Considering Alternatives to Vancomycin for MRSA

Rachel Britt, PharmD, BCIDP, clinical practice specialist in infectious diseases at University Health in San Antonio, Texas, says vancomycin has a storied history, with a long track record that demonstrates its noninferiority against other, newer antibiotics for treatment of methicillin-resistant Staphylococcus aureus (MRSA). However, the antibiotic does have its limitations.

“I would argue it's one of our most durable agents for MRSA infections over the years, but it's a more narrow therapeutic index drug,” Britt said. “There are some toxicities associated with it and a pretty heavy lift when it comes to therapeutic drug monitoring.”

These toxicity concerns, combined with a limited understanding of vancomycin dosing, especially in an era of area under the curve and minimum inhibitory concentration, make it less attractive as a therapeutic option, she stated.

In terms of finding the right agent for patients, Britt reminds clinicians that there are other options and that diagnostics and making therapeutic adjustments are key.

“Vancomycin monotherapy has not really been the standard,” Britt said. “And fortunately, we have some other options, like combination therapy, daptomycin and ceftaroline, and other agents that are used in those cases.... Vancomycin has not been the only first-line recommended agent for MRSA bacteremia in the guidelines since 2011. So I know some people think that vancomycin, you have to start there and that's the way to go, but that's not necessarily what the guidelines currently say. There are some concerns with other newer agents, specifically daptomycin with treatment-emergent resistance. So I still see a lot of providers starting with vancomycin.

“I would advise to choose your therapy based on the clinical progression of the patient. If their cultures are clearing or not, how ill they are and how well they're doing, to really decide what therapy you're going to switch to or continue on…. A lot of times, vancomycin alternatives are really great when you're transitioning out of the hospital. So vancomycin, logistically, is very difficult and has increased risk of harms when you're doing it in an OPAT [outpatient parenteral antimicrobial therapy] setting. So daptomycin is a great agent for that when it's a once-a-day dosing.”

Reference
Britt R. Should vancomycin be replaced in the MRSA guidelines? Presented at: IDWeek 2025; October 19-22, 2025; Atlanta, GA.