Two Artificial Tears Outbreak-Associated Cases of Extensively Drug-Resistant Pseudomonas aeruginosa Detected Through Whole Genome Sequencing-Based Surveillance.

We describe 2 cases of extensively drug-resistant Pseudomonas aeruginosa infection caused by a strain of public health concern, as it was recently associated with a nationwide outbreak of contaminated artificial tears. Both cases were detected through database review of genomes in the Enhanced Detection System for Hospital-Associated Transmission (EDS-HAT), a routine genome sequencing-based surveillance program. We generated a high-quality reference genome for the outbreak strain from an isolate from our center and examined the mobile elements encoding blaVIM-80 and bla-GES-9 carbapenemases. We used publicly available Pseudomonas aeruginosa genomes to explore the genetic relatedness and antimicrobial resistance genes of the outbreak strain.

Remediation of Mucorales-contaminated Healthcare Linens at a Laundry Facility Following an Investigation of a Case Cluster of Hospital-acquired Mucormycosis.

BACKGROUND: In an investigation of hospital-acquired mucormycosis cases among transplant recipients, healthcare linens (HCLs) delivered to our center were found to be contaminated with Mucorales. We describe an investigation and remediation of Mucorales contamination at the laundry supplying our center. METHODS: We performed monthly RODAC cultures of HCLs upon hospital arrival, and conducted site inspections and surveillance cultures at the laundry facility. Remediation was designed and implemented by infection prevention and facility leadership teams. RESULTS: Prior to remediation, 20% of HCLs were culture-positive for Mucorales upon hospital arrival. Laundry facility layout and processes were consistent with industry standards. Significant step-ups in Mucorales and mold culture-positivity of HCLs were detected at the post-dryer step (0% to 12% [P = .04] and 5% to 29% [P = .01], respectively). Further increases to 17% and 40% culture-positivity, respectively, were noted during pre-transport holding. Site inspection revealed heavy Mucorales-positive lint accumulation in rooftop air intake and exhaust vents that cooled driers; intake and exhaust vents that were facing each other; rooftop and plant-wide lint accumulation, including in the pre-transport clean room; uncovered carts with freshly-laundered HCLs. Following environmental remediation, quality assurance measures and education directed toward these sources, Mucorales culture-positivity of newly-delivered HCLs was reduced to 0.3% (P = .0001); area of lint-contaminated rooftop decreased from 918 m2 to 0 m2 on satellite images. CONCLUSIONS: Targeted laundry facility interventions guided by site inspections and step-wise culturing significantly reduced Mucorales-contaminated HCLs delivered to our hospital. Collaboration between infection prevention and laundry facility teams was crucial to successful remediation.

Whole-Genome Sequencing Surveillance and Machine Learning of the Electronic Health Record for Enhanced Healthcare Outbreak Detection.

BACKGROUND: Most hospitals use traditional infection prevention (IP) methods for outbreak detection. We developed the Enhanced Detection System for Healthcare-Associated Transmission (EDS-HAT), which combines whole-genome sequencing (WGS) surveillance and machine learning (ML) of the electronic health record (EHR) to identify undetected outbreaks and the responsible transmission routes, respectively. METHODS: We performed WGS surveillance of healthcare-associated bacterial pathogens from November 2016 to November 2018. EHR ML was used to identify the transmission routes for WGS-detected outbreaks, which were investigated by an IP expert. Potential infections prevented were estimated and compared with traditional IP practice during the same period. RESULTS: Of 3165 isolates, there were 2752 unique patient isolates in 99 clusters involving 297 (10.8%) patient isolates identified by WGS; clusters ranged from 2-14 patients. At least 1 transmission route was detected for 65.7% of clusters. During the same time, traditional IP investigation prompted WGS for 15 suspected outbreaks involving 133 patients, for which transmission events were identified for 5 (3.8%). If EDS-HAT had been running in real time, 25-63 transmissions could have been prevented. EDS-HAT was found to be cost-saving and more effective than traditional IP practice, with overall savings of $192 408-$692 532. CONCLUSIONS: EDS-HAT detected multiple outbreaks not identified using traditional IP methods, correctly identified the transmission routes for most outbreaks, and would save the hospital substantial costs. Traditional IP practice misidentified outbreaks for which transmission did not occur. WGS surveillance combined with EHR ML has the potential to save costs and enhance patient safety.

