Whole genome sequence typing and microarray profiling of nasal and blood stream methicillin-resistant Staphylococcus aureus isolates: Clues to phylogeny and invasiveness

Hamed, Mohamed; Nitsche-Schmitz, D. Patric; Ruffing, Ulla; Steglich, Matthias; Dordel, Janina; Nguyen, Duy; Brink, Jan-Hendrik; Chhatwal, Gursharan S.; Herrmann, Mathias; Nübel, Ulrich; Helms, Volkhard; Müller, Lutz von

doi:10.1016/j.meegid.2015.08.020

Cited by 7 publications

(7 citation statements)

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“…The knowledge of epidemiological links between isolates of our study cohort made us confident that the genomic outbreak view was more plausible and therefore more reliable than MLVA type clustering. While in line with previous reports spa typing concurred with WGS-based phylogeny 29,30 , it lacked the required resolution as exemplified by the five separate outbreaks that were identified under spa type t091 using comparative genomics. www.nature.com/scientificreports www.nature.com/scientificreports/ Because our specified genomic methods including particular SNP confidence requirements have not been applied before, the selected SNP threshold cannot be directly compared to that in other genomic outbreak studies.…”

Section: Discussionsupporting

confidence: 65%

“…A relative limitation of our genomic method is that Illumina sequencing followed by de novo assembly does not allow for complete reconstruction of bacterial genomes, partly at the expense of repetitive elements. Although this issue can be overcome by long-read sequencing technologies such as Oxford Nanopore [10] or Pacific Biosciences single-molecule real-time sequencing [10,30], it is unsure whether genetic information from such complex regions would improve outbreak tracing. Although the genomic analyses as performed in this initial study are computationally demanding, they served well for sorting unresolved transmission chains.…”

Section: Discussionmentioning

confidence: 99%

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Surveillance-embedded genomic outbreak resolution of methicillin-susceptible Staphylococcus aureus in a neonatal intensive care unit

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et al. 2020

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We observed an increase in methicillin-susceptible Staphylococcus aureus (MSSA) infections at a Dutch neonatal intensive care unit. Weekly neonatal MSSA carriage surveillance and cross-sectional screenings of health care workers (HCWs) were available for outbreak tracing. Traditional clustering of MSSA isolates by spa typing and Multiple-Locus Variable number tandem repeat Analysis (MLVA) suggested that nosocomial transmission had contributed to the infections. We investigated whether whole-genome sequencing (WGS) of MSSA surveillance would provide additional evidence for transmission. MSSA isolates from neonatal infections, carriage surveillance, and HCWs were subjected to WGS and bioinformatic analysis for identification and localization of high-quality single nucleotide polymorphisms, and in-depth analysis of subsets of isolates. By measuring the genetic diversity in background surveillance, we defined transmission-level relatedness and identified isolates that had been unjustly assigned to clusters based on MLVA, while spa typing was concordant but of insufficient resolution. Detailing particular subsets of isolates provided evidence that HCWs were involved in multiple outbreaks, yet it alleviated concerns about one particular HCW. The improved resolution and accuracy of genomic outbreak analyses substantially altered the view on outbreaks, along with apposite measures. Therefore, inclusion of the circulating background population has the potential to overcome current issues in genomic outbreak inference. In the third level neonatal intensive care unit (NICU) of our hospital, we observed a rise in methicillin-susceptible S. aureus (MSSA) infections in two consecutive years. Traditional MSSA typing methods brought the suspicion of health care workers (HCWs) being repeatedly involved in the outbreak transmission chains. However, as these traditional typing methods fell short in providing definitive answers, we set out to improve the resolution of our outbreak analysis by bacterial whole-genome sequencing (WGS). Neonates have an immature immune system and are susceptible to opportunistic bacterial infections, especially in case of premature birth. Important bacteria involved in outbreaks at NICUs causing neonatal infections are Enterobacteriaceae and S. aureus. Although many studies have emphasized transmission of MRSA (methicillin-resistant S. aureus), its susceptible variant MSSA is, depending on local epidemiology, generally a more frequent cause of neonatal infections 1-3. Neonatal bacterial infections are preceded by bacterial spread which involves both direct transmission by close interaction with visiting parents and HCWs and indirect

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Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Surveillance-embedded genomic outbreak resolution of methicillin-susceptible Staphylococcus aureus in a neonatal intensive care unit

Cremers

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Bleeker‐Rovers

et al. 2020

Sci Rep

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“…The knowledge of epidemiological links between isolates of our study cohort made us confident that the genomic outbreak view was more plausible and therefore more reliable than MLVA type clustering. While in line with previous reports Spa typing concurred with WGS-based phylogeny (26,27), it lacked the required resolution as exemplified by the five separate outbreaks that were identified under spa type t091 using comparative genomics. Because our specified genomic methods including particular SNP confidence requirements have not been applied before, the selected SNP threshold cannot be directly compared to that in other genomic outbreak studies.…”

