Hebrew University researchers develop test to help fight superbugs
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Hebrew University researchers develop test to help fight superbugs

Mathematical model predicts whether bacteria will develop tolerance to a particular antibiotic, thus helping doctors prescribe treatment with best chance of success

Illustrative close up of medical technician working on a bacterial culture (Credit: 10174593_258, iStock by Getty Images)
Illustrative close up of medical technician working on a bacterial culture (Credit: 10174593_258, iStock by Getty Images)

Researchers at the Hebrew University of Jerusalem say they have developed a lab test that is able to predict if a patient with a bacterial infection will respond well to a given certain antibiotic treatment.

Every year in the US, more than 35,000 people die and 2.8 million get sick from antibiotic-resistant infections. Now, a team led by Hebrew University of Jerusalem Professor Nathalie Balaban and Shaare Zedek Medical Center’s Dr. Maskit Bar-Meir says it has developed a laboratory test that can help identify patients who are liable to develop antibiotic tolerance.

The study was published in Science magazine.

Like all living organisms, germs such as bacteria develop defenses against hostile elements in their environment. One common tactic is “tolerance,” that is, lying dormant during antibiotic treatment. In this way, bacteria evade antibiotic treatment because antibiotics can only spot and kill growing targets.

Hebrew University Professor Nathalie Balaban (Hebrew University of Jerusalem)

However, this intermediary stage called “antibiotic tolerance” lasts only a few days and cannot be detected in standard medical labs; once the tolerance window closes, the bacteria become resistant and the opportunity to treat them with antibiotics is lost.

This does not affect most healthy adults, but for patients fighting off a serious infection with a weakened immune system, it could mean the difference between life and death, the researchers said in a statement.

In a previous study, Balaban and PhD student Irit Levin-Reisman studied lab-controlled bacteria. They developed a mathematical model that, when applied to bacteria taken from the blood, successfully described, measured and predicted when bacteria would develop tolerance to a particular antibiotic. They also observed that when bacteria developed tolerance to one antibiotic, they were more likely to develop tolerance to other antibiotics in the same cocktail.

“We observed that bacteria acquired tolerance within a few days. These tolerance mutations then acted as a steppingstone to acquiring resistance and, ultimately, treatment failure,” said Balaban.

Balaban’s lab and Dr. Jiafeng Liu teamed up with Bar-Meir and repeated their study, this time using the mathematical model on bacteria samples taken from hospitalized patients with life-threatening, persistent methicillin-resistant Staphylococcus aureus (MRSA) infections.

The pattern that they found was similar to their lab findings: the patients’ bacteria developed tolerance, then resistance, and ultimately antibiotic treatment failed.

In the short term, Balaban and Bar-Meir said the study offers new hope for patients with life-threatening infections and that medical centers should to adopt the laboratory test they developed to gauge antibiotic tolerance.

The test would enable doctors to quickly and easily detect whether a patient’s bacteria is tolerant of a planned antibiotic treatment before it’s administered, they said in a statement.

Further, based on the patient’s bacteria profile, doctors could pick antibiotics with a greater chance of success and avoid prescribing those for which the patient may have already developed a tolerance.

“Using the right combination of available antibiotic drugs at the outset could dramatically increase a patient’s survival rate before their infection becomes tolerant to all the antibiotics in our arsenal,” Balaban said.

Looking ahead, Balaban said that it may also be worth checking whether cancer cells act the same way as bacteria in developing tolerance to medication. For example, tumor cells might first become tolerant of chemotherapy, then develop resistance to it, and then develop resistance to other cancer drugs, as well.

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