A “superbug”, resistant to all antibiotics, kills Nevada woman

PBS reports on the death of a Nevada woman who had a bacterial infection resistant to all known antibiotics (they tried 26). Microbes, it seems, are evolving resistance faster than humans can devise new antibiotics.

The report from the Centers for Disease Control is here; the bit below is an extract from the PBS article:

Public health officials from Nevada are reporting on a case of a woman who died in Reno in September from an incurable infection. Testing showed the superbug that had spread throughout her system could fend off 26 different antibiotics.

“It was tested against everything that’s available in the United States … and was not effective,” said Dr. Alexander Kallen, a medical officer in the Centers for Disease Control and Prevention’s division of health care quality promotion.

The case involved a woman who had spent considerable time in India, where multi-drug-resistant bacteria are more common than they are in the U.S. She had broken her right femur — the big bone in the thigh — while in India a couple of years back. She later developed a bone infection in her femur and her hip and was hospitalized a number of times in India in the two years that followed. Her last admission to a hospital in India was in June of last year.

The unnamed woman — described as a resident of Washoe County who was in her 70s — went into hospital in Reno for care in mid-August, where it was discovered she was infected with what is called a CRE — carbapenem-resistant enterobacteriaceae. That’s a general name to describe bacteria that commonly live in the gut that have developed resistance to the class of antibiotics called carbapenems — an important last-line of defense used when other antibiotics fail. CDC Director Dr. Tom Frieden has called CREs “nightmare bacteria” because of the danger they pose for spreading antibiotic resistance.

In the woman’s case, the specific bacteria attacking her was called Klebsiella pneumoniae, a bug that often causes of urinary tract infections.

Here, from Wikipedia, is K. pneumoniae growing on an agar plate;


And here’s a video about the superbug:

One thing I think could have been usefully added to the PBS piece—and to the video above—was that this is a case of evolution in action. They don’t even mention that “antibiotic resistance” is simply the result of natural selection: those bacteria who can survive an antibiotic are those that leave offspring, and those offspring carry the genes for antibiotic resistance. Many people harbor the misconception that “antibiotic resistance” somehow involves the infected human acclimating to the antibiotic, when it fact it’s the bacterium undergoing natural selection in the body.

Second, it’s always puzzled me that when bacteria resistant to antibiotics become resistant to a new antibiotic, they doesn’t lose resistance to the old ones. In many cases in evolution, there are “costs to resistance”: it takes special enzymes or physiological changes in a bacterium to fend off antibiotics, and those would reduce its reproduction in the absence of the antibiotic. (These are also called “tradeoffs”.) For example, if you adapt fruit flies to a medium that’s high in salt, they will adapt to it, but then if you put them back on normal medium, they’ll lose the salt tolerance. That’s because the salt tolerance involves adaptations that, in the absence of the salt, reduce your reproduction compared to non-tolerant individuals.

This doesn’t appear to be happening in bacteria: they seem to have an infinite ability to acquire resistance to one antibiotic after another, without losing resistance to the antibiotics they previously encountered but are no longer exposed to. That’s what makes the whole problem so hard, because otherwise we could just go back and try old antibiotics, not used for years, on bugs that have acquired resistance to new ones.

Why is there no “cost to resistance” in bacteria? I’m not sure, but I suspect some readers will know. My own guess is that the resistance is often due not to simple mutations in the bacterium’s own circular chromosome, but is carried in plasmids—bits of circular DNA that can be exchanged among bacteria, and that carry the genes for antibiotic resistance. Once you acquire a plasmid that confers resistance, it may simply be hard to get rid of it, for it’s just sitting there in your cell and either may not incur a reproductive cost (though I’d think it would, by slowing down reproduction). Alternatively, there may not be “mutant” bacteria that somehow lack the plasmids.

Still, the video above indicates that some antibiotic resistance comes from mutations in the bacterial DNA itself; and that implies that if you stopped using that antibiotic, the bacteria would, due to the cost of resistance, revert to being sensitive again after a period of time when it’s not exposed to the antibiotic. (That reversion to sensitivity is itself produced by natural selection; individuals with resistance are at a reproductive disadvantage in the absence of the antibiotic.)

