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. 2025 Aug 13:e2512543.
doi: 10.1001/jama.2025.12543. Online ahead of print.

Dalbavancin for Treatment of Staphylococcus aureus Bacteremia: The DOTS Randomized Clinical Trial

Nicholas A Turner  1 , Toshimitsu Hamasaki  2 , Sarah B Doernberg  3 , Thomas P Lodise  4 , Heather A King  5   6   7 , Varduhi Ghazaryan  8 , Sara E Cosgrove  9 , Timothy C Jenkins  10 , Catherine Liu  11 , Shrabani Sharma  12 , Smitha Zaharoff  12 , Lana Wahid  13   14 , Valerie J Renard  13   14 , Paul Cook  15 , Issam Raad  16 , Ray Hachem  16 , Anne-Marie Chaftari  16 , Matthew Sims  17 , Carmen DeMarco  17 , Loren G Miller  18 , Matthew W McCarthy  19 , Caryn G Morse  20 , Chris Lucasti  21 , Graeme N Forrest  22 , Kartikeya Cherabuddi  23   24 , Christopher Polk  25 , Tasaduq Fazili  26 , Mark E Rupp  27 , George R Thompson 3rd  28 , Kami Kim  24 , Luke Strnad  29 , Amanda E Schnee  30 , James A McKinnell  31 , Mayur Ramesh  32 , Fernanda P Silveira  33 , Todd P McCarty  34 , Todd C Lee  35 , Emily G McDonald  36 , Kristopher Paolino  37   38   39 , Katie Wiegand  40 , Alison Wall  40 , Todd Riccobene  41 , Rinal Patel  41 , Urania Rappo  42 , Scott Evans  2 , Henry F Chambers  3 , Vance G Fowler Jr  1   12 , Thomas L Holland  1   12 ; Antibacterial Resistance Leadership Group
Collaborators, Affiliations

Dalbavancin for Treatment of Staphylococcus aureus Bacteremia: The DOTS Randomized Clinical Trial

Nicholas A Turner et al. JAMA. .

Abstract

Importance: Dalbavancin is a long-acting intravenous lipoglycopeptide that may be effective for treatment of complicated Staphylococcus aureus bacteremia without requiring long-term intravenous access.

Objective: To evaluate the efficacy and safety of dalbavancin vs standard therapy for completion of treatment of complicated S aureus bacteremia.

Design, setting, and participants: Open-label, assessor-masked, randomized clinical trial conducted from April 2021 to December 2023 at 23 medical centers in the US (n = 22) and Canada (n = 1). Participant follow-up lasted 70 days (180 days for participants with osteomyelitis); date of final follow-up was December 1, 2023. Hospitalized adults with complicated S aureus bacteremia who achieved blood culture clearance following at least 72 hours but no more than 10 days of initial antibacterial therapy were included. Participants were excluded if they had central nervous system infection, retained infected prosthetic material, left-sided endocarditis, or severe immune compromise.

Interventions: Participants were randomly assigned to receive either 2 doses of intravenous dalbavancin (n = 100; 1500 mg on days 1 and 8) or 4 to 8 total weeks of standard intravenous therapy (n = 100; cefazolin or antistaphylococcal penicillin if methicillin susceptible; vancomycin or daptomycin if methicillin resistant).

Main outcomes and measures: The primary outcome was the desirability of outcome ranking (DOOR) at day 70, which involved 5 components (clinical success, infectious complications, safety complications, mortality, and health-related quality of life) and was assessed for superiority (achieved if the 95% CI for the probability of dalbavancin having a superior DOOR was >50%). Secondary outcomes included clinical efficacy at day 70 (prespecified noninferiority margin of 20%) and safety.

Results: Of 200 participants randomized (mean [SD] age, 56 [16.2] years; 62 females [31%]), 167 (84%) survived to day 70 and had an efficacy assessment. Participants without a day 70 efficacy assessment were treated as clinical failures in the analyses. The probability of a more desirable day 70 outcome with dalbavancin vs standard therapy was 47.7% (95% CI, 39.8% to 55.7%). Regarding secondary outcomes, clinical efficacy was documented in 73 of 100 for dalbavancin and 72 of 100 for standard therapy (difference, 1.0% [95% CI, -11.5% to 13.5%]), meeting the noninferiority criterion. Serious adverse events were reported in 40 of 100 participants who received dalbavancin and 34 of 100 participants who received standard therapy; treatment-related adverse events were uncommon in both groups.

Conclusions and relevance: Among adult participants with complicated S aureus bacteremia who achieved blood culture clearance, dalbavancin was not superior to standard therapy by desirability of outcome ranking. When considered with other efficacy and safety outcomes these findings may help inform use of dalbavancin in clinical practice.

