The second is to manage our current arsenal of drugs better so that they remain effective for as long as possible. The key to doing this is to reduce the global burden of antibiotic resistance by decreasing the quantity of drugs we use.
Delivering drugs differently
The first strategy of response to antibiotic resistance is not as easy as it sounds. While there are many potential new therapies that could be effective, there are few incentives for industry to invest in their development.
If an antibiotic works well, it is used for a short time — a few days to a couple of weeks at the most. The commercial return on a drug designed to treat longer lasting non-communicable illnesses, like cancer, for instance, can be much higher because the drugs are used for longer.
The logic of the second strategy is straightforward. The widespread use of antibiotics in medicine and agriculture means that a drug-resistant variant of a bacterium will enjoy a strong selective advantage and can quickly spread. So by reducing the use of drugs, we reduce the selection pressure on resistance and slow the rate at which resistance evolves and spreads. Simple.
Except it’s not. How, precisely, should we reduce the volume of drugs we use?
We can’t just introduce a blanket ban on prescriptions and stop using drugs altogether. If my loved one is sick and there is a drug that can make them better, I want that drug.
But maybe we could deliver our drugs in ways that would make it harder for resistance to evolve and spread? And so prolong the amount of time a drug remains effective?
Creating drug sanctuaries
One suggestion that my research group has been exploring is to make use of drug sanctuaries, or drug-free environments — to effectively reduce the strength of selection for resistance.
If drug-sensitive variants of microbes have a growth advantage over resistant ones when no drug is around, then sensitive variants would predominate in drug-free refuges and help keep resistant ones from taking over the population.
Drug sanctuaries could be used in hospitals. For example, different wards could restrict the use of certain drugs (generating a form of spatial sanctuary) or could alternate the use of a drug on the same ward over time (a form of temporal sanctuary).
Evolutionary models can help guide us here. Variation in time is like paying taxes: You can’t avoid it. A variant that evolves in a temporally varying environment is the one that does best across all conditions experienced.
Variation in space, on the other hand, provides more options because the different locations can act as refuges for the specialized variants of bacteria. Because those locations are always available, then specialists can coexist indefinitely. At least in theory.
Buying us time
This seems to be what happened when we did an experiment to test the theory.
Resistance to the commonly used antibiotic ciprofloxacin took longer to spread in laboratory populations of the opportunistic pathogen Pseudomonas aeruginosa — a bacterium that causes acute infections in hospitals, especially intensive- care units, and chronic infections in the lungs of cystic fibrosis patients — when drug sanctuaries were experienced in space rather than time.
Resistant and sensitive genetic variants actually coexisted in spatial sanctuaries because of a trade-off between resistance and growth rate.
Resistant variants could withstand the drug, but grew far more slowly than sensitive ones in the sanctuary. The result was that neither could be eliminated by natural selection.