Traditionally, complete drug doses were recommended to prevent antibiotic resistance, but evidence suggests that lower doses could be effective in certain situations. Mutants resistant to antibiotics often have a fitness cost, similar to wearing armor that provides protection but hinders movement. When susceptible counterparts are present, resistant mutants struggle to compete, but in the presence of drugs that eliminate competitors, they thrive. By administering smaller doses that control infection but maintain susceptible competitors, the growth of antibiotic resistant organisms can be limited. While following medical advice is crucial, future adjustments in drug doses may be explored.
An exciting but controversial line of research is exploring whether we should treat organisms or pathogens with a ‘hit fast and hard’ approach, or whether it would be better to reduce the drug dose and therefore the selective pressure.
We have traditionally been told to make sure you take your full prescribed dose of antibiotics, or else you could be responsible for resistance evolution. Now some evidence is coming out that that might in fact not be true in some situations.
The idea behind this is as follows:
Many resistant mutants pay a price for being resistant. It serves them well if there are drugs or insecticides around, but in their absence, they might not grow as well as their susceptible counterparts. We call this a fitness cost.
One way to think about a fitness cost is to think of a knight in shining armor. On the battlefield, that armor greatly protects him or her from attacking swords. However, outside of combat, wearing this armor comes with a cost; it can greatly reduce vision, and is very heavy and hot.
When an organism has a genetic mutation that makes them resistant to a drug, they don’t have the luxury of armor they can put on and take off when it suits them, they have to live with that mutation whether there are drugs around or not.
When there are plenty of those more susceptible counterparts around, these resistant mutants may have a hard time increasing in number because of the fitness cost. However, when drugs are around, and the majority of those competitors are killed, the resistant ones are able to grow to high numbers.
So, if we want to keep the resistant organisms small in number, perhaps we should keep these susceptible competitors around! One way to do that might be by not giving this high, aggressive dose of drugs, but a smaller dose that would control the infection but leave enough susceptible competitors to out-compete the resistant ones.
We tested this principle using a rodent malaria model. We infected mice with both susceptible malaria parasites and a few resistant ones to mimic a situation where resistant parasites are rare. When those mice were not treated with drugs, we rarely saw those resistant parasites again. When we gave a very high, curative drug dose, we cleared the susceptible parasites which then allowed the resistant parasites to grow to large numbers too. The less drugs we gave, the less of an advantage we gave to the resistant parasites.
The treatment of cancer faces a similar problem: resistant cells are suppressed by susceptible cells but as soon as you wipe out the susceptible cells, the resistant ones grow to high numbers, which might ultimately lead to an untreatable tumor. A pilot clinical trial of metastatic prostate cancer which gave only enough chemotherapy as was necessary to control the growth of the tumor, but not intended to eradicate it, was very successful in prolonging the time to cancer progression with the added benefit of less chemotherapy for the patient.
Now, you should always follow your doctor’s advice; the research is too young yet to make it a good idea for you to only take half your course of medication! But in the future, we might just adjust the dose.
