NIH awards UF Health researchers $11.8 million grant

The National Institutes of Health (NIH) has awarded UF Health researchers an $11.8 million grant to study how combinations of antibiotics can fight resistant bacteria.

UF Health announced the grant Wednesday and said the research has the potential to save tens of thousands of lives that are lost each year due to infections.

The grant will go to the UF College of Medicine and the UF College of Pharmacy , which will support scientists working to uncover the mechanics of how bacteria and antibiotics interact.

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"That mechanistic knowledge has become crucial as bacteria become ever-more resistant to antibiotics," the UF Health release said. "Few pharmaceutical companies are developing new antibiotics, leaving scientists to find novel methods to make older drugs more effective when used in combination."

Operating under NIH, the National Institute of Allergy and Infectious Diseases, asked for proposals to address what researchers call a crisis.

"It's very clear on these serious infections with antibiotic-resistant bacteria that monotherapy cannot work," Jürgen Bulitta, Ph.D. , a co-principal investigator on the project, said in a statement. "Using one antibiotic at a time, you cannot win. You must tag-team with more than one drug to have any chance against serious infections."

Researchers hope to "dial in" these antibiotics using newfound insight from the laboratory.

"It's like understanding an enemy's weaknesses to form a battle plan that takes advantage of those chinks in the armor," the UF Health release said. "What receptors on bacteria are best targeted by antibiotics? What precise dosages in a drug cocktail will kill a bacterial population without resistant stragglers surviving to multiply?"

Bulitta's co-principal investigator is Dr. George L. Drusano , a professor and director of the UF College of Medicine's Institute of Therapeutic Innovation . They will focus on two of the most deadly resistant bacteria, Acinetobacter baumannii and Klebsiella pneumoniae.

The bacteria, also known as "superbugs," are often found in hospitals and infect patients with weakened immune systems. They are adept at eluding the drugs hunting them.

"These bacteria are not only multi-resistant to antibiotics, they're also hypervirulent," Drusano said in a statement. "They have turned into really nasty, nasty bugs that wreak havoc on patients' bodies and too often kill them. We have some great antibiotics. But we need to optimize them and find new approaches that will cure people and get them out of the hospital."

The researchers are using advanced computer modeling techniques and in vitro (outside-the-body) testing, such as a relatively new method called the hollow fiber infection model.

This technique uses a collection of hollow fibers 200 microns in diameter — roughly twice the thickness of a human hair — to culture cells and bacteria. The method reproduces what happens in the human body and helps scientists measure how bacteria respond to drugs and develop resistance.

These bacteria reproduce and evolve in rapid cycles of life and death as short as 20 to 30 minutes, and generations of reproduction are achieved in days. A severe infection might generate billions of bacteria in the lungs, making it highly probable that a beneficial bacterial adaptation will get a toehold, defanging an antibiotic.

Even with a patient's natural immune defense and antibiotics, Bulitta said, bacteria are reproducing so rapidly, "it's a near certainty you will still have 100 to 1,000 resistant bacteria remaining in severe lung infections."

Multidrug therapy seeks to reduce the population of that bacteria with one antibiotic regimen, then hitting it with a second or third using different drugs. This can reduce bacterial numbers before the superbugs can again adapt new protections.

"It's a game of cat and mouse," Bulitta said.

UF Health is leading this multicenter investigation, which also includes researchers at Case Western Reserve University in Cleveland; the Children's Hospital of Los Angeles, Monash University in Australia; St. Jude's Children's Research Hospital in Memphis; Northern Arizona University in Flagstaff, Arizona; and the University of Central Florida in Orlando.