If you know that answer to this puzzle, weigh in below.

h/t: Mark N.


  1. GBJames
    Posted January 16, 2017 at 9:07 am | Permalink


  2. eric
    Posted January 16, 2017 at 9:10 am | Permalink

    I don’t know the answer, but one thought is that the widespread and ‘production use’ distribution of antibiotics to feed animals has the effect of putting evolutionary pressure on bacteria to keep those resistances high. A brief googling tells me that 80% of all the antibiotics consumed in the US are production use in feed animals.

    So, when you get sick and need a regular antibiotic, keep in mind there’s four pigs that have been using it on a practically daily basis. Guess where the antibiotic-resistant strains might be coming from?

    • reasonshark
      Posted January 16, 2017 at 10:56 am | Permalink

      I was going to speculate that it was a result of horizontal gene transfer – that non-resistant backteria were simply copying the resistance genes from neighbours in times of crisis – but this sounds much more plausible.

    • infiniteimprobabilit
      Posted January 16, 2017 at 7:08 pm | Permalink

      My thoughts too. Combine that with the greenhouse gases emitted by livestock and farms are worse environmental offenders than strip-mining or Hummer drivers…


  3. Posted January 16, 2017 at 9:18 am | Permalink

    Two questions come to mind when reading this.

    1) is it possible there is a bacteria trade off, we just don’t know what it is yet?

    2) is there a trade off in human immunity? If I get the flu jab each year for a decade to get immunity to that season’s virus, is there a trade off?

    • Posted January 16, 2017 at 9:41 am | Permalink

      There is probably always a hidden trade off somewhere in the system, since very few things in life are free. For us humans it could be something like a marginal energy cost that barely affects us. But for a bacterium I’d imagine every marginal cost is significant.

    • Mark Sturtevant
      Posted January 16, 2017 at 10:42 am | Permalink

      My knowledge is not too deep on this, but I have read from time to time that resistant bacteria are less fit in some way in the absence of antibiotic. I have no idea how general this is.

  4. Posted January 16, 2017 at 9:21 am | Permalink

    Could the “cost of resistance” (I’ve also heard the term “metabolic load”) explain why superbacteria infections haven’t spread to the scale of an epidemic? Strep throat makes the rounds every season, for example, but we haven’t seen something like a super-strep pandemic. The super infections seem to be more isolated, spreading usually to immuno compromised people. If I’m mistaken about that, then I need to start constructing my personal bubble.

  5. ThyroidPlanet
    Posted January 16, 2017 at 9:26 am | Permalink

    I don’t know if the order of antibiotic application matters, if there are specific conditions in the host which could interfere with antibiotics – drugs or health problems like smoking, if there are virulence factors, bacteriophages which could have been accounted for that might have helped – and perhaps it’s still a matter of research. Sometimes the clinician gives a multi-antibiotic cocktail.

    • ThyroidPlanet
      Posted January 16, 2017 at 9:27 am | Permalink

      Also where the bugs came from – what if a host could cultivate, unwittingly, a bug that could be such a problem.

    • Mark Sturtevant
      Posted January 16, 2017 at 10:46 am | Permalink

      For this patient, I expect there were at least two added complications. It was a bacteria that resided in deep tissue, which is harder to treat since antibiotics can’t easily get to ’em while the body meanwhile works to flush it out. Also, she was old and that too presents a complication with circulating the drug to her, and for her immune system.
      Doctors know well that any infection (or surgery) on the elderly poses special problems because they just don’t resolve it as quickly as younger people can.

      • mikeyc
        Posted January 16, 2017 at 11:58 am | Permalink

        I suspect her age was the primary problem. Although bugs like this are resistant to all those antibiotics, most immune systems can take care of them. Most clinically significant bacterial infections, whether resistant or not, arise in cases of trauma or in people with compromised immune systems, such as (I think) is the case with the poor woman. It is an unfortunate fact of aging that by our mid 50s we no longer make new T cell receptors and precious few B cell receptors. If the receptor that can clear the pathogen (or initiate the clearance) is not present and new ones are not generated, we must rely on antibiotics. But if the bacteria is resistant to them…well that’s scary.

