Cutting the Cord: Oral Cefadroxil Holds Its Own for Gram-Positive Bacteremia—and Osteomyelitis

For generations, bacteremia—especially Staphylococcus aureus bacteremia—has almost reflexively meant prolonged IV therapy. But the evidence base continues to chip away at the idea that the route of administration is itself the treatment.

A terrific new multicenter study in Open Forum Infectious Diseases, including our world-class infectious-disease colleagues at LA General Medical Center and the Los Angeles County safety-net system, adds another important brick to the growing “oral is the new IV” wall. The work comes from a team that includes Brad Spellberg and colleagues, who have been pushing hard—and thoughtfully—against long-standing antibiotic dogma.

What did they study?

Clark and colleagues performed a multicenter retrospective cohort study across four Los Angeles County safety-net hospitals, examining adults with susceptible gram-positive bloodstream infections caused by methicillin-susceptible S. aureus, S. lugdunensis, or streptococci. Importantly, patients could have nonvertebral osteomyelitis accompanying the bacteremia. Prosthetic infections, central nervous system infections, and vertebral osteomyelitis were excluded.

Patients receiving oral cefadroxil transitional therapy were compared with patients remaining on IV therapy and with patients transitioned to other oral agents.

And the headline? The IV did not appear to have magical properties.

At 90 days, survival without clinical failure was remarkably similar:

94% with continued IV therapy
91% with cefadroxil
93% with alternative oral therapy

Bacteremia recurrence was likewise uncommon: 0%, 3%, and 3%, respectively.

Serious grade 3–4 adverse events were also rare—3% with IV therapy, 0% with cefadroxil, and 2% with alternative oral therapy.

Perhaps most immediately relevant to patients and health systems, median hospital length of stay was about 8.5 days in the IV cohort versus 6 days in the cefadroxil cohort, a statistically significant reduction. The journal summarizes the study as showing cefadroxil to be an effective and safe oral transitional therapy for bloodstream infection, with or without nonvertebral osteomyelitis.

Why does this matter?

An IV catheter is a delivery system—not a badge of therapeutic seriousness.

When we can achieve adequate antimicrobial exposure orally in a carefully selected, clinically stable patient, every unnecessary day tethered to an IV potentially brings additional cost, hospitalization, line complications, nursing burden, and disruption of normal life.

That idea is particularly attractive in limb preservation. Our patients frequently sit at the intersection of bacteremia, soft-tissue infection, osteomyelitis, diabetes, vascular disease, and prolonged courses of therapy. Getting someone out of the hospital and walking back into their life is itself an important clinical outcome.

Cefadroxil has another practical advantage: its pharmacokinetics permit less frequent dosing than cephalexin. Earlier work from the LA General/USC group found similar clinical outcomes using cefadroxil for MSSA and streptococcal bloodstream infections and highlighted twice-daily dosing as an attractive outpatient option.

A very important caveat

This is not a randomized trial, and it should not be read as “bacteremia means send everyone home on cefadroxil.”

Selection is everything. Source control, organism and susceptibility, clinical stability, clearance of bacteremia, metastatic infection, adherence, absorption, dosing, and appropriate infectious-disease evaluation still matter enormously. And while patients with nonvertebral osteomyelitis were included, this was not specifically a diabetic foot osteomyelitis trial.

But that caveat should sharpen the message rather than obscure it: for appropriately selected patients, oral therapy increasingly deserves to be considered an active treatment strategy rather than a therapeutic compromise.

The bigger picture

Brad Spellberg and colleagues have spent years asking a wonderfully disruptive question: how many of our antibiotic traditions are biology—and how many are simply inherited ritual? Randomized and observational evidence across osteomyelitis, bacteremia, endocarditis, pneumonia and other serious infections has increasingly supported earlier oral treatment in selected patients.

This new study pushes that frontier another step forward.

The goal isn’t “oral instead of IV.” The goal is the least burdensome therapy that reliably cures the patient.

And sometimes, taking out the IV may be part of putting the patient back together.

Clark DC, et al. Cefadroxil as Oral Transitional Therapy for Gram-Positive Bacteremia With or Without Non-Vertebral Osteomyelitis: A Multicenter Retrospective Cohort Study. Open Forum Infectious Diseases. 2026;13(8):ofag413.