Association Between the Sequence of β-lactam and Vancomycin Administration and Mortality in Patients with Suspected Sepsis.

Background: Timely antibiotic initiation is critical to sepsis management, but there are limited data on the impact of giving β-lactams first vs vancomycin first amongst patients prescribed both agents.

Methods: We retrospectively analyzed all adults admitted to 5 US hospitals from 2015-2022 with suspected sepsis (blood culture collected, antibiotics administered, and organ dysfunction) treated with vancomycin and a broad-spectrum β-lactam within 24h of arrival. We estimated associations between β-lactam vs vancomycin first strategies and in-hospital mortality using inverse probability weighting (IPW) to adjust for potential confounders.

Assessment of Racial, Ethnic, and Sex-Based Disparities in Time-to-Antibiotics and Sepsis Outcomes in a Large Multihospital Cohort.

Objectives: To characterize associations between race/ethnicity/sex, time-to-antibiotics, and mortality in patients with suspected sepsis or septic shock.

Design: Retrospective cohort study, with race/ethnicity/sex as the exposure, and time-to-antibiotics (relative to emergency department arrival) and in-hospital mortality as the outcome.

Setting: Five Massachusetts hospitals.

Morbidity and Mortality of Hospital-Onset SARS-CoV-2 Infections Due to Omicron Versus Prior Variants : A Propensity-Matched Analysis.

Background: Many hospitals have scaled back measures to prevent nosocomial SARS-CoV-2 infection given large decreases in the morbidity and mortality of SARS-CoV-2 infections for most people. Little is known, however, about the morbidity and mortality of nosocomial SARS-CoV-2 infections for hospitalized patients in the Omicron era.

Objective: To estimate the effect of nosocomial SARS-CoV-2 infection on hospitalized patients' outcomes during the pre-Omicron and Omicron periods.

Risk of Misleading Conclusions in Observational Studies of Time-to-Antibiotics and Mortality in Suspected Sepsis.

Background: Influential studies conclude that each hour until antibiotics increases mortality in sepsis. However, these analyses often (1) adjusted for limited covariates, (2) included patients with long delays until antibiotics, (3) combined sepsis and septic shock, and (4) used linear models presuming each hour delay has equal impact. We evaluated the effect of these analytic choices on associations between time-to-antibiotics and mortality.

In Support of Universal Admission Testing for SARS-CoV-2 During Significant Community Transmission.

Many hospitals have stopped or are considering stopping universal admission testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We discuss reasons why admission testing should still be part of a layered system to prevent hospital-acquired SARS-CoV-2 infections during times of significant community transmission. These include the morbidity of SARS-CoV-2 in vulnerable patients, the predominant contribution of presymptomatic and asymptomatic people to transmission, the high rate of transmission between patients in shared rooms, and data suggesting surveillance testing is associated with fewer nosocomial infections.

Timing and Spectrum of Antibiotic Treatment for Suspected Sepsis and Septic Shock: Why so Controversial?

Sepsis guidelines and mandates encourage increasingly aggressive time-to-antibiotic targets for broad-spectrum antimicrobials for suspected sepsis and septic shock. This has caused considerable controversy due to weaknesses in the underlying evidence and fear that overly strict antibiotic deadlines may harm patients by perpetuating or escalating overtreatment. Indeed, a third or more of patients currently treated for sepsis and septic shock have noninfectious or nonbacterial conditions.

Real-Time Investigation of a Large Nosocomial Influenza A Outbreak Informed by Genomic Epidemiology.

Background: Nosocomial respiratory virus outbreaks represent serious public health challenges. Rapid and precise identification of cases and tracing of transmission chains is critical to end outbreaks and to inform prevention measures.

Methods: We combined conventional surveillance with influenza A virus (IAV) genome sequencing to identify and contain a large IAV outbreak in a metropolitan healthcare system.

PathoSPOT genomic epidemiology reveals under-the-radar nosocomial outbreaks.

