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Practical vs Recent Clinical Trial Use Of Dalbavancin
Introduction
Clinical trial populations often differ from patients in practice due to restrictive inclusion criteria and recruitment.1,2 Dalbavancin, a long-acting intravenous lipoglycopeptide approved for gram-positive acute bacterial skin and skin structure infections, has been increasingly used off-label for bacteremia.3,4 The Dalbavancin as an Option for Treatment of Staphylococcus aureus Bacteremia (DOTS) trial found that dalbavancin was noninferior to standard intravenous antibiotics for complicated S aureus bacteremia.5
It is unclear how DOTS participants compare to patients in clinical practice receiving dalbavancin after clearance of bacteremia. We evaluated patients receiving dalbavancin at our institution who retrospectively met DOTS criteria and compared them to DOTS participants. We sought to compare characteristics and outcomes of these patients receiving dalbavancin who retrospectively met DOTS criteria with those enrolled in the DOTS trial.
Methods
This quality-improvement study was deemed not human participants research by the University of Nebraska Medical Center institutional review board and therefore was exempt from review and informed consent. We retrospectively evaluated adults treated at Nebraska Medicine (January 1, 2019, to December 31, 2024) who received at least 2 dalbavancin doses after clearance of bacteremia and met DOTS criteria. Our center participated in DOTS (April 2021 to December 2023); 6 patients who enrolled in DOTS were not included in this analysis. This study is reported following the Standards for Quality Improvement Reporting Excellence (SQUIRE) reporting guideline.
Dalbavancin use at our institution is guided by infectious diseases consultation and is typically preferentially used for patients with barriers to prolonged intravenous therapy (eg, unstable housing, substance use, cannot complete outpatient therapy). Insurance approval and cost also influence selection.
Data included demographics, infection characteristics, and outcomes. Race and ethnicity were obtained from the electronic health record and reflect patient self-report when available. The primary end point was day-70 clinical success, as defined in DOTS.5 Outcomes were assessed 60 to 90 days after initiation. Comparisons are descriptive, given nonindependence of populations. We did not maintain a prospective screening log and could not fully characterize screened or excluded patients. Data were analyzed using SAS version 9.4 (SAS Institute) from September 26 to December 2, 2025.
Results
A total of 31 patients were included in analysis, compared with 200 participants in the DOTS trial. Patients who met DOTS criteria and received dalbavancin in clinical practice were younger than DOTS participants (mean [SD] age, 44.9 [14.9 years vs 56.8 [22.4] years). Both groups were predominantly male (21 [68%] vs 138 [69%] male). There were 1 (3%) vs 2 (2%) American Indian or Alaska Native participants, 0 vs 6 (6%) Asian participants, 3 (10%) vs 49 (25%) Black participants, and 23 (74%) vs 137 (71%) White participants; 4 participants (13%) vs 25 participants (13%) were Hispanic or Latino (Table 1). In our group, 29 patients (94%) spoke English primarily, 6 patients (19%) were unhoused, 9 patients (29%) reported injection drug use, 11 patients (36%) had Medicaid, 7 patients (23%) had Medicare, 4 patients (13%) had private insurance, and 9 patients (29%) were self-pay. DOTS did not report these metrics.
