Colistin Resistance Is Now Linked to Carbapenem Resistance: We Failed

For those just tuning in, a little over a month ago, the microbiology and public health world was rocked by the discovery of plasmid-borne colistin resistance:

First, some background: polymyxins, including polymyxin E also known as colistin, are the last line of defense against antibiotic-resistant Gram-negative bacteria, such as E. coli, Klebsiella, and others. For regular readers, you might remember that I’ve referred to carbapenem antibiotics as the last line. That’s because the efficacy of colistin is debatable: some studies show a very good cure rate, others do not. It doesn’t help that colistin can have severe side effects such as kidney failure. Nonetheless, as carbapenem-resistance enterobacteriaceae (E. coli and pals, often referred to as ‘CRE’) increase, colistin is what we have.

Bacterial resistance to colistin has been seen, but its saving grace, such as it is, is that this resistance is not very transmissible. In other words, a colistin-resistant bacterial strain can spread, but it won’t transfer that resistance into another strain*.

Until this paper. This group, in China, discovered a plasmid (a bacterial mini-chromosome that can move to genetically different bacteria–think of it as a flash drive with EVIL) that has a gene, mcr-1, that confers resistance to colistin.

As I put it:

This is really bad news, since colistin is the last line of defense against carbapenem-resistant enterobacteriaceae (‘CREs’). Were this plasmid to move into a CRE, we would have no treatment options.

Well, shit (boldface mine):

Laurent Poirel and colleagues in Switzerland have identified an E. coli strain, recovered from an 83-year-old Swiss man who was hospitalized last month, that possesses both colistin resistance and also VIM resistance to the carbapenems, the family of antibiotics that was considered the last and toughest before colistin. The colistin-resistance gene shared a plasmid with genes conferring resistance to chloramphenicol, flofenicol and co-trimoxazole. The authors warn, “Such accumulation of multidrug resistance traits may correspond to an ultimate step toward pandrug resistance.”

Marisa Haenni and collaborators in France and Switzerland queried the Resapath network in France, which conducts surveillance for antibiotic resistance in animals, found that 21 percent of bacterial samples collected from veal calves on French farms between 2005 and 2014 carried the signal of mobile colistin resistance, the gene mcr-1. There were 106 positive samples (out of 517) and they came from 94 different farm properties. On seven of those isolates, the mcr gene lived alongside ones for ESBL resistance—that’s to penicillins and to the first three generations of cephalosporin drugs—and also genes for resistance to sulfa drugs and tetracycline.

Linda Falgenhauer and collaborators in the Reset consortium in Germany examined the sequences of 577 isolates taken from human patients and livestock and from the environment since 2009. They identified four carrying the mcr-1 gene, three from humans and one from a hog. The three from swine also possessed ESBL resistance; the one from the human was also carbapenem-resistant (KPC-2). One of the swine samples dated back to 2010. They say, somberly: “Our data suggest that the advent of untreatable infections has already arrived, as every colistin-resistant isolate described in this study is also resistant to either third-generation cephalosporins or to carbapenems.”

On a science-y note, the linkage with the VIM carbapenemase suggests we also need to be looking in Central and South America (because one can never despair too much).

I guess this is a good practice run for managing my emotions when we finally face the full-on effects of failing to deal significantly with climate change.

To be blunt, we failed: we are exiting the antibiotic era. The only good news, for U.S-ians anyway, is that it doesn’t appear mcr-1 is in the U.S. yet, though it’s just a matter of time. In the U.S., we need to ban the use of polymyxins in agriculture, now.

Back to cataloguing the apocalypse…

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5 Responses to Colistin Resistance Is Now Linked to Carbapenem Resistance: We Failed

  1. doug says:

    Mike, or anyone:
    I have seen a claim, unsupported by any reference, that in the absence of on-going selective pressure (antibiotic exposure) that acquired resistance-conferring plasmids will tend to disappear from populations because under such circumstances they cause a slight disadvantage, requiring extra resources for their maintenance. This seems to me to perhaps have some slight plausibility. Any comments? Recommended references?

  2. Crap. And I had just finished briefing my boss, telling her that this particular scenario hadn’t been documented yet, so everyone needed to chill. (This was after it had just been revealed that a retrospective analysis found mcr-1 in two ground beef specimens and in one patient here in Canada in 2009 and 2010 respectively. See here: http://www.cbc.ca/news/health/antibiotic-resistance-superbug-colistin-1.3391434 ).

    Like the analogy of “flashdrive with EVIL” btw.

  3. Aaron says:

    Doug, it’s a bit old, but this review article by Richard Lenski does a good job of addressing that question:
    Lenski, R.E. (1998). Bacterial evolution and the cost of antibiotic resistance. International Microbiology, 1(4), 265-270. PDF: http://www.im.microbios.org/04december98/06%20Lenski.pdf

    It’s true that the acquisition of antibiotic resistance, either by plasmid transfer or chromosomal mutation, usually comes at a cost to naive bacteria. However, experiments demonstrate that bacteria can acquire compensatory mutations to mitigate that cost fairly rapidly.

    • doug says:

      Thanks, Aaron.
      I haven’t read it yet, but definitely will. The original remark to which I referred was in a comment on a CBC article. I suspect the person who made the comment could have cited a reference, but commenting was closed before I could ask.

  4. mrtoads says:

    “In the U.S., we need to ban the use of polymyxins in agriculture, now.”

    We’ll add that to all the other things we need to do now, including lose 50 pounds and start saving money. Somehow I suspect we’re about equally likely to get around to it. It’s horribly fascinating to watch how the only suicidal animal I know of (that would be humans) manages things. I suppose it might be different if we weren’t built for snap decisions and short-term thinking, but we are and there it is. Oh, well – at least we’re very, very good at hindsight regrets, rationalization and blame-shifting.

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