Gram-Negative Infections and the Evolving Paradigm for OPAT

This is part of a short series, looking at Gram-negative infections including diagnostics, treatment coordination, and newer agent uptake.

Outpatient Parenteral Antibiotic Therapy (OPAT) refers to patients receiving IV antibiotic treatment outside of the hospital setting, and can include patients’ homes, clinics, nursing or rehab facilities. Typically, patients receiving OPAT are not being treated for severe Gram-negative infections and are well enough to be discharged from the hospital. However, Monica V. Mahoney PharmD, BCPS, BCIDP, FCCP, FIDSA, FIDP, FMSHP, clinical specialist at Beth Israel Deaconess Medical Center, who works in this space, is seeing a paradigm shift with more patients who are not critically ill, and are dealing with these infections. And with the introduction of new Gram-negative agents, IV antibiotic infusion schedules can be highly irregular and questions around treatment stability become a front and center concern.

“There are logistical challenges with the infusion times of these newer medications in order to take advantage of their pharmacokinetic or pharmacodynamic properties. They're given over 2 hours or over 3 hours, so you're asking the patients to give that dose for that long amount of time and, oh, by the way, repeat it, and then 3 or 4 hours for your next dose,” Mahoney said. “There are stability concerns. The drugs, once they're reconstituted in the form that's going to be infused in the patient, they are maybe good at room temperature for 4 hours in the refrigerator and for maybe up to 24 hours, if we're lucky. That doesn't work when the patient's at home…the home infusion company will deliver the medications, ideally once per week. So we want longer stability data that you know you can keep this compounded medication in your refrigerator for the entire week.”

When considering OPAT with newer agents and thinking about stewardship, Mahoney says there are a number of factors to consider.

“Is this going to be easy for the patient to take? Can we give a regimen that's simple enough for the patient or their family member to administer? If they won't take the medication, because it's too complicated, they won't treat their infection. If they don't treat their infection, they're going to end up back into the hospital with the same cycle, possibly with a more resistant organism."

“While we still have the same core principles of stewardship in the outpatient setting, there are different priorities maybe that we will place,” she said.

In terms of adoption of newer agents for Gram-negative infections, Mahoney keeps the option open, but acknowledges there are a few considerations including the therapy’s availability, logistics, and coordination.

“If the patient is well enough to go home, if they have an organism that needs to be treated, we will investigate whatever we can to try to make it happen,” Mahoney said. “But it's a less contained environment. It is not our pharmacy; It is not our nurses; they are not within our institution. We need to coordinate with a lot of different people. We need to make sure that the home infusion company has it on their formulary. Sometimes they lag behind on adding these. If the patient's going to rehab, we have to make sure that they will accept this patient with the level of complexity as well, and that the appropriate follow up and monitoring is in place to make sure that the patient is getting better.”

“As a clinician, obviously I want to give the drug the patient needs, but sometimes the answer we come back to is, ‘unfortunately, we can't discharge you because you need to be on this medication, and the best place for you to be is in the hospital to finish out your course of therapy,” she said.

Check out our next episode in the series when Ryan Shields PharmD, MS, discusses new agents for Gram-negative infections.