Table 1. Cohort Characteristics Compared to the DOTS Trial Dalbavancin Cohort View LargeDownload (opens in new tab)Go to Figure in ArticleCharacteristicPatients, No. (%)DOTS trial (n = 200)Clinical dalbavancin recipients (n = 31)Age, y Mean (SD)a56.8 (22.4)44.9 (14.9) ≥805 (5)1 (3)Sexb Female62 (32)10 (32) Male138 (69)21 (68)Gender identityb MaleNA8 (26) FemaleNA5 (16) Not providedNA18 (58)Race American Indian or Alaska Native2 (2)1 (3) Asian6 (6)0 Black49 (25)3 (10) White137 (71)23 (74) Other, not reported, or >1 listedc6 (6)4 (13)Hispanic or Latino ethnicity25 (13)4 (13)Primary language is EnglishNA29 (94)Insurance type MedicaidNA11 (36) MedicareNA7 (23) PrivateNA4 (13) Self-pay or noneNA9 (29)Injection drug use29 (15)9 (29)Active substance useNA17 (55)UnhousedNA6 (19)Medical comorbidities Diabetes92 (46)9 (29) Immunosuppressed condition61 (31)7 (23) Heart failure40 (20)5 (16) Receiving dialysis25 (13)3 (10) Liver disease22 (11)11 (36)Methicillin-resistant S aureus66 (33)14 (45)Source of infectiond Soft tissue infection70 (35)4 (13) Osteomyelitis43 (22)8 (26) Septic arthritis26 (13)0 Septic thrombophlebitis or catheter-related bloodstream infection24 (12)7 (23) Pneumonia or empyema16 (8)1 (3) Right-sided endocarditis10 (5)9 (29) Cardiac device infection6 (3)2 (6) Prosthetic joint infection2 (1)0Days of bacteremia <2141 (71)5 (16) 2-447 (24)21 (68) >412 (6)5 (16)Underwent source control interventions Surgical debridement50 (25)5 (16) Central venous catheter removal23 (12)4 (13) Percutaneous drainage8 (4)1 (3) Hardware, device, or graft removal10 (5)4 (13)Intended duration of therapy, median (IQR), dNA33 (28-42)Completed dalbavancin regimen as intendede Overall96 (96)29 (94) Second dose completed, but delayed10 (10)3 (10)
Methicillin-resistant S aureus and right-sided endocarditis were more common in our group. Soft tissue infection, septic arthritis, and pneumonia or empyema were more common in DOTS. Our cohort had a higher percentage of patients with at least 2 days of bacteremia compared with DOTS participants. Despite this, documented clinical failure rates remained low.
Day 70 clinical success occurred in 20 patients (65%) in our group and 80 patients (80%) in DOTS (Table 2), driven by more loss to follow-up in our cohort. Nine patients (29%) were lost to follow-up, which may affect outcome assessment. However, our cohort had similarly low documented clinical failure rates, no deaths or adverse events, and high rates (29 patients [94%]) of therapy completion.
Table 2. Cohort Outcomes Comparisons View LargeDownload (opens in new tab)Go to Figure in ArticleSelected DOOR component outcomesPatients, No. (%)DOTS trial (n = 100)Clinical dalbavancin recipients (n = 31)Clinical success at day 70 Overall80 (80)20 (65) Clinical success80 (80)11 (36) Presumed clinical successaNA9 (29) Presumed clinical failureaNA1 (3) Clinical failure5 (5)1 (3) Lost to follow-up11 (11)9 (29) Death4 (4)0Infectious complications13 (13)4 (13)Serious adverse events leading to discontinuation3 (3)0Composite clinical efficacy at day 7073 (73)19 (61)
Discussion
In this quality-improvement study, patients treated with dalbavancin in clinical practice had high rates of substance use and social vulnerability, consistent with higher rates of right-sided endocarditis. These findings suggest dalbavancin may be a useful option for patients with barriers to adherence and follow-up.
While patients may meet the same inclusion criteria, trial populations may differ from those in practice due to socioeconomic instability, barriers to care, and comorbidities. At our center, dalbavancin use prior to DOTS occurred in a highly selective subgroup.
Despite more patients with at least 2 days of bacteremia in our cohort, clinical failure remained low, suggesting dalbavancin may still be effective in higher-risk presentations, although interpretation is limited by sample size and loss to follow-up. Although day 70 clinical success was lower in our clinical cohort, outcomes remained favorable, and therapy completion was high despite follow-up challenges.
Because our institution participated in DOTS, this cohort reflects eligible patients not enrolled due to clinician decision or patient preference, introducing potential selection bias into this observational cohort. Due to the retrospective design, we were unable to systematically identify all patients retrospectively eligible for DOTS or capture outcomes for those not receiving dalbavancin. This highlights challenges in retrospective assessment and the importance of transparent screening and exclusion reporting.
