Interview with Dr Estée Török

I’m Fahad Khokhar. I’m a research scientist based here at the University of Cambridge. I’m delighted to be joined today by Dr. Estée Török And we’re going to have a chat about AMR. Dr. Török, thank you for agreeing to talk to us today. Please, could you give us a brief introduction about your role here in Cambridge? Thank you, Fahad. So I’m a consultant in infectious diseases and medical microbiology at Addenbrooke’s Hospital in Cambridge. I’m also a research scientist at the University of Cambridge. And my work aims to translate microbial sequencing from a research tool into clinical practise. And I’m particularly interested in antimicrobial resistance and health-care-associated infections.

Our course participants have been learning about the various laboratory techniques involved in identifying bacteria and how to ascertain whether some organisms are resistant to certain antibiotics. In your experience, how has the introduction of sequencing technology such as Illumina and Oxford Nanopore aided to and improved the response to the threat of potential outbreaks? So most of the traditional methods that we use for identifying bacteria looking for antibiotic resistance involve culturing bacteria on agar plates and doing antimicrobial susceptibility testing using antibiotic discs impregnated with antibiotics. And the problem with that is, although it’s relatively cheap and inexpensive, it can take a few days to generate the results.

So the advent of sequencing technologies has basically enabled us to increase the speed with which we identify bacteria and also identify antimicrobial resistance genes. And in particular, the Oxford Nanopore technology platform enables us to sequence directly from clinical samples. In terms of the advantages, you get far greater amount of information on organism identity, species antimicrobial resistance genes, and also, you can look at relatedness of bacteria to determine transmission of organisms between patients or transmission of resistance mechanisms between bacteria. So it really is a step change in what we are capable of doing in terms of understanding antimicrobial resistance. Fantastic. And can this information then be sent back to the doctors on the wards?

And can they take preventative actions to prevent an outbreak? Yes, so that’s ideally what we want to do. So although sequencing and bioinformatic analysis of the data is quite complicated, our aim is really to present the data in a simple, user-friendly format so that it can be used both by clinicians on the ward to guide clinical management and for infection control teams to investigate outbreaks and manage outbreaks. This is work that we’ve been doing for several years in Cambridge. And we’re getting closer to being able to achieve it. But it’s taken a bit longer than we’d anticipated.

So our aim, really, is to take the information that we get from genomic sequencing and communicate it back to the doctors on the ward so that they can use it to make treatment decisions, and also to infection control teams so they can use it to investigate and manage outbreaks in real time. Great. So how much more information can be gained from sequencing organisms rather than just using the standard laboratory techniques? So the main difference, really, is that you can get a lot of information in a single experiment.

So by sequencing the DNA of bacteria, you can identify the species, you can identify antimicrobial resistance genes, you can identify much larger pieces of DNA, such as plasmids, that may contain multiple antibiotic resistance determinants. And then you can also look at how related the bacteria are in order to determine whether there’s been transmission of the bacteria between patients or transmission of resistance mechanisms between different bacterial species. So it gives you much, much more detailed information than we used to be able to get before from using many, many different techniques.

Given the great potential for real-time sequencing to monitor transmission in a potential outbreak, why do you think there are not more hospitals or health care settings that are actively encouraging these techniques? I think one of the issues with uptake– well, there are a number of issues with uptake. First of all, it does involve a certain amount of laboratory expertise. So you have to have both the sequencing machines available and also somebody who is trained to use them. Secondly, you need somebody who’s able to analyse the data, because at the moment, although there are software programs that can do some automated analysis, they are not readily available to all clinicians and all scientists.

And then finally, I guess, it’s a new technology. So when you try and bring a new technology into a laboratory, you have to validate it. You have to show that it’s reliable, that it’s robust, that it produces results that can be used by clinicians and sort of validated externally. So there are a number of sort of both technical and regulatory issues as to why I think this isn’t more widely available. But I think that is going to change in the next 5 to 10 years. Finally, there are lots of daunting statistics regarding the increasing global threat of AMR.

What do you think are the major issues we should be focusing more of at the moment to minimise the current projections of these threats? Well, I think there are a lot of concerns about the risks of AMR and the implications over the next 10 to 15 years, namely that infections will become untreatable. And in fact, the O’Neill Review, which was commissioned by the previous government, illustrated a number of ways in which we can tackle antimicrobial resistance. And I think they came up with 10 different strategies. In terms of the ones that I think are most important, I think improving laboratory diagnostics, their point-of-care diagnostics so that you are only given antibiotic when it is needed.

I think using the antibiotics that we have prudently is very important, so trying to use as narrow spectrum antibiotics as possible, rather than using broad spectrum antibiotics, and also thinking about reducing the course of treatment. The other things that are important are the use of vaccination to reduce bacterial diseases. And finally, I think you have to mention development of new drugs. And that’s a major hurdle because it will require the cooperation of academia, industry, and governments in order to bring new antibiotics to markets. But I think those are perhaps four of the strategies that one could think about to tackle antimicrobial resistance. But it requires a global, concerted, international effort.

And I think that’s something that the United Kingdom is leading on at the moment. Dr. Török, thank you very much for your time. And I’m sure our course participants will find this talk fascinating. Thank you, Fahad. It’s a pleasure to be here.