Impact of clinical symptoms on interpretation of diagnostic assays for Clostridium difficile infections.

Asymptomatic Clostridium difficile colonization is common in hospitalized patients. Existing C. difficile assay comparisons lack data on severity of diarrhea or patient outcomes, limiting the ability to interpret their results in regard to the diagnosis of C. difficile infection (CDI). The objective of this study was to measure how including patient presentation with the C. difficile assay result impacted assay performance to diagnose CDI. Stool specimens from 150 patients that met inclusion and exclusion criteria were selected. Nine methods to detect C. difficile in stool were evaluated. All patients were interviewed prospectively to assess diarrhea severity. We then assessed how different reference standards, with and without the inclusion of patient presentation, impact the sensitivity, specificity, and positive and negative predictive values of the assays to diagnose CDI. There were minimal changes in sensitivity; however, specificity was significantly lower for the assays Tox A/B II, C. diff Chek-60, BD GeneOhm Cdiff, Xpert C. difficile, and Illumigene C. difficile and for toxigenic culture (P was <0.01 for all except Tox A/B II from fresh stool, for which the P value was 0.016) when the reference standard was recovery of toxigenic C. difficile from stool plus the presence of clinically significant diarrhea compared to when the reference standard was having at least four assays positive while ignoring diarrhea severity. There were 15 patients whose assay result was reported as negative but subsequently found to be positive by at least four assays in the comparison. None suffered from any CDI-related adverse events. In conclusion, clinical presentation is important when interpreting C. difficile diagnostic assays.

A Clostridium difficile infection "intervention": change in toxin assay results in fewer C difficile infection cases without changes in patient outcomes.

BACKGROUND: Clostridium difficile infection (CDI) is most commonly diagnosed using toxin enzyme immunoassays (EIAs). A sudden decrease in CDI incidence was noted after a change in the EIA used at Barnes-Jewish Hospital in St Louis. The objective of this study was to determine whether the decreased CDI incidence related to the change in EIA resulted in adverse patient outcomes. METHODS: Electronic hospital databases were used to collect data on demographics, outcomes, and treatment of inpatients who had a C difficile toxin assay performed between January 4, 2009, and April 3, 2009 (period A, preassay change) and between May 21, 2009, and August 17, 2009 (period B, postassay change). RESULTS: Assays were positive in 240 of 1,221 patients (19.7%) during period A and in 106 of 1160 patients (9.1%) during period B (P < .01). There was no difference in mortality or discharge to hospice between the 2 periods (10.3% vs 10.1%; P = .90). Patients tested in period B were less likely to receive metronidazole or oral vancomycin (P < .01). CONCLUSIONS: The new EIA resulted in fewer positive tests and reduced anti-CDI therapy. There was no difference in mortality between the 2 periods, suggesting that the decreased incidence was due to increased assay specificity, not decreased sensitivity.

Identification of a pseudo-outbreak of Clostridium difficile infection (CDI) and the effect of repeated testing, sensitivity, and specificity on perceived prevalence of CDI.

OBJECTIVE: To describe a pseudo-outbreak of Clostridium difficile infection (CDI) caused by a faulty toxin assay lot and to determine the effect of sensitivity, specificity, and repeated testing for C. difficile on perceived CDI burden, positive predictive value, and false-positive results. DESIGN: Outbreak investigation and criterion standard. PATIENTS: Patients hospitalized at a tertiary care hospital who had at least 1 toxin assay for detection of C. difficile performed during the period from July 1, 2004, through June 30, 2006. METHODS: The run control chart method and the chi(2) test were used to compare CDI rates and the proportion of positive test results before, during, and after the pseudo-outbreak. The effect of repeated testing was evaluated by using 3 hypothetical models with a sample of 10,000 patients and various assay sensitivity and specificity estimates. RESULTS: In November of 2005, the CDI rate at the hospital increased from 1.5 to 2.6 cases per 1,000 patient-days (P < .01), and the proportion of positive test results increased from 13.6% to 22.1% (P < .01). An investigation revealed a pseudo-outbreak caused by a faulty toxin assay lot. A decrease of only 1.2% in the specificity of the toxin assay would result in a 32% increase in perceived incidence of CDI at this institution. When calculated by use of the manufacturer's stated specificity and sensitivity and this institution's testing practices, the positive predictive value of the test decreased from 80.6% to 4.1% for patients who received 3 tests. CONCLUSION: Specificity is as important as sensitivity when testing for CDI. False-positive CDI cases can drain hospital resources and adversely affect patients. Repeated testing for C. difficile should be performed with caution.