ECCMID in a couple of hours!

“So I couldn’t go to ECCMID – what should I catch up on?”

If you didn’t manage to get to ECCMID this year at Copenhagen, this is designed to point you in the direction of a few of the outstanding talks I attended, or heard about. I was ‘on-call’ for my group, so the content very much represents their interests- resistance, genomics, microbiomes and oh yes more resistance…   Links to the ECCMID Live presentations included – a fabulous resource- kudos ECCMID!  Again, I’ve tried to be as accurate as I can, but please tell me if I’ve messed up attributions, names, science etc. – no co-authors or reviewers on this blog…

This isn’t in any particular order, in fact I’ve put the most important theme clinically (resistance) last, mainly as clinically it sort of dwarfs anything you say after it, even it is very relevant. Rather like telling someone that a tsunami is coming in 10 minutes to destroy us all, but in good news they’ve just managed to make the tsunami early-warning system 10% more reliable… but onwards…

THEME 1 – GENOMICS – Not ‘Coming Soon’ to Clinical Care – but ‘Advance previews already in theatres – general release imminent’

THEME 2 – MICROBIOMES – Witnessing a paradigm shift in human/bacterial ecology

THEME 3 – ANTIBIOTIC STEWARDSHIP – Its about hearts and minds and measuring your outcomes, however messy they may be

THEME 4 – RESISTANCE- superplasmids, super-everything, super-everywhere

continued….

THEME 1 – GENOMICS – Not ‘Coming Soon’ to Clinical Care – but ‘Advance previews already in theatres – general release imminent!”‘

The main story from the presentations at ECCMID was that pathogen genomics is no longer just a research technique, but can be used to directly inform patient care- not just to retrospectively analyse outbreaks, but to intervene in them (if you have the resources…).Highly recommended is the presentation by Martin Llewelyn working with Public Health England, as a great historical overview of WGS, and demonstrations of use in the study of transmission it’s well worth a look.   If you head to around 24 minutes in, you’ll see that Public Health England is currently piloting whole genome sequencing alongside routine diagnostics for TB samples, validation ongoing and promising, with the aim to replace traditional diagnostics within a few years for both outbreak analysis and resistotyping. Pathogen WGS isn’t ‘coming soon’, for mycobacterial diagnostics, it’s here. (note: my group works closely with Martin, and Phelim, below- but talks chosen because I thought they were great).

I also thought Matthew Holden gave an outstanding talk demonstrating the utility WGS both to understand disease transmission and inform infection control practice, specifically MRSA/Staph. Aureus, where outbreak data was used to identify index cases (Mojo the Index Dog) and ‘super-spreaders’ (concerningly, often healthcare workers). Ready for clinical care? Well, as Frederic Laurent pointed out- this depends on where you are, and whether you have links to a group that can do proper genomics. Clearly there needs to be a big think about how it’s all done to give access – genomic hubs?  In fact a number of senior voices were making big calls for a better model of datasharing/sequence sharing/standardisation. Admittedly currently the cost/time of sequencing precludes  WGS for routine practice for most cases, but hopefully with the costs of sequencing decreasing rapidly, it’s exciting times in the world of clinical pathogen genomics.

If you’re a clinician and you were thinking of doing a bit of genomics, you might want to look at a couple of sessions by Nick Loman  -a great primer for the beginner in the complex issues associated with doing high-quality genomic analysis -essentially, you really need to know what you’re doing.  Or alternatively, one can develop user-friendly tools for the nonspecialist!  If you want to see how you might be using genomics in the not-too-distant-future for clinical care, have a quick look at the talk by Phelim Bradley here, presenting Mykrobe, a resistance gene finder using shotgun WGS data.  Drop your file into something that looks straight out of Apple (‘iGene’ if you like) and it gives you the resistance phenotype. Works for Staph aureus  (based on previous work developing and validating a resistance gene database by Claire Gordon). Developing an MTB/gram negative version.  To mangle a catchphrase, ‘The future’s bright, the future’s shiny user interfaces designed by a chap who did the Guardian website, (apparently)’. Or more appropriately, the future’s about here.

THEME 2 – MICROBIOMES – A paradigm shift in human/bacterial  bacterial ecology

“The human body expects a microbiome, it develops with a microbiome, the immune system expects to see a colonising microbiome” – a quote from William Wade, who presented the Oral Microbiome session. For the generalist wanting to know more about microbiomics I’ll say what I said in earlier roundups and basically just recommend sitting down with a cup of tea (or non-UK equivalent) and having a good watch of some great talks. Paul Cotter’s talk is a nice introduction to the field, and our understanding of the factors that affect the gut microbiota. On a more Infectious Diseases-specific approach,  Mary-Claire Roghmann and  Stephan Harbarth talked about a wide range of subjects- faecal transplantation, colonisation, and the ‘unintended consequences’ of antimicrobials and antiseptics on our microbiota. Basically highlighting this is an area with huge huge potential, but also one with significant  knowledge gaps on how we interact with our microbiota (My Microbiome Made me do it….). Highlighting the awesome CDC infographic shown at the first talk on antibiotic resistance here. Also well worth a watch is the microbiome session on the lung/gut axis, presenting some thought-provoking work on how antibiotics may increase susceptibility to infection by wiping out the colonising microbiome. Interesting stuff. Highlights how incomplete the ‘sterile world, protect against invaders’ view is – and how increasingly the role of microbiology is in the ecology and curation of the microbiota, rather than rocket-launcher-toting four-star generals…

THEME 3 – ANTIBIOTIC STEWARDSHIP – Its about hearts and minds and measuring your outcomes, however messy they may be

I think my favorite quote from this years session about Antibiotic Stewardship I heard from Esmita Charani from Imperial (though I don’t know the origin) – “Culture eats Evidence for breakfast”. THIS.

