Preliminary SABEDTIO data from IDWeek 2026 show early dual IV therapy cut prolonged S aureus bacteremia to 6% from 16%, with safe oral transition at 72 hours.
Up-front dual IV antibiotic therapy within 72 hours lowered the rate of prolonged Staphylococcus aureus bacteremia (SAB) to 6% from 16% vs single IV therapy, according to preliminary SABEDTIO trial results presented at IDWeek 2026, held October 21-24 in Washington, DC.¹ Mortality was similar in both arms at about 20%, and most patients moved safely to oral antibiotics once blood cultures cleared.¹
Standard practice adds a second IV agent only after a patient fails to clear blood cultures, and SAB is typically treated with a prolonged IV course.¹ Investigators at West Virginia University tested whether reversing this escalation approach, paired with early oral transition, would shorten bacteremia and improve outcomes.¹
SABEDTIO (NCT07148960) is an ongoing open-label, pragmatic, randomized controlled trial at six hospitals in one rural health system.¹ Investigators plan to randomly assign 300 patients with mostly complicated methicillin-resistant (MRSA) or methicillin-susceptible S aureus (MSSA) bacteremia 2:1 to early dual or single IV therapy. Experimental regimens were daptomycin plus ceftaroline or cefazolin plus ertapenem.¹
All patients switch to oral antibiotics once blood cultures are negative at 72 hours, with therapy duration guided by source control and C-reactive protein normalization.¹ The composite primary outcome includes mortality, prolonged bacteremia of 6 or more days, and seeding of a new site at 12 weeks. From September 15, 2025, through July 31, 2026, 193 patients enrolled and 152 (79%) completed the trial.¹
Demographics, infection site, and MRSA proportion were similar between groups.¹ Prolonged bacteremia occurred in 6% of experimental patients vs 16% of controls (P = .05), while mortality was about 20% in each arm.¹ Arif R. Sarwari, MD, MSc, MBA, associate dean for Clinical Affairs, School of Medicine professor, Infectious Diseases, West Virginia University, said the findings suggest patient-related factors, rather than the antibiotic strategy, drive most SAB mortality.
“The difference in duration of bacteremia, I think, is going to end up being a real difference, and it will be interesting to see if this can be replicated with other trials of dual therapy with different agents,” said Sarwari.
Most patients (87%) transitioned to oral antibiotics per protocol, and 71% completed treatment in 4 weeks or less, mostly with oral agents.¹ Relapsed bacteremia occurred in 5% of patients, compared with relapse rates of up to 9% reported historically.¹ The investigators concluded early oral transition once cultures are negative at 72 hours is safe.¹
The oral strategy builds on the team’s Comparing Oral versus Parenteral Antimicrobial Therapy (COPAT) trial, in which early oral transition was significantly safer with equivalent efficacy.² Staphylococcus aureus was the most commonly isolated organism in COPAT, and SABEDTIO extends this work to SAB specifically.
Investigators observed high rates of linezolid toxicity with advancing age and declining renal function, which led to a new dosing protocol.¹ Joy J. Juskowich, MD, assistant professor, West Virginia University, said toxicity presented most often as cytopenias, particularly low platelet counts.
“We started with a simple preemptive dose reduction from full-dose linezolid at 600 mg twice a day for a default six weeks to 600 mg daily after the initial two weeks,” said Juskowich. “We then refined it once therapeutic drug monitoring became available.”
The current protocol, developed with infectious diseases pharmacy colleagues, combines therapeutic drug monitoring with preemptive dose reduction and now applies to all trial and outpatient oral therapy program patients. Sarwari added the team aims to keep linezolid courses to four weeks or less when possible.
Enrollment continues toward 300 patients, and the investigators expect the full dataset to favor early dual therapy on prolonged bacteremia, length of stay, and antibiotic duration. Sarwari noted access and resource constraints in rural systems are common elsewhere, suggesting the approach may apply beyond rural settings.
