Pathogens developing resistance to antibiotics is one of the gravest threats to modern medicine, according to the World Health Organization, but new research may have found a way to help doctors fight such germs.
Researchers at The Hebrew University of Jerusalem say they have found a simple method for measuring a bacteria’s tolerance, or the time it takes to kill a bacterial population. This will enable clinicians to more effectively treat strains that are on their path to becoming resistant, the researchers say.
This tolerance has been “largely overlooked in the clinical setting,” according to Nathalie Balaban, the study’s senior author. The protocol exposes a sample population of a bacteria to different concentrations of antibiotics for varied time periods to see how many survive and for how long.
“Routinely measuring tolerance could supply valuable information about the duration of antibiotic treatments, reducing the chance of both under- and over-treatment,” Balaban said. “Furthermore, data compiled from such measurements could give an estimate of how widespread the phenomenon of tolerance really is, which is currently a complete unknown.”
Currently, doctors test for bacterial resistance, which is an active quality, to decide which antibiotic and dosage to prescribe a patient. The new method, called MDK99, or the minimum duration for killing 99 percent of the population, measures a different quality — bacterial tolerance, which is inactive. Instead of fighting the drug, these bacteria sleep through its presence, only dying when they wake up. If any survive, they can quickly replenish once treatment has stopped. By measuring tolerance, doctors can better decide which antibiotic to administer to kill all of the bacteria.
Resistant strains continue to grow despite exposure to high drug concentrations, while tolerant strains can survive lethal concentrations of an antibiotic for a long period of time before succumbing to its effects. Tolerance is more common than resistance, as it is found in any bacteria population. It is often associated with treatment failure and relapse, and is considered a steppingstone toward the evolution of antibiotic resistance. But unlike resistance, tolerance is poorly understood and is currently not evaluated in healthcare settings.
“The lack of a quantitative measure means that this aspect of the treatment relies largely on the experience of the individual physician or the community,” said Asher Brauner, the study’s first author and a PhD student in Balaban’s lab.
Tolerance has been overlooked
Tolerance has been overlooked because in healthy patients, the immune system can deal with a few surviving bacteria. But more patients now have weaker immune systems than in the past, including the elderly and patients whose immune system has been compromised by disorder or disease, Balaban said.
Doctors are encountering more cases of infections not being resistant but still not being cured by treatment, so tolerance is the suspected culprit.
The study was published in Biophysical Journal on June 20. Balaban’s team will use the method in future studies to examine the evolution of tolerance in patients. It could also enable a classification system for labeling strains as tolerant, resistant or persistent, which would help guide treatment decisions.
“A take-home message from this is that it is important to complete a course of antibiotic treatment as prescribed, even after the disappearance of the symptoms,” Balaban said. “Partial treatment gives tolerance and persistence mutations a selective advantage, and these, in turn, hasten the development of resistance.”