With new grant funding, School of Pharmacy Assistant Professor Cecilia Volk and colleagues explore oritavancin dosing
By Nicole Sweeney Etter
Gram-positive bacteria can cause serious bloodstream and bone infections that can be tough to treat. Patients sometimes require daily oral medication or IV infusions — for weeks, if not months.
But what if a weekly or biweekly regimen could eradicate the infection and make treatment easier and less expensive for patients? Cecilia Volk (PharmD ’20), assistant professor of pharmacy at the University of Wisconsin–Madison School of Pharmacy, aims to answer to that question.
With a new grant from Melinta Therapeutics, Volk is the principal investigator on a study of multidose regimens of oritavancin, a long-acting IV antibiotic commonly used to treat acute skin infections. She hopes to better understand how oritavancin can be used to treat more invasive types of gram-positive infections. Assistant Professor of Pharmacy Sin Yin Lim and Professor of Pharmacy Warren Rose are collaborators on the project.
“We know there’s a huge clinical need,” Volk says.
The problem: Gram-positive bacterial infections in the bloodstream or bone can require six to eight weeks of antibiotics, and current treatment options aren’t ideal. With growing antibiotic resistance, oral antibiotics aren’t always effective. Some patients also aren’t good about adhering to a daily medication routine, and daily IV infusions can be inconvenient.
“Sometimes patients will have to manage those pumps at home and self-administer IV medications multiple times a day,” Volk says.
Complicating matters, the U.S. Food and Drug Administration has approved oritavancin only as a single-dose treatment for skin infections.
“However, a lot of clinicians are using it for longer durations for more serious infections, and there’s not great evidence for how to dose the antibiotic for these longer-term treatment regimens,” Volk explains.
A few published case reports show that a weekly multidose regimen of oritavancin can be effective for treating more invasive infections. But without clear dosing guidelines for the off-label use, clinicians sometimes call the School of Pharmacy looking for guidance.
“We see it all the time. Lots of clinicians are very confused,” Volk says. “The few case reports we have have all shown favorable outcomes, so we know what’s working, but no one really knows the details. Are we giving too much? Do we have to give it weekly? Can we spread it out to every two weeks, maybe even every three weeks? How can we make it as easy on our patients as possible?”
The approach: “Our goal is to do a pharmacokinetic analysis and build some computerized simulations to look at some of these different dosing regimens and hopefully determine the optimal regimen,” Volk explains.
The team will use data from previous clinical trials to build the models based on a variety of patient factors, such as weight and kidney function. Then the researchers will use the simulations to test different dosage regimens to see how the average patient might respond.
“Our ultimate goal is that clinicians have some solid evidence to back up their dosing recommendations and can feel more confident in how they’re treating these patients.”
–Cecilia Volk
The benefit: If the evidence shows that a weekly or even less frequent treatment is effective, it could decrease the burden for patients and increase their adherence to treatment.
“It’s a lot easier on patients if they can come in for a once-a-week infusion versus having to deal with this every single day,” Volk says. “And if we don’t have to give it as often, we can give fewer doses, and then it’s cheaper for the patient, too.”
Volk plans to complete the study and publish her results next year. Because clinicians are already prescribing oritavancin for off-label uses, the study has the potential to inform practice immediately. It could also pave the way for clinical trials to further refine treatment options.
“Our ultimate goal is that clinicians have some solid evidence to back up their dosing recommendations and can feel more confident in how they’re treating these patients,” Volk says.
