Dalbavancin Non-Inferior, But Not Superior, to Standard Therapy for Treatment of Complicated Staphylococcus aureus Bacteremia
CLINICAL QUESTION: Among patients with complicated Staphylococcus aureus bacteremia who achieve blood culture clearance with initial therapy, is completion of treatment with dalbavancin superior to standard therapy?
BACKGROUND: Standard therapy for complicated S aureus bacteremia typically includes at least four IV antibiotics, which can pose challenges to completion of treatment related to prolonged IV access and other factors. Dalbavancin is a long-acting, intravenous, anti-staphylococcal lipoglycopeptide antibiotic that has the potential to treat complicated S aureus bacteremia (including methicillin-resistant S aureus) via a two-dose regimen administered one week apart following initial blood culture clearance. Previously, robust data comparing the effectiveness of dalbavancin to standard therapy were lacking.
STUDY DESIGN: Open-label, assessor-masked, randomized, clinical trial
SETTING: Hospitalized adults at 23 medical centers across North America (U.S. and Canada) between April 2021 and December 2023 with complicated S aureus bacteremia who achieved blood culture clearance between days three and 10 of initial antibiotic therapy.
SYNOPSIS: Patients were randomized 1:1 to the control arm (n=100, standard therapy for four to eight weeks) or the treatment arm (n=100, dalbavancin in two 1,500-mg doses given one week apart) and evaluated for probability of a superior desirability for outcome ranking (DOOR) score at Day 70 (primary outcome) and non-inferiority by clinical efficacy (secondary outcome). DOOR includes assessment of five components: clinical efficacy, safety, complications, mortality, and quality of life. Dalbavancin treatment did not achieve the primary outcome (47.7%; 95% CI, 39.8 to 55.7%, threshold 50% for superiority) but did achieve the secondary outcome with a 1% difference (95% CI, -11.5 to 13.5%, threshold 20% for non-inferiority) in clinical efficacy between dalbavancin and standard therapy.
Study limitations include open-label design, selection of patients only after blood culture clearance (which may select for patients with less severe infections), numerically higher number of patients with four or more days of bacteremia before culture clearance in the control group, and the incorporation of treatment discontinuation in the composite endpoint, as dalbavancin—a long acting agent—cannot be discontinued after administration, unlike standard therapies.
BOTTOM LINE: For treatment of complicated S aureus bacteremia in adults who achieve blood culture clearance, dalbavancin is a non-inferior, but not superior, treatment option when compared to standard therapy in terms of safety and efficacy.
CITATION: Turner NA, et al. Dalbavancin for treatment of Staphylococcus aureus bacteremia: the DOTS randomized clinical trial. JAMA. 2025:e2512543. doi: 10.1001/jama.2025.12543.
Dr. Goldlust is a hospitalist and assistant professor of medicine at Columbia University Irving Medical Center in New York.