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Existing tools for phylogeographic and epidemiological visualisation primarily provide a macro-geographic view of epidemic and pandemic transmission events but offer little support for detailed investigation of outbreaks in healthcare settings. Here, we present HAIviz, an interactive web-based application designed for integrating and visualising genomic epidemiological information to improve the tracking of healthcare-associated infections (HAIs). HAIviz displays and links the outbreak timeline, building map, phylogenetic tree, patient bed movements, and transmission network on a single interactive dashboard. HAIviz has been developed for bacterial outbreak investigations but can be utilised for general epidemiological investigations focused on built environments for which visualisation to customised maps is required. This paper describes and demonstrates the application of HAIviz for HAI outbreak investigations.

To investigate an outbreak of vancomycin-resistant Enterococcus faecium (VREfm) sequence type 78 (ST78) in a large tertiary Australian hospital. A collection of 63 VREfm ST78 isolates, identified during a routine genomic surveillance program, were subjected to genomic epidemiological analysis based on whole-genome sequencing (WGS) data. The population structure was reconstructed using phylogenetic analysis, and a collection of publicly available VREfm ST78 genomes were used to provide global context. Core genome single nucleotide polymorphism (SNP) distances and available clinical metadata were used to characterize outbreak clusters and reconstruct transmission events. In silico genotyping confirmed that all study isolates were vanB -type VREfm carrying virulence characteristics of the hospital-associated E. faecium. Phylogenetic analysis identified two distinct phylogenetic clades, only one of which was responsible for a hospital outbreak. Four outbreak subtypes could be defined with examples of recent transmissions. Inference on transmission trees suggested complex transmission routes with unknown environmental reservoirs mediating the outbreak. WGS-based cluster analysis with publicly available genomes identified closely related Australian ST78 and ST203 isolates, highlighting the capacity for WGS to resolve complex clonal relationships between the VREfm lineages. Whole genome-based analysis has provided a high-resolution description of an outbreak of vanB -type VREfm ST78 in a Queensland hospital. Combined routine genomic surveillance and epidemiological analysis have facilitated better understanding of the local epidemiology of this endemic strain, providing valuable insight for better targeted control of VREfm. IMPORTANCE Vancomycin-resistant Enterococcus faecium (VREfm) is a leading cause of health care-associated infections (HAIs) globally. In Australia, the spread of hospital-adapted VREfm is largely driven by a single clonal group (clonal complex [CC]), CC17, to which the lineage ST78 belongs. While implementing a genomic surveillance program in Queensland, we observed increased incidence of ST78 colonizations and infections among patients. Here, we demonstrate the use of real-time genomic surveillance as a tool to support and enhance infection control (IC) practices. Our results show that real-time whole-genome sequencing (WGS) can efficiently disrupt outbreaks by identifying transmission routes that in turn can be targeted using resource-limited interventions. Additionally, we demonstrate that by placing local outbreaks in a global context, high-risk clones can be identified and targeted prior to them becoming established within clinical environments. Finally, the persistence of these organism within the hospital highlights the need for routine genomic surveillance as a management tool to control VRE transmission., Competing Interests: The authors declare no conflict of interest.

