产金属β-内酰胺酶肠杆菌属菌血症患者使用头孢他啶-阿维巴坦联合氨曲南与其他活性抗生素治疗的死亡率比较：一项多中心目标试验模拟研究
Mortality of metallo-β-lactamase-producing Enterobacterales bacteremias with combined ceftazidime-avibactam plus aztreonam vs. other active antibiotics: a multicenter target trial emulation.
作者信息
Huespe Ivan Alfredo, Huaier Arriazu Emilio Felipe, Sanchez Marisa, Stanek Vanina, Pollán Javier Alberto, Bauque Susana, Ávila Poletti Débora, Monzón Verónica, Novelli Poisson Paola, Boutet María Virginia, Cunto Eleonora, Chediack Viviana, Beloso Melina Tatiana, Rucci Victoria, Lagostena Marina, Cabrera Ricardo, Gutiérrez María José, Gómez María Georgina, Arias Sebastián Gabriel, Taffarel Clarisa, Ivulich Daniel, Garzón Maria Isabel, Cornistein Wanda, Gira Alicia, Kriger Sonia Guadalupe, Duarte Leonora, Estenssoro Elisa, Mirofsky Matias, Castro Maximiliano Gabriel, Vaena Mariana
机构信息
Hospital Italiano de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
Sociedad Argentina de Medicina, Argentina.
出版信息
Lancet Reg Health Am. 2025 Jul 5;49:101175. doi: 10.1016/j.lana.2025.101175. eCollection 2025 Sep.
BACKGROUND
Bacteremias caused by metallo-β-lactamase (MBL)-producing Enterobacterales are a critical challenge due to their limited treatment options. Although ceftazidime-avibactam (CAZAVI) combined with aztreonam (ATM) has shown in vitro efficacy, no prior studies have rigorously compared its clinical effectiveness to Other Active Antibiotics (OAAs). This study aims to evaluate the efficacy and safety of CAZAVI + ATM vs. OAAs in a large cohort of MBL bacteremia.
METHODS
A retrospective, multicenter, target trial emulation was conducted across 17 hospitals in Argentina between January 2016 and October 2024. Patients with confirmed MBL bacteremia who initiated active antibiotic treatment within 24 h of MBL identification and 96 h of blood sampling were included. Inverse probability of treatment weighting (IPTW) was used to reduce indication bias, and the analysis accounted for hospital clustering within Argentina's public, private, and social security health systems. The primary outcome was 30-day all-cause mortality, with secondary outcomes including clinical failure (relapse, complications, or death) and adverse events.
FINDINGS
Among 243 patients (93 receiving CAZAVI + ATM and 150 receiving OAAs), the 30-day mortality rate was 35% in the CAZAVI + ATM group vs. 47% in the OAA group (adjusted odds ratio [OR] 0·63, 95% CI 0·43-0·91, p < 0·01). Clinical failure occurred in 46% of the CAZAVI + ATM group and 53% of the OAA group (adjusted hazard ratio [HR] 0·65, 95% CI 0·44-0·97; p = 0·03). Adverse events were lower with CAZAVI + ATM (9·6% vs. 22·8%, p = 0·014).
INTERPRETATION
These findings suggest CAZAVI + ATM might be associated with lower mortality, reduced clinical failure, and fewer adverse events compared to OAAs in patients with MBL-type Enterobacterales bacteremia. Further prospective studies are warranted to confirm these observations.
FUNDING
No specific funding was provided for this study.
背景
由产金属β-内酰胺酶（MBL）的肠杆菌科细菌引起的菌血症是一项严峻挑战，因为其治疗选择有限。尽管头孢他啶-阿维巴坦（CAZAVI）联合氨曲南（ATM）已显示出体外疗效，但此前尚无研究将其临床疗效与其他活性抗生素（OAA）进行严格比较。本研究旨在评估CAZAVI + ATM与OAA在一大群MBL菌血症患者中的疗效和安全性。
方法
2016年1月至2024年10月期间，在阿根廷的17家医院进行了一项回顾性、多中心、目标试验模拟研究。纳入在MBL鉴定后24小时内及采血后96小时内开始接受活性抗生素治疗的确诊MBL菌血症患者。采用治疗权重逆概率（IPTW）来减少指征偏倚，分析考虑了阿根廷公共、私立和社会保障卫生系统内的医院聚类情况。主要结局是30天全因死亡率，次要结局包括临床失败（复发、并发症或死亡）和不良事件。
结果
在243例患者中（93例接受CAZAVI + ATM，150例接受OAA），CAZAVI + ATM组的30天死亡率为35%，而OAA组为47%（调整后的优势比[OR]为0·63，95%置信区间为0·43 - 0·91，p < 0·01）。CAZAVI + ATM组46%的患者出现临床失败，OAA组为53%（调整后的风险比[HR]为0·65，95%置信区间为0·44 - 0·97；p = 0·03）。CAZAVI + ATM的不良事件较少（9·6%对22·8%，p = 0·014）。
解读
这些发现表明，在MBL型肠杆菌科细菌菌血症患者中，与OAA相比，CAZAVI + ATM可能与更低的死亡率、更少的临床失败和更少的不良事件相关。需要进一步的前瞻性研究来证实这些观察结果。
资金
本研究未提供特定资金。
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