Genomic Diversity of Hospital-Acquired Infections Revealed through Prospective Whole-Genome Sequencing-Based Surveillance

Mustapha, Mustapha M.; Srinivasa, Vatsala Rangachar; Griffith, M. Patrick; Cho, Shu-Ting; Evans, Daniel R.; Waggle, Kady; Ezeonwuka, Chinelo; Snyder, Donald R.; Marsh, Jane W.; Harrison, Lee H.; Cooper, Vaughn S.; Tyne, Daria Van

doi:10.1128/msystems.01384-21

Cited by 19 publications

(27 citation statements)

References 64 publications

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Section: Discussionmentioning

confidence: 99%

“…Even with the increased scope of our genomic and epidemiologic analysis, we postulate that our findings still underestimate the true extent to which horizontal plasmid transfer occurs among nosocomial bacterial pathogens. The large number of hybrid-assembled reference plasmids we used to search for evidence of plasmid sharing were sequenced from only 56 isolates from a single hospital, 8 representing a small subset of the bacteria that infected hospitalized patients during the two-year period of this study. Within this relatively limited dataset, we nonetheless identified several plasmids that exhibited evidence of further recombination and rearrangement while circulating among patients in the hospital.…”

Section: Discussionmentioning

confidence: 99%

“…The application of our methods to a large genomic dataset from a single hospital resolved horizontal plasmid transfer at an unprecedented scale and demonstrated the added value of routine whole-genome sequencing of nosocomial bacterial pathogens in hospital infection prevention. 8,9,35 Applying these refined, plasmid-focused approaches in healthcare settings could help infection prevention teams better understand signs and risk factors for the dissemination of drug resistance, allowing them to improve their approaches to reduce the risk of severe infections among patients. 5,7,35 Future work in this area should focus on refining similarity thresholds and surveillance methods, further examining patterns of mutation and genetic plasticity among circulating plasmids, and implementing these methods in real-time to control the spread of plasmid-borne antimicrobial resistance and virulence factors that exacerbate nosocomial infections.…”

Section: Discussionmentioning

confidence: 99%

“…All bacterial isolates analyzed in this study were collected through the Enhanced Detection System for Hospital-Associated Transmission (EDS-HAT) project, using previously published eligibility criteria for selection of isolates. 8,9,11 EDS-HAT uses a combination of WGS surveillance of selected hospital-associated pathogens and machine learning of the electronic health record to identify otherwise undetected outbreaks and the responsible transmission routes, respectively. Isolates were identified using TheraDoc software (Version 4.6, Premier, Inc, Charlotte NC).…”

Section: Collection Of Clinical Bacterial Isolates and Corresponding ...mentioning

confidence: 99%

“…The first was to establish sequence similarity thresholds to infer horizontal transfer of plasmids among bacteria collected from a single hospital. The second was to apply these thresholds to a large dataset of whole-genome sequences of nosocomial bacterial pathogens from a tertiary hospital, 8,9 and to investigate epidemiologic links between patients infected with genetically unrelated bacteria encoding the same plasmid. The intended outcome was to demonstrate that these methods augment our knowledge of plasmid dynamics in healthcare settings at the scale of an entire hospital, further supporting the value of whole-genome sequencing (WGS) in healthcare epidemiology.…”

Section: Introductionmentioning

confidence: 99%

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Empirical genomic methods for tracking plasmid spread among healthcare-associated bacteria

Evans

Sundermann

Griffith

et al. 2022

Preprint

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Background: Healthcare-associated bacterial pathogens frequently carry plasmids that contribute to antibiotic resistance and virulence. The horizontal transfer of plasmids in healthcare settings has been previously documented, but genomic and epidemiologic methods to study this phenomenon remain underdeveloped. The objectives of this study were to develop a method to systematically resolve and track plasmids circulating in a single hospital, and to identify epidemiologic links that indicated likely horizontal plasmid transfer. Methods: We derived empirical thresholds of plasmid sequence similarity from comparisons of plasmids carried by bacterial isolates infecting individual patients over time, or involved in hospital outbreaks. We then applied those metrics to perform a systematic screen of 3,074 genomes of nosocomial bacterial isolates from a single hospital for the presence of 89 plasmids. We also collected and reviewed data from electronic health records for evidence of geotemporal associations between patients infected with bacteria encoding plasmids of interest. Findings: Our analyses determined that 95% of analyzed genomes maintained roughly 95% of their plasmid genetic content at a nucleotide identity at least 99.985%. Applying these similarity thresholds to identify horizontal plasmid transfer identified 45 plasmids circulating among clinical isolates. Ten plasmids met criteria for geotemporal links associated with horizontal transfer. Several plasmids with shared backbones also encoded different additional mobile genetic element content, and these elements were variably present among the sampled clinical isolate genomes. Interpretation: The horizontal transfer of plasmids among nosocomial bacterial pathogens is frequent within hospitals and can be monitored with whole genome sequencing and comparative genomics approaches. These approaches should incorporate both nucleotide identity and reference sequence coverage to study the dynamics of plasmid transfer in the hospital. Funding: This research was supported by the US National Institute of Allergy and Infectious Disease (NIAID) and the University of Pittsburgh School of Medicine.

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