        • Brad
          Posted January 16, 2017 at 12:43 pm | Permalink

          Joint (and presumably bone) infections are subject to difficulties not shared with well-perfused tissues. In the cattle industry Chloramphenicol was the go-to drug for treating joint and navel infections in calves, it was effective because it did reach effective concentrations in those tissues. With other antibiotics, treatment worked but was subject to relapse because there remained sources of reinfection where the antibiotic didn’t reach therapeutic levels.

          Issues with misuse and failure to adhere to withdrawal periods led to it becoming unavailable, and nothing as good is available nowadays. It could occasionally lead to aplastic anemia in humans, even at extremely low exposure levels. It is still available – as ointments for treating ear infections in dogs and cats.

          I would have thought there would have been a metabolic cost to having so many modes of antibiotic resistance, but apparently not.

          • Linda Calhoun
            Posted January 16, 2017 at 3:19 pm | Permalink

            Fluorphenicol is the reformulation. It does not, so far, have the same side effects, and seems to work as well, at least for me. L

  6. Randall Schenck
    Posted January 16, 2017 at 9:36 am | Permalink

    I could not answer the question but it seems as if the super bug contains a vaccine like immunity and therefore, avoids the trade off. Purely a layman thinking outloud. Not stating this is evolution and natural selection seems very odd?

    • mikeyc
      Posted January 16, 2017 at 11:46 am | Permalink

      It’s not immunity in the way vaccines work. Antibiotic resistance in bacteria is complex but there are essentially two “modes”; resistance by modification of the targets (these are primarily encoded on the chromosome) and resistance by enzymatic degradation of the target or by pumps that remove the target from the cell. Often the later are encoded on accessory elements, such as plasmids.

      Vaccines work by activating cell populations that bear specific receptors.

  7. Stephen Barnard
    Posted January 16, 2017 at 9:41 am | Permalink

    Your guess about plasmids carrying the resistance genetic information is plausible. What is the cost of reproducing a plasmid? Is it very low? If it is, with an enormous population of bacteria exchanging an even more enormous population of plasmids, my intuition is that they could persist in the gene pool for a very long time.

    I wonder how many antibiotics are derived from or similar to naturally occurring compounds (like penicillin). It could be that when bacteria acquire resistance it helps them fight these naturally occurring substances that they couldn’t crack before. (Acquiring resistance is hard.) The acquired resistance would be adaptive in environments other than people, and would persist.

    • eric
      Posted January 16, 2017 at 10:38 am | Permalink

      This is true, and AIUI (I’m just a layperson) the really worrying thing about this case is that this woman’s bug wasn’t just immune to the regular antibiotics everyone gets, but the ones that the medical field holds back and which are molecularly very different – our ‘break glass in case of emergency’ antibiotics, the carbapenems. You have to be hospitalized before you get those. So the fact that she was immune to them is bad news. Could be that India has a more blasé attitude towards them than we do.

      Incidentally, the ‘looks like’ phenomenon can also work in our favor; that’s how the flu vaccine works. There are loads of different new strains of flu that evolve every year. So every year, the medical community does a genetic survey of all the strains in existence in the US, picks a handful of them that genetically span the range of the rest, and creates the vaccine for those 5-10 strains. We rely on the fact that every other strain will be genetically similar to at least one of the picked strains for the vaccine to work.

    • Mark Sturtevant
      Posted January 16, 2017 at 10:52 am | Permalink

      The measures for resistance can have a cost for the bacteria. Plasmids exact an energy cost, and many antibiotics select for bacteria with higher and higher copy #s of plasmids. Those bacteria should spend a lot of energy replicating the extra DNA. Also, bacteria are generally resistant by modifying something about their biochemistry (as shown in the video). That can mean they have poorer performance in that modified biochemical activity.
      But in the presence of the antibiotic, they are the most fit bacteria around, despite the energy costs and/or crappy biochemistry.

  8. serendipitydawg
    Posted January 16, 2017 at 9:51 am | Permalink

    They don’t even mention that “antibiotic resistance” is simply the result of natural selection: those bacteria who can survive an antibiotic are those that leave offspring, and those offspring carry the genes for antibiotic resistance.

