Methods for cost-efficient, whole genome sequencing surveillance for enhanced detection of outbreaks in a hospital setting
Authors: Waggle Kady D. , Griffith Marissa Pacey , Rokes Alecia B. , Srinivasa Vatsala Rangachar , Ereifej Deena , Patrick Rose , Coyle Hunter , Chaudhary Shurmin , Raabe Nathan J. , Sundermann Alexander J. , Cooper Vaughn S. , Harrison Lee H. , Pless Lora Lee 
Published: December 2024

2.

Introduction

Outbreaks of healthcare-associated infections (HAI) result in substantial patient morbidity and mortality; mitigation efforts by infection prevention teams have the potential to curb outbreaks and prevent transmission to additional patients. The incorporation of whole genome sequencing (WGS) surveillance of suspected high-risk pathogens often identifies outbreaks that are not detected by traditional infection prevention methods and provides evidence for transmission. Our approach to real-time WGS surveillance, the Enhanced Detection System for Healthcare-Associated Transmission (EDS-HAT), has 1) identified serious outbreaks that were otherwise undetected and 2) shown the potential to be cost saving because HAIs are expensive to treat and WGS has become relatively inexpensive.

Methods

We describe a cost-efficient method to perform WGS surveillance and data analysis of pathogens for hospitals that are interested in incorporating WGS surveillance. We provide an overview of the weekly workflow of EDS-HAT, discussing both the laboratory and bioinformatics methods utilized, as well as the costs associated with performing these methods.

Results

In an average week at our tertiary healthcare system, we sequenced 48 samples at a cost of less than $100 per sample, inclusive of laboratory reagents and staff salaries. The average turnaround time, from sample collection to data reporting to the infection prevention and control team, was ten days.

Conclusions

Our findings demonstrate that performing EDS-HAT in real-time can be both affordable and time-efficient. Providing such timely information to aid in outbreak investigations can identify transmission events sooner and thus increase patient safety.

3.

Impact statement

Whole genome sequencing (WGS) surveillance to confirm or refute suspected outbreaks of potential healthcare-associated infections (HAI) is a highly effective approach for outbreak detection. Since November 2021, we have been conducting WGS surveillance in real-time through a program called the Enhanced Detection System for Hospital-Associated Transmission (EDS-HAT), to assist our hospital infection prevention and control (IP&C) team to identify and stop outbreaks. To our knowledge, our laboratory is the only group in the United States that has successfully implemented real-time WGS surveillance of multiple pathogens in the hospital setting. Our weekly workflow includes identifying HAI pathogens and performing WGS, followed by a variety of bioinformatic analyses that include species confirmation, determination of sequence type, and genetic relatedness comparisons. Based on this information, transmission clusters are identified, and the electronic health record is reviewed to determine probable transmission routes. Finally, IP&C implements appropriate interventions to mitigate the spread of infection. We detail the laboratory and analytical methods, along with the cost associated for laboratory materials and staff salary, for successful implementation of WGS surveillance in real-time establishing EDS-HAT as a unique and effective tool to detect HAI outbreaks.