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.

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.

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.

Incidence and transmission associated with respiratory viruses in an acute care facility: An observational study.

We estimated the extent of respiratory virus transmission over three pre-COVID-19 seasons. Of 16,273 assays, 22.9% (3,726) detected ≥1 respiratory virus. The frequency of putatively hospital-acquired infection ranged from 6.9% (influenza A/B) to 24.7% (adenovirus). The 176 clusters were most commonly associated with rhinovirus/enterovirus (70) and influenza A/B (62).

Immediate-use steam sterilization and the effect on surgical site infection risk in an acute care facility.

Immediate-use steam sterilization (IUSS) shortens the time of sterilization but may increase the risk of surgical site infection (SSI). Among 23,919 procedures with 416 (1.7%) procedures resulting in SSI, IUSS was associated with a 1.52 (95% CI, 1.10-2.11) times higher risk of SSI. IUSS should be minimized.

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.

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.

Strategies for deployment of ultraviolet disinfection in an acute care facility: A quality improvement initiative.

BACKGROUND: Mobile ultraviolet (UV) disinfection uses UV-C light to render microorganisms nonviable and reduce environmental transmission of pathogens in hospital settings. Optimal strategies for deployment must consider the cost, physical layout, and staffing resources. The aim of this quality improvement study was to increase UV disinfection utilization by developing novel deployment strategies without adding resources. METHODS: A novel deployment strategy and tools were developed by a multidisciplinary group that included infection prevention, environmental services, and nursing unit staff. Utilization was tracked via a manufacturer-supported database. The infection prevention team analyzed the weekly UV disinfection minutes, cycles, and proportions of cycles completed in defined areas across 4 periods: baseline, pilot, baseline 2, and intervention. RESULTS: The median (range) disinfection cycle times per week during a geographically confined pilot (4,985 minutes [3,476-6,551] minutes) and the intervention period (1,454 [512-3,085] minutes) were lower than either baseline period (5,394 [3,953-6,987] and 6,641 [2,830-7,276] minutes, respectively). Cycles per week were lower in the intervention period than in the preceding 3 periods. CONCLUSIONS: Use of UV disinfection in acute care settings should be guided by multidisciplinary groups balancing resources against efficacy and using tailored tools to promote efficiency.

The impact of autocancellation of uncollected Clostridioides difficile specimens after 24 hours on reported healthcare-associated infections: A quality improvement intervention.

OBJECTIVE: To assess the impact of a 24-hour autocancellation of uncollected Clostridioides difficile samples in reducing reported healthcare-associated infections (HAIs). DESIGN: Quality-improvement, before-and-after implementation study. SETTING: The study was conducted in 17 hospitals in Pennsylvania. INTERVENTIONS: Clostridioides difficile tests that are not collected within 24 hours are automatically canceled ("autocancel") through the electronic health record. The intervention took place at 2 facilities (intervention period November 2021-July 2022) and subsequently at 15 additional facilities (April 2022-July 2022). Quality measures included percentage of orders canceled, C. difficile HAI rate, percent positivity of completed tests, and potential adverse outcomes of canceled or delayed testing. RESULTS: Of 6,101 orders, 1,090 (17.9%) were automatically canceled after not being collected for 24 hours during the intervention periods. The reported C. difficile HAI rates per 10,000 patient days did not significantly change. These rates were 8.07 in the 6-month preintervention period and 8.77 in the intervention period for facilities A and B combined (incidence rate ratio [IRR], 1.09; 95% CI, 0.88-1.34; P = .43), and were 5.23 HAIs per 10,000 patient days in the 6-month preintervention period and 5.33 in the intervention period for facilities C-Q combined (IRR, 1.02; 95% CI, 0.79-1.32; P = .87). From the preintervention to the intervention periods, the percent positivity rates of completed C. difficile tests increased by 1.1% for facilities A and B and by 1.4% for facilities C-Q. No adverse outcomes were observed. CONCLUSIONS: The 24-hour autocancellation of uncollected C. difficile orders reduced testing but did not result in reported HAI reduction.

A novel approach to correcting attribution of Clostridioides difficile in a healthcare setting.