    Selection certainly but natural? To me this is more akin to the fancy pigeon breeding that so fascinated Darwin, except that it is careless use of antibiotics rather than aesthetic criteria that are driving the process.

    • Posted January 16, 2017 at 10:04 am | Permalink

      It’s an adaption to change within the “natural” environment of the bacteria (in this case, a human). Of course *we* know that the change didn’t occur naturally, but for the bacteria, it’s just exposure to a new challenge, their natural habitat just threw at them.

      • serendipitydawg
        Posted January 16, 2017 at 10:26 am | Permalink

        Oh I don’t disagree that they are evolving in response to change in their natural environment; I merely baulk at natural rather than artificial, albeit unintentional, selection.

        I was called an idiot by my history teacher at school (mid 1960’s Grammar school) who claimed we were in a golden age of antibiotics and evidently had a simplistic view that they killed 100% of the bad bacteria. I think I got a detention for suggesting he attend one of our biology classes…

        We had a superb biology teacher, it was only the smell of formalin that turned me off the subject (which genius scheduled lessons involving dissection just before lunch?)

        • Gregory Kusnick
          Posted January 16, 2017 at 12:37 pm | Permalink

          Artificial selection is by definition intentional and purposeful. If we define it to include unintended consequences, then every predator becomes an agent of unintentional “artificial” selection.

          • serendipitydawg
            Posted January 16, 2017 at 2:31 pm | Permalink

            Good point.

    • Mark Sturtevant
      Posted January 16, 2017 at 10:56 am | Permalink

      Good question. Technically, evolution of antibiotic resistance is considered to ‘natural selection’ rather than ‘artificial selection’ because it is unintentional even though man-made.

      Now, if we were to deliberately generate resistant bugs, then I suppose that should be considered artificial selection.

  9. Michael Finfer, MD
    Posted January 16, 2017 at 9:55 am | Permalink

    I think you are correct. I cannot come up with a solid example of a bacterium losing a plasmid off the top of my head. It may just be that this has never been looked for in a rigorous way or that my memory is defective, but I just don’t know for sure.

    Is there any fitness cost to carrying a plasmid? I am not sure that there is, at least I cannot remember learning about any. This may be another piece of the puzzle.

    There was a article in Science a few years ago that reported finding a vancomycin resistance gene in DNA obtained from 30,000 year old permafrost in Siberia. I suspect that this explains why we are running into a brick wall after only 70 years of antibiotic use. Many of these resistance genes may not be new, but have been present in nature all along and had some other function. They are now giving us grief.

  10. Posted January 16, 2017 at 10:19 am | Permalink

    Whenever there is an incident like that, I am wondering if they sequenced the DNA of the person to see a pattern (if there is any). With enough data (lots of dead people) we may be closer to at least an understanding of the problem.

  11. josef johann
    Posted January 16, 2017 at 10:21 am | Permalink

    Jerry, there is a RadioLab episode titled “Staph Retreat” that apparently shows a microbe that lost its resistance to an old remedy.

    A paper was published about it here: http://mbio.asm.org/content/6/4/e01129-15.full

    (hopefully the link survives the comment filter).

  12. David Duncan
    Posted January 16, 2017 at 10:33 am | Permalink

    I studied microbiology and immunology many moons ago and I seem to remember that bacteria do lose resistance to antibiotics after a while, but can fairly quickly re acquire it. I think we’ve been very lucky so far.

    • josef johann
      Posted January 16, 2017 at 11:02 am | Permalink

      I suppose the hope is that bacteria would lose resistances over time, and antibiotics could be put on rotation. But the radiolab thing I mentioned above appears to refer to a remedy that’s roughly a millenia old. If it takes that long to lose a resistance (or however long), and it re-acquires the resistance super quickly, then so much for the rotation strategy.

      CRISPR, save us!

