University of Florida Health scientists exploring how combinations of antibiotics can fight resistant bacteria, have been awarded an $11.8 million grant.
 
The National Institutes of Health, or NIH, grant to the UF College of Medicine and the UF College of Pharmacy will support scientists working to uncover the mechanics of how bacteria and antibiotics interact, down to the molecular level.
 
That mechanistic knowledge has become crucial as bacteria become increasingly resistant to antibiotics. Few pharmaceutical companies are developing new antibiotics, leaving scientists to find novel methods to make older drugs more effective when used in combination.
 
“It’s very clear on these serious infections with antibiotic-resistant bacteria that monotherapy cannot work,” said Jürgen Bulitta, Ph.D., a co-principal investigator on the project at the UF Research and Academic Center at Lake Nona, Orlando. “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.”
 
The goal is to “dial in” these antibiotics using newfound insight from the laboratory. 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 and UF Health researcher and co-principal investigator George L. Drusano, M.D., a professor and director of the UF College of Medicine’s Institute of Therapeutic Innovation, will examine two of the deadliest resistant bacteria, Acinetobacter baumannii and Klebsiella pneumoniae.
 
The bacteria, sometimes called “superbugs,” are often found in hospitals, usually infecting patients with weakened immune systems. They are adept at finding genetic adaptations to elude the drugs hunting them.
 
“These bacteria are not only multi-resistant to antibiotics, they’re also hypervirulent,” said Drusano. “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 testing, such as a relatively new method called the hollow fiber infection model. The method reproduces what happens in the human body and helps scientists measure how bacteria respond to drugs and develop resistance.
 
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.