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.

Use of online tools for antimicrobial resistance prediction by whole-genome sequencing in methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE).

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.

Automated data mining of the electronic health record for investigation of healthcare-associated outbreaks.

Background: 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.

Statistical outbreak detection by joining medical records and pathogen similarity.

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.

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.

Phylogenomics of colistin-susceptible and resistant XDR Acinetobacter baumannii.

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.

Origin of the plasmid-mediated fosfomycin resistance gene fosA3.

Background: fosA3 is the most commonly reported plasmid-mediated fosfomycin resistance gene among Enterobacteriaceae.

Objectives: To identify the origin of fosA3.

Methods: The chromosome of Kluyvera georgiana clinical strain YDC799 was fully sequenced with single-molecule real-time sequencing.

Frequency and Mechanisms of Spontaneous Fosfomycin Nonsusceptibility Observed upon Disk Diffusion Testing of Escherichia coli.

Fosfomycin maintains activity against most clinical isolates, but the growth of colonies within the zone of inhibition around the fosfomycin disk is occasionally observed upon susceptibility testing. We aimed to estimate the frequency of such nonsusceptible inner colony mutants and identify the underlying resistance mechanisms. Disk diffusion testing of fosfomycin was performed on 649 multidrug-resistant clinical isolates collected between 2011 and 2015.

Structural modification of LPS in colistin-resistant, KPC-producing Klebsiella pneumoniae.

Background: Colistin resistance in Klebsiella pneumoniae typically involves inactivation or mutations of chromosomal genes mgrB, pmrAB or phoPQ, but data regarding consequent modifications of LPS are limited.

Objectives: To examine the sequences of chromosomal loci implicated in colistin resistance and the respective LPS-derived lipid A profiles using 11 pairs of colistin-susceptible and -resistant KPC-producing K. pneumoniae clinical strains.

Chromosomal 16S Ribosomal RNA Methyltransferase RmtE1 in Escherichia coli Sequence Type 448.

We identified rmtE1, an uncommon 16S ribosomal methyltransferase gene, in an aminoglycoside- and cephalosporin-resistant Escherichia coli sequence type 448 clinical strain co-harboring bla. Long-read sequencing revealed insertion of a 101,257-bp fragment carrying both resistance genes to the chromosome. Our findings underscore E.

Draft Genome Sequences of Four Hospital-Associated Pseudomonas putida Isolates.

We present here the draft genome sequences of four Pseudomonas putida isolates belonging to a single clone suspected for nosocomial transmission between patients and a bronchoscope in a tertiary hospital. The four genome sequences belong to a single lineage but contain differences in their mobile genetic elements.

Understanding the Unattached Population in Ontario: Evidence from the Primary Care Access Survey (PCAS).

To measure primary care access on an ongoing basis, the Ontario Ministry of Health and Long-Term Care implemented the Primary Care Access Survey (PCAS) in 2006. The PCAS, a cross-sectional telephone survey, samples approximately 8,400 Ontario adults each year. It collects information on access to a family doctor, use of services, health status and socio-demographics.

Gold, nickel and copper mining and processing.

Ore mining occurs in all Canadian provinces and territories except Prince Edward Island. Ores include bauxite, copper, gold, iron, lead and zinc. Workers in metal mining and processing are exposed, not only to the metal of interest, but also to various other substances prevalent in the industry, such as diesel emissions, oil mists, blasting agents, silica, radon, and arsenic.

Geographic dimensions of aging in Canada, 1991-2001.

Although population aging on a national scale has received much attention in Canada, its geographical dimensions have not. This paper examines the demographic processes that underlie population aging at the provincial and metropolitan scales for the periods 1991 to 1996 and 1996 to 2001. We differentiate between the effects of aging-in-place and net migration on population aging.

Biotransformation of selamectin with Streptomyces lydicus SX-1298 using a novel static agar fermentation system with Reemay mesh.