  13. KD33
    Posted January 16, 2017 at 10:49 am | Permalink

    I work on the periphery of microbiology, and I’m not aware of any cases where a strain or species re-acquired sensitivity to an antibiotic. Im not sure if this is due to some fundamentally irreversibility, or the persistence of the environmental pressure the caused a mutation to “stick” in the first place. Few if any antibiotics have actually been put out of circulation. Looking into this more …

    A related question: I’ve seen references to horizontal gene transfer between different bacterial species. (Not sure of this was mediated by plasmids or by transduction by phages). If one species acquired a resistant gene from a different species, would this be unique in evolution? If this is interesting I can try to dig up references.

    About 10 seconds of Googling came up with this, trying to generalize the idea to all of evolution (sounds sketchy):


    • Mark Sturtevant
      Posted January 16, 2017 at 11:24 am | Permalink

      Horizontal gene transfer thru plasmids, phage, or thru simple bacterial transformation, is more common in the bacterial realm.
      There are certainly cases of cross-species lines HGT associated with the origin of various resistant bacteria and also pathogenic strains of bacteria. I had read somewhere that MRSA (methicillin resistant Staph. aureus) was in part formed by HGT across species lines. Also, the notorious pathogenic strain of E. coli known as O157:H7 has this freaky genome where genes were inserted by virus from who-knows-where and large portions of the E. coli genome were lost.

    • Ken Pidcock
      Posted January 16, 2017 at 12:12 pm | Permalink

      Resistance due to chromosomal mutations – such as penicillin resistance in Streptococcus pneumoniae can be lost in the absence on antibiotic selection. Presumably, the mutations are disadvantageous in the absence of the antibiotic. Unfortunately, that’s not usually the case with resistance genes on plasmids, who are as wily as any other parasite.

  14. mikeyc
    Posted January 16, 2017 at 10:50 am | Permalink

    I saw this news report last week and read up a bit on antibiotic resistance. Since I read WEIT daily, I was most interested in evolutionary aspects of ab resistance. This morning on WEIT I find the very question discussed so thought I’d chime in.

    It seemed to me that the persistence of antibiotics resistance in cultures that are no longer under selection is that there is no cost to carrying it. Plasmid or viral vectors seem a good way to spread resistance though I should think there is significant cost to that in the absence of selection.

    One paper I read, from 1999, (The biological cost of antibiotic resistance. D.I.Anderson & B.I.Levin, Current Opinion in Microbiology Volume 2, Issue 5, 1 October 1999) had this to say about the costs of antibiotic resistance;

    “..it has been long thought that antibiotic-resistance genes and accessory elements would engender a cost in the fitness of bacteria, the actual evidence for this being the case is, at best, modest and that which has been gathered recently does not paint a rosy picture for the future of the resistance problem. Resistance mutations, such as those found in the bacteria from patients treated with antibiotics, have virtually no cost when measured by competition experiments in vitro or in experimental animals. Moreover, in those cases where resistance mutations and accessory elements engender a cost, subsequent evolution in the absence of antibiotics commonly results in the amelioration of those costs rather than reversion to drug sensitivity. If these laboratory observations reflect the situation for bacteria in hospital and community acquired infections, even low levels of antibiotic use could be sufficient for the ascent and long-term persistence of resistance.”

    This suggests to me that ab resistance can persist in the absence of selection simply because there is no cost to it.

    • Posted January 16, 2017 at 11:59 am | Permalink

      I give as examples of beneficial mutations some single-nucleotide substitutions in the bacterial beta-lactamase gene that confer resistance to the beta-lactam antibiotics; and I haven’t yet come across any finding of cost of these mutations, or their displacement by the wildtype when antibiotics are withheld.

  15. TJR
    Posted January 16, 2017 at 10:53 am | Permalink

    I must admit that bacteria not losing “old” resistances is something that never occurred to me before.

    Fascinating and scary in equal measure.

  16. BobTerrace
    Posted January 16, 2017 at 11:08 am | Permalink

    Could this be partially due to the sheer numbers of bacteria?

    When there are trillions of trillions of the little buggers, almost anything is possible?

  17. Posted January 16, 2017 at 11:18 am | Permalink

    Reblogged this on The Logical Place and commented:
    This news is quite alarming.

