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奥马环素在哨兵抗菌监测项目(2015 - 2023年)中对骨/关节感染细菌分离株及罕见病原体的体外活性

In vitro activity of omadacycline against bacterial isolates from bone/joint infections and rare pathogens in the SENTRY antimicrobial surveillance program (2015-2023).

作者信息

Huband Michael D, Rhomberg Paul R, Fedler Kelley A, Blankers Christopher, Anastasiou Diane, Serio Alisa W, Castanheira Mariana

机构信息

Element Materials Technology (JMI Laboratories), North Liberty, IA, USA.

Element Materials Technology (JMI Laboratories), North Liberty, IA, USA.

出版信息

J Glob Antimicrob Resist. 2025 Jun;43:271-284. doi: 10.1016/j.jgar.2025.04.027. Epub 2025 May 3.

Abstract

OBJECTIVES

Omadacycline is an aminomethylcycline (tetracycline class) antibacterial approved by the United States Food and Drug Administration (2018) for treatment of adults with acute bacterial skin and skin structure infection (ABSSSI) and community acquired bacterial pneumonia (CABP) caused by indicated organisms (oral and iv formulations). Omadacycline has activity against bacterial isolates expressing common tetracycline resistance mechanisms (ribosomal protection proteins and efflux pumps), which render older generation tetracyclines inactive. Omadacycline in vitro activity was assessed against 919 bacterial isolates collected from patients with bone/joint infections in the United States and Europe (2015-2023) and 3945 rarely encountered bacterial pathogens from patients (multiple infection sites) in the United States (2015-2023) as part of the SENTRY Antimicrobial Surveillance Program.

METHODS

Broth microdilution susceptibility testing followed Clinical and Laboratory Standards Institute M07 (2024) and M100 (2024) guidelines.

RESULTS

Omadacycline demonstrated susceptibilities of ≥90.0% (FDA breakpoints) against Staphylococcus aureus (including MRSA), Staphylococcus lugdunensis, Enterococcus faecalis (including vancomycin-resistant), and streptococci including Streptococcus anginosus, Streptococcus pneumoniae, and Streptococcus pyogenes from patient with bone/joint infections. Omadacycline demonstrated potent in vitro activity against rare Gram-positive pathogens (multiple infection sites), inhibiting 97.3%, 91.3%, and 99.4% of uncommon staphylococci, streptococci, and enterococci isolates at or below current FDA approved ABSSSI breakpoints for S. aureus, S. pyogenes, and E. faecalis.

CONCLUSIONS

The potent omadacycline activity observed in this study suggests potential clinical utility for treatment of bone/joint infections and rarely encountered Gram-positive infections caused by various staphylococci, streptococci, and enterococci isolates and supports ongoing clinical trials for these disease indications.

摘要

目的

奥马环素是一种氨甲基环素(四环素类)抗菌药物,于2018年获美国食品药品监督管理局批准,用于治疗由特定病原体引起的急性细菌性皮肤及皮肤结构感染(ABSSSI)和社区获得性细菌性肺炎(CABP)的成人患者(口服和静脉注射制剂)。奥马环素对表达常见四环素耐药机制(核糖体保护蛋白和外排泵)的细菌分离株具有活性,而这些机制会使老一代四环素失去活性。作为哨兵抗菌监测计划的一部分,对从美国和欧洲(2015 - 2023年)骨/关节感染患者中收集的919株细菌分离株以及从美国(2015 - 2023年)患者(多个感染部位)中收集的3945株罕见细菌病原体进行了奥马环素的体外活性评估。

方法

采用肉汤微量稀释药敏试验,遵循临床和实验室标准协会M07(2024年)和M100(2024年)指南。

结果

对于骨/关节感染患者的金黄色葡萄球菌(包括耐甲氧西林金黄色葡萄球菌)、路邓葡萄球菌、粪肠球菌(包括耐万古霉素菌株)以及包括咽峡炎链球菌、肺炎链球菌和化脓性链球菌在内的链球菌,奥马环素的敏感性≥90.0%(美国食品药品监督管理局的断点值)。奥马环素对罕见革兰氏阳性病原体(多个感染部位)表现出强大的体外活性,在当前美国食品药品监督管理局批准的针对金黄色葡萄球菌、化脓性链球菌和粪肠球菌的ABSSSI断点值及以下,分别抑制了97.3%、91.3%和99.4%的罕见葡萄球菌、链球菌和肠球菌分离株。

结论

本研究中观察到的奥马环素的强大活性表明,其在治疗由各种葡萄球菌、链球菌和肠球菌分离株引起的骨/关节感染和罕见革兰氏阳性感染方面具有潜在的临床应用价值,并支持针对这些疾病适应症正在进行的临床试验。

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