Rapid Whole-Genome Sequencing in a Neonatal MRSA Outbreak

Although rapid whole-genome sequencing has been successfully used as a research tool with discriminatory power in outbreaks, it is also potentially useful for its possible clinical utility in a diagnostic setting. A compelling target is invasive methicillin-resistant Staphylococcus aureus (MRSA) infection, a major public health problem related primarily to healthcare.

In 2005, an estimated 94,360 invasive MRSA infections (including 18,900 hospital-acquired cases of bacteremia) occurred in the United States; those 94,360 infections were associated with 18,650 deaths. Hospital stays for MRSA infections are costly compared with all other stays, and usually require twice the length of hospitalization.

It has been shown that whole-genome sequencing can be used to describe the intercontinental and local transmission of MRSA, however, the inability to provide sequence data within a clinically relevant time frame has been an obstacle for application in the clinical setting. In this retrospective investigation of a 2009 MRSA outbreak in an intensive-care unit in the United Kingdom [N Engl J Med. 2012;366(24):2267-2275], the authors used a rapid-sequencing platform to overcome the temporal barrier.

In 2009, an infant (Patient 1, the index case), who was colonized with MRSA, was admitted to the Rosie Hospital in Cambridge, where a 17-bassinet NICU and a 10-bassinet Special Care Baby Unit (SCBU) are located. All infants admitted to these units are screened for MRSA carriage on admission and then weekly thereafter.

The antibiogram of the MRSA isolate revealed differences from the prevalent MRSA clone in the authors’ hospital and across the United Kingdom (the epidemic MRSA clone EMRSA-15, sequence type 22, typically resistant to cefoxitin, erythromycin, and ciprofloxacin): the isolate from Patient 1 was also resistant to gentamicin and mupirocin. Infection-control measures were initiated, and a decolonization protocol undertaken, but this failed to eradicate MRSA colonization.

Patient 2 was admitted a week after Patient 1, with a negative result on MRSA screening, but MRSA colonization was found on repeat screening 37 days later. This isolate from Patient 2 had the same unusual antibiogram as the isolate from Patient 1, suggesting a transmission event. The hospital set up an investigation of the outbreak and instituted a program of targeted measures. Staff and parents were asked to comply with infection-control procedures. All infants and staff were screened for MRSA carriage. New admissions were screened, and all patients were screened weekly thereafter.

The investigators retrospectively sequenced the MRSA bacteremia isolate from Patient 1 and 6 others with MRSA carriage, who were believed to be part of the outbreak, as well as 7 others not thought to be associated with the outbreak. A phylogenetic tree was built by comparing single-nucleotide polymorphisms (SNPs) in the core genome to EMRSA-15, which revealed a distinct cluster of outbreak isolates and clear separation between these and the nonoutbreak isolates.

An artificial resistome of antibiotic-resistance genes was created, which demonstrated concordance between it and the results of phenotypic susceptibility testing. The authors also created a similar toxome that was comprised of toxin genes.

The authors stated that whole-genome sequencing could provide clinically relevant data within a time frame that can influence patient care, but that the need for automated data interpretation and provision of clinically meaningful reports are obstacles to clinical implementation.