  18. rickflick
    Posted January 16, 2017 at 11:19 am | Permalink

    The EU banned antibiotics in animal feed in 2006. Our outgoing POTUS has attempted to influence such use in cattle as a source of superbugs.

    “…President Obama signed(2014) an executive order to establish a new task force dedicated to addressing antibiotic resistance. And last year, the FDA announced a plan to cut down on animal antibiotic use…”

    The new administration may not concur. We’ll just have to wait and see how widely the wrecking ball swings.

    • GBJames
      Posted January 16, 2017 at 1:10 pm | Permalink

      The new administration is likely to dismantle monitoring of the problem and pretend that it went away.

  19. Derek Freyberg
    Posted January 16, 2017 at 11:30 am | Permalink

    I wonder whether, at least to some extent, resistance to abs is achieved not by developing individual resistance to yet another ab, but developing a more generic resistance. So, bugs meet penicillin A, some die, some live. Those that live (resistant to pen A) meet pen B. Again, some die, some live. There are two possibilities: those that live have developed a separate resistance to pen B, and now carry resistance to each separately; those that live have developed a more generic resistance to penicillins – perhaps not good against all penicillins, but working against both pen A and pen B. And so on. At some point, it becomes either a bunch of individual resistances or a pan-resistance; or I suppose some blend of the two. So a bug that is already resistant to many penicillins might well be resistant (or at least less susceptible) to a new one. But bring on a new class of abs, say penems, and the bugs would have to start afresh. Developing a generic resistance would tie in with not losing resistance over time, because losing the generic resistance would be much more of an all-or-nothing proposition than losing resistance to a single ab.
    Total speculation from a non-biologist.

  20. bonetired
    Posted January 16, 2017 at 11:32 am | Permalink

    Lats year the British government published a seminal report on antibiotic resistance from a committee chaired by Lord O’Neil. It is well worth a read:


  21. Dominic
    Posted January 16, 2017 at 11:42 am | Permalink

    No time to read all the comments – but don’t bacteria swap genes with other bacteria? The phrase you used “evolution in action” was the first thing I thought when I heard this on the news at the weekend!

    • Posted January 16, 2017 at 11:55 am | Permalink

      Yes, they do (horizontal gene transfer).

  22. Bruce Byers
    Posted January 16, 2017 at 11:59 am | Permalink

    I think there is a fairly large literature on the persistence of antibiotic resistance. Andersson and Hughes have written a couple of reviews; the one at http://dx.doi.org/10.1111/j.1574-6976.2011.00289.x seems to be available for free. One interesting mechanism is that, when bacteria populations evolve for a long time in the presence of antibiotics, competition favors the preservation of compensatory mutations that reduce the cost of resistance. This can result in evolution of resistant strains that are no less fit than susceptible strains even in antibiotic-free environments.

  23. Ken Pidcock
    Posted January 16, 2017 at 12:07 pm | Permalink

    I’ve done a good bit of work with carbapenem-resistant Klebsiella pneumonae, and they don’t look like that on MacConkey. I don’t know where these photographs are coming from – that pink growth on a clear plate seems to have become stock for CRE – but that ain’t K. pneumoniae on MacConkey.

  24. Posted January 16, 2017 at 12:16 pm | Permalink

    Should we be worried about all those ethanol based hand sanitizers that are everywhere now?

    • Joe Pickard
      Posted January 16, 2017 at 12:31 pm | Permalink

      If you mean bacteria becoming resistant, it’s pretty much impossible, afaik. The only way to survive it is forming spores, which isn’t something E. coli or Klebsiella will figure out how to do anytime soon.

      • Posted January 16, 2017 at 8:01 pm | Permalink

        I think that is correct Joe. I think I recall from bacteriology about 50 years ago that ethanol and similar solvents kill bacteria by dissolving lipids in their cell membranes, rather than having to be taken into the cell by some mechanism and then attacking internal metabolic functions. It’s probably more difficult to evolve a way to repair direct chemical damage to the cell membrane than to by-pass or modify some internal metabolic step.

        • Posted January 17, 2017 at 11:20 am | Permalink

          Interesting, if true. I wondered whether it was doing something similar to what happens when us eukaryotes use too much ethanol. (I thought that would be nifty, because it would suggest a very ancient biochemical pathway, I guess.) Oh well.

