NEW YORK (GenomeWeb) – Wayne State University has received a $4.8 million grant from the National Institutes of Health to optimize the use of the antibiotic polymyxin B to treat Gram-negative bacterial infections resistant to other treatments and identify protein biomarkers of drug-associated toxicity.
The five-year grant began on June 19 and is worth $924,298 in its first year.
Since polymyxin B was released in the 1950s, its pharmacokinetics, pharmacodynamics, and toxicodynamics have never been defined, according to the grant's abstract. Recent research on polymyxins has largely focused on colistin methanesulfonate (CMS), finding that it has significant limitations. Dosage recommendations for CMS, however, are not applicable to polymyxin B since it has fewer limitations.
As such, Wayne State researchers aim to define the optimal dosage regimens for polymyxin B by determining the association between dose and the timing of nephrotoxicity. They also will use next-generation proteomics to identify the most predictive biomarkers of polymyxin B-associated nephrotoxicity.
It is expected that the study will inform clinicians about the best ways to administer polymyxin B to patients in order to prevent drug resistance in Gram-negative bacteria against other medicines.
"Patients being treated with intravenous polymyxin B will be identified and will have blood collected at various times surrounding a dose of polymyxin B between days one and five of therapy," Wayne State researcher Keith Kaye, who is leading the effort, said in a statement. "Development of nephrotoxicity, clinical response, and bacteriological response will be examined. Total and free plasma concentrations of polymyxin B will be determined, and bacterial isolates will be examined for the emergence of polymyxin resistance."
Researchers from Australia and Singapore are collaborating on the research.