Real-time whole genome sequencing (RT-WGS) & spread of resistant bacteria

At last weeks’ ICPIC I crossed arguments with John Rossen on the question whether RT-WGS helps us to control the spread of resistant bacteria. The setting is the hospital and the definition of RT is “in time to guide essential decision making”. Is RT-WGS a “need-to-have” or a “nice-to-have” thing?

What steps do we make in controlling spread of resistant bacteria? We identify so-far-unidentified carriers (then called index patients and treated in some form of isolation) and screen others for carriage (patients and sometimes healthcare workers, HCW). The aim is to stop transmission in order to minimize occurrence of difficult-to-treat infections, that have attributable morbidity, mortality and costs. RT-WGS would help us if it (1) reduces diagnostic delay and (2) provides essential information to guide the control strategy. If the benefits (less costs for control and better patient outcome) outweigh the costs, it would even be cost-effective.

Diagnostic delay

Index patients are – by definition – identified unexpectedly, and the routine practice takes about 24 hours for the conventional culture to grow, another 24 for susceptibility testing and then a few hours (say between 1 and 6) for genotype confirmation (e.g., by PCR); total delay 49 to 54 hours. The RT-WGS would start with the resistant isolate (at 48 hours). Even the most sophisticated lab will have turn-around-times for RT-WGS exceding 1-6 hours. Targeted screening on selective media has a shorter delay, but still RT-WGS would kick-in with the grown isolate.

Essential information

Our current practice is guided almost exclusively by phenotypes, as we don’t have a different strategy for differen genotypes of MRSA, VanA/B VRE or MDR-GNB. RT-WGS could, therefore, at best help in reducing the number of “to-be-screened” patients (or HCW) if a new carrier appears to carry a different genotype.

Is there published evidence for the use of RT-WGS? I found 2 studies that both claim so. In the first, RT-WGS was used to control an MRSA-outbreak in a NICU, where the outbreak strain clearly differed phenotypically from other MRSA isolates (mupirocin-R versus S). In the discussion the authors state that “RT-WGS showed that the infection-control team had correctly identified an outbreak and associated transmission events, aided by an unusual antibiogram for our setting.” In the other study, it looks like the infection control policy was adapted based on RT-WGS information; GNB resistant to 3 antibiotic classes (but not carbapenems) apparently hardly spread in period 1 and discontinuation of strict isolation of carriers in period 2 (which started 6 months after the first one ended) did not result in more transmission. For me, difficult to see this as RT-WGS.

So, my conclusion: currently, application of (true) RT-WGS does not reduce diagnostic delay and hardly provides essential information for guiding infection control. No need to discuss finances.

Yet, I am convinced that this may change in the (may be not so) near future. Turn-around-times get shorter, metagenomics may (at least partly) replace conventional cultures, infection control strategies might become more genotype-tailor-made and costs will reduce. For future applications I recommend an excellent review, supervised by my debate-opponent. It ends with (summarized): “The role of NGS in medical microbiology laboratories will increase during the next years, ….. However, further studies are required to shorten turnaround times, reduce costs,  develop automatic pipelines for data-analyses and easy-to use software, develop more established typing schemes for pathogens and cut-off values for typing schemes…. Only then will patient guidance and infection control management …. become a possibility, leading to personalised microbiology.” I couldn’t agree more.

With that I rest my case and wait fort he next generation to benefit from next-gen sequencing in infection control. Slides attached, here.

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One thought on “Real-time whole genome sequencing (RT-WGS) & spread of resistant bacteria

  1. Great post, Marc, and thanks for attaching the slides. I agree with you, and began asking a similar question several years ago about how soon WGS would fulfill the infection prevention promises we’ve been hearing. Your post caused me to go back in our archives, and was surprised that this post is already almost 5 years old: http://haicontroversies.blogspot.com/2012/11/riding-epidemic-curve-to-glory-wgs.html
    Had you asked me then, I’d have expressed the hope we’d have wider availability and increased utility of this powerful tool by mid-2017.

    Like

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