Whole-genome sequencing for analysis of an outbreak of meticillin-resistant Staphylococcus aureus: a descriptive study

Abstract

Background: The emergence of meticillin-resistant Staphylococcus aureus (MRSA) that can persist in the community and replace existing hospital-adapted lineages of MRSA means that it is necessary to understand transmission dynamics in terms of hospitals and the community as one entity. We assessed the use of whole-genome sequencing to enhance detection of MRSA transmission between these settings.

Methods: We studied a putative MRSA outbreak on a special care baby unit (SCBU) at a National Health Service Foundation Trust in Cambridge, UK. We used whole-genome sequencing to validate and expand findings from an infection-control team who assessed the outbreak through conventional analysis of epidemiological data and antibiogram profiles. We sequenced isolates from all colonised patients in the SCBU, and sequenced MRSA isolates from patients in the hospital or community with the same antibiotic susceptibility profile as the outbreak strain.

Findings: The hospital infection-control team identified 12 infants colonised with MRSA in a 6 month period in 2011, who were suspected of being linked, but a persistent outbreak could not be confirmed with conventional methods. With whole-genome sequencing, we identified 26 related cases of MRSA carriage, and showed transmission occurred within the SCBU, between mothers on a postnatal ward, and in the community. The outbreak MRSA type was a new sequence type (ST) 2371, which is closely related to ST22, but contains genes encoding Panton-Valentine leucocidin. Whole-genome sequencing data were used to propose and confirm that MRSA carriage by a staff member had allowed the outbreak to persist during periods without known infection on the SCBU and after a deep clean.

Interpretation: Whole-genome sequencing holds great promise for rapid, accurate, and comprehensive identification of bacterial transmission pathways in hospital and community settings, with concomitant reductions in infections, morbidity, and costs.

Funding: UK Clinical Research Collaboration Translational Infection Research Initiative, Wellcome Trust, Health Protection Agency, and the National Institute for Health Research Cambridge Biomedical Research Centre.

Figure

Epidemiology and phylogeny of an outbreak of MRSA sequence type 2371 (A) Epidemiological map of 14 infants on the SCBU (patients 1–14). (B) Phylogenetic tree based on whole-genome sequencing of MRSA isolates from patients 1–14. (C) Epidemiological map of patients 1–14 and ten other patients (patients 16, 17, and 19–26) with linked MRSA infection detected in the community; coloured lines link members of the same family. (D) Phylogenetic tree based on whole-genome sequencing of MRSA isolates from patients 1–14 and patients 16, 17, and 19–26. (E) Epidemiological map of all cases of MRSA identified by whole-genome sequencing, and one patient (patient 18) suspected of being linked to the outbreak but for whom no MRSA colonisation was detected. (F) Phylogenetic tree of all cases of MRSA in the outbreak; 20 individual MRSA colonies from a staff member are shown in red boxes, with multiple colonies from the staff member shown in parentheses. Boxes shown for infants on SCBU in panel A represent duration of hospital stay (black boxes show infants included by the infection-control investigation and white boxes show infants excluded by the infection-control team). Grey vertical blocks in A, C, and E show times on the SCBU when there were no known carriers of MRSA. MRSA=meticillin-resistant Staphylococcus aureus. SCBU=special care baby unit. SNP=single-nucleotide polymorphism. P=patient.*Out-group was the sequence type 22 reference genome.