Integration of genomic and clinical data augments surveillance of healthcare-acquired infections

Abstract

Background:Determining infectious cross-transmission events in healthcare settings involves manual surveillance of case clusters by infection control personnel, followed by strain typing of clinical/environmental isolates suspected in said clusters. Recent advances in genomic sequencing and cloud computing now allow for the rapid molecular typing of infecting isolates.Objective:To facilitate rapid recognition of transmission clusters, we aimed to assess infection control surveillance using whole-genome sequencing (WGS) of microbial pathogens to identify cross-transmission events for epidemiologic review.Methods:Clinical isolates of Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, and Klebsiella pneumoniae were obtained prospectively at an academic medical center, from September 1, 2016, to September 30, 2017. Isolate genomes were sequenced, followed by single-nucleotide variant analysis; a cloud-computing platform was used for whole-genome sequence analysis and cluster identification.Results:Most strains of the 4 studied pathogens were unrelated, and 34 potential transmission clusters were present. The characteristics of the potential clusters were complex and likely not identifiable by traditional surveillance alone. Notably, only 1 cluster had been suspected by routine manual surveillance.Conclusions:Our work supports the assertion that integration of genomic and clinical epidemiologic data can augment infection control surveillance for both the identification of cross-transmission events and the inclusion of missed and exclusion of misidentified outbreaks (ie, false alarms). The integration of clinical data is essential to prioritize suspect clusters for investigation, and for existing infections, a timely review of both the clinical and WGS results can hold promise to reduce HAIs. A richer understanding of cross-transmission events within healthcare settings will require the expansion of current surveillance approaches.

Genomic interrogation of the burden and transmission of multidrug-resistant pathogens within and across hospital networks

“…Australia has one the highest rates of VRE in the world (47.0% in 2017 [13]), having been dominated by vanB until the last five years, when vanA VRE has emerged rapidly across multiple states [14]. Whilst the patient risk factors of MDRO acquisition are well understood for most of these organisms [15-22], further analysis using whole genome sequencing has the potential to add further insights, particularly defining the relatedness of isolates by genomics (and hence putative transmission when combined with epidemiologic data), which to date has only just started to be applied in a clinical setting [23, 24].…”

Whole-genome sequencing for neonatal intensive care unit outbreak investigations: Insights and lessons learned

“…WGS can identify transmission events that are missed by less discriminatory methods, 30 and it can expand our ability to detect unsuspected nosocomial transmissions, as well as to identify chance clusters. 31,32 WGS has the potential to provide pertinent clinical information regarding antimicrobial resistance and virulence genes that may not be detected by phenotypic or targeted molecular testing. 4 The robust capacity and scale of WGS has been useful to document transmission both within and between hospitals, as well as on an intercontinental scale.…”

“…Prospective surveillance with WGS has been shown to be feasible and may result in cost savings. 10,32,35 Although there have been significant advances in the accessibility of WGS in the past decade, several challenges remain in its implementation as a routine tool for outbreak investigation. The largest hurdles are turnaround time, accessibility, cost, and standardization.…”

Community-acquired in name only: A cluster of carbapenem-resistantAcinetobacter baumanniiin a burn intensive care unit and beyond

“…Most genomically linked clusters are not detected using routine surveillance methods. 23 The use of WGS for large-scale prospective surveillance to track pathogen transmission events has shown potential to alter the way outbreaks are identified and controlled. Real-time sequencing of recent viral oubreaks of Ebola 24 and Zika 25 has demonstrated the utility of sequencing for public health epidemiological surveillance.…”

“…Targeted sampling, made possible through approaches leveraging electronic health data, could help to focus sequencing efforts. 23,30 Fig . 4.…”