Rapid Whole-Genome Sequencing for Investigation of a Neonatal MRSA Outbreak

By C. Köser, M. Holden, M. Ellington, E. Cartwright, N. Brown, A. Ogilvy-Stuart, L. Hsu, C. Chewapreecha, Nicholas J. Croucher, Simon R. Harris and 10 more. New England Journal of Medicine, 2012

673 citations recorded by the source corpus.

Background Isolates of methicillin-resistant Staphylococcus aureus (MRSA) belonging to a single lineage are often indistinguishable by means of current typing techniques. Whole-genome sequencing may provide improved resolution to define transmission pathways and characterize outbreaks. Methods We investigated a putative MRSA outbreak in a neonatal intensive care unit. By using rapid high-throughput sequencing technology with a clinically relevant turnaround time, we retrospectively sequenced the DNA from seven isolates associated with the outbreak and another seven MRSA isolates associated with carriage of MRSA or bacteremia in the same hospital. Results We constructed a phylogenetic tree by comparing single-nucleotide polymorphisms (SNPs) in the core genome to a reference genome (an epidemic MRSA clone, EMRSA-15 [sequence type 22]). This revealed a distinct cluster of outbreak isolates and clear separation between these and the nonoutbreak isolates. A previously missed transmission event was detected between two patients with bacteremia who were not part of the outbreak. We created an artificial “resistome” of antibiotic-resistance genes and demonstrated concordance between it and the results of phenotypic susceptibility testing; we also created a “toxome” consisting of toxin genes. One outbreak isolate had a hypermutator phenotype with a higher number of SNPs than the other outbreak isolates, highlighting the difficulty of imposing a simple threshold for the number of SNPs between isolates to decide whether they are part of a recent transmission chain. Conclusions Whole-genome sequencing can provide clinically relevant data within a time frame that can influence patient care. The need for automated data interpretation and the provision of clinically meaningful reports represent hurdles to clinical implementation. (Funded by the U.K. Clinical Research Collaboration Translational Infection Research Initiative and others.)

Subfields: Clinical Biochemistry, Infectious Diseases, Public Health, Environmental and Occupational Health

View Paper: https://www.semanticscholar.org/paper/908deda7523ca675e5f8a28da7145a4941a2951a

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Citations in the corpus

Circlator: automated circularization of genome assemblies using long sequencing reads (2015, background): “Whole-genome sequencing is already providing improved resolution in bacterial epidemiology [6] and allowing in silico prediction of antimicrobial resistance [7].”
Methicillin-Resistant Staphylococcus aureus: Molecular Characterization, Evolution, and Epidemiology (2018, methodology): “Further investigation is needed to define a cutoff for differences in identified SNPs and develop a strategy for automated data interpretation of an outbreak in clinical practice (361).”
Insights from 20 years of bacterial genome sequencing (2015, background): “The first (Köser et al. 2012) is a much more practical discussion on how to implement the routine use of WGS for diagnostics, biosurveillance, and public health benefits.”
Real-Time Whole-Genome Sequencing for Routine Typing, Surveillance, and Outbreak Detection of Verotoxigenic Escherichia coli (2014, background): “Several recent studies have already proved the usefulness of rapid benchtop sequencing for investigations of various outbreaks (4, 31, 32).”
High-Throughput Sequencing Technologies (2015, methodology): “HTS has also been employed in clinical contexts to monitor pathogen outbreaks, such as methicillinresistant S. aureus infections (Köser et al., 2012).”