Right drug, right dosage, right away
Figuring out which antibiotics will be most effective against a given infection currently takes at least a day, and often longer. A Mizzou Engineering researcher is working on a method to cut that time down to less than six hours so that effective treatment can begin quickly.
ImpeDx Diagnostics, a startup co-founded by Shramik Sengupta, Associate Professor of Biomedical, Biological and Chemical Engineering, recently received a National Science Foundation (NSF) Small Business Innovation Research (SBIR) Phase II grant to develop a low-cost system to monitor whether candidate antibiotics are able to effectively kill or prevent the further growth of pathogens. While the work sponsored by the NSF will focus primarily on pathogens causing bloodstream infections, ImpeDx has also entered into a contract with the Centers for Disease Control and Prevention (CDC) to develop a similar system focused more directly on gonorrhea.
In general, to prescribe the right antibiotic, doctors need to know which strain of bacteria is causing the problem and the concentration of the drug that will most greatly inhibit its growth, called the minimum inhibitory concentration (MIC). In order to determine the MIC, one needs to create suspensions of bacteria free from other material such as human cells. Current protocols require putting suspensions containing bacteria and other cells on a petri dish, where the bacteria form colonies, which can be picked and re-suspended in clear liquid to get suspensions containing bacteria alone.
“Because you have to grow colonies, you lose a day or maybe more to your results,” Sengupta said. “What we said is that we can do this directly from the sample.”
Sengupta proposes a method through which he utilizes nanoparticles to isolate the bacteria in a matter of minutes. He then checks for their growth or death in the presence of candidate antibiotics by eliciting an electric response — charge accumulation — in the membrane of living bacteria cells.
“If the cells are doubling or increasing in number, you see an increase in the capacitance, a measure of charge stored,” Sengupta explained. “If cells are dying off or losing membrane potential, you will see a decrease in capacitance.”
For the project funded by the NSF, rapidly identifying effective antibiotics will enable clinicians to move away from less effective broad-spectrum antibiotics quickly. Not only are broad spectrum antibiotics less effective, but their overuse causes more strains to become drug resistant. In the CDC’s case, this is key because there are several known strains of gonorrhea that are already resistant to multiple drugs.
There also other challenges when it comes to gonorrhea.
“It needs just the right amount of carbon dioxide, and it doesn’t much like to grow in solution, so there are some technical challenges to growing that in that environment,” Sengupta said. Nevertheless, he feels these challenges can be overcome, and the products could help in delivering better outcomes to patients and cutting overall healthcare costs.