Using a computer model, researchers have identified a simple way to optimize dosing that could bring back a whole arsenal of first-line antibiotics and preserve last-resort antibiotics in the fight against drug-resistant bacteria.
Writing in the journal PLOS Computational Biology, researchers at Duke University in Durham, NC, describe how a computer simulation developed in their lab shows that a dosing regimen based on the recovery time of a target bacteria could eliminate an otherwise resistant strain.
In his Nobel Prize acceptance speech in 1945, Sir Alexander Fleming – the doctor and bacteriologist who revolutionized medicine with his discovery of penicillin – warned that there will come a time when penicillin will be so easy to acquire that “the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug, make them resistant.”
Seventy years later, the era Fleming predicted is upon us. The World Health Organization (WHO) describe antibiotic resistance as a major threat to global public health; bacteria are becoming resistant faster than we can develop new drugs to fight them.
This means there is a pressing need to use the antibiotics we already have more effectively.
First author Hannah Meredith, creator of the computer model and biomedical engineering graduate fellow at Duke, says:
“We hope this research will help hospitals improve patient outcomes while also making our antibiotics last as long as possible.”
The computer model simulates the relationship between bacteria and antibiotics while focusing on the activity of a bacterial enzyme called beta-lactamase. The enzyme attacks beta-lactam antibiotics – one of the largest and most-used class of antibiotics.
Many beta-lactam antibiotics are overlooked because doctors believe the infection they are treating is completely resistant to them, even if they are shown to be effective in lab tests.
However, the computer model shows there is a period – before the beta-lactamase degrades the drug – when the bacterium is sensitive to the antibiotic.
Senior author Lingchong You, an associate professor of biomedical engineering who heads the lab Meredith works in, explains:
“You can think of this as a race between the cells and the antibiotics. Before their beta-lactamase degrades the antibiotics, the cells are still sensitive and can be killed. But the antibiotics degrade faster than the cell population declines, allowing some cells to survive and repopulate.”
When doctors realize an infection is resistant, they often go straight to a last-resort antibiotic. But the study suggests if they were to stick to the first-line antibiotic and change the dosing frequency so each dose hits the bacteria during their recovery period while they are weak, some infections could be cleared without reaching for the last resort.
The team says, in theory, a database of recovery times for different combinations of bacteria and antibiotics could allow first-line antibiotics to clear many resistant infections.
There are other important considerations when administering antibiotics. For example, doctors need to take care not to wipe out native populations of bacteria that are important for health.
A database of the responses of different strains to different antibiotics could allow the simulation to find the optimum dosing regimen that keeps total exposure to a minimum. It could also show whether multiple doses are likely to work and let doctors know when it is time to reach for the stronger drug.
Prof. You explains that others are already working on how to determine antibiotic dosing schedules, but they are typically using models based on complex biological mechanisms. Such approaches are time-consuming, he adds, and there are thousands of new strains evolving all the time – it is impossible to keep up.
“We’re trying to see if this one, easy-to-test metric of recovery time can make a good enough prediction without years of study,” says Prof. You.
Work on developing the database has already started and early results are promising, says Meredith:
“Our preliminary data have confirmed many of the clinical aspects of the model’s predictions, so we are tremendously excited by those. If this strategy is successful, it could potentially reintroduce a large number of first-line antibiotics for patient treatment.”
The National Science Foundation, the National Institutes of Health and a number of Fellowship awards helped fund the study.
Meanwhile, Medical News Today recently learned of another intriguing study that showed maple syrup helps antibiotics defeat bacteria.
Writing in the journal Applied and Environmental Microbiology, researchers from McGill University in Canada describe how they found concentrated maple syrup extract makes disease-causing bacteria more susceptible to antibiotics.