Antimicrobial Resistance – Links to papers /resources

*** For any stewardship/education sessions – this post will serve as a resource for links to the evidence quoted- I’ll try and keep it up-to-date as I can***

“Hi, I’d really like an overview on where we are with antibiotic resistance!”  – recommend the CDC overview- colorful, diagramatic, comprehensive

“Hi, tell me about Carbapenem-Resistant Enterobacteriaceae (CRE)  and why everyone thinks this is seriously bad stuff” – great review in the Mayo Clinic Proceedings – Vasoo et al 2015

****Selection and transmission of resistance*****

Sub-lethal doses of antibiotic can select for resistance (eg wastewater…)  Gulberg  2011
Sublethal doses of biocide can select for resistance Forbes 2014
Resistance spread by the bacteriophage network – Modi 2013
Rapid spread of carbapenem resistance between multiple species (Klebsiella, Enterobacter, Serratia, E.coli… )  caused by jump of plasmid to multiple species – Mathers 2011, Conlan 2012 and  then jumping to high-fitness strains, evolving and spreading further.
Nepal MDR Klebsiella outbreak featuring horizontal gene transfer –Chung 2015
Antibiotic levels in wastewater above serum therapeutic levels –Larsson 2007
The widely-quoted correlation between antibiotic use on a population level and antibiotic resistance –Albrich 2004
Antibiotic resistance genes in cave microbiome Bhullar 2012
Is there a link between resistance in food-animals and resistance in humans? Examples:
Lazarus2015 Systematic review– plenty of studies saying probably, yes
More under the cut….

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Methods, artistic and scientific

A couple of months ago I started trying to create some cool effects with chromogenic agar on cloth, inspired by Anna Dumitriu’s bioart. Not wanting to take up resources or paid time, I remember at 6pm embarking with glee upon my project, armed with past-expiry-date agar, and lab equipment discards, and exclaiming to myself “Oh Great! Now I’m doing Art, I can be free, and no longer shall I need to be careful and spend ages documenting!”.  (Anyone who has ever been with me in a lab will attribute to my almost pathological inability to follow slow, systematic instructions to the letter, and magnetic attraction to messing around…)

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Reflections from the front line: why doctors don’t listen to the ‘impending doom’ of antibiotic resistance

Using antibiotics to treat ‘medical uncertainty’, the ethics of patient vs population, and why the acute physician yawns every time you start talking Doomsday, up at Reflections on Infection Prevention and Control here!

Also highly recommend a great blog by Tom Lewis on using information to change minds, rather than just telling them what to do here  – Cognitive dissonance, and turning evidence into behaviour change in antibiotic stewardship.

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….

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Squirrel Walk – the Song

Continuing the Songs for Genomics theme – presenting the Squirrel Walk song, reference to the real-time TB genome matching algorithm for large datasets.  Written to explain squirrel walk to our department. Not very successful mainly as it has to be played very loud with full distortion guitar which somewhat limits its audience.

VERSE

If you’ve GOt a bug to TRy and appraise

and a KNown database of  SEquences

You want to FInd the one that’s MOst the same

And you DOn’t want to play the WAIting game

inSTead of blasting HUge amounts of

REads against a THOusand counts of

SEquences you’ve alrREady got

you can JUnk all that and HAve a shot

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ECCMID Day 4 Roundup – Genomics and Microbiomes are here for clinical care

**Standard disclaimer: these are my notes taken during the sessions, as accurate as I can make them, please let me know if any inaccuracies. I’m putting them here as others have said they found them useful. However worth re-checking anything before you re-quote it. If this continues to be useful, I’ll continue. If it’s clear i’m not reaching the standards of accuracy I’m aiming for, I’ll review future posting plans.**

Final day at ECCMID! There was a very high quality Microbiome session, with two outstanding talks from the speakers, as overviews on the applications of microbiome research – highly recommended viewing and links below.

The massive highlight of the genomics session for me was a presentation by one of our collaborators – Phelim Bradley presenting the work done in the Iqbal group and Mykrobe – a tool that uses WGS data to predict antibiotic resistance. I’ll be right up and admit I work with these chaps, and I don’t want to appear biased, but I can only say that the first time I saw this working a few weeks ago I went Oh My GOD…

As fundamentally a clinician taking a ride in the fun world of genomics, this is the first time I’ve seen something involving genomic analysis I can see myself using on the ward. The user interface looked straight out of Apple & something I could teach my granny (/my senior much-respected Consultant population) how to use.  And validated on over 1000 Staph. aureus samples,  with major and very major error rates <1% compared with culture phenotype. TB and Gram-neg versions also developed. For any clinician agnostic about whether WGS is ready for direct use in patient treatment, the link for the 10 min presentation available at  ECCMID live : here  ( -worth a look even if you just skip to the demo!)

Updated: for a view of the  granny-friendly Apple-esque look – slides up at slideshare:

(ok maybe not granny, unless she’s a Microbiologically-literate elder, but given I’ve spent the last year in a field where people tell you they’ve written a really user-friendly genomic analysis interface which is super easy to use with just basic python scripting – I’m very grateful to any bioinformaticians who consider the intended end-user of their product… )

A very good question from the audience – given cost of sequencing and current times taken to extract DNA/analyse  –  how can it be used to treat patients (and what benefits over current clinical workflow). Agree – for that reason, I think at the present moment in time for routine diagnostics, in Staph. aureus it certainly would be hard to justify. But given TB takes weeks/months to phenotype, and the cost of sequencing is going down (and nanopore is looking increasingly promising…) incredibly exciting times.

Previous sessions posited that the use of WGS in day-to-day clinical practice was probably a few years away, and also suggested a key challenge is presenting WGS analysis in a way that can be used by non-specialists. The Mykrobe presentation suggested that perhaps we’re really much closer than previously thought…

Rest of the summaries  below.

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