Clinical Symptoms and Risk Factors To Refine Performance Characteristics of Laboratory Assays for Clostridium difficile Infections

Current laboratory diagnostic assays for Clostridium difficile infection (CDI) vary in their performance characteristics, timeliness, and cost. The gold standard diagnostic assay, toxigenic culture, has a turnaround time of 4-7 days which makes it impractical for routine clinical use. Furthermore, There is no widely accepted standard for the laboratory diagnosis of CDI, and a variety of FDA-approved diagnostic assays are used at the discretion of hospital laboratories. Therefore, this study was conducted during November 2011-February 2012 on 524 stool samples from 427 patients to examine the performance characteristics (sensitivity, specificity, positive predictive value, negative predictive value) of five diagnostic assays including newer molecular assays. Toxigenic culture was used as the gold standard. To examine the possibility that the newer generation of molecular assays are identifying asymptomatic carriers, a retrospective chart review was conducted for patients with discrepant test patterns. In the absence of clinical data, molecular nucleic acid based assays (RT-PCR, iLAMP) possess superior performance characteristics. Additionally, there are no significant differences between mean C. difficile likelihood scores when comparing discrepant groups. Further, when examining presence of three main clinical factors including diarrhea, inpatient exposure, and antibiotic usage, there was no significant difference in the percentage of patients expressing these factors between each discrepant result group. Therefore, it is unlikely to refine the performance characteristics when incorporating clinical data. When examining semi-quantitative toxigenic culture which indicated C. difficile concentration in colony forming units per gram, there was no significant difference in scores between groups, indicating that C. difficile patients were likely to have CDI regardless of concentration. Similarly, the percentage of positive results on each toxin-detecting assay did not vary significantly. Furthermore, 54-100% of patients in all semi-quantitative culture groups possessed all three clinical factors, indicating no relationship between presence of these factors and concentration. Public Health Implications: Clostridium difficile infection (CDI) is one of the most common healthcare-associated infections. Since its discovery in 1978 as the cause of antibiotic associated pseudomembranous colitis, its incidence has increased significantly affecting a greater number of populations. Determining a diagnostic assay for use in clinical setting which possesses excellent performance characteristics allows for the reduction of disease burden