Accuracy of Infection Control Surveillance in Identifying Genomically Confirmed Cross Transmission Clusters

Background: Infection prevention surveillance for cross transmission is often performed by manual review of microbiologic culture results to identify geotemporally related clusters. However, the sensitivity and specificity of this approach remains uncertain. Whole-genome sequencing (WGS) analysis can help provide a gold-standard for identifying cross-transmission events. Objective: We employed a published WGS program, the Philips IntelliSpace Epidemiology platform, to compare accuracy of two surveillance methods: (i.) a virtual infection practitioner (VIP) with perfect recall and automated analysis of antibiotic susceptibility testing (AST), sample collection timing, and patient location data and (ii) a novel clinical matching (CM) algorithm that provides cluster suggestions based on a nuanced weighted analysis of AST data, timing of sample collection, and shared location stays between patients. Methods: WGS was performed routinely on inpatient and emergency department isolates of Enterobacter cloacae, Enterococcus faecium, Klebsiella pneumoniae, and Pseudomonas aeruginosa at an academic medical center. Single-nucleotide variants (SNVs) were compared within core genome regions on a per-species basis to determine cross-transmission clusters. Moreover, one unique strain per patient was included within each analysis, and duplicates were excluded from the final results. Results: Between May 2018 and April 2019, clinical data from 121 patients were paired with WGS data from 28 E. cloacae, 21 E. faecium, 61 K. pneumoniae, and 46 P. aeruginosa isolates. Previously published SNV relatedness thresholds were applied to define genomically related isolates. Mapping of genomic relatedness defined clusters as follows: 4 patients in 2 E. faecium clusters and 2 patients in 1 P. aeruginosa cluster. The VIP method identified 12 potential clusters involving 28 patients, all of which were “pseudoclusters.” Importantly, the CM method identified 7 clusters consisting of 27 patients, which included 1 true E. faecium cluster of 2 patients with genomically related isolates. Conclusions: In light of the WGS data, all of the potential clusters identified by the VIP were pseudoclusters, lacking sufficient genomic relatedness. In contrast, the CM method showed increased sensitivity and specificity: it decreased the percentage of pseudoclusters by 14% and it identified a related genomic cluster of E. faecium. These findings suggest that integrating clinical data analytics and WGS is likely to benefit institutions in limiting expenditure of resources on pseudoclusters. Therefore, WGS combined with more sophisticated surveillance approaches, over standard methods as modeled by the VIP, are needed to better identify and address true cross-transmission events. Funding: This study was supported by Philips Healthcare. Disclosures: None