Background: Prospective whole-genome sequencing (WGS)-based surveillance may be the optimal approach to rapidly identify transmission of multi-drug resistant (MDR) bacteria in the healthcare setting., Methods: We prospectively collected methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), carbapenem-resistant Acinetobacter baumannii (CRAB), extended-spectrum beta-lactamase (ESBL-E), and carbapenemase-producing Enterobacterales (CPE) isolated from blood cultures, sterile sites, or screening specimens across three large tertiary referral hospitals (2 adult, 1 paediatric) in Brisbane, Australia. WGS was used to determine in silico multi-locus sequence typing (MLST) and resistance gene profiling via a bespoke genomic analysis pipeline. Putative transmission events were identified by comparison of core genome single nucleotide polymorphisms (SNPs). Relevant clinical meta-data were combined with genomic analyses via customised automation, collated into hospital-specific reports regularly distributed to infection control teams., Results: Over 4 years (April 2017 to July 2021) 2660 isolates were sequenced. This included MDR gram-negative bacilli (n = 293 CPE, n = 1309 ESBL), MRSA (n = 620), and VRE (n = 433). A total of 379 clinical reports were issued. Core genome SNP data identified that 33% of isolates formed 76 distinct clusters. Of the 76 clusters, 43 were contained to the 3 target hospitals, suggesting ongoing transmission within the clinical environment. The remaining 33 clusters represented possible inter-hospital transmission events or strains circulating in the community. In 1 hospital, proven negligible transmission of non-multi-resistant MRSA enabled changes to infection control policy., Conclusions: Implementation of routine WGS for MDR pathogens in clinical laboratories is feasible and can enable targeted infection prevention and control interventions., Competing Interests: Potential conflicts of interest. P. N. A. H. reports research grants from Merck, Sandoz, and Shionogi, outside the submitted work; has served on advisory boards for Sandoz and Merck, and has received speaker's fees from Pfizer, Sandoz, and Sumitomo. D. L. P reports research grants from Merck, Pfizer, and Shionogi outside the submitted work; has received honoraria for advisory board membership from Merck, Pfizer, Shionogi, GSK, QPex, Entasis, VenatoRx, BioMerieux, and Accelerate. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The epidemiology of Moraxella species bloodstream infection (BSI) is poorly defined due to their rarity. We sought to determine the incidence, risk factors, and outcomes of Moraxella species BSI in a large Australian population. All Moraxella species BSIs in patients admitted to Queensland (population estimate 5 million) public health facilities between 2000 and 2019 and submitted to Queensland pathology laboratory-based surveillance were included. Clinical and hospitalisation data were matched with laboratory-based surveillance data. Incidence rate ratios (IRR) with 95% confidence intervals (CI) were calculated. In total, 375 incident Moraxella species BSI occurred during 86 million person-years of surveillance, with an annualised age and sex standardised incidence of 4.3 per million residents. Isolates were most commonly identified as M. catarrhalis (n = 128; 34%) and community-associated (n = 225; 60%). Incidence was highest in infants, with increasing age associated with lower incidence rate. Males were at higher risk (incidence 2.9 vs. 2.0 per million, IRR1.4; 95% CI, 1.2-1.8), this was most pronounced at age extremes. Two-thirds of adults and 43% of children with Moraxella BSI had at least one comorbid illness. When compared to infections in adults, children were more likely to have community-associated disease, and a head and neck source focus of infection. The all-cause 30-day case-fatality rate was 4% (15/375) and this was significantly higher among adults (14/191; 7% vs 1/183; 1%; p < 0.001). Our findings demonstrate the low burden of Moraxella species BSI in a state-wide cohort, for which young children have the highest risk., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Although obesity is a major healthcare problem that is increasing in many populations worldwide, there are limited studies that have examined its contribution to infectious diseases morbidity and mortality. The aim of this study was to examine the clinical determinants and outcomes of bloodstream infections among patients with obesity. All adults within the publicly funded healthcare system in Queensland, Australia, identified with a BSI during 2017-2019 were included and the presence of obesity was based on discharge International Classification of Diseases (ICD-10) codes. Clinical features, microbiology, and outcomes were compared among obese and non-obese subjects. A total of 24,602 incident BSI were identified among 21,613 Queensland residents; of which 4,579 (21.2%) and 17,034 (78.8%) were classified as obese or non-obese, respectively. Obese patients were less likely to have community associated infections and were more likely to be younger, female, have higher comorbidity scores, and have bone and joint or soft tissue infections as compared to non-obese subjects. Obese patients had a lower proportion of Escherichia coli BSI and higher proportions of b-haemolytic streptococci. Although obese patients had longer hospital admissions and more repeat incident BSI within 1 year, they had lower overall case fatality. In a logistic regression model, obesity was associated with a lower risk for 30-day case fatality (adjusted odds ratio 0.51, 95% confidence interval 0.45-0.58). Obesity is associated with significant differences in the determinants and outcome of BSI. Increasing rates of obesity is likely to influence the epidemiology of BSI in populations., (© 2022. The Author(s).)

