Diagnosis of Clostridium difficile-associated disease: examination of multiple algorithms using toxin EIA, glutamate dehydrogenase EIA and loop-mediated isothermal amplification.
The laboratory diagnosis of Clostridium difficile infection (CDI) needs to be accurate and timely to ensure optimal patient management, infection control and reliable surveillance. Three methods are evaluated using 810 consecutive stool samples against toxigenic culture: CDT TOX A/B Premier enzyme immunoassay (EIA) kit (Meridian Bioscience, Europe), Premier EIA for C. difficile glutamate dehydrogenase (GDH) (Meridian Bioscience, Europe) and the Illumigene kit (Meridian Bioscience, Europe), both individually and within combined testing algorithms. The study revealed that the CDT TOX A/B Premier EIA gave rise to false-positive and false-negative results and demonstrated poor sensitivity (56.47%), compared to Premier EIA for C. difficile GDH (97.65%), suggesting this GDH EIA can be a useful negative screening method. Results for the Illumigene assay alone showed sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of 91.57%, 98.07%, 99.03% and 84.44%, respectively. A two-stage algorithm using Premier EIA for C. difficile GDH/Illumigene assay yielded superior results compared with other testing algorithms (91.57%, 98.07%, 99.03% and 84.44%, respectively), mirroring the Illumigene performance. However, Illumigene is approximately half the cost of current polymerase chain reaction (PCR) methods, has a rapid turnaround time and requires no specialised skill base, making it an attractive alternative to assays such as the Xpert C. difficile assay (Cepheid, Sunnyvale, CA). A three-stage algorithm offered no improvement and would hamper workflow.
Medical Microbiology, Wirral University Teaching Hospitals, Clatterbridge Hospital, Bebington, Wirral, UK.
A I
AI
Bamber
K
K
Fitzsimmons
J G
JG
Cunniffe
C C
CC
Beasor
C A
CA
Mackintosh
G
G
Hobbs
D000465:Algorithms; D001426:Bacterial Proteins / Q000032:analysis / Q000235:genetics / Q000633:toxicity; D001427:Bacterial Toxins / Q000032:analysis / Q000235:genetics / Q000633:toxicity; D001431:Bacteriological Techniques / Q000379:methods*; D018929:Cell Culture Techniques; D016360:Clostridioides difficile / Q000235:genetics / Q000302:isolation & purification*; D003015:Clostridium Infections / Q000175:diagnosis* / Q000382:microbiology*; D004768:Enterotoxins / Q000032:analysis / Q000235:genetics / Q000633:toxicity; D005243:Feces / Q000382:microbiology; D005969:Glutamate Dehydrogenase / Q000032:analysis*; D006801:Humans; D007124:Immunoenzyme Techniques / Q000379:methods; D009500:Neutralization Tests; D016133:Polymerase Chain Reaction / Q000379:methods; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004768:Enterotoxins; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile; D005969:Glutamate Dehydrogenase