title: Toxin B PCR cycle threshold as a predictor of poor outcome of Clostridium difficile infection: a derivation and validation cohort study.
abstract: OBJECTIVE
  Prediction of patients with poor outcome is necessary in order to plan the proper management of Clostridium difficile infection (CDI); however, clinical criteria are insufficient. In a previous study, we observed that high toxigenic C. difficile cfu stool counts at diagnosis were associated with a poor outcome. Our objective was to investigate the role of the PCR toxin B amplification cycle threshold (Ct) in the prediction of CDI poor outcome and to derive and validate a high-risk prediction rule using this marker.
  
  
  METHODS
  We prospectively included patients with CDI (derivation cohort, January 2013 to June 2014; and validation cohort, December 2014 to May 2015), who were followed for at least 2 months after their last episode/recurrence. All samples were tested with Xpert™ C. difficile.
  
  
  RESULTS
  For the derivation cohort (n = 129) toxin B Ct was independently associated with poor outcome (P < 0.001). The receiver operating characteristic (ROC) curve yielded an AUC of 0.816. Using a cut-off of <23.5 cycles for high risk of poor outcome, the diagnostic accuracy was 81.4%, the sensitivity was 46.5% (95% CI 32.5-61.1) and the specificity was 98.8% (95% CI 93.7-99.8). For the validation cohort (n = 170), the diagnostic accuracy was 81.8%, the sensitivity was 88.4% (95% CI 75.5-94.9) and the specificity was 79.5% (95% CI 71.7-85.6). The ROC curve yielded an AUC of 0.857.
  
  
  CONCLUSIONS
  Low toxin B Ct values from samples collected at the initial moment of diagnosis appears to be a strong marker for poor outcome. This available test may identify, at an early stage, patients who are at higher risk of a poor outcome CDI.
authors: Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain Medicine Department, School of Medicine, Universidad Complutense de Madrid (UCM), Madrid, Spain Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain helenrei@hotmail.com.
authors: E
authors: E
authors: Reigadas
authors: Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain CIBER de Enfermedades Respiratorias (CIBERES CB06/06/0058), Madrid, Spain.
authors: L
authors: L
authors: Alcalá
authors: Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain Medicine Department, School of Medicine, Universidad Complutense de Madrid (UCM), Madrid, Spain.
authors: M
authors: M
authors: Valerio
authors: Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain Medicine Department, School of Medicine, Universidad Complutense de Madrid (UCM), Madrid, Spain Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain CIBER de Enfermedades Respiratorias (CIBERES CB06/06/0058), Madrid, Spain.
authors: M
authors: M
authors: Marín
authors: Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
authors: A
authors: A
authors: Martin
authors: Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain Medicine Department, School of Medicine, Universidad Complutense de Madrid (UCM), Madrid, Spain Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain CIBER de Enfermedades Respiratorias (CIBERES CB06/06/0058), Madrid, Spain.
authors: E
authors: E
authors: Bouza
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001426:Bacterial Proteins / Q000032:analysis* / Q000235:genetics*; D001427:Bacterial Toxins / Q000032:analysis* / Q000235:genetics*; D016360:Clostridioides difficile / Q000235:genetics*; D003015:Clostridium Infections / Q000175:diagnosis*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods*; D011379:Prognosis; D011446:Prospective Studies; D012372:ROC Curve; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; C031815:toxB protein, Clostridium difficile