This study has several limitations, including its retrospective design, small sample size, inability to identify all eligible patients, and substantial loss to follow-up. Importantly, our study period (2019-2024) preceded publication of the DOTS trial in 2025. Therefore, differences between our cohort and DOTS participants likely reflect pretrial prescribing patterns rather than implementation of trial findings. Post-DOTS studies will be important to evaluate how clinical practice evolves in response to these results. These findings highlight opportunities for future studies to better characterize clinical populations, improve transparency in screening and enrollment, and assess how trial results translate into practice.
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Article Information
Accepted for Publication: April 14, 2026.Published: June 3, 2026. doi:10.1001/jamanetworkopen.2026.16508Open Access: This is an open access article distributed under the terms of the CC-BY-NC-ND License, which does not permit alteration or commercial use, including those for text and data mining, AI training, and similar technologies. © 2026 Uhm SA et al. JAMA Network Open.Corresponding Author: Jasmine R. Marcelin, MD, Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, 985400 Nebraska Medical Center, Omaha, NE 68198-5400 (jasmine.marcelin@unmc.edu).Author Contributions: Ms Uhm and Dr Marcelin had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.Concept and design: Uhm, Alexander, Cortes-Penfield, Azimi, Keintz, Miller, Rupp, Marcelin.Acquisition, analysis, or interpretation of data: Uhm, Alexander, Lyden, Cortes-Penfield, Sayles, Rupp, Marcelin.Drafting of the manuscript: Uhm, Alexander, Marcelin.Critical review of the manuscript for important intellectual content: All authors.Statistical analysis: Lyden, Sayles.Supervision: Uhm, Alexander, Azimi, Keintz, Rupp, Marcelin.Conflict of Interest Disclosures: Ms Uhm reported receiving grants from Global Virus Network outside the submitted work. Dr Alexander reported receiving grants from Merck and personal fees from Astellas Pharma outside the submitted work. Dr Rupp reported receiving grants from the National Institutes of Health Duke Clinical Research Institute (paid to institution) outside the submitted work. Dr Marcelin reported serving as vice chair of the external advisory board of the Antibacterial Resistance Leadership Group outside the submitted work. No other disclosures were reported.Data Sharing Statement: See the Supplement.Additional Information: We acknowledge the investigators and patients of the Dalbavancin as an Option for Treatment of Staphylococcus aureus Bacteremia trial for generating high-quality clinical trial data that informed outcome definitions and provided a benchmark for comparison in this analysis. No individuals were specifically compensated for contributions to this work.
References
1.Paul
M, Dishon-Benattar
Y, Dickstein
Y, Yahav
D. Optimizing patient recruitment into clinical trials of antimicrobial-resistant pathogens. JAC Antimicrob Resist. 2023;5(1):dlad005. doi:10.1093/jacamr/dlad005PubMedGoogle ScholarCrossref2.Shou
Y, Yeo
JE, Pang
AS, Paterson
DL, Mo
Y. Informed consent and risk communication challenges in antimicrobial clinical trials: a scoping review. BMJ Open. 2024;14(11):e082096. doi:10.1136/bmjopen-2023-082096PubMedGoogle ScholarCrossref3.Bao
H, Igwilo-Alaneme
R, Sonia
F, Cowman
K, Kahn
M, Nori
P. Dalbavancin as an alternative to traditional outpatient parenteral antimicrobial therapy for deep gram-positive infections—an observational, retrospective review. Ther Adv Infect Dis. 2024;11:20499361241245523. doi:10.1177/20499361241245523PubMedGoogle ScholarCrossref4.Taylor
K, Williamson
J, Luther
V,
et al. Evaluating the use of dalbavancin for off-label indications. Infect Dis Rep. 2022;14(2):266-272. doi:10.3390/idr14020032PubMedGoogle ScholarCrossref5.Turner
NA, Hamasaki
T, Doernberg
SB,
et al; Antibacterial Resistance Leadership Group. Dalbavancin for treatment of Staphylococcus aureus bacteremia: the DOTS randomized clinical trial. JAMA. 2025;334(10):866-877. doi:10.1001/jama.2025.12543PubMedGoogle ScholarCrossref
