A National Institutes of Health-supported clinical trial has demonstrated that a simplified two-dose antibiotic regimen performs as well as standard long-term intravenous therapy for treating complicated Staphylococcus aureus bloodstream infections. The findings, published in the Journal of the American Medical Association, offer clinicians and patients a new treatment option for these severe infections that affect nearly 120,000 Americans annually and result in approximately 20,000 deaths.
Study Design and Patient Population
The Phase 2b trial, known as "Dalbavancin as an Option for Treatment of S. aureus Bacteremia" (DOTS), enrolled 200 hospitalized adults with complicated S. aureus bacteremia at 23 medical centers across the United States and Canada between 2021 and 2023. Participants initially received three to 10 days of preliminary treatment with broad-spectrum antibiotics and had no fever with undetectable S. aureus in blood cultures at randomization.
Patients were randomly assigned to receive either dalbavancin 1500 mg intravenously on days one and eight, or standard therapy for four to eight weeks. Standard therapy consisted of cefazolin or anti-Staphylococcal penicillin for methicillin-susceptible S. aureus, and vancomycin or daptomycin for methicillin-resistant S. aureus (MRSA).
Treatment Outcomes and Safety Profile
The study team evaluated treatment success using a comprehensive approach that measured not only clinical outcomes but also patient experience during therapy. A committee of four infectious disease experts ranked participants based on overall treatment outcome after 70 days, considering clinical success, infectious complications, safety complications, death, and health-related quality of life.
Results showed that a participant randomly selected from the dalbavancin group had a 47.7% likelihood of having a better overall treatment outcome than a participant from the standard therapy group, indicating non-superiority but equivalent effectiveness. Individual components of overall outcome, including clinical success rates, were similar between the two groups.
"Our findings give patients and healthcare providers the data to support an extra choice when deciding on treatment for complicated S. aureus bacteremia," said Nicholas A. Turner, M.D., assistant professor of medicine at Duke University School of Medicine and first author of the study.
Clinical Advantages of Simplified Dosing
Standard therapy for complicated S. aureus bloodstream infections typically requires insertion of a peripherally inserted central catheter (PICC) line, which remains in place for the full treatment duration and can lead to complications including blood clots and additional infections. The PICC line also limits patient mobility and requires specialized nursing care.
In contrast, dalbavancin therapy requires only temporary insertion of a short catheter twice, for one hour each time. As expected, the rate of side effects leading to treatment discontinuation and complications such as catheter-associated blood clots were greater in the standard therapy group compared to the dalbavancin group.
Addressing Unmet Medical Need
"Given the small number of antimicrobial drugs available to treat Staphylococcus aureus bloodstream infections and the bacteria's growing drug resistance, establishing dalbavancin as a beneficial therapy for these severe infections gives us a vital new alternative to treat them," said John Beigel, M.D., acting director of the Division of Microbiology and Infectious Diseases at NIH's National Institute of Allergy and Infectious Diseases.
The study results provide the clearest evidence to date for the safety and effectiveness of dalbavancin therapy for complicated S. aureus bloodstream infections, expanding antimicrobial treatment options in an era of increasing antibiotic resistance.
Future Research Directions
Contrary to investigators' expectations, study participants in both groups reported similar health-related quality of life scores. Researchers noted this finding may reflect limitations in the quality-of-life survey used or suggest that antibiotic delivery method had less impact on patient experience than anticipated.
The research team is currently conducting a cost-effectiveness analysis to further compare the two treatment approaches. The study was led by Thomas L. Holland, M.D., professor of medicine at Duke University School of Medicine, under the NIH's Antibacterial Resistance Leadership Group.
