The rising threat of antibiotic resistance

Last month, researchers from the University of California, Los Angeles (UCLA) revealed findings that showed that utilising antibiotics in combination proved far more effective against antibiotic-resistant bacteria than using them alone. Pamela Yeh, UCLA Assistant Professor of Ecology and Evolutionary Biology, spoke to Pharmafocus on her recent work and the greater importance of battling the increasing threat of antibiotic resistance.

"Our recent work provides a new conceptual framework for looking at higher-order interactions. We are able to now say, for any three (or more) drug combinations: is this a novel synergistic interaction, or does the synergy come from lower-order (for example, two-drug) interactions?  If it’s a novel, emergent interaction, it means you need all three drugs present to obtain that synergy.  If it’s not an emergent interaction, it means you could’ve gotten that synergy mostly from just two of the three drugs.  This framework lets you rationally design drug combinations that are both effective and have interactions that are genuinely synergistic, meaning you actually need all three drugs.  Our hope is people will use it to develop new combination treatments that are very powerful, perhaps unexpectedly powerful.

We now have cases where pathogens have evolved resistance to every drug we have - for example, XDR-TB. Or the recent case that was in the news of the woman in Nevada who had a bacterial infection from a CRE that was resistant to all 26 antibiotics the doctors had. I think evolution of resistance is such a threat because with bacteria, evolution is (typically) working in the bacteria’s favour, and not in ours, as the human host. That’s because bacteria replicate so rapidly, and thus mutations can evolve so rapidly, and some of those mutations can give resistance to antibiotics.  So, it’s a hard game for us humans to win, but my lab and several other labs are definitely very interested in seeing if we can use evolutionary ideas and principles to tilt the situation back towards us, at least a little bit. 

If you look at the percentage of cases of antibiotic-resistance that is found today compared with just a couple decades ago, and if you look at the numbers of cases where we don’t have any antibiotics that work, I think antibiotic resistance is becoming a point of crisis. People talk about the "post-antibiotic" era, which might be much like the pre-antibiotic era, and it sounds like a nightmare.  Innocuous things like skinning your knee could become life-threatening.

I don’t think anyone knows what a post-antibiotic world would actually look like, but people do know what the pre-antibiotic world looked like, and frankly, the stories I hear scare me. For example, we would likely not have elective surgery procedures anymore.  This doesn’t sound terrible if you just equate elective surgery with, say, breast implants or a facelift or some other form of vanity.  But it could also mean no more surgeries that could vastly improve your quality of lift –for example, to improve movement in some way. I think the consequences could be profound. 

I think the problem of antibiotic resistance is an issue of policy as well as an issue of biology. I’m by no means an expert on policy, but I think it’s pretty clear that agricultural use of antibiotics is driving a significant amount of evolution of drug resistance. Thus, one of the simplest things we could do as a country and a society is to make sure that antibiotics go where it is needed: in people with bacterial infections.

The thing about the agriculture industry using antibiotics is that they don’t use it when animals get sick, they just dump it in the feed and all individuals then ingest antibiotics.  The antibiotics allow the animals to grow a little faster, which means of course more profit. That profit is coming at a huge cost which is the evolution of resistant pathogens.  I don’t think we know for sure how much of the resistance is a result of agricultural use, but I know some groups are studying this. 

Whatever ideas we have, however outrageous, I think it’s worth at least thinking about, testing in some way.  So whether it’s trying to find new targets for antibiotics, trying to tweak existing drugs - 4th, 5th, 6th generation antibiotics - or whether it’s using drugs in combinations or looking at phage therapy, I think we need to pursue all possible paths.

Honestly, I’m not sure if R&D is moving in these directions enough; I think scientists and funding agencies can be quite conservative. Critically, because antibiotics do not make pharmaceutical companies much money, most of them have abandoned this work.  So it’s extremely important that governments and non-profits fund this: I think antibiotics are very much a public good, just like roads, traffic lights, bridges, libraries, and schools.  We need them to function optimally as a society."