Genomically Informed Surveillance for Drug-Resistant Pathogens

What is it about?

We used whole genome sequencing (WGS) of drug resistant bacteria to identify the genetic causes of resistance, means by which these genes could be transmitted to other species, and whether strains seen over a 3-year period were the same or different. Importantly, we integrated clinical microbiological test results with new resources developed within the hospital to leverage these datasets so timely information could be provided to help infection control efforts identify whether strains were associated with an outbreak or sporadic entry from external sources.

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Why is it important?

Globally, >1 million patients develop infections caused by multi-drug resistant and hospital-acquired pathogens. These pathogens cause thousands of deaths/year, with substantive additional morbidity, adding billions of dollars in healthcare costs. Yet, we know little regarding the dynamics of these strains within our hospitals, including their entry from referring institutions, means of internal spread, and presence or absence of mobile elements that transmit resistance. To address these complex problems, a team in the Department of Pathology at Brigham & Women’s Hospital and Harvard Medical School, and FDA Center for Food Safety and Nutrition (CFSAN), leveraged real-time querying of clinical microbiology results to identify phenotypic carbapenem-resistant Enterobacteriaceae (CRE). Strains where then genome sequenced to identify (1) whether carbapenem resistant strains were clonal or sporadic, (2) the genes causing resistance, and (3) their genomic context on mobile elements or the chromosome, which greatly refined strain patterns and improved epidemiologic analyses. Further, using the CREs as a example case, (4) the team sought to develop clinical infrastructure to provide timely information to aid infection control efforts within the hospital, and further improve clinical testing for drug-resistant species. Warehousing of the genomic findings, combined with reference genomes from GenBank and other public repositories, was thus critical to aid in strain analyses, and reduce the time needed to analyze new strains. Our analyses showed the diversity of strains, carbapenemase carrying vectors, and multi-gene causes of phenotypic carbapenem resistance that occurred. Notably the majority of isolates were sporadic in nature and not associated with internal outbreaks. The findings highlighted the diversity of drug resistant strains that can enter healthcare institutions, and use of prospective genomic analyses to more rapidly identify the cause and sources of antimicrobial resistance.