Real-time genomic epidemiologic investigation of a multispecies plasmid-associated hospital outbreak of NDM-5-producing Enterobacterales infections.

OBJECTIVES: New Delhi metallo-ß-lactamase (NDM) is an emergent mechanism of carbapenem resistance associated with high mortality and limited treatment options. Because the blaNDM resistance gene is often carried on plasmids, traditional infection prevention and control (IP&C) surveillance methods and reactive whole genome sequencing (WGS) may not detect plasmid transfer in multispecies outbreaks. METHODS: Initial outbreak detection of NDM-producing Enterobacterales identified at an acute care hospital occurred via traditional IP&C methods and was supplemented by real-time WGS surveillance performed weekly. To resolve NDM-encoding plasmids, we performed long-read sequencing and constructed hybrid assemblies. WGS data for suspected outbreaks was shared with the IP&C team for assessment and intervention. RESULTS: We observed a multispecies outbreak of NDM-5-producing Enterobacterales isolated from 15 patients between February 2021 and February 2023. The 19 clinical and surveillance isolates sequenced included 7 bacterial species encoding the same NDM-5 plasmid. WGS surveillance and epidemiologic investigation characterized 10 horizontal plasmid transfer events and 6 bacterial transmission events between patients in varying hospital units. CONCLUSIONS: Our investigation revealed a complex, multispecies outbreak of NDM involving multiple plasmid transfer and bacterial transmission events. We highlight the utility of combining traditional IP&C and prospective genomic methods in identifying and containing plasmid-associated outbreaks.

Genomic Epidemiologic Investigation of a Multispecies Hospital Outbreak of NDM-5-Producing Enterobacterales Infections.

Background: New Delhi metallo-ß-lactamase (NDM) represents an emergent mechanism of carbapenem resistance associated with high mortality and limited antimicrobial treatment options. Because the blaNDM resistance gene is often carried on plasmids, traditional infection prevention and control (IP&C) surveillance methods like speciation, antimicrobial resistance testing, and reactive whole genome sequencing (WGS) may not detect plasmid transfer in multispecies outbreaks. Methods: Initial outbreak detection of NDM-producing Enterobacterales identified at an acute care hospital occurred via traditional IP&C methods and was supplemented by real-time WGS surveillance, which was performed weekly using the Illumina platform. To resolve NDM-encoding plasmids, we performed long-read Oxford Nanopore sequencing and constructed hybrid assemblies using Illumina and Nanopore sequencing data. Reports of relatedness between NDM-producing organisms and reactive WGS for suspected outbreaks were shared with the IP&C team for assessment and intervention. Findings: We observed a multispecies outbreak of NDM-5-producing Enterobacterales isolated from 15 patients between February 2021 and February 2023. The 19 clinical and surveillance isolates sequenced included seven bacterial species and each encoded the same NDM-5 plasmid, which showed high homology to NDM plasmids previously observed in Asia. WGS surveillance and epidemiologic investigation characterized ten horizontal plasmid transfer events and six bacterial transmission events between patients housed in varying hospital units. Transmission prevention focused on enhanced observation and adherence to basic infection prevention measures. Interpretation: Our investigation revealed a complex, multispecies outbreak of NDM that involved multiple plasmid transfer and bacterial transmission events, increasing the complexity of outbreak identification and transmission prevention. Our investigation highlights the utility of combining traditional IP&C and prospective genomic methods in identifying and containing plasmid-associated outbreaks. Funding: This work was funded in part by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) (R01AI127472) (R21AI1783691).

Transmission visualizations of healthcare infection clusters: A scoping review.

Objective: To evaluate infectious pathogen transmission data visualizations in outbreak publications. Design: Scoping review. Methods: Medline was searched for outbreak investigations of infectious diseases within healthcare facilities that included ≥1 data visualization of transmission using data observable by an infection preventionist showing temporal and/or spatial relationships. Abstracted data included the nature of the cluster(s) (pathogen, scope of transmission, and individuals involved) and data visualization characteristics including visualization type, transmission elements, and software. Results: From 1,957 articles retrieved, we analyzed 30 articles including 37 data visualizations. The median cluster size was 20.5 individuals (range, 7-1,963) and lasted a median of 214 days (range, 12-5,204). Among the data visualization types, 10 (27%) were floor-plan transmission maps, 6 (16%) were timelines, 11 (30%) were transmission networks, 3 (8%) were Gantt charts, 4 (11%) were cluster map, and 4 (11%) were other types. In addition, 26 data visualizations (70%) contained spatial elements, 26 (70%) included person type, and 19 (51%) contained time elements. None of the data visualizations contained contagious periods and only 2 (5%) contained symptom-onset date. Conclusions: The data visualizations of healthcare-associated infectious disease outbreaks in the systematic review were diverse in type and visualization elements, though no data visualization contained all elements important to deriving hypotheses about transmission pathways. These findings aid in understanding the visualizing transmission pathways by describing essential elements of the data visualization and will inform the creation of a standardized mapping tool to aid in earlier initiation of interventions to prevent transmission.