Method for Economic Evaluation of Bacterial Whole Genome Sequencing Surveillance Compared to Standard of Care in Detecting Hospital Outbreaks.

BACKGROUND: Whole genome sequencing (WGS) surveillance and electronic health record data mining have the potential to greatly enhance the identification and control of hospital outbreaks. The objective was to develop methods for examining economic value of a WGS surveillance-based infection prevention (IP) program compared to standard of care (SoC). METHODS: The economic value of a WGS surveillance-based IP program was assessed from a hospital's perspective using historical outbreaks from 2011-2016. We used transmission network of outbreaks to estimate incremental cost per transmission averted. The number of transmissions averted depended on the effectiveness of intervening against transmission routes, time from transmission to positive culture results and time taken to obtain WGS results and intervene on the transmission route identified. The total cost of an IP program included cost of staffing, WGS, and treating infections. RESULTS: Approximately 41 out of 89 (46%) transmissions could have been averted under the WGS surveillance-based IP program, and it was found to be a less costly and more effective strategy than SoC. The results were most sensitive to the cost of performing WGS and the number of isolates sequenced per year under WGS surveillance. The probability of the WGS surveillance-based IP program being cost-effective was 80% if willingness to pay exceeded $2400 per transmission averted. CONCLUSIONS: The proposed economic analysis is a useful tool to examine economic value of a WGS surveillance-based IP program. These methods will be applied to a prospective evaluation of WGS surveillance compared to SoC.

Outbreak of Pseudomonas aeruginosa Infections from a Contaminated Gastroscope Detected by Whole Genome Sequencing Surveillance.

BACKGROUND: Traditional methods of outbreak investigations utilize reactive whole genome sequencing (WGS) to confirm or refute the outbreak. We have implemented WGS surveillance and a machine learning (ML) algorithm for the electronic health record (EHR) to retrospectively detect previously unidentified outbreaks and to determine the responsible transmission routes. METHODS: We performed WGS surveillance to identify and characterize clusters of genetically-related Pseudomonas aeruginosa infections during a 24-month period. ML of the EHR was used to identify potential transmission routes. A manual review of the EHR was performed by an infection preventionist to determine the most likely route and results were compared to the ML algorithm. RESULTS: We identified a cluster of 6 genetically related P. aeruginosa cases that occurred during a 7-month period. The ML algorithm identified gastroscopy as a potential transmission route for 4 of the 6 patients. Manual EHR review confirmed gastroscopy as the most likely route for 5 patients. This transmission route was confirmed by identification of a genetically-related P. aeruginosa incidentally cultured from a gastroscope used on 4of the 5 patients. Three infections, 2 of which were blood stream infections, could have been prevented if the ML algorithm had been running in real-time. CONCLUSIONS: WGS surveillance combined with a ML algorithm of the EHR identified a previously undetected outbreak of gastroscope-associated P. aeruginosa infections. These results underscore the value of WGS surveillance and ML of the EHR for enhancing outbreak detection in hospitals and preventing serious infections.

Outbreak of Vancomycin-resistant Enterococcus faecium in Interventional Radiology: Detection Through Whole-genome Sequencing-based Surveillance.

BACKGROUND: Vancomycin-resistant enterococci (VRE) are a major cause of hospital-acquired infections. The risk of infection from interventional radiology (IR) procedures is not well documented. Whole-genome sequencing (WGS) surveillance of clinical bacterial isolates among hospitalized patients can identify previously unrecognized outbreaks. METHODS: We analyzed WGS surveillance data from November 2016 to November 2017 for evidence of VRE transmission. A previously unrecognized cluster of 10 genetically related VRE (Enterococcus faecium) infections was discovered. Electronic health record review identified IR procedures as a potential source. An outbreak investigation was conducted. RESULTS: Of the 10 outbreak patients, 9 had undergone an IR procedure with intravenous (IV) contrast ≤22 days before infection. In a matched case-control study, preceding IR procedure and IR procedure with contrast were associated with VRE infection (matched odds ratio [MOR], 16.72; 95% confidence interval [CI], 2.01 to 138.73; P = .009 and MOR, 39.35; 95% CI, 7.85 to infinity; P < .001, respectively). Investigation of IR practices and review of the manufacturer's training video revealed sterility breaches in contrast preparation. Our investigation also supported possible transmission from an IR technician. Infection prevention interventions were implemented, and no further IR-associated VRE transmissions have been observed. CONCLUSIONS: A prolonged outbreak of VRE infections related to IR procedures with IV contrast resulted from nonsterile preparation of injectable contrast. The fact that our VRE outbreak was discovered through WGS surveillance and the manufacturer's training video that demonstrated nonsterile technique raise the possibility that infections following invasive IR procedures may be more common than previously recognized.