  25. Flaffer
    Posted January 16, 2017 at 1:42 pm | Permalink

    In the Frontline documentary on Superbugs, they did mention an antibiotic which helped stop superbugs because they had lost their resistance to it. The antibiotic had deadly side effects which caused it to go out of favor quickly. Not sure it was tried in the ’26’ which were tested and showed bacterial immunity.

    Doc is here: http://www.pbs.org/wgbh/frontline/film/hunting-the-nightmare-bacteria/

  26. loren russell
    Posted January 16, 2017 at 1:55 pm | Permalink

    Several commenters here have referred to our “luck”, and in many respects older and middle-aged Americans have been exceptionally lucky to live in an era of reasonably effective and reasonably accessible medical care. Antibiotics were a huge contributor to both, and I’m pretty sure my own life — or one or more of my limbs– were saved on more than one occasion by a 10 dollar vial of pills. Notably, the scariest episode, thirty years ago was fighting a bug I acquired from a very simple surgical procedure.

    Like the petroleum-based economy, this seems to be a one-off — we had the antibiotics, and as a society decided to burn through them, rather than conserving for the future. Tough luck, you youngs!

    There may be a few classes of antibiotics that we haven’t stumbled over yet, but I think the best hope to maintain an edge on infectious diseases may be a return to work on bacteriophages that was largely abandoned in favor of broad-spectrum antibiotics.

  27. Hempenstein
    Posted January 16, 2017 at 3:19 pm | Permalink

    Retired biochemist/enzymologist here. This is all off the top of my head, and any comments on it would be welcome.

    Resistance only requires the bug to produce as little as a single enzyme capable of acting on the antibiotic to modify it in any way that renders it ineffective. (Are there any studies that have shown this?) It’s easy to suppose that such an enzyme arises from scratch, but in reality I suspect that an existing enzyme – one that probably has a low activity on the antibiotic in question – becomes more efficient through one or more mutations. Assuming that most antibiotics have at least one hydrolyzable link, the category of enzymes called hydrolases may be the most likely candidates – there are all sorts of hydrolases, and they don’t require energy input from ATP, so mutation of the substrate-recognition site of any hydrolase could turn it into an antibiotic-neutralizing enzyme.

    I coincidentally ran across years ago called Bleomycin hydrolase that I suspect might be an example of this. The enzyme is in the family of thiol proteases (which was what I discovered from less than a half-hour’s looking at the amino acid sequence of the hydrolase. The lab that had been studying that enzyme thought they had a special enzyme. What I found suggested that it was just another thiol protease that happened to recognize bleomycin. (I don’t recall what part of the bleomycin molecule the hydrolase acts on, but I suspect there must be an amide linkage in it somewhere).

    Now, if that occurs, the enzyme may well still retain activity on whatever substrate it originally acted – maybe less robust activity, maybe not. In any event, there’s no reason to suspect that an antibiotic-resistant bug will be less viable otherwise. Maybe, but maybe not.

    Thoughts esp from anyone up on any relevant enzymology literature?

  28. Linda Calhoun
    Posted January 16, 2017 at 3:22 pm | Permalink

    At least in a few cases, bacteria do lose their resistance to the original antibiotics.

    I know that many years ago I treated pasteurella pneumonia with tetracycline, which eventually lost its effectiveness.

    I now mostly use Naxcel. Sometimes I get a kid that will relapse after a course of Nax, and then I switch to Fluophenicol.

    But, once in a while if neither drug works after a course, I go back to tetracycline, and it has worked. L

  29. Torbjörn Larsson
    Posted January 16, 2017 at 3:35 pm | Permalink

    I have read about these scare reports before, and the bottom line is that there has never been a report of total resistance. There wasn’t in this case either. The bacteria tested negative for the mcr-1 gene against colistin, and was “intermediately” resistant to some other antibiotics [see the CDC report]. “The isolate had a relatively low fosfomycin MIC of 16 μg/mL by ETEST.* However, fosfomycin is approved in the United States only as an oral treatment of uncomplicated cystitis; an intravenous formulation is available in other countries.” “Pan-” vs “omni-” resistant?