Section: Discussionsupporting

confidence: 71%

Surveillance-embedded genomic outbreak resolution of methicillin-susceptibleStaphylococcus aureusin a neonatal intensive care unit

Cremers

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Bleeker-Rovers³

et al. 2019

Preprint

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BackgroundWe observed an increase in methicillin-susceptible Staphylococcus aureus (MSSA) infections among neonates at a Dutch third level neonatal intensive care unit. Weekly surveillance data of MSSA carriage among neonates and cross-sectional screenings of health care workers (HCWs) were available for outbreak tracing. While traditional typing of MSSA isolates by staphylococcal protein A gene (spa typing) and Multiple-Locus Variable number tandem repeat Analysis (MLVA) suggested that nosocomial transmission had contributed to the infections, here they lacked the resolution to draw solid conclusions. Methods MSSA isolates from neonatal infections, carriage surveillance, and HCWs were subjected to whole-genome sequencing and compared by a series of automated tools including de novo assembly, identification and localization of high-quality single nucleotide polymorphisms, and in-depth analysis of subsets of isolates. Outbreaks were defined as isolates that were more closely related than was to be expected from the genetic diversity in background surveillance. Results Genomic analysis identified isolates that had been unjustly assigned to clusters based on MLVA typing, while spa typing was concordant but of insufficient resolution. Detailing particular subsets of isolates further improved resolution and although it provided evidence that HCWs were involved in multiple outbreaks, it alleviated heavy concerns about one particular HCW. Genomic clustering of isolates based on deviations from background surveillance matched epidemiological patient linkage. Compared to MLVA typing, the genomic analysis demonstrated more, shorter, and re-assorted nosocomial transmission chains during this outbreak. Conclusions In this study the improved resolution and accuracy of genomic outbreak analyses compared to spa typing and MVLA substantially altered the view on outbreaks, along with apposite outbreak measures. Inclusion of the circulating background population has the potential to overcome current issues in genomic outbreak inference.

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“…Spa typing identified a total of 20 different spa types, with t003 being the most frequently represented type, and t504 genotype also being relatively frequent; the latter being a very typical regional strain closely related to the predominant t003 [ 49 ]. Both spa types encomprise 76% of the MRSA isolates recovered while other spa types were only sparsely encountered.…”

Section: Discussionmentioning

confidence: 99%

Methicillin-Resistant Staphylococcus aureus in Saarland, Germany: The Long-Term Care Facility Study

et al. 2016

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BackgroundMultiresistant organisms pose a threat for patients and care recipients. Control interventions need to be tailored to region, the type of institution considered, and risk factors. The German state of Saarland is ideally suited to study colonisation epidemiology throughout its various health and care institutions. After conclusion of a large admission prevalence study in acute care hospitals, we now performed a methicillin-resistant Staphylococcus aureus (MRSA) point prevalence study in Saarland long term care facilities (LTCF), allowing for a direct comparison with respect of MRSA prevalence and associated risk factors between these two institutional types located within a confined region.Methodology and Principal FindingsOf all LTCF of the region, 65/136 participated in the study performed between 09/2013 and 07/2014. Overall, complete microbiological specimen and questionnaires of 2,858 of 4,275 (66.8%) LTCF residents were obtained. 136/2,858 (4.8%) screened residents revealed MRSA carrier status. Multivariate risk factor analysis yielded ulcer/deep soft tissue infection, urinary tract catheter, and MRSA history with multiple MRSA decolonisation cycles to be independently associated with MRSA carrier status.ConclusionAs already known from previous studies, colonisation with MRSA is common in LTCF residents even in an area with relatively low MRSA prevalence. This found prevalence can now be related to the acute care admission prevalence (2.2%) as well as to the admission prevalence in acute care geriatric departments (7.6%). The common clonal attribution (spa type) of MRSA isolates prevalent in the LTCF population as well as in the acute care admission population points towards a close relationship between both types of institutions. However, the ostensible absence of risk factors such as “previous hospitalisation” in conjunction with newly identified factors such as “multiple decolonisation cycles” refers to MRSA colonisation risks independent of contact with acute care facilities. Overall, this large LTCF point prevalence study allows data-based, region-tailored decisions on MRSA screening policies and provides a basis for additional preventative measures.

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Whole genome sequence typing and microarray profiling of nasal and blood stream methicillin-resistant Staphylococcus aureus isolates: Clues to phylogeny and invasiveness

Cited by 7 publications

References 43 publications

Surveillance-embedded genomic outbreak resolution of methicillin-susceptible Staphylococcus aureus in a neonatal intensive care unit

Surveillance-embedded genomic outbreak resolution of methicillin-susceptible Staphylococcus aureus in a neonatal intensive care unit

Surveillance-embedded genomic outbreak resolution of methicillin-susceptibleStaphylococcus aureusin a neonatal intensive care unit

Methicillin-Resistant Staphylococcus aureus in Saarland, Germany: The Long-Term Care Facility Study

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