Background: Whole-genome sequencing (WGS) is increasingly used to map the spread of bacterial and viral pathogens in nosocomial settings. A limiting factor for more widespread adoption of WGS for hospital infection prevention practices is the availability of standardized tools for genomic epidemiology.

Methods: We developed the Pathogen Sequencing Phylogenomic Outbreak Toolkit (PathoSPOT) to automate integration of genomic and medical record data for rapid detection and tracing of nosocomial outbreaks.

Epigenomic characterization of Clostridioides difficile finds a conserved DNA methyltransferase that mediates sporulation and pathogenesis.

Clostridioides (formerly Clostridium) difficile is a leading cause of healthcare-associated infections. Although considerable progress has been made in the understanding of its genome, the epigenome of C. difficile and its functional impact has not been systematically explored.

A Complete Genome Screening Program of Clinical Methicillin-Resistant Staphylococcus aureus Isolates Identifies the Origin and Progression of a Neonatal Intensive Care Unit Outbreak.

Whole-genome sequencing (WGS) of is increasingly used as part of infection prevention practices. In this study, we established a long-read technology-based WGS screening program of all first-episode methicillin-resistant (MRSA) blood infections at a major urban hospital. A survey of 132 MRSA genomes assembled from long reads enabled detailed characterization of an outbreak lasting several months of a CC5/ST105/USA100 clone among 18 infants in a neonatal intensive care unit (NICU).

Comprehensive innate immune profiling of chikungunya virus infection in pediatric cases.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes global epidemics of debilitating disease worldwide. To gain functional insight into the host cellular genes required for virus infection, we performed whole-blood RNA-seq, 37-plex mass cytometry of peripheral blood mononuclear cells (PBMCs), and serum cytokine measurements of acute- and convalescent-phase samples obtained from 42 children naturally infected with CHIKV Semi-supervised classification and clustering of single-cell events into 57 sub-communities of canonical leukocyte phenotypes revealed a monocyte-driven response to acute infection, with the greatest expansions in "intermediate" CD14CD16 monocytes and an activated subpopulation of CD14 monocytes. Increases in acute-phase CHIKV envelope protein E2 expression were highest for monocytes and dendritic cells.

Genome Plasticity of -Defective Staphylococcus aureus during Clinical Infection.

Therapy for bacteremia caused by is often ineffective, even when treatment conditions are optimal according to experimental protocols. Adapted subclones, such as those bearing mutations that attenuate -mediated virulence activation, are associated with persistent infection and patient mortality. To identify additional alterations in -defective mutants, we sequenced and assembled the complete genomes of clone pairs from colonizing and infected sites of several patients in whom demonstrated a within-host loss of function.

Genetic Basis of Emerging Vancomycin, Linezolid, and Daptomycin Heteroresistance in a Case of Persistent Enterococcus faecium Bacteremia.

Whole-genome sequencing was used to examine a persistent bacteremia that acquired heteroresistance to three antibiotics in response to prolonged multidrug therapy. A comparison of the complete genomes before and after each change revealed the emergence of known resistance determinants for vancomycin and linezolid and suggested that a novel mutation in , encoding a fatty acid synthase, was responsible for daptomycin nonsusceptibility. Plasmid recombination contributed to the progressive loss of vancomycin resistance after withdrawal of the drug.

Estimating Local Costs Associated With Clostridium difficile Infection Using Machine Learning and Electronic Medical Records.

BACKGROUND Reported per-patient costs of Clostridium difficile infection (CDI) vary by 2 orders of magnitude among different hospitals, implying that infection control officers need precise, local analyses to guide rational decision making between interventions. OBJECTIVE We sought to comprehensively estimate changes in length of stay (LOS) attributable to CDI at a single urban tertiary-care facility using only data automatically extractable from the electronic medical record (EMR). METHODS We performed a retrospective cohort study of 171,938 visits spanning a 7-year period.

High-dimensional CyTOF analysis of dengue virus-infected human DCs reveals distinct viral signatures.

