title: Real-time polymerase chain reaction correlates well with clinical diagnosis of Clostridium difficile infection.
abstract: OBJECTIVE
  To determine the clinical utility of a rapid molecular assay for Clostridium difficile infection (CDI) in an acute hospital setting.
  
  
  METHODS
  From March to September 2011, stool specimens from inpatients in two acute hospitals with suspected CDI were tested prospectively by routine cell culture cytotoxin neutralization assay (CCNA), real-time polymerase chain reaction (PCR) using the GeneXpert (Cepheid Inc., Sunnyvale, CA, USA), and a dual testing algorithm [glutamate dehydrogenase (GDH)/toxin enzyme immuno-assay, Premier, Launch Diagnostics, Longfield, UK]. All patients with positive PCR, CCNA or discrepant results were reviewed by a multi-disciplinary team (treating clinician, gastroenterologist, microbiologist and infection control nurse).
  
  
  RESULTS
  C. difficile detection rates were 11.7% (PCR), 6% (CCNA) and 13.8% (GDH). Out of 1034 stool specimens included in the study, 974 (94.1%) had concordant CCNA and PCR results. Eighty-nine percent (886/985) had concordant CCNA, PCR and GDH results, and 94.4% (930/985) had concordant GDH and PCR results. Using clinical diagnosis as the reference, PCR had sensitivity of 99.1%, specificity of 98.9%, positive predictive value (PPV) of 91.9% and negative predictive value (NPV) of 99.9%. CCNA on a single sample had sensitivity of 51%, specificity of 99.4%, PPV of 91.9% and NPV of 94.3%. GDH had sensitivity of 83.8%, specificity of 94.5%, PPV of 64.7% and NPV of 97.9%. Almost twice as many patients were positive by PCR compared with CCNA (121 vs 62); 54/59 of those with discrepant results were clinically confirmed as CDI.
  
  
  CONCLUSIONS
  Rapid diagnosis of CDI using PCR was timely, accurate and correlated well with clinical diagnosis.
authors.affiliation: Public Health Wales Microbiology Abertawe Bro Morgannwg, Singleton Hospital, Swansea, UK. Electronic address: nidhika.berry@wales.nhs.uk.
authors.forename: N
authors.initials: N
authors.lastname: Berry
authors.affiliation: College of Human and Health Science, Swansea University, Swansea, UK.
authors.forename: B
authors.initials: B
authors.lastname: Sewell
authors.affiliation: Gastroenterology Department, Singleton Hospital, Swansea, UK.
authors.forename: S
authors.initials: S
authors.lastname: Jafri
authors.affiliation: Gastroenterology Department, Singleton Hospital, Swansea, UK.
authors.forename: C
authors.initials: C
authors.lastname: Puli
authors.affiliation: Public Health Wales Microbiology Abertawe Bro Morgannwg, Singleton Hospital, Swansea, UK.
authors.forename: S
authors.initials: S
authors.lastname: Vagia
authors.affiliation: Public Health Wales Microbiology Abertawe Bro Morgannwg, Singleton Hospital, Swansea, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: Lewis
authors.affiliation: Infection Control, Morriston Hospital, Abertawe Bro Morgannwg University Health Board, Swansea, UK.
authors.forename: D
authors.initials: D
authors.lastname: Davies
authors.affiliation: Public Health Wales Microbiology Abertawe Bro Morgannwg, Singleton Hospital, Swansea, UK.
authors.forename: E
authors.initials: E
authors.lastname: Rees
authors.affiliation: Gastroenterology Department, Singleton Hospital, Swansea, UK.
authors.forename: C L
authors.initials: CL
authors.lastname: Ch'ng
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016360:Clostridioides difficile / Q000302:isolation & purification; D003015:Clostridium Infections / Q000175:diagnosis* / Q000382:microbiology; D003967:Diarrhea / Q000175:diagnosis* / Q000382:microbiology; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods*; D012680:Sensitivity and Specificity; D006113:United Kingdom; D055815:Young Adult
keywords: Cell culture cytotoxin neutralization assay; Clinical diagnosis; Clostridium difficile; Glutamate dehydrogenase; Polymerase chain reaction; Toxin enzyme immuno-assay