We noted three key inconsistencies in the Moderna-funded cost-effectiveness analysis by Fust et al [...
View Article and Find Full Text PDFBackground: 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.
View Article and Find Full Text PDFThis review summarizes the recent Global Meningococcal Initiative (GMI) regional meeting, which explored meningococcal disease in North America. Invasive meningococcal disease (IMD) cases are documented through both passive and active surveillance networks. IMD appears to be decreasing in many areas, such as the Dominican Republic (2016: 18 cases; 2021: 2 cases) and Panama (2008: 1 case/100,000; 2021: <0.
View Article and Find Full Text PDFHealthcare-associated infections (HAIs) cause mortality, morbidity, and waste of health care resources. HAIs are also an important driver of antimicrobial resistance, which is increasing around the world. Beginning in November 2016, we instituted an initiative to detect outbreaks of HAIs using prospective whole-genome sequencing-based surveillance of bacterial pathogens collected from hospitalized patients.
View Article and Find Full Text PDFCarbapenem-resistant Acinetobacter baumannii (CR) is a major cause of health care-associated infections. CR is typically multidrug resistant, and infection is difficult to treat. Despite the urgent threat that CR poses, few systematic studies of CR clinical and molecular epidemiology have been conducted.
View Article and Find Full Text PDFSevere infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are often complicated by persistent bacteremia (PB) despite active antibiotic therapy. Antibiotic resistance rarely contributes to MRSA-PB, suggesting an important role for antibiotic tolerance pathways. To identify bacterial factors associated with PB, we sequenced the whole genomes of 206 MRSA isolates derived from 20 patients with PB and looked for genetic signatures of adaptive within-host evolution.
View Article and Find Full Text PDFBackground: 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.
Meningococcal disease is a life-threatening illness caused by the human-restricted bacterium Neisseria meningitidis. Outbreaks in the USA involve at least two cases in an organization or community caused by the same serogroup within three months. Genome comparisons, including phylogenetic analysis and quantification of genome distances can provide confirmatory evidence of pathogen transmission during an outbreak.
View Article and Find Full Text PDFBackground: 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.
Background: The mechanisms by which Neisseria meningitidis cause persistent human carriage and transition from carriage to invasive disease have not been fully elucidated.
Methods: Georgia and Maryland high school students were sampled for pharyngeal carriage of N. meningitidis during the 2006-2007 school year.
Multidrug-resistant bacteria pose a serious health threat, especially in hospitals. Horizontal gene transfer (HGT) of mobile genetic elements (MGEs) facilitates the spread of antibiotic resistance, virulence, and environmental persistence genes between nosocomial pathogens. We screened the genomes of 2173 bacterial isolates from healthcare-associated infections from a single hospital over 18 months, and identified identical nucleotide regions in bacteria belonging to distinct genera.
View Article and Find Full Text PDFWe describe 2 human cases of infection with a new Neisseria species (putatively N. brasiliensis), 1 of which involved bacteremia. Genomic analyses found that both isolates were distinct strains of the same species, were closely related to N.
View Article and Find Full Text PDFOXA-232 is an OXA-48-group class D β-lactamase that hydrolyzes expanded-spectrum cephalosporins and carbapenems at low levels. Clinical strains producing OXA-232 are sometimes susceptible to carbapenems, making it difficult to identify them in the clinical microbiology laboratory. We describe the development of carbapenem resistance in sequential clinical isolates of carrying in a hospitalized patient, where the ertapenem MIC increased from 0.
View Article and Find Full Text PDFCarbapenem-resistant (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 outbreak-causing lineages at a large tertiary care hospital over 8 years.
View Article and Find Full Text PDFWe report patient-to-patient transmission of isolates with reduced susceptibility to ceftazidime-avibactam due to production of KPC-40, a variant of KPC-3 with a two-amino-acid insertion in the Ω-loop region (L167_E168dup). The index patient had received a prolonged course of ceftazidime-avibactam therapy, whereas the second patient had not received the agent and still became colonized with the KPC-40-producing strain. The complex dynamics of KPC ( carbapenemase) described here highlight several key diagnostic and therapeutic considerations.
View Article and Find Full Text PDFBackground: 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.
View Article and Find Full Text PDFBackground: OXA-2 is a class D β-lactamase that confers resistance to penicillins, as well as narrow-spectrum cephalosporins. OXA-2 was recently reported to also possess carbapenem-hydrolysing activity. Here, we describe a KPC-2-encoding Klebsiella pneumoniae isolate that demonstrated reduced susceptibility to ceftazidime and ertapenem due to production of OXA-2.
View Article and Find Full Text PDFObjective: Describe the epidemiological and molecular characteristics of an outbreak of Klebsiella pneumoniae carbapenemase (KPC)-producing organisms and the novel use of a cohorting unit for its control.
Design: Observational study.
Setting: A 566-room academic teaching facility in Milwaukee, Wisconsin.
Objectives: The antimicrobial resistance (AMR) crisis represents a serious threat to public health and has resulted in concentrated efforts to accelerate development of rapid molecular diagnostics for AMR. In combination with publicly available web-based AMR databases, whole-genome sequencing (WGS) offers the capacity for rapid detection of AMR genes. Here we studied the concordance between WGS-based resistance prediction and phenotypic susceptibility test results for methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) clinical isolates using publicly available tools and databases.
View Article and Find Full Text PDFBackground: Identifying routes of transmission among hospitalized patients during a healthcare-associated outbreak can be tedious, particularly among patients with complex hospital stays and multiple exposures. Data mining of the electronic health record (EHR) has the potential to rapidly identify common exposures among patients suspected of being part of an outbreak.
Methods: We retrospectively analyzed 9 hospital outbreaks that occurred during 2011-2016 and that had previously been characterized both according to transmission route and by molecular characterization of the bacterial isolates.
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.
View Article and Find Full Text PDFJ Antimicrob Chemother
November 2018
Background: Acinetobacter baumannii is a healthcare-associated pathogen with high rates of carbapenem resistance. Colistin is now routinely used for treatment of infections by this pathogen. However, colistin use has been associated with development of resistance to this agent.
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