Lessons learned for COVID-19 in the cruise ship industry.

The coronavirus disease 2019 (COVID-19) pandemic has created widespread disruption in individuals' personal and occupational lives all around the world. Vacationers and tourism, recreation, and leisure employees were among those who experienced substantial disruption. Cruise ships, especially, faced turmoil on a global scale for both their customers and workers. COVID-19 outbreaks were reported on cruise ships beginning in February 2020, presenting new and unique challenges for the industry. Conditions on cruise ships, including close and frequent contact between passengers and crew members, use of common areas, the confined nature of the vessels, and gathering of passengers from different countries, aided in transmitting the disease both onboard and in the community. As the pandemic evolved, federal and state governments and industries worldwide, including cruise ship companies, developed response plans. In this article, we provide a high-level overview of the US government and cruise ship industry's response to the COVID-19 pandemic, as well as a brief commentary on lessons learned, and recommendations for the cruise ship sector going forward. The outlined suggestions may be used as a starting point to increase emergency preparedness and to inform outbreak response plans in the event of future infectious disease outbreaks.

Return to normal operations: COVID-19 mitigation strategies for workplaces.

As spikes and resurgences of COVID-19 cases continue to increase in different geographical regions across the United States, more and more companies are left with numerous questions about reopening or restarting their operations. The current pandemic in the United States poses unique challenges unlike any other for businesses and employers as they begin to reopen. Businesses and employers are forced to ensure that they are not only in compliance with federal guidances but also with state and local guidances. In addition to the complex and ever evolving guidances, we are still learning about and adapting best practices during these reopening phases. Therefore, it is crucial for businesses to stay up-to-date not only with the released guidances but also with the latest understanding and information about SARS-CoV-2. As part of reopening, it is crucial for businesses to have comprehensive reopening plans prior to restart of operation. These plans must be clear, concise, and flexible enough to include updated guidances and information. In this publication, we describe reopening frameworks, considerations, and strategies that can be used as a starting point for businesses to further optimize and tailor to their unique operations.

Advancing toward normal operations for arenas and stadiums.

The reopening of arenas and stadiums following closures due to the 2019 coronavirus disease (COVID-19) pandemic presents unique challenges related to large crowds and close contact between players, vendors, and spectators. While each venue should be assessed individually for development and implementation of reopening plans, the general guidance presented in this document can serve as a minimum baseline for considerations to reduce the risk of COVID-19 transmission in these venues. The intention of these guidelines is to provide a layered approach to risk mitigation for various aspects of particular concern in arenas and stadiums, including crowd management, tailgating and parking, restrooms, high-contact surfaces, face masks, food and merchandising, communications, athletes and support staff, press and third parties, intermissions/breaks, and downtime. The implementation of these multifaceted approaches in each area of concern, along with the integration of regulations and requirements from local, state, and federal government bodies and agencies, will reduce the risk of a single point of failure and offer some protection to those at arenas and stadiums from COVID-19 transmission. The approaches outlined are dynamic and should be regularly reviewed and revised as new information becomes available regarding the transmission of COVID-19.

How Clean Is the Linen at My Hospital? The Mucorales on Unclean Linen Discovery Study of Large United States Transplant and Cancer Centers.

Mucormycosis outbreaks have been linked to contaminated linen. We performed fungal cultures on freshly-laundered linens at 15 transplant and cancer hospitals. At 33% of hospitals, the linens were visibly unclean. At 20%, Mucorales were recovered from >10% of linens. Studies are needed to understand the clinical significance of our findings.

Statistical outbreak detection by joining medical records and pathogen similarity.