Background: Small case series and reports suggest that Sphingomonas paucimobilis is predominantly a cause of nosocomial bloodstream infections (BSI) with very low associated mortality. Our objective was to describe the epidemiology and outcome of Sphingomonas species BSI in a large Australian population., Methods: We included all residents of Queensland, Australia, with BSI because of Sphingomonas species identified within the publicly funded system from 2000 to 2019., Results: A total of 282 incident episodes of Sphingomonas species BSI were identified for an age- and sex-adjusted incidence of 3.2 per million population annually. Incidence rates were highest in the tropical regions of the state. Most (94%) of the isolates were confirmed as Sphingomonas paucimobilis. In addition, 77% of the infections were community-onset, of which 48% were community-associated, and 30% were healthcare-associated. The very young, the old, and male patients were at the highest risk. Patients with community-associated disease were, on average, younger, had fewer co-morbidities, and were less likely to have polymicrobial infections. At least 1 co-morbidity was identified in 62% of patients, with malignancy, diabetes, and lung disease most prevalent. The overall all-cause 30-day case-fatality rate was 6%., Conclusion: Sphingomonas paucimobilis BSI is a predominantly community-onset disease associated with a significant risk of death., Competing Interests: Conflict of interest The authors declare they have no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background. Infections caused by carbapenem-resistant Acinetobacter baumannii (CR-Ab) have become increasingly prevalent in clinical settings and often result in significant morbidity and mortality due to their multidrug resistance (MDR). Here we present an integrated whole-genome sequencing (WGS) response to a persistent CR-Ab outbreak in a Brisbane hospital between 2016-2018. Methods . A. baumannii, Klebsiella pneumoniae, Serratia marcescens and Pseudomonas aeruginosa isolates were sequenced using the Illumina platform primarily to establish isolate relationships based on core-genome SNPs, MLST and antimicrobial resistance gene profiles. Representative isolates were selected for PacBio sequencing. Environmental metagenomic sequencing with Illumina was used to detect persistence of the outbreak strain in the hospital. Results. In response to a suspected polymicrobial outbreak between May to August of 2016, 28 CR-Ab (and 21 other MDR Gram-negative bacilli) were collected from Intensive Care Unit and Burns Unit patients and sent for WGS with a 7 day turn-around time in clinical reporting. All CR-Ab were sequence type (ST)1050 (Pasteur ST2) and within 10 SNPs apart, indicative of an ongoing outbreak, and distinct from historical CR-Ab isolates from the same hospital. Possible transmission routes between patients were identified on the basis of CR-Ab and K. pneumoniae SNP profiles. Continued WGS surveillance between 2016 to 2018 enabled suspected outbreak cases to be refuted, but a resurgence of the outbreak CR-Ab mid-2018 in the Burns Unit prompted additional screening. Environmental metagenomic sequencing identified the hospital plumbing as a potential source. Replacement of the plumbing and routine drain maintenance resulted in rapid resolution of the secondary outbreak and significant risk reduction with no discernable transmission in the Burns Unit since. Conclusion. We implemented a comprehensive WGS and metagenomics investigation that resolved a persistent CR-Ab outbreak in a critical care setting.

Objective: To predict the cost and health effects of routine use of whole-genome sequencing (WGS) of bacterial pathogens compared with those of standard of care., Design: Budget impact analysis was performed over the following 5 years. Data were primarily from sequencing results on clusters of multidrug-resistant organisms across 27 hospitals. Model inputs were derived from hospitalisation and sequencing data, and epidemiological and costing reports, and included multidrug resistance rates and their trends., Setting: Queensland, Australia., Participants: Hospitalised patients., Interventions: WGS surveillance of six common multidrug-resistant organisms ( Staphylococcus aureus , Escherichia coli , Enterococcus faecium , Klebsiella pneumoniae , Enterobacter sp and Acinetobacter baumannii ) compared with standard of care or routine microbiology testing., Primary and Secondary Outcomes: Expected hospital costs, counts of patient infections and colonisations, and deaths from bloodstream infections., Results: In 2021, 97 539 patients in Queensland are expected to be infected or colonised with one of six multidrug-resistant organisms with standard of care testing. WGS surveillance strategy and earlier infection control measures could avoid 36 726 infected or colonised patients and avoid 650 deaths. The total cost under standard of care was $A170.8 million in 2021. WGS surveillance costs an additional $A26.8 million but was offset by fewer costs for cleaning, nursing, personal protective equipment, shorter hospital stays and antimicrobials to produce an overall cost savings of $30.9 million in 2021. Sensitivity analyses showed cost savings remained when input values were varied at 95% confidence limits., Conclusions: Compared with standard of care, WGS surveillance at a state-wide level could prevent a substantial number of hospital