Abstract

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) may cause prolonged outbreaks of infections in neonatal intensive care units (NICUs). While the specific factors favouring MRSA spread on neonatal wards are not well understood, colonized infants, their relatives, or health-care workers may all be sources for MRSA transmission. Whole-genome sequencing may provide a new tool for elucidating transmission pathways of MRSA at a local scale.Methods and FindingsWe applied whole-genome sequencing to trace MRSA spread in a NICU and performed a case-control study to identify risk factors for MRSA transmission. MRSA genomes had accumulated sequence variation sufficiently fast to reflect epidemiological linkage among individual patients, between infants and their mothers, and between infants and staff members, such that the relevance of individual nurses’ nasal MRSA colonization for prolonged transmission could be evaluated. In addition to confirming previously reported risk factors, we identified an increased risk of transmission from infants with as yet unknown MRSA colonisation, in contrast to known MRSA-positive infants.ConclusionsThe integration of epidemiological (temporal, spatial) and genomic data enabled the phylogenetic testing of several hypotheses on specific MRSA transmission routes within a neonatal intensive-care unit. The pronounced risk of transmission emanating from undetected MRSA carriers suggested that increasing the frequency or speed of microbiological diagnostics could help to reduce transmission of MRSA.

Highlights

  • Methicillin-resistant Staphylococcus aureus (MRSA) may cause prolonged outbreaks of infections in neonatal intensive care units (NICUs), which may require aggressive, multi-faceted infection control measures [1,2,3,4]

  • The integration of epidemiological and genomic data enabled the phylogenetic testing of several hypotheses on specific MRSA transmission routes within a neonatal intensive-care unit

  • The pronounced risk of transmission emanating from undetected MRSA carriers suggested that increasing the frequency or speed of microbiological diagnostics could help to reduce transmission of MRSA

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Summary

Introduction

Methicillin-resistant Staphylococcus aureus (MRSA) may cause prolonged outbreaks of infections in neonatal intensive care units (NICUs), which may require aggressive, multi-faceted infection control measures [1,2,3,4]. Epidemiological linkage between individual patients can be tested phylogenetically for pathogens that accumulate nucleic acid variation over sufficiently short timescales [14,15,16,17] While this concept and associated analysis tools were applied to rapidly evolving RNA viruses in the past, it was established only recently that MRSA may constitute such ‘‘measurably evolving populations’’, suggesting that sequencing MRSA genomes may provide a new tool to elucidate transmission chains and pathogen reservoirs [18,19]. Two recent papers reported that MRSA whole-genome sequencing was able to distinguish outbreak strains from unrelated strains within the same hospital Such sequence data could be generated and analysed quickly enough to impact on patient care [20,21]. Whole-genome sequencing may provide a new tool for elucidating transmission pathways of MRSA at a local scale

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