Friday 7 December 2012

MRSA testing by NGS

A recent Lancet paper (Whole-genome sequencing for analysis of an outbreak of meticillin-resistant Staphylococcusaureus: a descriptive study) describes work in the Rosie’s special care bay unit at Addenbrookes hospital in Cambridge (just across the road from where I work).

The group studied a putative outbreak of MRSA in the SCBU and demonstrated that the carrier responsible for reintroduction was a member of staff. The paper is an excellent demonstration of how NGS is going to change our lives. I hear a lot about personalised cancer medicine and it is undoubtedly going to impact patient treatment, but public health is likely to get a boost as well. If we can screen communities in a similar manner than detecting diseases before symptomatic outbreak occurs could have a major impact on health. Combine this kind of testing with hand-held PCR and MinION and there could be opportunities to take these tests to sub-Saharan Africa, the Indian sub-continent and other far-flung parts of the world.

Is this paper going to have a similar impact as John Snows manuscript on cholera from 1854? Probably not but I expect it is going to be highly cited and I’d certainly recommend you read it even if this is not your area of speciality. It received a lot of media coverage and the comment I heard most was “how do you decolonise someone of MRSA?”

The paper say the whole genome sequencing of MRSA cost £95 per isolate. I’m not sure, but the sequencing of a single isolate is likely to be a tiny fraction of a MiSeq run. Combined with a modified diluted Nextera library prep this could be done for perhaps as little as £5. The MRSA had to be cultured before sequencing could be performed, so perhaps the culturing is the expensive bit? Prof Robert Brooks at the American Academy of Orthopaedic Surgeons suggests that culturing cost $20 per sample and a PCR test is $200. Sequencing is in the middle today and could easily become cheaper than the culturing currently required. As costs continue to fall this also raises the possibility of longitudinal sequencing across multiple colonies in multiple patients which should tell us something about the dynamics of MRSA infection.

In the discussion the authors said that MRSA transmission was almost certainly missed because a weekly screening program is currently used. Some babies were MRSA negative on admission but the unit left within seven days and later developed MRSA. The speed of this kind of test means continuous testing could be just around the corner.

It looks likely that whole-genome sequencing of MRSA could be coming to a hospital near you soon. I don’t know if it is possible to detect MRSA in the blood but I’d love to try and see if it is possible. A Taiwanese group published a qPCR assay for MRSA testing in blood.

PS: If the authors would like to try and analyse blood I know a core facility with some experience of developing this kind of method!

1 comment:

  1. Hi James. Culture is very cheap, a few quid. You can do about 15-25 MRSA genomes on a v1 MiSeq run (2Mb genome x 30-fold coverage, allowing for some variation in coverage. So that's between £30 and £50 for the sequencing per isolate. The rest will be library prep, again around £50 for barcoded Nextera. How do you get Nextera down to a fiver a throw? We would love to do that!


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