We present a statistical inference model for the detection and characterization of outbreaks of hospital associated infection. The approach combines patient exposures, determined from electronic medical records, and pathogen similarity, determined by whole-genome sequencing, to simultaneously identify probable outbreaks and their root-causes. We show how our model can be used to target isolates for whole-genome sequencing, improving outbreak detection and characterization even without comprehensive sequencing. Additionally, we demonstrate how to learn model parameters from reference data of known outbreaks. We demonstrate model performance using semi-synthetic experiments.

Navigating the network: a narrative overview of AMR surveillance and data flow in the United States.

The antimicrobial resistance (AMR) surveillance landscape in the United States consists of a data flow that starts in the clinical setting and is maintained by a network of national and state public health laboratories. These organizations are well established, with robust methodologies to test and confirm antimicrobial susceptibility. Still, the bridge that guides the flow of data is often one directional and caught in a constant state of rush hour that can only be refined with improvements to infrastructure and automation in the data flow. Moreover, there is an absence of information in the literature explaining the processes clinical laboratories use to coalesce and share susceptibility test data for AMR surveillance, further complicated by variability in testing procedures. This knowledge gap limits our understanding of what is needed to improve and streamline data sharing from clinical to public health laboratories. Successful models of AMR surveillance display attributes like 2-way communication between clinical and public health laboratories, centralized databases, standardized data, and the use of electronic health records or data systems, highlighting areas of opportunity and improvement. This article explores the roles and processes of the organizations involved in AMR surveillance in the United States and identifies current knowledge gaps and opportunities to improve communication between them through standardization, communication, and modernization of data flow.

Impact of discontinuation of contact precautions on surveillance- and whole genome sequencing-defined methicillin-resistant Staphylococcus aureus healthcare-associated infections.

Objective: Prior studies evaluating the impact of discontinuation of contact precautions (DcCP) on methicillin-resistant Staphylococcus aureus (MRSA) outcomes have characterized all healthcare-associated infections (HAIs) rather than those likely preventable by contact precautions. We aimed to analyze the impact of DcCP on the rate of MRSA HAI including transmission events identified through whole genome sequencing (WGS) surveillance. Design: Quasi experimental interrupted time series. Setting: Acute care medical center. Participants: Inpatients. Methods: The effect of DcCP (use of gowns and gloves) for encounters among patients with MRSA carriage was evaluated using time series analysis of MRSA HAI rates from January 2019 through December 2022, compared to WGS-defined attributable transmission events before and after DcCP in December 2020. Results: The MRSA HAI rate was 4.22/10,000 patient days before and 2.98/10,000 patient days after DcCP (incidence rate ratio [IRR] 0.71 [95% confidence interval 0.56-0.89]) with a significant immediate decrease (P = .001). There were 7 WGS-defined attributable transmission events before and 11 events after DcCP (incident rate ratio 0.90 [95% confidence interval 0.30-2.55]). Conclusions: DcCP did not result in an increase in MRSA HAI or, in WGS-defined attributable transmission events. Comprehensive analyses of the effect of transmission prevention measures should include outcomes specifically measuring transmission-associated HAI.

Genomic sequencing surveillance of patients colonized with vancomycin-resistant Enterococcus (VRE) improves detection of hospital-associated transmission.

Background: Vancomycin-resistant enterococcal (VRE) infections pose significant challenges in healthcare. Transmission dynamics of VRE are complex, often involving patient colonization and subsequent transmission through various healthcare-associated vectors. We utilized a whole genome sequencing (WGS) surveillance program at our institution to better understand the contribution of clinical and colonizing isolates to VRE transmission. Methods: We performed whole genome sequencing on 352 VRE clinical isolates collected over 34 months and 891 rectal screening isolates collected over a 9-month nested period, and used single nucleotide polymorphisms to assess relatedness. We then performed a geo-temporal transmission analysis considering both clinical and rectal screening isolates compared with clinical isolates alone, and calculated 30-day outcomes of patients. Results: VRE rectal carriage constituted 87.3% of VRE acquisition, with an average monthly acquisition rate of 7.6 per 1000 patient days. We identified 185 genetically related clusters containing 2-42 isolates and encompassing 69.6% of all isolates in the dataset. The inclusion of rectal swab isolates increased the detection of clinical isolate clusters (from 53% to 67%, P<0.01). Geo-temporal analysis identified hotspot locations of VRE transmission. Patients with clinical VRE isolates that were closely related to previously sampled rectal swab isolates experienced 30-day ICU admission (17.5%), hospital readmission (9.2%), and death (13.3%). Conclusions: Our findings describe the high burden of VRE transmission at our hospital and shed light on the importance of using WGS surveillance of both clinical and rectal screening isolates to better understand the transmission of this pathogen. This study highlights the potential utility of incorporating WGS surveillance of VRE into routine hospital practice for improving infection prevention and patient safety.

