Goodman-Meza David, Weiss Robert E, Poimboeuf Michelle L, Feng Jeffrey, Vijayan Tara, Martinello Marianne, Matthews Gail V, Dore Gregory J
Kirby Institute, University of New South Wales Sydney, Sydney, Australia.
Division of Infectious Diseases, David Geffen School of Medicine at UCLA (University of California, Los Angeles), Los Angeles.
JAMA Netw Open. 2025 May 1;8(5):e2511641. doi: 10.1001/jamanetworkopen.2025.11641.
Serious bacterial infections such as bacteremia, endocarditis, osteomyelitis, and septic arthritis typically require prolonged intravenous antibiotics. Long-acting lipoglycopeptides (laLGPs), such as dalbavancin and oritavancin, offer extended treatment intervals for gram-positive infections that may benefit populations with barriers to traditional treatment, including persons who use drugs (PWUD individuals).
To assess the effectiveness of laLGPs in managing serious bacterial infections in both PWUD and non-PWUD populations compared with standard-of-care (SOC) antibiotics.
DESIGN, SETTING, AND PARTICIPANTS: This comparative effectiveness study using a target trial emulation framework included data extracted from the US Cerner Real World Data platform. Individuals hospitalized and discharged for serious bacterial infections between October 1, 2015, and October 1, 2022, were included in the analysis. Data were analyzed from July 7, 2023, to February 28, 2025.
Receipt of an laLGP (dalbavancin or oritavancin) vs SOC antibiotics.
The primary outcome measure was a composite of readmission, emergency department visit, and inpatient death or discharge to hospice within 90 days post discharge from the index admission. Analyses were stratified by PWUD and non-PWUD status. Clone censor weighting was used to emulate a per-protocol analysis. Hazard ratios (HR) of time to the composite event and 95% CIs were calculated using bootstrapping.
Among 42 067 included individuals, median age was 61 (IQR, 47-73) years, 24 704 were male (58.7%), and 5047 (12.0%) were classified as PWUD. laLGPs were prescribed in 825 individuals (2.0%). There was no statistically significant difference in the composite outcome between the laLGP and SOC groups in both the PWUD (HR, 1.01; 95% CI, 0.88-1.13) and non-PWUD (HR, 0.93; 95% CI, 0.86-1.00) participants.
In this study of laLGPs vs SOC, findings suggested that laLGPs were effective as step-down treatment of serious gram-positive bacterial infections, offering comparable outcomes to those of SOC antibiotics in PWUD and non-PWUD individuals. Clinicians may consider laLGPs as alternative step-down options to SOC antibiotics for the treatment of serious gram-positive bacterial infections.
严重的细菌感染，如菌血症、心内膜炎、骨髓炎和脓毒性关节炎，通常需要长期静脉使用抗生素。长效脂糖肽类药物（laLGPs），如达巴万星和奥利万星，为革兰氏阳性感染提供了更长的治疗间隔，这可能使那些在接受传统治疗时存在障碍的人群受益，包括吸毒者（PWUD个体）。
评估与标准治疗（SOC）抗生素相比，laLGPs在治疗PWUD人群和非PWUD人群严重细菌感染中的有效性。
设计、设置和参与者：这项使用目标试验模拟框架的比较有效性研究纳入了从美国Cerner真实世界数据平台提取的数据。分析纳入了2015年10月1日至2022年10月1日期间因严重细菌感染住院并出院的个体。数据于2023年7月7日至2025年2月28日进行分析。
接受laLGP（达巴万星或奥利万星）与SOC抗生素治疗。
主要结局指标是再入院、急诊就诊以及在首次入院出院后90天内住院死亡或转至临终关怀的综合指标。分析按PWUD和非PWUD状态进行分层。采用克隆审查加权法来模拟符合方案分析。使用自抽样法计算复合事件发生时间的风险比（HR）和95%置信区间（CI）。
在纳入的42067名个体中，中位年龄为61岁（四分位间距，47 - 73岁），24704名男性（58.7%），5047名（12.0%）被归类为PWUD个体。825名个体（2.0%）使用了laLGPs。在PWUD参与者（HR，1.01；95% CI，0.88 - 1.13）和非PWUD参与者（HR，0.93；95% CI，0.86 - 1.00）中，laLGP组和SOC组的复合结局无统计学显著差异。
在这项laLGPs与SOC的研究中，结果表明laLGPs作为严重革兰氏阳性细菌感染的降阶梯治疗是有效的，在PWUD个体和非PWUD个体中与SOC抗生素的治疗效果相当。临床医生在治疗严重革兰氏阳性细菌感染时，可考虑将laLGPs作为SOC抗生素的替代降阶梯选择。
