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.
N. Shetty, None
M. Wren, None
D. Crook, None
M. Wilcox, None
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