A Complete Genome Screening Program of Clinical Methicillin-Resistant Staphylococcus aureus Isolates Identifies the Origin and Progression of a Neonatal Intensive Care Unit Outbreak

ABSTRACT Whole-genome sequencing (WGS) of Staphylococcus aureus is increasingly used as part of infection prevention practices. In this study, we established a long-read technology-based WGS screening program of all first-episode methicillin-resistant Staphylococcus aureus (MRSA) blood infections at a major urban hospital. A survey of 132 MRSA genomes assembled from long reads enabled detailed characterization of an outbreak lasting several months of a CC5/ST105/USA100 clone among 18 infants in a neonatal intensive care unit (NICU). Available hospital-wide genome surveillance data traced the origins of the outbreak to three patients admitted to adult wards during a 4-month period preceding the NICU outbreak. The pattern of changes among complete outbreak genomes provided full spatiotemporal resolution of its progression, which was characterized by multiple subtransmissions and likely precipitated by equipment sharing between adults and infants. Compared to other hospital strains, the outbreak strain carried distinct mutations and accessory genetic elements that impacted genes with roles in metabolism, resistance, and persistence. This included a DNA recognition domain recombination in the hsdS gene of a type I restriction modification system that altered DNA methylation. Transcriptome sequencing (RNA-Seq) profiling showed that the (epi)genetic changes in the outbreak clone attenuated agr gene expression and upregulated genes involved in stress response and biofilm formation. Overall, our findings demonstrate the utility of long-read sequencing for hospital surveillance and for characterizing accessory genomic elements that may impact MRSA virulence and persistence.

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An Outbreak of Methicillin-Resistant Staphylococcus aureus in a Neonatal Intensive Care Unit

Infection Control and Hospital Epidemiology ◽

10.1086/502217 ◽

2003 ◽

Vol 24 (5) ◽

pp. 317-321 ◽

Cited By ~ 107

Author(s):

Lisa Saiman ◽

Alicia Cronquist ◽

Fann Wu ◽

Juyan Zhou ◽

David Rubenstein ◽

...

Keyword(s):

Intensive Care Unit ◽

Staphylococcus Aureus ◽

Intensive Care ◽

Neonatal Intensive Care Unit ◽

Neonatal Intensive Care ◽

Methicillin Resistant ◽

Children's Hospital ◽

Surveillance Cultures ◽

Children’S Hospital ◽

Incident Cases

AbstractObjective:To describe the epidemiologic and molecular investigations that successfully contained an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) in a neonatal intensive care unit (NICU).Design:Isolates of MRSA were typed by pulsed-field gel electrophoresis (PFGE) and S. aureus protein A (spa).Setting:A level III-IV, 45-bed NICU located in a children's hospital within a medical center.Patients:Incident cases had MRSA isolated from clinical cultures (eg, blood) or surveillance cultures (ie, anterior nares).Interventions:Infected and colonized infants were placed on contact precautions, cohorted, and treated with mupirocin. Surveillance cultures were performed for healthcare workers (HCWs). Colonized HCWs were treated with topical mupirocin and hexachlorophene showers.Results:From January to March 2001, the outbreak strain of MRSA PFGE clone B, was harbored by 13 infants. Three (1.3%) of 235 HCWs were colonized with MRSA. Two HCWs, who rotated between the adult and the pediatric facility, harbored clone C. One HCW, who exclusively worked in the children's hospital, was colonized with clone B. From January 1999 to November 2000, 22 patients hospitalized in the adult facility were infected or colonized with clone B. Spa typing and PFGE yielded concordant results. PFGE clone B was identified as spa type 16, associated with outbreaks in Brazil and Hungary.Conclusions:A possible route of MRSA transmission was elucidated by molecular typing. MRSA appears to have been transferred from our adult facility to our pediatric facility by a rotating HCW. Spa typing allowed comparison of our institution's MRSA strains with previously characterized outbreak clones.

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