April 17, 2020
Gauri Rao, Pharm.D, MS, an assistant professor at the UNC Eshelman School of Pharmacy’s Division of Pharmacotherapy and Experiential Education, recently received a $3 million grant from the National Institutes of Health, titled ‘Pharmacology of intrathecal/intraventricular polymyxins: A systems-based approach.’
Current dosing recommendations for intrathecal and intraventricular polymyxins are entirely empirical, as there is very little understanding of the pharmacokinetics-pharmacodynamics of polymyxin B and, importantly, there are no data on potential neurotoxicity, Rao said.
This cutting edge, multi-disciplinary five-year research project is the first to elucidate the mechanism of disposition and potential toxicity of intrathecal and intraventricular polymyxins. It utilizes systems pharmacology and cutting-edge imaging to optimize therapy using dynamic hollow fibre infection model and a rat CNS infection model combined with mechanism-based PK/PD modeling.
This will help generate the necessary pharmacokinetic-pharmacodynamic and toxicity data to support safer and more efficacious intrathecal and intraventricular therapy of polymyxins for life-threatening central nervous system (CNS) due to Gram-negative ‘superbugs.’
“I became interested in the design and optimization of antibiotic therapy during my clinical rotations,” Rao said. “I found infectious diseases very interesting and thought I could combine my background in engineering to truly make a difference.”
Rao said this research will help physicians treat CNS infections by providing adequate drug exposure at the site of infection, reducing the emergence of antibiotic resistance. She said the most important impact of this study will be to preserve the effectiveness of polymyxins as a last line of defense in the treatment of CNS.
“If bacteria continue to develop resistance to multiple antibiotics at the present rate, given the paucity of treatment options, there could be catastrophic costs to healthcare and society globally,” Rao said.
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