Molecular characterization of MRSA collected during national surveillance between 2008 and 2019 in the Netherlands

BACKGROUND: Although the Netherlands is a country with a low endemic level, methicillin-resistant Staphylococcus aureus (MRSA) poses a significant health care problem. Therefore, high coverage national MRSA surveillance has been in place since 1989. To monitor possible changes in the type-distribution and emergence of resistance and virulence, MRSA isolates are molecularly characterized.METHODS: All 43,321 isolates from 36,520 persons, collected 2008-2019, were typed by multiple-locus variable number tandem repeats analysis (MLVA) with simultaneous PCR detection of the mecA, mecC and lukF-PV genes, indicative for PVL. Next-generation sequencing data of 4991 isolates from 4798 persons were used for whole genome multi-locus sequence typing (wgMLST) and identification of resistance and virulence genes.RESULTS: We show temporal change in the molecular characteristics of the MRSA population with the proportion of PVL-positive isolates increasing from 15% in 2008-2010 to 25% in 2017-2019. In livestock-associated MRSA obtained from humans, PVL-positivity increases to 6% in 2017-2019 with isolates predominantly from regions with few pig farms. wgMLST reveals the presence of 35 genogroups with distinct resistance, virulence gene profiles and specimen origin. Typing shows prolonged persistent MRSA carriage with a mean carriage period of 407 days. There is a clear spatial and a weak temporal relationship between isolates that clustered in wgMLST, indicative for regional spread of MRSA strains.CONCLUSIONS: Using molecular characterization, this exceptionally large study shows genomic changes in the MRSA population at the national level. It reveals waxing and waning of types and genogroups and an increasing proportion of PVL-positive MRSA.</p

Dina D\u27Malkhuta Dina (The Law of the Kingdom is the Law)

A principle of Jewish law set forth in the Talmud is the law of the kingdom is the law . The Talmud attributes this principle to the Amora, Samuel, and it is quoted in his name a number of times.

Analytische beschrijving van vochtprofielen tijdens drogen

Het drogen van een materiaal wordt veelal beschreven met behulp van een niet-lineaire diffusievergelijking. Tot nu toe kon deze alleen worden opgelost met behulp van numerieke simulaties, maar die geven geen beter inzicht in het droogprobleem. Dit artikel geeft een analytische oplossing waarmee kan worden aangetoond dat het intrekkend droogfront een constante snelheid heeft die omgekeerd evenredig is met de lengte van het preparaat. Tot slot wordt een vergelijking gemaakt tussen met behulp van magnetische kernspinresonantie gemeten vochtprofielen en het analytische model

A VIM-1 positive strain in a near-drowning patient: evidence for interspecies plasmid transfer within the patient.

Aim: To show that a strain of Aeromonas hydrophila became resistant to carbapenems by interspecies transfer of a plasmid using long-read sequencing. Material & methods: Whole genome sequencing of the four isolates was done using Illumina Hiseq, while the plasmid was reconstructed using the MinION sequencer. The resistome was identified with ResFinder. Results: Whole genome sequencing and long-read sequencing showed that all isolates carried a blaVIM-1 gene located on a 165 kb incA/C plasmid. ResFinder confirmed that the resistome of the plasmid, comprising 13 resistance genes, was identical within all isolates. Discussion: Long-read sequencing using the MinION successfully reconstructed a plasmid that was identical in all isolates, providing evidence for horizontal gene transfer of this blaVIM-1 gene carrying plasmid within the patient

A VIM-1 positive strain in a near-drowning patient: evidence for interspecies plasmid transfer within the patient.

Aim: To show that a strain of Aeromonas hydrophila became resistant to carbapenems by interspecies transfer of a plasmid using long-read sequencing. Material & methods: Whole genome sequencing of the four isolates was done using Illumina Hiseq, while the plasmid was reconstructed using the MinION sequencer. The resistome was identified with ResFinder. Results: Whole genome sequencing and long-read sequencing showed that all isolates carried a blaVIM-1 gene located on a 165 kb incA/C plasmid. ResFinder confirmed that the resistome of the plasmid, comprising 13 resistance genes, was identical within all isolates. Discussion: Long-read sequencing using the MinION successfully reconstructed a plasmid that was identical in all isolates, providing evidence for horizontal gene transfer of this blaVIM-1 gene carrying plasmid within the patient

Next-Generation Sequence Analysis Reveals Transfer of Methicillin Resistance to a Methicillin-Susceptible Staphylococcus aureus Strain That Subsequently Caused a Methicillin-Resistant Staphylococcus aureus Outbreak: a Descriptive Study.

Resistance to methicillin in Staphylococcus aureus is caused primarily by the mecA gene, which is carried on a mobile genetic element, the staphylococcal cassette chromosome mec (SCCmec). Horizontal transfer of this element is supposed to be an important factor in the emergence of new clones of methicillin-resistant Staphylococcus aureus (MRSA) but has been rarely observed in real time. In 2012, an outbreak occurred involving a health care worker (HCW) and three patients, all carrying a fusidic acid-resistant MRSA strain. The husband of the HCW was screened for MRSA carriage, but only a methicillin-susceptible S. aureus (MSSA) strain, which was also resistant to fusidic acid, was detected. Multiple-locus variable-number tandem-repeat analysis (MLVA) typing showed that both the MSSA and MRSA isolates were MT4053-MC0005. This finding led to the hypothesis that the MSSA strain acquired the SCCmec and subsequently caused an outbreak. To support this hypothesis, next-generation sequencing of the MSSA and MRSA isolates was performed. This study showed that the MSSA isolate clustered closely with the outbreak isolates based on whole-genome multilocus sequence typing and single-nucleotide polymorphism (SNP) analysis, with a genetic distance of 17 genes and 44 SNPs, respectively. Remarkably, there were relatively large differences in the mobile genetic elements in strains within and between individuals. The limited genetic distance between the MSSA and MRSA isolates in combination with a clear epidemiologic link supports the hypothesis that the MSSA isolate acquired a SCCmec and that the resulting MRSA strain caused an outbreak

Attention deficit hyperactivity disorder late birthdate effect common in both high and low prescribing international jurisdictions: systematic review.