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.

The future of automated infection detection: Innovation to transform practice (Part III/III).

Current methods of emergency-room-based syndromic surveillance were insufficient to detect early community spread of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) in the United States, which slowed the infection prevention and control response to the novel pathogen. Emerging technologies and automated infection surveillance have the potential to improve upon current practice standards and to revolutionize the practice of infection detection, prevention and control both inside and outside of healthcare settings. Genomics, natural language processing, and machine learning can be leveraged to improve identification of transmission events and aid and evaluate outbreak response. In the near future, automated infection detection strategies can be used to advance a true "Learning Healthcare System" that will support near-real-time quality improvement efforts and advance the scientific basis for the practice of infection control.

Leveraging electronic data to expand infection detection beyond traditional settings and definitions (Part II/III).

The rich and complex electronic health record presents promise for expanding infection detection beyond currently covered settings of care. Here, we review the "how to" of leveraging electronic data sources to expand surveillance to settings of care and infections that have not been the traditional purview of the National Healthcare Safety Network (NHSN), including a discussion of creation of objective and reproducible infection surveillance definitions. In pursuit of a 'fully automated' system, we also examine the promises and pitfalls of leveraging unstructured, free-text data to support infection prevention activities and emerging technological advances that will likely affect the practice of automated infection surveillance. Finally, barriers to achieving a completely 'automated' infection detection system and challenges with intra- and interfacility reliability and missing data are discussed.

Sensitivity of National Healthcare Safety Network definitions to capture healthcare-associated transmission identified by whole-genome sequencing surveillance.

The National Healthcare Safety Network (NHSN) definitions are critical for standardizing healthcare-associated infection surveillance in US healthcare facilities. However, their use in accurately detecting healthcare-associated transmission (HAT) has not been measured. Using whole-genome sequencing surveillance data, we show that the NHSN has a sensitivity of 44.4% in detecting HAT.

Empirically derived sequence similarity thresholds to study the genomic epidemiology of plasmids shared among healthcare-associated bacterial pathogens.

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 apply whole-genome sequencing to systematically resolve and track plasmids carried by nosocomial pathogens in a single hospital, and to identify epidemiologic links that indicated likely horizontal plasmid transfer. METHODS: We performed an observational study of plasmids circulating among bacterial isolates infecting patients at a large hospital. We first examined plasmids carried by isolates sampled from the same patient over time and isolates that caused clonal outbreaks in the same hospital to develop thresholds with which horizontal plasmid transfer within a tertiary hospital could be inferred. We then applied those sequence similarity thresholds to perform a systematic screen of 3074 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 links 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 and accumulated fewer than 15 SNPs per 100 kb of plasmid sequence. Applying these similarity thresholds to identify horizontal plasmid transfer identified 45 plasmids that potentially circulated among clinical isolates. Ten highly preserved 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: Evidence suggests that the horizontal transfer of plasmids among nosocomial bacterial pathogens appears to be 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.

Two artificial tears outbreak-associated cases of XDR Pseudomonas aeruginosa detected through whole genome sequencing-based surveillance.

We describe two cases of XDR Pseudomonas aeruginosa infection caused by a strain of public health concern recently associated with a nationwide outbreak of contaminated artificial tears. Both cases were detected through database review of genomes in the Enhanced Detection System for Hospital-Associated Transmission (EDS-HAT), a routine genome sequencing-based surveillance program. We generated a high-quality reference genome for the outbreak strain from one of the case isolates from our center and examined the mobile elements encoding bla VIM-80 and bla GES-9 carbapenemases. We then used publicly available P. aeruginosa genomes to explore the genetic relatedness and antimicrobial resistance genes of the outbreak strain.