Pathogen genomics in healthcare: overcoming barriers to proactive surveillance.

Pathogen genomic surveillance in healthcare has the potential to enhance patient safety by detecting outbreaks earlier, thereby reducing morbidity and mortality. Despite benefits, there are barriers to adoption, including cost, expertise, and lack of standardized methodologies and incentives. This commentary advocates for 1) investment from healthcare payors, public health, and regulatory bodies and 2) additional research on genomic surveillance for improving patient outcomes and reducing infections.

Multiplexed PCR to measure growth rates of uropathogenic during experimental urinary tract infection.

Measuring bacterial growth rates is routine, however, determining growth rates during infection in host has been more challenging. Peak-to-trough ratio (PTR) is a technique for studying microbial growth dynamics, calculated using the ratio of replication origin () copies to that of the terminus (), as originally defined by whole genome sequencing (WGS). WGS presents significant challenges in terms of expense and data analysis complexity due to the presence of host DNA in the samples.

Flagellar switch inverted repeat impacts flagellar invertibility and varies RT027/MLST1 virulence.

RT027 strains cause infections that vary in severity from asymptomatic to lethal, but the molecular basis for this variability is poorly understood. Through comparative analyses of RT027 clinical isolates, we determined that isolates that exhibit greater variability in their flagellar gene expression exhibit greater virulence . flagellar genes are phase-variably expressed due to the site-specific inversion of the 5'UTR region, which reversibly generates ON vs.

Performance of CHROMagar ESBL media for the surveillance of extended-spectrum cephalosporin-resistant (ESCrE) from rectal swabs in Botswana.

Lack of laboratory capacity hampers consistent national antimicrobial resistance (AMR) surveillance. Chromogenic media may provide a practical screening tool for detection of individuals colonized by extended-spectrum beta-lactamase (ESBL)-producing organisms. CHROMagar ESBL media represent an adequate screening method for the detection of extended-spectrum cephalosporin-resistant (ESCrE), isolated from rectal swabs.

Association of patient clinical and gut microbiota features with vancomycin-resistant enterococci environmental contamination in nursing homes: a retrospective observational study.

Background: Preventing transmission is crucial for reducing infections with multidrug-resistant organisms (MDROs) in nursing homes. To identify resident characteristics associated with MDRO spread, we investigated associations between patient characteristics and contamination of their proximate room surfaces with vancomycin-resistant enterococci (VRE).

Methods: In this retrospective observational study, we used demographic and clinical data (including data on comorbidities, physical independence, catheter use within the past 30 days, and antibiotic exposure within the past 30 days) and surveillance cultures of patient body sites and room surfaces at enrolment and during weekly follow-up visits within the first month, and monthly thereafter (up to 6 months), in six US nursing homes collected in a previous clinical trial (September, 2016, to August, 2018).

Virulence and genomic diversity among clinical isolates of ST1 (BI/NAP1/027) Clostridioides difficile.

Clostridioides difficile produces toxins that damage the colonic epithelium, causing colitis. Variation in disease severity is poorly understood and has been attributed to host factors and virulence differences between C. difficile strains.

Distinct Origins and Transmission Pathways of across Three U.S. States.

Carbapenem-resistant (CRE) are among the most concerning antibiotic resistance threats due to high rates of multidrug resistance, transmissibility in health care settings, and high mortality rates. We evaluated the potential for regional genomic surveillance to track the spread of -carrying CRE (KPC-CRE) by using isolate collections from health care facilities in three U.S.

Getting the Most Out of Your Genome-Wide Association Study Using Polygenic Risk Scores.

Determining the risk of a phenotypic outcome is a complex balance of variants "for" or "against" the phenotype, which in the context of human genetic diseases have been summarized using polygenic risk scores. In a previously published article (K. T.

Virulence and genomic diversity among clinical isolates of ST1 (BI/NAP1/027) .

, a leading cause of nosocomial infection, produces toxins that damage the colonic epithelium and results in colitis that varies from mild to fulminant. Variation in disease severity is poorly understood and has been attributed to host factors (age, immune competence and intestinal microbiome composition) and/or virulence differences between strains, with some, such as the epidemic BI/NAP1/027 (MLST1) strain, being associated with greater virulence. We tested 23 MLST1(ST1) clinical isolates for virulence in antibiotic-treated C57BL/6 mice.

Genomic Investigation to Identify Sources of Severe Acute Respiratory Syndrome Coronavirus 2 Infection Among Healthcare Personnel in an Acute Care Hospital.