Dengue virus (DENV) is the most prevalent mosquito-borne virus causing human disease. Of the 4 DENV serotypes, epidemiological data suggest that DENV-2 secondary infections are associated with more severe disease than DENV-4 infections. Mass cytometry by time-of-flight (CyTOF) was used to dissect immune changes induced by DENV-2 and DENV-4 in human DCs, the initial targets of primary infections that likely affect infection outcomes.

Genomic confirmation of vancomycin-resistant Enterococcus transmission from deceased donor to liver transplant recipient.

In a liver transplant recipient with vancomycin-resistant Enterococcus (VRE) surgical site and bloodstream infection, a combination of pulsed-field gel electrophoresis, multilocus sequence typing, and whole genome sequencing identified that donor and recipient VRE isolates were highly similar when compared to time-matched hospital isolates. Comparison of de novo assembled isolate genomes was highly suggestive of transplant transmission rather than hospital-acquired transmission and also identified subtle internal rearrangements between donor and recipient missed by other genomic approaches. Given the improved resolution, whole-genome assembly of pathogen genomes is likely to become an essential tool for investigation of potential organ transplant transmissions.

Whole-genome sequencing identifies emergence of a quinolone resistance mutation in a case of Stenotrophomonas maltophilia bacteremia.

Whole-genome sequences for Stenotrophomonas maltophilia serial isolates from a bacteremic patient before and after development of levofloxacin resistance were assembled de novo and differed by one single-nucleotide variant in smeT, a repressor for multidrug efflux operon smeDEF. Along with sequenced isolates from five contemporaneous cases, they displayed considerable diversity compared against all published complete genomes. Whole-genome sequencing and complete assembly can conclusively identify resistance mechanisms emerging in S.

How next-generation sequencing and multiscale data analysis will transform infectious disease management.

Recent reviews have examined the extent to which routine next-generation sequencing (NGS) on clinical specimens will improve the capabilities of clinical microbiology laboratories in the short term, but do not explore integrating NGS with clinical data from electronic medical records (EMRs), immune profiling data, and other rich datasets to create multiscale predictive models. This review introduces a range of "omics" and patient data sources relevant to managing infections and proposes 3 potentially disruptive applications for these data in the clinical workflow. The combined threats of healthcare-associated infections and multidrug-resistant organisms may be addressed by multiscale analysis of NGS and EMR data that is ideally updated and refined over time within each healthcare organization.

A user-editable web-based platform to streamline clinical information flow.

Frequent turnover of staff in medical clinics creates challenges in the maintenance of clinical protocols, workflows, and information management. Care coordination between providers in such a setting can be complex; disruptions in communication may lead to poorer health outcomes and patient satisfaction. Furthermore, protocols change frequently in response to new guidelines, which demands rapid updates to maintain compliance.

ChromoZoom: a flexible, fluid, web-based genome browser.

Unlabelled: Current web-based genome browsers require repetitious user input to scroll over long distances, alter the drawing density of elements or zoom through multiple orders of magnitude. Generally, either the server or the client is responsible for the majority of data processing, resulting in either servers having to receive and handle data relevant only to one user, or clients redundantly processing widely viewed data. ChromoZoom pre-renders and caches general-use tracks into tiled images on the server and serves them in an interactive web interface with inertial scrolling and precise, fluent zooming via the mouse wheel or trackpad.

Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins.

Genotypic differences greatly influence susceptibility and resistance to disease. Understanding genotype-phenotype relationships requires that phenotypes be viewed as manifestations of network properties, rather than simply as the result of individual genomic variations. Genome sequencing efforts have identified numerous germline mutations, and large numbers of somatic genomic alterations, associated with a predisposition to cancer.

Sequence-based estimation of minisatellite and microsatellite repeat variability.

Variable tandem repeats are frequently used for genetic mapping, genotyping, and forensics studies. Moreover, variation in some repeats underlies rapidly evolving traits or certain diseases. However, mutation rates vary greatly from repeat to repeat, and as a consequence, not all tandem repeats are suitable genetic markers or interesting unstable genetic modules.