Objective: To describe a novel attribution metric estimating the causal source location of healthcare-associated Clostridioides difficile and compare it with the current US National Healthcare Safety Network (NHSN) surveillance reporting standard. Design: Quality improvement study. Setting: Two acute care facilities. Methods: A novel attribution metric assigned days of attribution to locations where patients were located for 14 days before and the day of their C. difficile diagnosis. We correlated the NHSN-assigned unit attribution with the novel attribution measure and compared the proportion of attribution assigned to inpatient units. Results: During a 30-month period, there were 727 NHSN C. difficile healthcare-associated infections (HAIs) and 409 non-HAIs; the novel metric attributed 17,034 days. The correlation coefficients for NHSN and novel attributions among non-ICU units were 0.79 (95% CI, 0.76-0.82) and 0.74 (95% CI, 0.70-0.78) and among ICU units were 0.70 (95% CI, 0.63-0.76) and 0.69 (95% CI, 0.60-0.77) at facilities A and B, respectively. The distribution of difference in percent attribution showed higher inpatient unit attribution using NHSN measure than the novel attribution metric: 38% of ICU units and 15% of non-ICU units in facility A, and 20% of ICU units and 25% of non-ICU units in facility B had a median difference >0; no inpatient units showed a greater attribution using the novel attribution metric. Conclusion: The novel attribution metric shifts attribution from inpatient units to other settings and correlates modestly with NHSN methodology of attribution. If validated, the attribution metric may more accurately target C. difficile reduction efforts.

Endoscopic retrograde cholangiopancreatography and endoscopic ultrasound endoscope reprocessing: Variables impacting contamination risk.

OBJECTIVE: To evaluate variables that affect risk of contamination for endoscopic retrograde cholangiopancreatography and endoscopic ultrasound endoscopes. DESIGN: Observational, quality improvement study. SETTING: University medical center with a gastrointestinal endoscopy service performing ∼1,000 endoscopic retrograde cholangiopancreatography and ∼1,000 endoscopic ultrasound endoscope procedures annually. METHODS: Duodenoscope and linear echoendoscope sampling (from the elevator mechanism and instrument channel) was performed from June 2020 through September 2021. Operational changes during this period included standard reprocessing with high-level disinfection with ethylene oxide gas sterilization (HLD-ETO) was switched to double high-level disinfection (dHLD) (June 16, 2020-July 15, 2020), and duodenoscopes changed to disposable tip model (March 2021). The frequency of contamination for the co-primary outcomes were characterized by calculated risk ratios. RESULTS: The overall pathogenic contamination rate was 4.72% (6 of 127). Compared to duodenoscopes, linear echoendoscopes had a contamination risk ratio of 3.64 (95% confidence interval [CI], 0.69-19.1). Reprocessing using HLD-ETO was associated with a contamination risk ratio of 0.29 (95% CI, 0.06-1.54). Linear echoendoscopes undergoing dHLD had the highest risk of contamination (2 of 18, 11.1%), and duodenoscopes undergoing HLD-ETO and the lowest risk of contamination (0 of 53, 0%). Duodenoscopes with a disposable tip had a 0% contamination rate (0 of 27). CONCLUSIONS: We did not detect a significant reduction in endoscope contamination using HLD-ETO versus dHLD reprocessing. Linear echoendoscopes have a risk of contamination similar to that of duodenoscopes. Disposable tips may reduce the risk of duodenoscope contamination.

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.

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).

Diagnostic stewardship for Clostridioides difficile testing in an acute care hospital: A quality improvement intervention.

Objective: To evaluate the impact of a diagnostic stewardship intervention on Clostridioides difficile healthcare-associated infections (HAI). Design: Quality improvement study. Setting: Two urban acute care hospitals. Interventions: All inpatient stool testing for C. difficile required review and approval prior to specimen processing in the laboratory. An infection preventionist reviewed all orders daily through chart review and conversations with nursing; orders meeting clinical criteria for testing were approved, orders not meeting clinical criteria were discussed with the ordering provider. The proportion of completed tests meeting clinical criteria for testing and the primary outcome of C. difficile HAI were compared before and after the intervention. Results: The frequency of completed C. difficile orders not meeting criteria was lower [146 (7.5%) of 1,958] in the intervention period (January 10, 2022-October 14, 2022) than in the sampled 3-month preintervention period [26 (21.0%) of 124; P < .001]. C. difficile HAI rates were 8.80 per 10,000 patient days prior to the intervention (March 1, 2021-January 9, 2022) and 7.69 per 10,000 patient days during the intervention period (incidence rate ratio, 0.87; 95% confidence interval, 0.73-1.05; P = .13). Conclusions: A stringent order-approval process reduced clinically nonindicated testing for C. difficile but did not significantly decrease HAIs.

