Clinical relevance of a positive molecular test in the diagnosis of Clostridium difficile infection

Background: In 2011, the Department of Health advised that a two-stage test approach should be used to improve accuracy of Clostridium difficile infection (CDI) diagnosis. No specific test protocol was established at that time. Aim: To compare clinical features of inpatient CDI cases identified by toxin enzyme immunoassay (EIA) with those identified as polymerase chain reaction (PCR) positive but toxin EIA negative. Methods: During a six-month period (2011-2012), 2181 liquid faeces samples submitted to North Bristol NHS Trust were tested by EIA for both toxin and glutamate dehydrogenase (GDH). A total of 215 toxin or GDH EIA-positive samples were tested by Cepheid Xpert PCR assay; 128 clinically evaluable inpatients were grouped by test result, and their duration of diarrhoea and 14-day mortality compared. Findings: Inpatients with a positive PCR but negative toxin EIA had a significantly lower 14-day all-cause mortality [11%; 95% confidence interval (CI): 4-23%] than patients with a positive PCR and positive toxin EIA test (37%; 95% CI: 19-59%; P = 0.01), and a smaller proportion of patients had prolonged diarrhoea (>5 days or unresolved at death: 19%; CI: 9-32%, vs 67%; CI: 45-84%; P < 0.001). A positive toxin EIA test was a significant independent predictor of death [odds ratio (OR): 4.7, 95% CI: 1.4-15.4; P = 0.01] and prolonged diarrhoea (OR: 8.6; CI: 2.9-25.6; P < 0.001), but a positive PCR (given positive GDH EIA) was not. Conclusion: The clinical significance of a positive PCR result without a positive toxin EIA is questionable; such a result is associated with a significantly lower mortality and shorter duration of symptoms than patients with a positive toxin EIA. (c) 2013 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.