CDI were tested prospectively by toxin EIA, by C. difficile NAAT, and with a reference standard toxigenic culture. Following completion of laboratory testing, retrospective chart reviews were performed to stratify patients into mild and severe disease groups based on clinical criteria using a standard point-based system. One hundred forty-three patients with CDI confirmed by toxigenic culture were evaluated in this study. Among the patients with mild CDI, 49% tested positive by toxin EIA and 98% tested positive by NAAT. Among patients with severe CDI, 58% tested positive by toxin EIA and 98% tested positive by NAAT. Increased CDI disease severity was not associated with an increased sensitivity of EIA (P = 0.31). These data demonstrate that toxin EIA performs poorly both for patients with severe CDI and for those with mild CDI and support the routine use of NAAT for the diagnosis of CDI. The presence of stool toxin measured by EIA does not correlate with disease severity.
authors.affiliation: Department of Pathology & Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA. rhumphries@mednet.ucla.edu
authors.forename: Romney M
authors.initials: RM
authors.lastname: Humphries
authors.forename: Daniel Z
authors.initials: DZ
authors.lastname: Uslan
authors.forename: Zachary
authors.initials: Z
authors.lastname: Rubin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D001431:Bacteriological Techniques / Q000379:methods*; D016360:Clostridioides difficile / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D003015:Clostridium Infections / Q000175:diagnosis* / Q000382:microbiology / Q000473:pathology; D003955:Diagnostic Tests, Routine / Q000379:methods*; D003967:Diarrhea / Q000175:diagnosis / Q000382:microbiology / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques / Q000379:methods; D008297:Male; D008875:Middle Aged; D021141:Nucleic Acid Amplification Techniques / Q000379:methods*; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D014481:United States
chemical_list: D001427:Bacterial Toxins