Trial registration: ClinicalTrials.gov Identifier: NCT04775953.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Turner reported grants from the Centers for Disease Control and Prevention, a clinical trial adjudication contract from Basilea, a research contract from PDI, a research contract from Purio, and a double-blind pharmaceutical consultation from Techspert outside the submitted work. Dr Doernberg reported grants from Pfizer, F2G Ltd, Chan Zuckerberg Initiative, Patient-Centered Outcomes Research Institute; Shionogi for clinical adjudication of a COVID-19 clinical trial; Basilea for clinical adjudication of a Staphylococcus aureus clinical trial; and personal fees from AstraZeneca outside the submitted work. Dr Lodise reported being an invited speaker for Paladin Pharma Inc during the conduct of the study. Dr King reported grants from Veterans Affairs (VA), National Institutes of Health (NIH), and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co Inc outside the submitted work; Dr King is also supported by the Durham Center of Innovation to Accelerate Discovery and Practice Transformation (CIN 13-410) at the Durham VA Health Care System. Dr Cosgrove reported personal fees from Duke Clinical Research Institute outside the submitted work. Dr Cook reported grants from East Carolina University during the conduct of the study and grants from Pfizer, Gilead, AbbVie, and Janssen outside the submitted work. Dr Raad reported personal fees from Citius for serving on its scientific advisory board pertaining to a novel antimicrobial lock solution for the salvage of central catheters in the setting of bacteremia outside the submitted work; in addition, Dr Raad had a patent for Minolok antimicrobial catheter lock solution with royalties paid from Citius and a patent for NiCE issued as a co-inventor on an MD Anderson technology pertaining to a novel antimicrobial lock solution for the prevention of central catheter–related bacteremia. Dr Chaftari reported grants from Citius Pharmaceuticals Inc outside the submitted work. Dr Sims reported grants from Seres, Pfizer, QIAGEN, Adaptive Phage Therapeutics, OpGen, Leonard-Meron Biosciences, Prenosis, Janssen, Applied Biocode, PhAST Corp, Locus Biosciences, Affinity Biosensors, Vedanta Biosciences, and AstraZeneca and personal fees from InflaaRx outside the submitted work; in addition, Dr Sims had a patent for methods of diagnosing increased risk of developing MRSA or CA-MRSA issued held by Corewell Health Research Institute. Dr Miller reported grants from Paratek, Merck, Contrafect, Armata, and GSK outside the submitted work. Dr Polk reported being employed by ViiV Healthcare. Dr Rupp reported personal fees from Citius Pharmaceuticals, MedPace, and Teleflex outside the submitted work. Dr Thompson reported grants from Astellas, Basilea, GSK, F2G, Elion, and Scynexis outside the submitted work. Dr Kim reported personal fees from Shionogi and grants from Regeneron, Duke/Antibacterial Resistance Leadership Group, AstraZeneca, NIH, Department of Defense, and Armata outside the submitted work. Dr Strnad reported membership on Infectious Diseases Society of American/European Society of Clinical Microbiology and Infectious Diseases Staphylococcus aureus bacteremia guideline writing panel (guideline in development); Dr Strnad’s work on this guideline had no involvement to date regarding any content related to the study drug (dalbavancin) or its comparison with any standard-of-care antimicrobial therapy. Dr McKinnell reported consulting for Premier Home Health and Infusion and Expert Stewardship and personal fees from ThermoFisher Scientific, Nestle Health Science, and AbbVie and grants from AstraZeneca and CalciMedica outside the submitted work. Dr Lee reported research salary support from Fonds de Recherche Quebec Santé during the conduct of the study. Dr McDonald reported research salary support from the Fonds de Recherche du Québec Santé. Dr Paolino reported personal fees from Sanofi Institut Pasteur paid to perform this work during the conduct of the study. Dr Riccobene reported being employed by and owning stock in AbbVie. Dr Patel reported being employed by and owning stock in AbbVie. Dr Rappo reported personal fees from Allergan during the conduct of the study. Dr Evans reported grants from National Institute of Allergy and Infectious Diseases (NIAID)/NIH during the conduct of the study. Dr Fowler reported grants from NIH during the conduct of the study and grants from Contrafect, Merck, Karius, Genentech, Basilea, Janssen, and AstraZeneca; EDE research grants to his institution; personal fees from Debiopharm, Genentech, Basilea, Contrafect, Destiny, Amphliphi Biosciences, Integrated Biotherapeutics, Armata, AstraZeneca, Akagera, Aridis, Roche, GSK, and MicuRx; stock options from ValanBio; and royalties from UpToDate outside the submitted work. In addition, Dr Fowler had a patent for sepsis diagnostic pending. Dr Holland reported personal fees from Basilea Pharmaceutica, Astellas Pharma, Concert, Karius, PSI, Affinivax, Advarra, Aridis, and UpToDate; and serving on the data and safety monitoring board for Spero outside the submitted work. No other disclosures were reported.

Comment in

  • doi: 10.1001/jama.2025.13717

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