title: Impact of strain type on detection of toxigenic Clostridium difficile: comparison of molecular diagnostic and enzyme immunoassay approaches.
abstract: A multicenter clinical trial assessed the performance of the Cepheid Xpert C. difficile assay on stool specimens collected from patients suspected of having Clostridium difficile infection (CDI). A total of 2,296 unformed stool specimens, collected from seven study sites, were tested by Xpert C. difficile enrichment culture followed by cell culture cytotoxicity testing of the isolates (i.e., toxigenic culture with enrichment) and the study sites' standard C. difficile test methods. The methods included enzyme immunoassay (EIA), direct cytotoxin testing, and two- and three-step algorithms using glutamate dehydrogenase (GDH) screening followed by either EIA or EIA and an in-house PCR assay. All C. difficile strains were typed by PCR-ribotyping. Compared to results for toxigenic culture with enrichment, the sensitivity, specificity, and positive and negative predictive values of the Xpert assay were 93.5, 94.0, 73.0, and 98.8%, respectively. The overall sensitivity of the EIAs compared to that of enrichment culture was 60.0%, and the sensitivity of combined GDH algorithms was 72.9%; both were significantly lower than that of Xpert C. difficile (P < 0.001 and P = 0.03, respectively). The sensitivity of the EIA was significantly lower than that of the Xpert C. difficile assay for detection of ribotypes 002, 027, and 106 (P < 0.0001, P < 0.0001, and P = 0.004, respectively, Fisher's exact test), and the sensitivity of GDH algorithms for ribotypes other than 027 was lower than that for Xpert C. difficile (P < 0.001). The Xpert C. difficile assay is a simple, rapid, and accurate method for detection of toxigenic C. difficile in unformed stool specimens and is minimally affected by strain type compared to EIA and GDH-based methods.
authors: Cepheid, 904 Caribbean Drive, Sunnyvale, CA 98089, USA. fred.tenover@cepheid.com
authors: Fred C
authors: FC
authors: Tenover
authors: Susan
authors: S
authors: Novak-Weekley
authors: Christopher W
authors: CW
authors: Woods
authors: Lance R
authors: LR
authors: Peterson
authors: Thomas
authors: T
authors: Davis
authors: Paul
authors: P
authors: Schreckenberger
authors: Ferric C
authors: FC
authors: Fang
authors: Andre
authors: A
authors: Dascal
authors: Dale N
authors: DN
authors: Gerding
authors: Jim H
authors: JH
authors: Nomura
authors: Richard V
authors: RV
authors: Goering
authors: Thomas
authors: T
authors: Akerlund
authors: Alice S
authors: AS
authors: Weissfeld
authors: Ellen Jo
authors: EJ
authors: Baron
authors: Edith
authors: E
authors: Wong
authors: Elizabeth M
authors: EM
authors: Marlowe
authors: Joseph
authors: J
authors: Whitmore
authors: David H
authors: DH
authors: Persing
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015373:Bacterial Typing Techniques / Q000379:methods; D001431:Bacteriological Techniques / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D016360:Clostridioides difficile / Q000302:isolation & purification*; D003015:Clostridium Infections / Q000175:diagnosis*; D005243:Feces / Q000382:microbiology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques / Q000379:methods; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D021521:Ribotyping / Q000379:methods; D012680:Sensitivity and Specificity; D018675:Toxicity Tests / Q000379:methods; D055815:Young Adult