patients infected with multidrug-resistant organisms and related deaths and save healthcare costs. Primary prevention through routine use of WGS is an investment priority for the control of serious hospital-associated infections., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The Elizabethkingia genus has gained global attention in recent years as containing sporadic, worldwide, nosocomial pathogens. Elizabethkingia spp. are intrinsically multidrug resistant, primarily infect immunocompromised individuals, and are associated with high mortality (∼20 to 40%). As yet, gaps remain in our understanding of transmission, global strain relatedness, antimicrobial resistance, and effective therapy. Over a 16-year period, 22 clinical and 6 hospital environmental isolates were collected from Queensland, Australia. Identification using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) (Vitek MS) and whole-genome sequencing was compared with a global strain data set. Phylogenomic reconstruction robustly identified 22 Elizabethkingia anophelis , 3 Elizabethkingia miricola , 2 Elizabethkingia meningoseptica , and 1 Elizabethkingia bruuniana isolates, most of which branched as unique lineages. Global analysis revealed that some Australian E. anophelis isolates are genetically closely related to strains from the United States, England, and Asia. Comparative genomics of clinical and environmental strains identified evidence of nosocomial transmission in patients, indicating probable infection from a hospital reservoir. Furthermore, broth microdilution against 39 antimicrobials revealed almost ubiquitous resistance to aminoglycosides, carbapenems, cephalosporins, and penicillins. Like other international strains, our isolates expressed susceptibility to minocycline and levofloxacin and the less common trimethoprim-sulfamethoxazole. Our study demonstrates important new insights into the genetic diversity, environmental persistence, and transmission of and potential effective therapy for Australian Elizabethkingia species., (© Crown copyright 2020.)

Klebsiella species are problematic pathogens in neonatal units and may cause outbreaks, for which the sources of transmission may be challenging to elucidate. We describe the use of whole-genome sequencing (WGS) to investigate environmental sources of transmission during an outbreak of extended-spectrum-β-lactamase (ESBL)-producing Klebsiella michiganensis colonizing neonates. Ceftriaxone-resistant Klebsiella spp. isolated from neonates (or their mothers) and the hospital environment were included. Short-read sequencing (Illumina) and long-read sequencing (MinION; Oxford Nanopore Technologies) were used to confirm species taxonomy, to identify antimicrobial resistance genes, and to determine phylogenetic relationships using single-nucleotide polymorphism profiling. A total of 21 organisms (10 patient-derived isolates and 11 environmental isolates) were sequenced. Standard laboratory methods identified the outbreak strain as an ESBL-producing Klebsiella oxytoca , but taxonomic assignment from WGS data suggested closer identity to Klebsiella michiganensis Strains isolated from multiple detergent-dispensing bottles were either identical or closely related by single-nucleotide polymorphism comparison. Detergent bottles contaminated by K. michiganensis had been used for washing milk expression equipment. No new cases were identified once the detergent bottles were removed. Environmental reservoirs may be an important source in outbreaks of multidrug-resistant organisms. WGS, in conjunction with traditional epidemiological investigation, can be instrumental in revealing routes of transmission and guiding infection control responses., (Copyright © 2020 American Society for Microbiology.)

Stenotrophomonas maltophilia is emerging as an important cause of disease in nosocomial and community-acquired settings, including bloodstream, wound and catheter-associated infections. Cystic fibrosis (CF) airways also provide optimal growth conditions for various opportunistic pathogens with high antibiotic tolerance, including S. maltophilia . Currently, there is no rapid, cost-effective and accurate molecular method for detecting this potentially life-threatening pathogen, particularly in polymicrobial specimens, suggesting that its true prevalence is underestimated. Here, we used large-scale comparative genomics to identify a specific genetic target for S. maltophilia , with subsequent development and validation of a real-time PCR assay for its detection. Analysis of 167 Stenotrophomonas spp. genomes identified a conserved 4 kb region in S. maltophilia , which was targeted for Black Hole Quencher assay design. Our assay yielded the positive detection of 89 of 89 (100%) clinical S. maltophilia strains, and no amplification of 23 non- S. maltophilia clinical isolates. S. maltophilia was detected in 10 of 16 CF sputa, demonstrating the assay's utility for direct detection in respiratory specimens. The assay demonstrated good sensitivity, with limits of detection and quantitation on pure culture of ~10 and ~100 genome equivalents, respectively. Our assay provides a highly specific, sensitive and cost-effective method for the accurate identification of S. maltophilia , and will improve the diagnosis and treatment of this under-recognized pathogen by enabling its accurate and rapid detection from polymicrobial clinical and environmental samples.