title: Clostridium difficile testing algorithms using glutamate dehydrogenase antigen and C. difficile toxin enzyme immunoassays with C. difficile nucleic acid amplification testing increase diagnostic yield in a tertiary pediatric population.
abstract: We evaluated the performance of the rapid C. diff Quik Chek Complete's glutamate dehydrogenase antigen (GDH) and toxin A/B (CDT) tests in two algorithmic approaches for a tertiary pediatric population: algorithm 1 entailed initial testing with GDH/CDT followed by loop-mediated isothermal amplification (LAMP), and algorithm 2 entailed GDH/CDT followed by cytotoxicity neutralization assay (CCNA) for adjudication of discrepant GDH-positive/CDT-negative results. A true positive (TP) was defined as positivity by CCNA or positivity by LAMP plus another test (GDH, CDT, or the Premier C. difficile toxin A and B enzyme immunoassay [P-EIA]). A total of 141 specimens from 141 patients yielded 27 TPs and 19% prevalence. Sensitivity, specificity, positive predictive value, and negative predictive value were 56%, 100%, 100%, and 90% for P-EIA and 81%, 100%, 100%, and 96% for both algorithm 1 and algorithm 2. In summary, GDH-based algorithms detected C. difficile infections with superior sensitivity compared to P-EIA. The algorithms allowed immediate reporting of half of all TPs, but LAMP or CCNA was required to confirm the presence or absence of toxigenic C. difficile in GDH-positive/CDT-negative specimens.
authors.affiliation: The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. otak@email.chop.edu
authors.forename: Kaede V
authors.initials: KV
authors.lastname: Ota
authors.forename: Karin L
authors.initials: KL
authors.lastname: McGowan
mesh_terms: D000293:Adolescent; D001426:Bacterial Proteins / Q000378:metabolism*; D001427:Bacterial Toxins / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D016360:Clostridioides difficile / Q000201:enzymology* / Q000235:genetics; D004761:Enterocolitis, Pseudomembranous / Q000175:diagnosis*; D005243:Feces / Q000201:enzymology / Q000382:microbiology; D005798:Genes, Bacterial; D005969:Glutamate Dehydrogenase / Q000378:metabolism*; D006801:Humans; D007223:Infant; D025202:Molecular Diagnostic Techniques; D021141:Nucleic Acid Amplification Techniques; D012680:Sensitivity and Specificity
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D005969:Glutamate Dehydrogenase