Turner Nicholas A, Hamasaki Toshimitsu, Doernberg Sarah B, Lodise Thomas P, King Heather A, Ghazaryan Varduhi, Cosgrove Sara E, Jenkins Timothy C, Liu Catherine, Sharma Shrabani, Zaharoff Smitha, Wahid Lana, Renard Valerie J, Cook Paul, Raad Issam, Hachem Ray, Chaftari Anne-Marie, Sims Matthew, DeMarco Carmen, Miller Loren G, McCarthy Matthew W, Morse Caryn G, Lucasti Chris, Forrest Graeme N, Cherabuddi Kartikeya, Polk Christopher, Fazili Tasaduq, Rupp Mark E, Thompson George R, Kim Kami, Strnad Luke, Schnee Amanda E, McKinnell James A, Ramesh Mayur, Silveira Fernanda P, McCarty Todd P, Lee Todd C, McDonald Emily G, Paolino Kristopher, Wiegand Katie, Wall Alison, Riccobene Todd, Patel Rinal, Rappo Urania, Evans Scott, Chambers Henry F, Fowler Vance G, Holland Thomas L
Division of Infectious Diseases, Department of Medicine, Duke University, Durham, North Carolina.
The Biostatistics Center and the Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, George Washington University, Rockville, Maryland.
JAMA. 2025 Aug 13. doi: 10.1001/jama.2025.12543.
Dalbavancin is a long-acting intravenous lipoglycopeptide that may be effective for treatment of complicated Staphylococcus aureus bacteremia without requiring long-term intravenous access.
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.
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).
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.
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.
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.
ClinicalTrials.gov Identifier: NCT04775953.
达巴万星是一种长效静脉注射脂糖肽，对于治疗复杂性金黄色葡萄球菌菌血症可能有效，且无需长期静脉通路。
评估达巴万星与标准疗法相比，在完成复杂性金黄色葡萄球菌菌血症治疗方面的疗效和安全性。
设计、地点和参与者：2021年4月至2023年12月在美国23个医疗中心（n = 22）和加拿大1个医疗中心进行的开放标签、评估者盲法随机临床试验。参与者随访持续70天（患有骨髓炎的参与者为180天）；最终随访日期为2023年12月1日。纳入在初始抗菌治疗至少72小时但不超过10天后实现血培养清除的复杂性金黄色葡萄球菌菌血症住院成人。如果参与者患有中枢神经系统感染、保留感染的假体材料、左侧心内膜炎或严重免疫功能低下，则被排除。
参与者被随机分配接受2剂静脉注射达巴万星（n = 100；第1天和第8天各1500毫克）或总共4至8周的标准静脉治疗（n = 100；如果对甲氧西林敏感，则使用头孢唑林或抗葡萄球菌青霉素；如果对甲氧西林耐药，则使用万古霉素或达托霉素）。
主要结局是第70天的结局排名合意性（DOOR），其涉及5个组成部分（临床成功、感染性并发症、安全性并发症、死亡率和健康相关生活质量），并评估其优越性（如果达巴万星具有更高DOOR概率的95%置信区间>50%，则达到优越性）。次要结局包括第70天的临床疗效（预先设定的非劣效性 margin为20%）和安全性。
在200名随机分组的参与者中（平均[标准差]年龄，56[16.2]岁；62名女性[31%]），167名（84%）存活至第70天并进行了疗效评估。在分析中，未进行第70天疗效评估的参与者被视为临床失败。与标准疗法相比，达巴万星在第70天获得更合意结局的概率为47.7%（95%置信区间，39.8%至55.7%）。关于次要结局，达巴万星组100名中有73名记录了临床疗效，标准治疗组100名中有72名记录了临床疗效（差异，1.0%[95%置信区间，-11.5%至13.5%]），符合非劣效性标准。接受达巴万星的100名参与者中有40名报告了严重不良事件，接受标准治疗的100名参与者中有34名报告了严重不良事件；两组中与治疗相关的不良事件均不常见。
在实现血培养清除的复杂性金黄色葡萄球菌菌血症成年参与者中，根据结局排名合意性，达巴万星并不优于标准疗法。结合其他疗效和安全性结局考虑，这些发现可能有助于为达巴万星在临床实践中的使用提供参考。
ClinicalTrials.gov标识符：NCT04775953。
