title: The Role of Glutamate Dehydrogenase (GDH) Testing Assay in the Diagnosis of Clostridium difficile Infections: A High Sensitive Screening Test and an Essential Step in the Proposed Laboratory Diagnosis Workflow for Developing Countries like China.
abstract: The incidence and severity of Clostridium difficile infection (CDI) in North America and Europe has increased significantly since the 2000s. However, CDI is not widely recognized in China and other developing countries due to limited laboratory diagnostic capacity and low awareness. Most published studies on laboratory workflows for CDI diagnosis are from developed countries, and thus may not be suitable for most developing countries. Therefore, an alternative strategy for developing countries is needed. In this study, we evaluated the performance of the Glutamate Dehydrogenase (GDH) test and its associated workflow on 416 fecal specimens from suspected CDI cases. The assay exhibited excellent sensitivity (100.0%) and specificity (92.8%), compared to culture based method, and thus could be a good screening marker for C. difficile but not for indication of toxin production. The VIDAS CDAB assay, which can detect toxin A/B directly from fecal specimens, showed good specificity (99.7%) and positive predictive value (97.2%), but low sensitivity (45.0%) and negative predictive value (88.3%), compared with PCR-based toxin gene detection. Therefore, we propose a practical and efficient GDH test based workflow strategy for the laboratory diagnosis of CDI in developing countries like China. By applying this new workflow, the CDI laboratory diagnosis rate was notably improved in our center, yet the increasing cost was kept at a minimum level. Furthermore, to gain some insights into the genetic population structure of C. difficile isolates from our hospital, we performed MLST and PCR toxin gene typing.
authors.affiliation: Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.|Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Jing-Wei
authors.initials: JW
authors.lastname: Cheng
authors.affiliation: Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Xiao
authors.affiliation: Centre for Infectious Diseases and Microbiology Laboratory Services, ICPMR-Pathology West, Westmead Hospital, University of Sydney, Darcy Road, Westmead, New South Wales, Australia.|The Charles Sturt University, Leeds Parade, Orange, New South Wales, Australia.
authors.forename: Timothy
authors.initials: T
authors.lastname: Kudinha
authors.affiliation: Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Zhi-Peng
authors.initials: ZP
authors.lastname: Xu
authors.affiliation: Teaching and Research Section of Clinical Laboratory, School of Public Health, Taishan Medical School, Taian, Shandong, China.
authors.forename: Lin-Ying
authors.initials: LY
authors.lastname: Sun
authors.affiliation: Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.|Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Hou
authors.affiliation: Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.|Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Fan
authors.affiliation: Centre for Infectious Diseases and Microbiology Laboratory Services, ICPMR-Pathology West, Westmead Hospital, University of Sydney, Darcy Road, Westmead, New South Wales, Australia.
authors.forename: Fanrong
authors.initials: F
authors.lastname: Kong
authors.affiliation: Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Ying-Chun
authors.initials: YC
authors.lastname: Xu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001426:Bacterial Proteins / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D001427:Bacterial Toxins / Q000032:analysis* / Q000096:biosynthesis; D015373:Bacterial Typing Techniques / Q000379:methods* / Q000592:standards; D001681:Biological Assay; D002648:Child; D002675:Child, Preschool; D002681:China; D016360:Clostridioides difficile / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D003906:Developing Countries; D004761:Enterocolitis, Pseudomembranous / Q000175:diagnosis* / Q000382:microbiology; D005243:Feces / Q000382:microbiology; D005260:Female; D005969:Glutamate Dehydrogenase / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D058885:Multilocus Sequence Typing; D016133:Polymerase Chain Reaction; D012680:Sensitivity and Specificity
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D005969:Glutamate Dehydrogenase