Antimicrobial resistance presents challenges related to the effectiveness of drug and insecticides. Strategies such as combination therapy, drug rotation, mosaic treatment, evolutionary refugia, low drug dosages, and limited usage can extend the effectiveness of treatments and slow down the evolution of drug and antibiotic resistance. The goal is to find tailored strategies for different scenarios and understand the similarities and differences among resistance-evolving organisms.

Currently, we deal with resistance evolution by running a treadmill of drug discovery, replacing failing drugs or insecticides with new ones. This is both dangerous and expensive, and having a new drug available to replace a weakening one is not always a given. For instance, we have no new drug to treat malaria, but our current treatments are beginning to fail. 

An alternative approach is resistance management. Here the aim is to extend the useful lifespan of a drug before it, almost inevitably, fails in the face of evolution.

There are several ways to do this: [FIG 1]

One method is combination therapy. Rather than using one single drug or chemical to treat infection or kill organisms, we combine different ones. To survive this double onslaught, the pathogen or pest has to have the mutation or mutations to resist both drugs. Resisting one isn’t enough, the second chemical would kill them and those genes would not be passed on. The chances are small for an organism to emerge that is resistant against one drug, so using two drugs at once drastically reduces the chances. 

A second method is rotating through different drugs. Mutants might be selected for drug A when you use it, but after a set period of time, drug A is replaced by drug B and those organisms are killed by drug B.

A variation of rotation is mosaic treatment. Instead of rotating the drugs in time, you rotate the drugs in space. This could mean that people for instance randomly receive either drug A or drug B. This makes it difficult for pathogens to adapt; even if they were resistant to the drug that their current host was taking, when they infect their next host, this host might be treated with drug B and stop further generations.

These three resistance management strategies assume we have different drugs that we can combine. But what if we have only one single chemical? 

One alternative in agriculture is to use evolutionary refugia, where some of the population is left untreated. This way, individuals who are not resistant are able to reproduce uncontrolled and spread their susceptible genes. By having untreated areas, you allow for the dilution of resistance genes, slowing the evolution of resistance. By sacrificing  part of their fields, farmers ensure that they can use their chemicals for a much longer time and have greater benefits. 

Similar to refugia, you might use low drug dosages. This method also aims to leave some susceptible pathogens alive to compete against the resistant mutants and prevent them from growing to larger numbers.

 Finally, the best resistance management strategy, our very first strategy, is to use drugs or chemicals only in situations where they are really needed. The less we use them, the less advantage we give to resistant organisms. This is the reason your doctor won’t prescribe antibiotics if you have a viral infection; not only will it not help, but it could also select for antibiotic resistant bacteria in your body. 

We’re finding the best strategy for each scenario. It’s unlikely that there is a one-size-fits-all, so our research focuses on understanding the commonalities and differences between these resistance-evolving organisms.