Background: Identifying the source of healthcare personnel (HCP) coronavirus disease 2019 (COVID-19) is important to guide occupational safety efforts. We used a combined whole genome sequencing (WGS) and epidemiologic approach to investigate the source of HCP COVID-19 at a tertiary-care center early in the COVID-19 pandemic.

Methods: Remnant nasopharyngeal swab samples from HCP and patients with polymerase chain reaction-proven COVID-19 from a period with complete sample retention (14 March 2020 to 10 April 2020) at Rush University Medical Center in Chicago, Illinois, underwent viral RNA extraction and WGS.

Risk Factors for Colistin-Resistant Carbapenem-Resistant in the Postacute Care Setting.

We assessed risk factors for colistin resistance among carbapenem-resistant (CRKP) from 375 patients in long-term acute care hospitals. Recent colistin or polymyxin B exposure was associated with increased odds of colistin resistance (adjusted odds ratio = 1.11 per day of exposure, 95% confidence interval = 1.

Characterization of resistance to newer antimicrobials among carbapenem-resistant in the post-acute-care setting.

We assessed susceptibility patterns to newer antimicrobial agents among clinical carbapenem-resistant (CRKP) isolates from patients in long-term acute-care hospitals (LTACHs) from 2014 to 2015. Meropenem-vaborbactam and imipenem-relebactam nonsusceptibility were observed among 9.9% and 9.

Threshold-free genomic cluster detection to track transmission pathways in health-care settings: a genomic epidemiology analysis.

Background: A crucial barrier to the routine application of whole-genome sequencing (WGS) for infection prevention is the insufficient criteria for determining whether a genomic linkage is consistent with transmission within the facility. We evaluated the use of single-nucleotide variant (SNV) thresholds, as well as a novel threshold-free approach, for inferring transmission linkages in a high-transmission setting.

Methods: We did a retrospective genomic epidemiology analysis of samples previously collected in the context of an intervention study at a long-term acute care hospital in the USA.

Strain Variation in Clostridioides difficile Cytotoxicity Associated with Genomic Variation at Both Pathogenic and Nonpathogenic Loci.

Clinical disease from Clostridioides difficile infection can be mediated by two toxins and their neighboring regulatory genes located within the five-gene pathogenicity locus (PaLoc). We provide several lines of evidence that the cytotoxicity of C. difficile may be modulated by genomic variants outside the PaLoc.

Ferric Citrate Uptake Is a Virulence Factor in Uropathogenic Escherichia coli.

More than half of women will experience a urinary tract infection (UTI), with uropathogenic Escherichia coli (UPEC) causing ~80% of uncomplicated cases. Iron acquisition systems are essential for uropathogenesis, and UPEC strains encode highly diverse iron acquisition systems, underlining their importance. However, a recent UPEC clinical isolate, HM7, lacks this diversity and instead encodes the synthesis pathway for a sole siderophore, enterobactin.

Phenotypic and Genomic Diversification in Complex Carbohydrate-Degrading Human Gut Bacteria.

Symbiotic bacteria are responsible for the majority of complex carbohydrate digestion in the human colon. Since the identities and amounts of dietary polysaccharides directly impact the gut microbiota, determining which microorganisms consume specific nutrients is central for defining the relationship between diet and gut microbial ecology. Using a custom phenotyping array, we determined carbohydrate utilization profiles for 354 members of the , a dominant saccharolytic phylum.

regentrans: a framework and R package for using genomics to study regional pathogen transmission.

Increasing evidence of regional pathogen transmission networks highlights the importance of investigating the dissemination of multidrug-resistant organisms (MDROs) across a region to identify where transmission is occurring and how pathogens move across regions. We developed a framework for investigating MDRO regional transmission dynamics using whole-genome sequencing data and created regentrans, an easy-to-use, open source R package that implements these methods (https://github.com/Snitkin-Lab-Umich/regentrans).

mikropml: User-Friendly R Package for Supervised Machine Learning Pipelines.

Machine learning (ML) for classification and prediction based on a set of features is used to make decisions in healthcare, economics, criminal justice and more. However, implementing an ML pipeline including preprocessing, model selection, and evaluation can be time-consuming, confusing, and difficult. Here, we present mikropml (prononced "meek-ROPE em el"), an easy-to-use R package that implements ML pipelines using regression, support vector machines, decision trees, random forest, or gradient-boosted trees.