A novel approach to biotransformation is described using a solid medium matrix and Reemay mesh that gives efficient biotransformation of compounds with minimal matrices in the ensuing gum solids. Using this approach with a newly isolated biotransforming organism, Streptomyces lydicus SX1298, a series of hydroxylations and an O-demethylation is described for selamectin the first endectocide for cats and dogs.

Avermectins and flea control: structure-activity relationships and the selection of selamectin for development as an endectocide for companion animals.

Evaluation of a wide range of avermectin derivatives for flea activity in an in vitro feeding screen using the cat flea, Ctenocephalides felis, revealed a narrow structure-activity relationship (SAR) with activity surprisingly associated with monosaccharides and especially their C-5-oximes. We discovered commercially exploitable flea activity in a single compound, selamectin 33, which also possessed the necessary antiparasitic spectrum and margin of safety for development as a broad-spectrum companion animal endectocide.

Selamectin: a novel broad-spectrum endectocide for dogs and cats.

Selamectin, 25-cyclohexyl-25-de(1-methylpropyl)-5-deoxy-22, 23-dihydro-5-(hydroxyimino)-avermectin B1 monosaccharide, is a novel endectocide with a unique combination of efficacy and safety in dogs and cats following both oral and topical administration. The compound is active against fleas and ticks, intestinal hookworms and ascarids, and immature heartworms. Also it is well tolerated at higher dosages than 22,23-dihydroavermectin B1a (DHAVM) or milbemycin oxime in Collies, which is a breed known to exhibit idiosyncratic sensitivity to avermectins.

Production of 6-deoxy-13-cyclopropyl-erythromycin B by Saccharopolyspora erythraea NRRL 18643.

Cyclopropane carboxylic acid was fed to Saccharopolyspora erythraea NRRL 18643 (6-deoxyerythromycin producer), resulting in the production of 6-deoxy-13-cyclopropyl-erythromycin B. These studies provide further evidence that deoxyerythronolide B synthase has a relaxed specificity for the starter unit.

Novel erythromycins from a recombinant Saccharopolyspora erythraea strain NRRL 2338 pIG1. I. Fermentation, isolation and biological activity.

In a previous report, a plasmid, pIG1, which contained the loading domain from the Streptomyces avermitilis polyketide synthase (PKS), promoters from Streptomyces coelicolor and the DEBS1-TE truncated PKS from Saccharopolyspora erythraea, was integrated into the S. erythraea chromosome, effectively replacing the natural erythromycin loading domain with the avermectin loading domain. In this paper, we report the feeding of short-chained fatty acids to this recombinant strain, and its parent, NRRL 2338.

Microbial oxidative metabolism of diclofenac: production of 4'-hydroxydiclofenac using Epiccocum nigrum IMI354292.

The 4'-hydroxylated metabolite of diclofenac was produced by biocatalysis for probing specific human drug-metabolising enzymes (CYP2C9). An initial screen of 11 microorganisms was carried out (50 ml scale) to identify the organism best suited to the regioselective conversion of diclofenac to its 4'-hydroxylated metabolite. From this screen, the fungus Epicoccum nigrum IMI354292 was selected as the most suitable microorganism.

C-13 beta-acyloxymilbemycins, a new family of macrolides. Discovery, structural determination and biological properties.

A family of novel milbemycins possessing C-13 beta-acyloxy substitution was produced by Streptomyces hygroscopicus ATCC 53718. These compounds were detected by HPLC diode array analysis and possess anthelmintic and ectoparasiticidal activity. The origin of the oxygen atom at C-13 is discussed.

Novel avermectins produced by mutational biosynthesis.

Avermectins with a wide range of novel C-25 substituents have been prepared by feeding carboxylic acids or their biosynthetic precursors to a Streptomyces avermitilis mutant strain ATCC 53568. This organism lacks the ability to form isobutyric and S-2-methylbutyric acids from their 2-oxo acid precursors and thus is unable to produce natural avermectins unless supplied with these acids. The novel avermectins produced by mutational biosynthesis possess broad-spectrum antiparasitic activity.