MRSA Outbreak Mystery Solved by DNA Sequencing

Joe Barber Jr, PhD

November 14, 2012

Whole-genome sequencing was used to successfully map methicillin-resistant Staphylococcus aureus (MRSA) transmission pathways that were missed by conventional methods, according to findings from a recent study.

Simon R. Harris, PhD, from the Wellcome Trust Sanger Institute in Cambridge, United Kingdom, and colleagues present their findings in an article published online November 14 in Lancet Infectious Disease.

The authors mention that the discriminatory power of whole-genome sequencing was previously established in the literature. "Whole-genome sequencing has sufficient discriminatory power to reconstruct intercontinental and local transmission of MRSA lineages," the authors write. "Furthermore, bench-top, rapid turnaround whole-genome sequencing was able to distinguish between MRSA isolates that were associated with a putative outbreak in a neonatal intensive care unit from those that were not associated with the outbreak."

As part of routine MRSA screening at the Cambridge University Hospital NHS Foundation Trust (a secondary and tertiary referral center) special care baby unit (SCBU), the authors identified 17 cases of MRSA carriage during a 6-month period, including 1 case identified after performing a deep clean and reinforcing infection control policy and practices. Although 12 of the 17 MRSA isolates were linked on the basis of their antibiotic susceptibility, the gaps in outbreaks and the lack of carriers detected during the gaps prevented the infection control team from determining whether an outbreak had occurred during the 6 months.

The authors then retrospectively assessed the 17 isolates by bacterial sequencing, which revealed that 14 of the isolates comprised a new sequence type that was designated ST2371. On expanding the investigation beyond the SCBU and initiating prospective surveillance, the authors identified an additional 10 cases of carriage of ST2371 isolates, 9 of which could be directly linked to the SCBU. Those patients received MRSA decolonization therapy.

Staff Member Carrier

Prospective surveillance led to the identification of a new MRSA carrier in the SBCU 64 days after the last previous MRSA-positive patient left the unit. After sequencing confirmed this patient carried an ST2371 isolate, the authors suspected that members of the staff could be carrying and transmitting the outbreak strain.

Screening of SCBU staff members revealed the colonization of a single staff member with MRSA, and sequencing revealed that the staff member carried an ST2371 isolate. Additional investigation revealed that genetic and phenotypic changes in the staff member's isolate corresponded with those of the last infected infants in the SCBU, further confirming the staff member as the source of the continued outbreak.

"Whole-genome sequencing of MRSA could make an important contribution to infection-control investigation and practice," the authors conclude. "Rapid sequencing would have confirmed the outbreak on SCBU close to its start point, and routine whole-genome sequencing of MRSA from all new cases identified in the microbiology laboratory would have rapidly drawn links between the SCBU and the community."

In a related commentary, Binh An Diep, PhD, from the University of California, San Francisco, and the University of California, Berkeley, agreed that whole-genome sequencing could make a substantial contribution to outbreak prevention and control. "The advent of high-throughput whole-genome sequencing has the potential to revolutionise outbreak investigations by providing a substantial advance in strain discriminatory power compared with traditional molecular methods such as pulsed-field gel electrophoresis and multilocus sequence typing," Dr. Diep writes.

One coauthor received support from Astellas Pharma to attend an advisory board meeting, one coauthor received support for conference travel and accommodation from Illumina, and one coauthor is a consultant for Pfizer. Dr. Harris, the remaining authors, and Dr. Diep have disclosed no relevant financial relationships.

Lancet Infect Dis. Published online November 14, 2012. Article abstract, Commentary extract