    But I can’t contribute much on the evolution of antibiotics resistance as of yet.

  30. Kun Lin
    Posted January 16, 2017 at 8:08 pm | Permalink

    Anyone know what they did to the patient after she is deceased? does the CDC have a protocol that deals with “super-bug” infections after the patients are deceased? Since bacteria don’t have to be alive to transmit virulence (known since Frederick Griffith’s famous experiment on mice with Streptococcus Pneumoniae), it wouldn’t come as a surprise that resistance could be transferred to other bacteria nearby once the cell is lysed. Killing off the multi-antibiotic resistance bacteria themselves is not enough to contain the possible spread. The plasmid, or whatever medium the resistance gene is carried on needs to be destroyed to prevent other cells from picking it up and acquire the resistance.

  31. Larry Smith
    Posted January 16, 2017 at 10:18 pm | Permalink

    Nothing useful to add here other than to say a) I read the article and b) skimmed the comments. It is very useful to have this site to come to and read a wide variety of scientific offerings. I’m sure that for every person who comments there are dozens if not hundreds who read these posts and get something useful out of it!

    • JoanL
      Posted January 16, 2017 at 11:57 pm | Permalink

      Absolutely. I read a headline in Google news and chose to wait for PCC’s coverage for a more informed review of the topic (via email). Came onsite specifically to read the comments.

  32. Dmitri
    Posted January 17, 2017 at 2:21 am | Permalink

    These bacteria usually have several multidrug efflux pumps that are involved in resistance, each of those able to expel different types of antibiotics from a single (and sometimes mutiple) class of AB.

    Is it possible then that a few mutations in the transporters required for drug efflux could enhance their specifity and extend the range drug exported, with little to no consequence on their affinity for drugs they could previously export.

    This would seem to decrease the “cost of resistance” since the bacteria would gain a new ability without compromising their pre-existing resistance phenotype and actually expanding it.

  33. chrism
    Posted January 17, 2017 at 5:58 am | Permalink

    Some comments:
    Firstly, I agree that the biggest issue is not misuse of antibiotics in humans (though it occurs and should be curbed), but the indiscriminate use of antibiotics in animal feed. Farm and abattoir workers have been shown to be more likely to acquire the same resistant gut bacteria as the cows they work with, so those bugs transfer to us easily enough. Related to that particular issue, I saw a fascinating phenomenon at a long term care home. Residents who broke a hip would go to the nearest hospital with an orthopedic service, and would routinely return with ESBL enterobacteria in their guts. Since nearly every urinary tract infection is caused by your own flora, they would develop, as the elderly will, UTIs with ESBL bugs, necessitating some unusual antibiotics that could eventually clear the urinary tract, but never the gut. Next UTI: ESBL again. Ditto repeato ad nauseam. The point, however, is that nursing staff who had not had broken hips would soon start developing UTIs of the same sort. Rather implying that despite their fanatical handwashing culture, bugs will be shared, with incontinent residents making that even more likely. Similarly, all patients admitted to our hospitals are swabbed for MRSA and VRE on admission and discharge. Funny part: if a staff member is admitted they are NOT swabbed. No one wants to know. It might mean sick leave or worker’s comp until they are cleared (if ever), and decimation of the workforce.
    Lastly, Jerry, you are right about the common patient misconception that they are the ones resistant, not the bugs. “Penicillin doesn’t work on me,” they’d say. “You have to give me Cipro.” Then the long arguments began. Many infections have protocols demanding the first treatment be an antibiotic to which resistance is common, but reserving those that work is our only strategy for slowing the development of resistance, and, dammit, the patient has the wrong end of the stick, and has undoubtedly had a couple of experiences where penicillin didn’t work, but that’s not their fault (unless they had wheedled a script for a cold, in which case they deserved what they got). Fight the good fight. Try to explain and educate. Result: you get way behind and the rest of the patients hate you, and the patient in question goes to one of your colleagues who will score a cheap point by saying “Of course” and handing over a bucket of Cipro. Such is life.

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