BACKGROUND: Multiple studies have found that the youngest children in a classroom are at elevated risk of being diagnosed with, or medicated for, ADHD. This systematic review was conducted to investigate whether this late birthdate effect is the norm and whether the strength of effect is related to the absolute risk of being diagnosed/medicated. METHODS: A literature search of the PubMed and ERIC databases and snowball and grey literature searching were conducted. RESULTS: A total of 19 studies in 13 countries covering over 15.4 million children investigating this relationship were identified. Three other studies exploring related topics were identified. The diversity of methodologies prevented a meta-analysis. Instead a systematic review of the 22 studies was conducted. A total of 17 of the 19 studies found that the youngest children in a school year were considerably more likely to be diagnosed and/or medicated than their older classmates. Two Danish studies found either a weak or no late birth date effect. There was no consistent relationship between per-capita diagnosis or medication rates and the strength of the relative age effect, with strong effects reported in most jurisdictions with comparatively low rates. CONCLUSIONS: It is the norm internationally for the youngest children in a classroom to be at increased risk of being medicated for ADHD, even in jurisdictions with relatively low prescribing rates. A lack of a strong effect in Denmark may be accounted for by the common practice of academic 'redshirting', where children judged by parents as immature have a delayed school start. Redshirting may prevent and/or disguise late birthdate effects and further research is warranted. The evidence of strong late birthdate effects in jurisdictions with comparatively low diagnosis/medication rates challenges the notion that low rates indicate sound diagnostic practices

Comparative analysis of IMP-4- and OXA-58-containing plasmids of three carbapenemase-producing Acinetobacter ursingii strains in the Netherlands.

A recent occurrence of carbapenemase-producing Acinetobacter ursingii was reported in the Netherlands and comprised three unrelated strains carrying the blaIMP-4 and blaOXA-58 encoding genes. The objective was to investigate a putative common source of the carbapenemase resistance genes and plasmids in these A. ursingii strains

Comparative analysis of IMP-4- and OXA-58-containing plasmids of three carbapenemase-producing Acinetobacter ursingii strains in the Netherlands.

A recent occurrence of carbapenemase-producing Acinetobacter ursingii was reported in the Netherlands and comprised three unrelated strains carrying the blaIMP-4 and blaOXA-58 encoding genes. The objective was to investigate a putative common source of the carbapenemase resistance genes and plasmids in these A. ursingii strains

bla OXA-48-like genome architecture among carbapenemase-producing and in the Netherlands.

Carbapenem-hydrolysing enzymes belonging to the OXA-48-like group are encoded by blaOXA-48-like alleles and are abundant among Enterobacterales in the Netherlands. Therefore, the objective here was to investigate the characteristics, gene content and diversity of the blaOXA-48-like carrying plasmids and chromosomes of Escherichia coli and Klebsiella pneumoniae collected in the Dutch national surveillance from 2014 to 2019 in comparison with genome sequences from 29 countries. A combination of short-read genome sequencing with long-read sequencing enabled the reconstruction of 47 and 132 complete blaOXA-48-like plasmids for E. coli and K. pneumoniae, respectively. Seven distinct plasmid groups designated as pOXA-48-1 to pOXA-48-5, pOXA-181 and pOXA-232 were identified in the Netherlands which were similar to internationally reported plasmids obtained from countries from North and South America, Europe, Asia and Oceania. The seven plasmid groups varied in size, G+C content, presence of antibiotic resistance genes, replicon family and gene content. The pOXA-48-1 to pOXA-48-5 plasmids were variable, and the pOXA-181 and pOXA-232 plasmids were conserved. The pOXA-48-1, pOXA-48-2, pOXA-48-3 and pOXA-48-5 groups contained a putative conjugation system, but this was absent in the pOXA-48-4, pOXA-181 and pOXA-232 plasmid groups. pOXA-48 plasmids contained the PemI antitoxin, while the pOXA-181 and pOXA-232 plasmids did not. Furthermore, the pOXA-181 plasmids carried a virB2-virB3-virB9-virB10-virB11 type IV secretion system, while the pOXA-48 plasmids and pOXA-232 lacked this system. A group of non-related pOXA-48 plasmids from the Netherlands contained different resistance genes, non-IncL-type replicons or no replicons. Whole genome multilocus sequence typing revealed that the blaOXA-48-like plasmids were found in a wide variety of genetic backgrounds in contrast to chromosomally encoded blaOXA-48-like alleles. Chromosomally localized blaOXA-48 and blaOXA-244 alleles were located on genetic elements of variable sizes and comprised regions of pOXA-48 plasmids. The blaOXA-48-like genetic element was flanked by a direct repeat upstream of IS1R, and was found at multiple locations in the chromosomes of E. coli. Lastly, K. pneumoniae isolates carrying blaOXA-48 or blaOXA-232 were mostly resistant for meropenem, whereas E. coli blaOXA-48, blaOXA-181 and chromosomal blaOXA-48 or blaOXA-244 isolates were mostly sensitive. In conclusion, the overall blaOXA-48-like plasmid population in the Netherlands is conserved and similar to that reported for other countries, confirming global dissemination of blaOXA-48-like plasmids. Variations in size, presence of antibiotic resistance genes and gene content impacted pOXA-48, pOXA-181 and pOXA-232 plasmid architecture