951. Toxin Gene Nucleic Acid Amplification Test Cycle Threshold Result is Associated with Severity of C. difficile Infection and Poor Patient Outcomes
Session: Poster Abstract Session: Clostridium difficile Infections: Epidemiology and Diagnostics
Friday, October 9, 2015
Room: Poster Hall
  • poster for ID week 2015 1.3 250915.pdf (368.2 kB)
  • Background:

    Qualitative results of C. difficile toxin gene nucleic acid amplification tests (tgNAATs ) have poor positive predictive value for CDI. We aimed to determine if a low tgNAAT cycle threshold (CT) result can predict severity of CDI and/or mortality in a large-scale multicentre study.


    Prospective faecal samples (Oct 2010-Sep 2011) at 4 UK hospitals were tested for the presence of C. difficile (cytotoxigenic culture, CC), toxins (cell cytotoxicity, CCTA) or DNA (tgNAAT, Cepheid). CDI severity markers (WCC, serum creatinine (Cr), serum albumin (Alb), & ribotype) and outcomes (30-day mortality, length of stay (LOS)) were determined and associations with low tgNAAT CT (<25) explored.


    There were 8853 samples from 7335 patients, 1281 (14.5%) of which were tgNAAT positive. Of these, 713 (55.7%) were CCTA positive and 971 (75.8%) CC positive. Median tgNAAT CT value of those patients who died was 25.5 vs 27.5 for those who survived (p=0.021); 436 (34%) tgNAAT positive samples had a CT<25. AUROC for death in those with tgNAAT CT<25 was 0.490 (95% CI 0.412-0.569).  By univariate analysis, CT<25 was significantly associated with stool toxin positivity (p <0.001) and presence of ribotype 027 (overall prevalence 11%) (16.9% vs 10.6%, p=0.025).

    A tgNAAT CT<25 was also associated with higher mean Cr (mean 92.4 vs 82.9mg/dL, p=0.54), lower mean Alb (mean 19.8 vs 21.0g/L, p = 0.257) and longer LOS (median 28 vs 23 days, p=0.772), but these were not significant. A tgNAAT CT <25 was not associated with a raised WCC.

    Mortality was significantly higher in CDIs with tgNAAT CT<25 (17.4% vs 12.0%, p=0.039) and was even higher for those with CT<25 and ribotype 027 vs non-027 ribotype (50% vs 18.6%, p=0.027).  The relative risk of mortality in CDIs with CT<25 was 1.45, this increased to 2.18 in those cases that were due to ribotype 027. Median LOS was significantly increased for CDIs with CT<25 and ribotype 027 vs non-027 (32.5 vs 28 days, p=0.018).


    Low CT results for tgNAAT are significantly associated with stool toxin positivity, mortality and presence of C. difficile ribotype 027. A CT of <25 could therefore guide treatment and patient management decisions in the most at risk patients.

    Kerrie Davies, MSc1, Timothy Planche, MD2, Nan Shetty, MD3, Mike Wren, PhD3, Derrick Crook, Professor4 and Mark Wilcox, MD1, (1)Microbiology, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom, (2)St George's Healthcare NHS Trust, London, United Kingdom, (3)University College London Hospitals, London, United Kingdom, (4)National Institute for Health Research Oxford Biomedical Research Centre, Oxford, United Kingdom


    K. Davies, None

    T. Planche, Cepheid: Independent Contractor , Speaker honorarium

    N. Shetty, None

    M. Wren, None

    D. Crook, None

    M. Wilcox, None

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