Alison Holmes made a great case for why stewardship needs to develop and integrate behavioural models into prescribing interventions.  (INTERVENTION… *miracle happens, minds change, spontaneous realisation by the entire physician population that they were wrong and they’ll do what you say*….RESULT? Yeah..nope. ). I love this stuff, mainly as it actually represents my/my colleagues experience on the shop floor. And makes much more sense than trying to change people’s minds with a hand-wavy belief in your own ineffable rightness,  together with the attitude that anyone who doesn’t change is either frustratingly anti-evidence, anti-you or just hasn’t been lectured at enough (death by educational intervention??).

I also remember hearing from Peter Davey a few years ago, talking about the 2005 Cochrane review of Antimicrobial Stewardship, and despairing of the ‘before and after audit’ approach to changing antimicrobial prescribing. The key points he had were that you need trends (not two timepoints) and sustained change, you need proper clinical (as well as prescribing) outcome data, and your intervention has got to be something more than measuring, telling people they did badly, then (surprise!) re-measuring and finding things better. Apart from the obvious Hawthorne effect going on, it’s just not sustainable, and we needed much more work on how to change prescribing effectively. Things at ECCMID really looked like the whole area has moved on a lot from what I remembered.

I would love someone to recommend a few Stewardship sessions to me as I was somewhat limited in my ability to attend, but of the short sessions I managed to catch I can highlight a few for anyone who wants to plan a stewardship programme and how to do it right. There was a good presentation from the  PRIOAM multilevel intervention-  organisational, educational and incorporating counselling/feedback. As well as measuring a decent and sustained decrease in antimicrobial prescribing, they also looked at their resistance data over time. This highlighted the difficulty with resistance data- other concurrent factors eg. outbreaks, can mean it may be very difficult to attribute changes in resistance to stewardship, but all in all I liked this a lot. For those interested, there were also some nice demonstrations of technology and applying the laudable behaviour change principles of ‘making it easier to do the right thing’ – Computerised Decision Support, iPhone formulary apps, and stewardship benchmarking online tools.

THEME 4 – RESISTANCE- super-resistance, superplasmids, super-everything

Does anyone else remember watching epic cartoon series? Where Episodes 1-5 built up to the scary big boss monster, only to be defeated and another boss monster come along that was way scarier? And by episode 20, monster 1 is either everyone’s friend or the comic relief character ? If you didn’t you totally missed out, but I digress. This is what it felt like to me, a Microbiology outsider, in all the presentations this year. ESBL resistance in gram negatives is old news – it’s all about CRE now. Previous big-bad meropenem-requiring isolates relegated to a footnote of ‘by the way 60-70% of our isolates were ESBLs’…

Or more. The talks  that stood out for me more than anything at ECCMID about resistance were relatively short oral abstracts worth watching by anyone who thinks resistance is a while off becoming a major problem. The first was by a group in Karachi  – highly highly recommend the presentation by Brekhna Hassan here  – looking  at resistance in their environmental isolates (water, insects, bird droppings…), together with  faecal carriage (Poster by Maria Carvalho here). With the conclusion that basically, resistance is everywhere – over 3000 rectal/site of infection swabs, and over 90% had ESBL Beta-lactamase CTX-M-15 presence, approaching 50% NDM1 Carbapenemase presence, and all of this also found in the normal flora of the hospital and its surroundings. And this is somewhere that has managed to find the resources to do the molecular investigation and will report its results- one can only speculate at the situation in more resource-limited /less-resistance-data-sharing areas.  A few other highlights – two presentations from Spain demonstrating the frightening ability of Carbapenem Resistant Enterobacteriaceae (CRE) to inoculate a hospital, then cause  rapidly spreading outbreaks (eg. from 8 to 284 CRE isolates in 2 years)- not just  clonal strains, but  as well as the usual E.coli/Klebsiella, add in Enterobacter cloacae, Enterobacter aerogenes, Serratia, Citrobacter…  A cautionary tale for anyone sitting in their castle feeling safe about their single-figure carbapenem-resistant isolates… And there were a huge number of posters and presentations about the multi-drug-resistance-conveying mobile genetic elements spreading rapidly,  all telling the same story – that they enable resistance to spread at a speed that far, far outpaces our current abilities and resources to control them. And they’re everywhere- environment, farms, companion animals… Well that’s a happy note to end on!

Most of all, what struck me about ECCMID was the disconnect between the views  and data being presented by Microbiologists on resistance, and the views that I encounter in the average UK physician, even the well-informed ones. There isn’t a lack of resistance data – ECCMID made that abundantly clear! Or a lack of National and International Statements of Seriousness.  but I worry about the ‘boy who cried wolf’ effect with resistance – once bored, louder and louder shouts get ignored, right up until the Pan-drug-resistant-Kleb-Wolf comes and takes over your hospital.

Well, also at ECCMID was a lot of work showing that we are making progress, we are developing the tools to help us understand what is going on, and how to work to prevent the spread of resistance. Such that we may not be triumphant winners, but hopefully we will be able to reach an impasse before it completely takes away our ability to perform chemotherapy and lifesaving operations.  Hopefully.  I can only wonder what ECCMID 2016 will bring…

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