title: Superiority of the DNA amplification assay for the diagnosis of C. difficile infection: a clinical comparison of fecal tests.
abstract: BACKGROUND
  Clostridium difficile infection (CDI) is a major infectious concern, accounting for substantial morbidity and resource utilization. Advances in microbiological and molecular techniques have resulted in an increasing number of testing options for CDI. A glutamate dehydrogenase (GDH) enzyme immunoassay (EIA) and a DNA amplification (DNA-A) test for the diagnosis of CDI have recently become commercially available.
  
  
  OBJECTIVE
  The aim of this prospective study was to compare the test performance characteristics of the traditional diagnostic modality for CDI diagnosis, the toxin A/B (TOX) EIA, with those of the GDH EIA and DNA-A test, utilizing enriched toxigenic culture (TGC) as the gold standard. Clinical variables predictive of CDI were also studied.
  
  
  METHODS
  Participants fulfilled one or more criteria placing them at increased risk for CDI. Each stool sample was tested by each of the methods mentioned above. Clinical data parameters were collected via a 12-month review of the electronic medical record prior to the index date of the first stool test.
  
  
  RESULTS
  A total of 272 stool samples from 144 admissions of 139 patients were evaluated for CDI. The sensitivity and positive predictive value (PPV) of the TOX EIA were 86.1 and 58.4 %, respectively, whereas the sensitivity and PPV of the GDH EIA and DNA-A test were 100 %. 1.8 % of the GDH tests yielded inconclusive results. Using TGC as the gold standard, nosocomial exposure with emphasis on nursing home residence, history of previous CDI, and female gender were predictive of CDI.
  
  
  CONCLUSIONS
  Test performance characteristics of the DNA-A test and GDH EIA were superior to those of the traditional TOX EIA. The GDH test is limited by inconclusive test results and requires a multi-step diagnostic algorithm. Therefore, the DNA-A test should be implemented as the diagnostic method of choice for CDI. CDI clinical predictors are important for diagnostic decision-making.
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine, P.O. Box 016960 (D49), Miami, FL 33101-6960, USA. jabarkin@med.miami.edu
authors.forename: Jodie A
authors.initials: JA
authors.lastname: Barkin
authors.forename: Neilanjan
authors.initials: N
authors.lastname: Nandi
authors.forename: Nancimae
authors.initials: N
authors.lastname: Miller
authors.forename: Alexandra
authors.initials: A
authors.lastname: Grace
authors.forename: Jamie S
authors.initials: JS
authors.lastname: Barkin
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Sussman
mesh_terms: D000368:Aged; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism; D016360:Clostridioides difficile / Q000235:genetics / Q000302:isolation & purification*; D003015:Clostridium Infections / Q000175:diagnosis* / Q000382:microbiology; D004269:DNA, Bacterial / Q000235:genetics / Q000302:isolation & purification*; D003967:Diarrhea / Q000382:microbiology; D004768:Enterotoxins / Q000235:genetics / Q000378:metabolism; D005243:Feces / Q000382:microbiology*; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D005969:Glutamate Dehydrogenase; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D021141:Nucleic Acid Amplification Techniques / Q000379:methods* / Q000592:standards; D011446:Prospective Studies; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004269:DNA, Bacterial; D004768:Enterotoxins; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile; D005969:Glutamate Dehydrogenase