title: Clostridium difficile ribotype 027: relationship to age, detectability of toxins A or B in stool with rapid testing, severe infection, and mortality.
abstract: BACKGROUND
  Clostridium difficile infection (CDI) can cause severe disease and death, especially in older adults. A better understanding of risk factors for adverse outcomes is needed. This study tests the hypotheses that infection with specific ribotypes and presence of stool toxins independently associate with severity and constructs predictive models of adverse outcomes.
  
  
  METHODS
  Cases of non-recurrent CDI were prospectively included after positive stool tests for toxins A and/or B by enzyme immunoassay (EIA) or tcdB by polymerase chain reaction. Outcomes included severe CDI (intensive care unit admission, colectomy, or death attributable to CDI within 30 days of diagnosis) and 30-day all-cause mortality. Adjusted models were developed to test hypotheses and predict outcomes.
  
  
  RESULTS
  In total, 1144 cases were included. The toxin EIA was positive in 37.2% and 35.6% of patients were of age >65 years. One of the 137 unique ribotypes was ribotype 027 (16.2%). Detectable stool toxin did not associate with outcomes. Adjusting for covariates, including age, Ribotype 027 was a significant predictor of severe CDI (90 cases; odds ratio [OR], 1.73; 95% confidence interval [CI], 1.03-2.89; P = .037) and mortality (89 cases; OR, 2.02; 95% CI, 1.19-3.43; P = .009). Concurrent antibiotic use associated with both outcomes. Both multivariable predictive models had excellent performance (area under the curve >0.8).
  
  
  CONCLUSIONS
  Detection of stool toxin A and/or B by EIA does not predict severe CDI or mortality. Infection with ribotype 027 independently predicts severe CDI and mortality. Use of concurrent antibiotics is a potentially modifiable risk factor for severe CDI.
authors.affiliation: Division of Infectious Diseases Department of Internal Medicine Division of Infectious Diseases, Veterans Affairs Ann Arbor Healthcare System, Michigan.
authors.forename: Krishna
authors.initials: K
authors.lastname: Rao
authors.affiliation: Department of Internal Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago, Illinois.
authors.forename: Dejan
authors.initials: D
authors.lastname: Micic
authors.affiliation: Department of Internal Medicine.
authors.forename: Mukil
authors.initials: M
authors.lastname: Natarajan
authors.affiliation: Department of Internal Medicine.
authors.forename: Spencer
authors.initials: S
authors.lastname: Winters
authors.affiliation: Department of Clinical Pathology.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Kiel
authors.affiliation: Department of Microbiology and Immunology, Montana State University, Bozeman.
authors.forename: Seth T
authors.initials: ST
authors.lastname: Walk
authors.affiliation: Division of Infectious Diseases Department of Internal Medicine.
authors.forename: Kavitha
authors.initials: K
authors.lastname: Santhosh
authors.affiliation: Division of Infectious Diseases Department of Internal Medicine.
authors.forename: Jill A
authors.initials: JA
authors.lastname: Mogle
authors.affiliation: Division of Geriatric Medicine Department of Biostatistics, University of Michigan School of Medicine, Ann Arbor.
authors.forename: Andrzej T
authors.initials: AT
authors.lastname: Galecki
authors.affiliation: Department of Clinical Pathology.
authors.forename: William
authors.initials: W
authors.lastname: LeBar
authors.affiliation: Division of Gastroenterology Department of Internal Medicine.
authors.forename: Peter D R
authors.initials: PD
authors.lastname: Higgins
authors.affiliation: Division of Infectious Diseases Department of Internal Medicine Department of Microbiology and Immunology.
authors.forename: Vincent B
authors.initials: VB
authors.lastname: Young
authors.affiliation: Division of Infectious Diseases Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: David M
authors.initials: DM
authors.lastname: Aronoff
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001905:Botulinum Toxins / Q000302:isolation & purification*; D016360:Clostridioides difficile / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity*; D004761:Enterocolitis, Pseudomembranous / Q000175:diagnosis* / Q000382:microbiology / Q000401:mortality*; D005243:Feces / Q000382:microbiology*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D012372:ROC Curve; D021521:Ribotyping; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D001905:Botulinum Toxins
keywords: Clostridium difficile infection; colitis; ribotype; risk prediction models
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