Real-Time Polymerase Chain Reaction Detection of Asymptomatic Clostridium difficile Colonization and Rising C. difficile–Associated Disease Rates

Objective. To evaluate the accuracy of real-time polymerase chain reaction (PCR) for Clostridium difficile–associated disease (CDAD) detection, after hospital CDAD rates significantly increased following real-time PCR initiation for CDAD diagnosis. Design. Hospital-wide surveillance study following examination of CDAD incidence density rates by interrupted time series design. Setting. Large university-based hospital. Participants. Hospitalized adult patients. Methods. CDAD rates were compared before and after real-time PCR implementation in a university hospital and in the absence of physician and infection control practice changes. After real-time PCR introduction, all hospitalized adult patients were screened for C. difficile by testing a fecal specimen by real-time PCR, toxin enzyme-linked immunosorbent assay, and toxigenic culture. Results. CDAD hospital rates significantly increased after changing from cell culture cytotoxicity assay to a real-time PCR assay. One hundred ninety-nine hospitalized subjects were enrolled, and 101 fecal specimens were collected. C. difficile was detected in 18 subjects (18%), including 5 subjects (28%) with either definite or probable CDAD and 13 patients (72%) with asymptomatic C. difficile colonization. Conclusions. The majority of healthcare-associated diarrhea is not attributable to CDAD, and the prevalence of asymptomatic C. difficile colonization exceeds CDAD rates in healthcare facilities. PCR detection of asymptomatic C. difficile colonization among patients with non-CDAD diarrhea may be contributing to rising CDAD rates and a significant number of CDAD false positives. PCR may be useful for CDAD screening, but further study is needed to guide interpretation of PCR detection of C. difficile and the value of confirmatory tests. A gold standard CDAD diagnostic assay is needed.