title: Clostridium difficile rates in asymptomatic and symptomatic hospitalized patients using nucleic acid testing.
abstract: BACKGROUND
  The Clostridium difficile rate in symptomatic patients represents both those with C. difficile infection (CDI) and those with colonization. To predict the extent of CDI overdiagnosis, we compared the asymptomatic colonization rate to the symptomatic positivity rate in hospitalized patients using nucleic acid testing.
  
  
  METHODS
  Between July 2014 and April 2015, formed stool samples were collected from asymptomatic patients after admission to 3 hospital wards at the Stanford Hospital. Stool samples from symptomatic patients with suspected CDI in the same wards were collected for testing per provider order. The GeneXpert C. difficile tcdB polymerase chain reaction (PCR) assay (Cepheid, Sunnyvale, CA, USA) was performed on all stool samples and PCR cycle threshold was used as a measure of genomic equivalents. Chart review was performed to obtain clinical history and medication exposure.
  
  
  RESULTS
  We found an asymptomatic C. difficile carriage rate of 11.8% (43/365) (95% confidence interval [CI], 8.5-15.1%) and a positivity rate in symptomatic patients of 15.4% (54/351) (95% CI, 11.6-19.2%; P=0.19). The median PCR cycle thresholds was not significantly different between asymptomatic carriers and symptomatic positives (29.5 versus 27.3; P=0.07). Among asymptomatic patients, 11.6% (5/43) of carriers and 8.4% (27/322; P=0.56) of noncarriers subsequently became symptomatic CDI suspects within the same hospitalization. Single and multivariate analysis did not identify any demographic or clinical factors as being significantly associated with C. difficile carriage.
  
  
  CONCLUSIONS
  Asymptomatic C. difficile carriage rate was similar to symptomatic positivity rate. This suggests the majority of PCR-positive results in symptomatic patients are likely due to C. difficile colonization. Disease-specific biomarkers are needed to accurately diagnose patients with C. difficile disease.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Truong
authors.affiliation: Department of Pathology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
authors.forename: Lee F
authors.initials: LF
authors.lastname: Schroeder
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Gaur
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Victoria Emma
authors.initials: VE
authors.lastname: Anikst
authors.affiliation: Patient Care Services, Stanford Health Care, Stanford, CA 94305, USA.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Komo
authors.affiliation: Patient Care Services, Stanford Health Care, Stanford, CA 94305, USA.
authors.forename: Colleen
authors.initials: C
authors.lastname: Watters
authors.affiliation: Patient Care Services, Stanford Health Care, Stanford, CA 94305, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: McCalley
authors.affiliation: Patient Care Services, Stanford Health Care, Stanford, CA 94305, USA.
authors.forename: Carole
authors.initials: C
authors.lastname: Kulik
authors.affiliation: Patient Care Services, Stanford Health Care, Stanford, CA 94305, USA.
authors.forename: David
authors.initials: D
authors.lastname: Pickham
authors.affiliation: Patient Care Services, Stanford Health Care, Stanford, CA 94305, USA.
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Lee
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Clinical Microbiology Laboratory, Stanford Health Care, Stanford, CA 94305, USA. Electronic address: nbanaei@stanford.edu.
authors.forename: Niaz
authors.initials: N
authors.lastname: Banaei
mesh_terms: D000368:Aged; D058345:Asymptomatic Infections; D002353:Carrier State / Q000382:microbiology; D016360:Clostridioides difficile / Q000235:genetics* / Q000302:isolation & purification*; D003015:Clostridium Infections / Q000382:microbiology*; D003428:Cross Infection / Q000382:microbiology*; D004761:Enterocolitis, Pseudomembranous / Q000382:microbiology; D005260:Female; D006760:Hospitalization; D006761:Hospitals; D006801:Humans; D008297:Male; D008875:Middle Aged; D009696:Nucleic Acids / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D012307:Risk Factors
chemical_list: D009696:Nucleic Acids
keywords: Asymptomatic; C. difficile; Carriage; Colonization; Infection