Bronchoscope-associated clusters of multidrug-resistant Pseudomonas aeruginosa and carbapenem-resistant Klebsiella pneumoniae.

OBJECTIVE: Recovery of multidrug-resistant (MDR) Pseudomonas aeruginosa and Klebsiella pneumoniae from a cluster of patients in the medical intensive care unit (MICU) prompted an epidemiologic investigation for a common exposure. METHODS: Clinical and microbiologic data from MICU patients were retrospectively reviewed, MICU bronchoscopes underwent culturing and borescopy, and bronchoscope reprocessing procedures were reviewed. Bronchoscope and clinical MDR isolates epidemiologically linked to the cluster underwent molecular typing using pulsed-field gel electrophoresis (PFGE) followed by whole-genome sequencing. RESULTS: Of the 33 case patients, 23 (70%) were exposed to a common bronchoscope (B1). Both MDR P. aeruginosa and K. pneumonia were recovered from the bronchoscope's lumen, and borescopy revealed a luminal defect. Molecular testing demonstrated genetic relatedness among case patient and B1 isolates, providing strong evidence for horizontal bacterial transmission. MDR organism (MDRO) recovery in 19 patients was ultimately linked to B1 exposure, and 10 of 19 patients were classified as belonging to an MDRO pseudo-outbreak. CONCLUSIONS: Surveillance of bronchoscope-derived clinical culture data was important for early detection of this outbreak, and whole-genome sequencing was important for the confirmation of findings. Visualization of bronchoscope lumens to confirm integrity should be a critical component of device reprocessing.

Evolution of Outbreak-Causing Carbapenem-Resistant Klebsiella pneumoniae ST258 at a Tertiary Care Hospital over 8 Years.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) strains belonging to sequence type 258 (ST258) are frequent causes of hospital-associated outbreaks and are a major contributor to the spread of carbapenemases. This genetic lineage emerged several decades ago and remains a major global health care challenge. In this study, genomic epidemiology was used to investigate the emergence, evolution, and persistence of ST258 carbapenem-resistant K. pneumoniae outbreak-causing lineages at a large tertiary care hospital over 8 years. A time-based phylogenetic analysis of 136 ST258 isolates demonstrated the succession of multiple genetically distinct ST258 sublineages over the 8-year period. Ongoing genomic surveillance identified the emergence and persistence of several distinct clonal ST258 populations. Patterns of multidrug resistance determinants and plasmid replicons were consistent with continued evolution and persistence of these populations. Five ST258 outbreaks were documented, including three that were caused by the same clonal lineage. Mutations in genes encoding effectors of biofilm production and iron acquisition were identified among persistent clones. Two emergent lineages bearing K. pneumoniae integrative conjugative element 10 (ICEKp10) and harboring yersiniabactin and colibactin virulence factors were identified. The results show how distinct ST258 subpopulations have evolved and persisted within the same hospital over nearly a decade.IMPORTANCE The carbapenem class of antibiotics is invaluable for the treatment of selected multidrug-resistant Gram-negative pathogens. The continued transmission of carbapenem-resistant bacteria such as ST258 K. pneumoniae is of serious global public health concern, as treatment options for these infections are limited. This genomic epidemiologic investigation traced the natural history of ST258 K. pneumoniae in a single health care setting over nearly a decade. We found that distinct ST258 subpopulations have caused both device-associated and ward-associated outbreaks, and some of these populations remain endemic within our hospital to the present day. The finding of virulence determinants among emergent ST258 clones supports the idea of convergent evolution of drug-resistant and virulent CRKP strains and highlights the need for continued surveillance, prevention, and control efforts to address emergent and evolving ST258 populations in the health care setting.