Mutational colistin resistance in CPE is the clear and present danger, not plasmid-mediated mcr genes

There has been a lot of concern in scientific journals and the mainstream media about colistin resistance in Enterobacteriaceae caused by plasmid-mediated resistance genes (the mcr genes). However, an article published today by our group suggests that mutational colistin resistance rather than plasmid-mediated mcr genes is a more pressing clinical threat.

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The antibiotic course has had its day?

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In a recent BMJ article, Llewelyn et al. argue that the old dogma of completing a prescribed course of antibiotics to prevent antibiotic-resistance is a myth, not based on evidence.  Actually the opposite, namely taking antibiotics for longer than necessary, increases the risk of resistance.

While I love breaking down old dogmas  (we actually had a poll on this topic some time back), many of today’s papers in the Netherlands (and I am pretty sure elsewhere, too) misinterpret the study, by slaughtering the message to patients to “always complete the full prescription”.  One of the Netherlands most influential newspapers the Volkskrant, already wrote: “Finishing antibiotic course? Nonsense.”

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Going for GNBSI

We’ll be publishing the results of the vote on whether or not we can halve HA-GNBSI by 2021 later this week. Right now, it looks like Martin is heading for a comfortable, if somewhat depressing victory (“No, we can’t halve GNBSI by 2021”) but there’s still time to ride a wave of positivity and vote with me that “Yes, we can halve GNBSI by 2021”. So, I thought that now would be an appropriate time to review the recent JHI paper that both Martin and I referred to, providing some enhanced epidemiological data on E. coli BSIs in England.

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KPC Casanova carbapenemase

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The risk of interspecies transmission of carbapenemase genes is a real concern. We can barely get our heads around many different types of carbapenemase in a whole host of Gram-negative bacteria (compare the relative simplicity of methicillin resistance in S. aureus: a single gene, in a single species). Throw in interspecies horizontal transmission of carbapenemases and things get really tricky! Do we implement different control strategies to try to interrupt the transmission of carbapenemases (in contrast to the organisms themselves)? Could you have a multispecies outbreak of a carbapenemase on your hands and not even realise it?

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Halving GNBSI

gnbsi-halved

The Department of Health announced last week their intention to halve the rate of E. coli BSI by 2020. Whilst this is a move that should be embraced, it will be an enormous challenge to achieve. The reduction that has been delivered with MRSA BSI could be seen as a model for success (and I suspect that if you were a politician, you would see it this way). However, it is vital to recognise that E. coli BSI and, more broadly, Gram-negative BSI (GNBSI) are not the same as MRSA BSI, and will require a different reduction strategy.

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Poultry production and antimicrobial resistance in India

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Take a look at these three stories on intensive poultry production and antimicrobial resistance in India published yesterday on the Bloomberg website. In accordance with what the movie industry does, these articles should be accompanied by a warning: “These articles contains scenes that some readers may find disturbing”. As the editor of the articles said in an email to colleagues that forwarded it to me: “I think you’ll agree that these are important stories and deserve attention (and hopefully a response from the appropriate authorities and the community).” Obviously, I do agree.

http://www.bloomberg.com/news/features/2016-03-29/antibiotic-apocalypse-fear-stoked-by-india-s-drugged-chickens

http://www.bloomberg.com/news/articles/2016-03-29/hen-s-eye-view-of-drug-use-in-the-fastest-growing-chicken-market

http://www.bloomberg.com/news/articles/2016-03-29/baby-s-death-shows-global-threat-from-wonder-drug-s-demise

We need to EMBRACE engineers in the fight against HCAI and AMR

Embrace logo ok

I attended the first EMBRACE seminar today at Imperial College London. EMBRACE (Engineering, Medicine, Natural Sciences and Physical Sciences Bridging Research in Antimicrobial resistance: Collaboration and Exchange) is a gap-bridging collaborative aiming to bring together Engineers, Scientists, Doctors, and others to find new ways to address AMR and tackle HCAI. I thought I’d share some of my highlights from the seminar.

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Review on AMR: progress to date

amr review

Like many others, I am keeping a close eye on the UK Government’s commissioned ‘Review on AMR’. The Review team have been tremendously productive over the last few years, already releasing detailed reports on:

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Colistin resistance in CPE: an emerging threat

colistin structure

I am becoming increasingly interested in colistin resistance in CPE, not least because of this work that we will be presenting on colistin resistance in CPE at ECCMID in a few months time. I have been brushing up on how colistin resistance occurs in CPE, and why it is important, so thought I’d share my findings. I started with a pubmed search for “colistin resistance mechanism” on 12/02/16 and this is what I found (85 hits from the initial search):

Colisin

Colistin is an old class (discovered during WWII) of cationic antibiotic. Colistin (polymyxin E) is a polypeptide bactericidal agent and is one of the two clinically available forms of polymyxin agents (polymyxin B and polymyxin E). Colistin interacts with lipopolysaccharide in the outer membrane, resulting in a leaky and ultimately dead bacterial cell.1 Issues with presumed nephrotoxicity have kept colistin very much on the top shelf, but the emergence of CPE has brought colistin down a shelf or two – and we are learning that the nephrotoxicity tradionally associated with colisin may not be so bad afterall.1

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Antibiotic surgical prophylaxis: stewardship’s ‘elephant in the room’?

Doxycycline_100mg_capsules

We are all pretty comfortable with the idea that we have used too many antibiotics in the past and now we are reaping the consequences. I think we are also all in agreement that we need to start using antibiotics much more rationally – and keep the big guns firmly on the top shelf, double-wrapped in password-protected packaging that you can only access with a fingerprint and retinal scan (whilst acknowledging that they will still somehow be prescribed by a junior doctor at 3am for a sniffle). But I get the feeling that we all have a bit of a blind spot (or soft spot) for surgical prophylaxis. Here, the situation is different, surely, because the consequence of an SSI is so great that the likely ‘cost’ of widespread surgical prophylaxis is outweighed by the gain of fewer SSIs? But has this become stewardship’s elephant in the room? We are comfortable talking about restricting carbapenem use in acute hospitals, but I don’t hear as much discussion about stopping the use of antibiotics for surgical prophylaxis! On one level, isn’t this is the same arguments as for ‘selective’ digestive or oral decontamination (SDD / SOD) in the ICU? Here, the argument in factor of SDD / SOD is compelling: fewer deaths and less spread of resistant bacteria. But indiscriminate use of antibiotics, which is bound to fuel antibiotic resistance in the long run, just cannot be a good idea, particularly in the high-risk ICU population.

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