Abstract
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.
Highlights
We observed an increase in methicillin-susceptible Staphylococcus aureus (MSSA) infections at a Dutch neonatal intensive care unit
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
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)
Summary
We observed an increase in methicillin-susceptible Staphylococcus aureus (MSSA) infections at a Dutch neonatal intensive care unit. 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. Traditional MSSA typing methods brought the suspicion of health care workers (HCWs) being repeatedly involved in the outbreak transmission chains. 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). To monitor the dynamics of potential pathogens in a NICU, carriage surveillance should be performed, as implemented at our NICU for Enterobacteriaceae and (both methicillin-susceptible and resistant) S. aureus These advanced surveillance practices have become pivotal to the outbreak analysis performed in this study. MLVA has the largest discriminatory power[12], it covers only a fraction of the bacterial genetic material, and it is sensitive to influential sequencing errors
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