The end of the super-bug? Probably not.

Some of you may have seen the recent BBC headline, “Scientists make ultra-tough antibiotic” ( ) reporting on a recent paper published in PNAS (“Peripheral modifications of [Ψ[CH2NH]Tpg4]vancomycin with added synergistic mechanisms of action provide durable and potent antibiotics”, published ahead of print May 30, 2017, doi: 10.1073/pnas.1704125114).  In their report, the BBC states that the lead author, Dale Boger, told them, "Doctors could use this modified form of vancomycin without fear of resistance emerging."  Similar gushing reviews appear in the Guardian and the British Medical Journal, amongst many others.  Stop and read that quote again.  Of course, this makes headlines, promising the end of the superbug era, but one wonders whether the author did indeed use these exact words, and, if so, why?

For avoidance of doubt, let’s be clear that the paper is an excellent piece of science, modifying the structure of vancomycin to introduce three synergistic killing mechanisms into a single molecule, specifically designed to address the nature of vancomycin resistance.  The new compound has been tested against vancomycin-resistant enterococci (VRE), which causes difficult wound and bloodstream infections, and for which there are few alternatives.  The new compound has been shown to be 1000x more potent than the parent, and able to kill samples of VRE in the lab and retain nearly full potency after 50 rounds of exposure to the bacterium (my italics).  At this point in time, the new compound has not been tested in an animal model of disease, never mind in a human.

Of course, we’ve heard all of this before.  In 1967, the US Surgeon General is supposed to have declared “it’s time to close the books on infectious diseases”, although this may be an urban myth.  The oxazolidinones (e.g. Linezolid™) were the first new class of antibiotic for over 40 years when they were first approved for use against Gram-positive bacteria in 2000.  Since they were entirely synthetic and therefore bugs had never encountered them before, a number of commentators said that resistance would not develop.  Of course it has, albeit to a so-far minor extent, with isolates of E. faecium, some streptococci and some stapylococci showing both the development of efflux pumps and modification to the 23S ribosomal RNA target.

Bacteria are survivors.  They’ve been around for a lot longer than these sentient mammals, and they’ll probably still be on the fried Earth when we’re long gone.  Given time, and enough exposure to something that’s trying to kill them, evolutionary pressure will inevitably produce yet another super-bug.  Statements that our new agent is not susceptible to the development of resistance might only lead to chronic over-use again, with every patient with a virus demanding it, and domestic food animals loaded up to the bottom lip with it as ‘growth enhancers’.  Perhaps, we should concentrate more closely not on what the authors say to the media, but on what they actually say in their paper, “Such antibiotics are expected to display durable antimicrobial activity not prone to rapidly acquired clinical resistance”.  That’s more like it.

We need new antibiotics; that is clear, but we also need a sensible worldwide usage strategy.  The best outcome for any single patient with a bacterial infection is to be given as many antibiotics in as large amounts as possible.  The best outcome for society is to do exactly the opposite.  This tragedy of the commons is also at play when parents are considering having their children vaccinated.

The work reported here is a potentially large step forward, providing another, better drug for the antibiotic armamentarium.  But, will resistance to super-new vancomycin ever develop?  History tells us that it will.