Antibiotic Resistance Update: Highest Dose Of Medication May Not Be Effective Drug Resistance Prevention

bacteria
Doctors and researchers are working on finding the right approach for treating bacterial infections. Pixabay Public Domain

If you’ve got a bacterial infection, chances are your doctor will give you a high dose of antibiotics to wipe out the problem. Though in theory, blasting microbial invaders with an aggressive amount of medication seems like the way to go, a new study shows this practice, while effective in the short term, is not the best idea when it comes to preventing the evolution of drug resistance.

“There is nothing in evolutionary theory that says that the dogma of hitting infections hard with high doses of medication should be the best rule of thumb to prevent drug resistance,” said Andrew Read, Evan Pugh Professor of Biology and Entomology and Eberly professor in Biotechnology at Penn State University, in a press release. “Our analysis demonstrates that although the traditional ‘hit hard’ approach often works, in some cases it also can be the very worst thing to do.”

Read, alongside his colleague Troy Day, a professor of mathematics, statistics, and biology at Queen’s University in Ontario, Canada, developed a model quantifying the two forces at work in the evolution of drug resistance in disease-causing microbes. They considered how often drug resistance occurs in microbes from genetic mutation, and then looked at the ability of microbes carrying such mutations to survive and increase their numbers. High doses of medication are usually effective at combating the first of these considerations.

“These infections — HIV is the classic case — where if you can kill everything by hitting it hard with a cocktail of medications, you should do it,” Read said. “Killing all of the infecting microbes obviously stops any further evolution of drug resistance, but we can’t do this in every case.”

In the event that a small number of microbes are already resistant to treatment, high doses of medication can allow resistant microbes to survive, precisely because they are killing off the other, drug-sensitive microbes.

“One of the main reasons drug-resistant microbes are rare is that they are in direct competition for resources with their drug-sensitive neighbors,” Read explained. “High doses of medication can quickly eliminate this competition for resources, allowing drug-resistant microbes to thrive.”

Read and Day propose that the right approach to combating the evolution of drug-resistant microbes can be either to use the highest safe dose, or to use the lowest dose that is effective.

“We’re extending the old rule of thumb to say that the best practice will either be the highest dose or the lowest dose of a drug,” Read said. “It’s going to be one of those two, but you can’t just toss a coin. Determining which is the best approach for a given infectious agent will need to be done on a case-by-case basis in clinical trials. By definition, both will make the patient better in the short term, but we don’t know ahead of time which course of action will be best for preventing the evolution of resistance, which leads to more problems in the long term.”

Source: Read A, Day T, et al. What is the optimal dose of medication to prevent the evolution of drug resistance? PLOS Computational Biology. 2016.

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