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克拉霉素改善社区获得性肺炎的临床结局:ACCESS试验的亚组分析

Clarithromycin for improved clinical outcomes in community-acquired pneumonia: A subgroup analysis of the ACCESS trial.

作者信息

Akinosoglou Karolina, Leventogiannis Konstantinos, Tasouli Elisavet, Kakavoulis Nikolaos, Niotis Georgios, Doulou Sarantia, Skorda Lamprini, Iliopoulou Konstantina, Papailiou Anna, Katsaounou Paraskevi, Rapti Vassiliki, Chrysos George, Seferlis Theodoros, Gerakari Styliani, Dakou Konstantina, Papanikolaou Ilias C, Milionis Haralampos, Kewitz Samantha, Georgiadou Sara, Kontopoulou Theano, Tzavara Vasiliki, Torres Antonio, Niederman Michael S, Giamarellos-Bourboulis Evangelos J

机构信息

Department of Internal Medicine, University of Patras, Rion, Greece.

4(th) Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.

出版信息

Int J Antimicrob Agents. 2025 Feb;65(2):107406. doi: 10.1016/j.ijantimicag.2024.107406. Epub 2024 Dec 6.

Abstract

BACKGROUND

In the ACCESS trial, the addition of clarithromycin to standard-of-care antibiotics (SoC) enhanced early clinical response and attenuated the inflammatory burden in adults with community-acquired pneumonia (CAP) requiring hospitalisation. A post-hoc analysis was performed to investigate the benefit in specific subgroups.

METHODS

The primary endpoint comprised two conditions to be met during the first 72 h: ≥50% decrease in respiratory symptom severity score; and any of ≥30% decrease in sequential organ failure assessment score and favourable change in the kinetics of procalcitonin (PCT, defined as ≥80% PCT decrease or PCT <0.25 ng/mL). In this exploratory post-hoc analysis, achievement of the study composite primary endpoint was compared between the two treatment groups within subsets differentiated by demographic characteristics, comorbidities, CAP severity, baseline laboratory findings and corticosteroid co-administration. The impact of clarithromycin treatment on the need for mechanical ventilation (MV) in all subgroups was also analysed.

RESULTS

The addition of clarithromycin significantly increased the proportion of patients achieving the primary endpoint across all subgroups and decreased the need for MV in 19 out of the 37 subgroups studied. For instance, the primary endpoint was attained in 32.7% of placebo-treated patients and in 67% of clarithromycin-treated patients with CURB-65 score ≥2 (P<0.0001), whereas MV was required in 18.8% and 7.4% of patients, respectively (P=0.022). The addition of corticosteroids alone was not as clinically advantageous as the use of clarithromycin alone, when added to SoC.

CONCLUSION

Adding clarithromycin to SoC in the ACCESS trial achieved early clinical anti-inflammatory responses and decreased the need for MV in subgroups of hospitalised patients with CAP.

摘要

背景

在ACCESS试验中,在标准治疗抗生素(SoC)基础上加用克拉霉素可增强早期临床反应,并减轻需要住院治疗的社区获得性肺炎(CAP)成人患者的炎症负担。进行了一项事后分析以研究特定亚组中的获益情况。

方法

主要终点包括在最初72小时内需要满足的两个条件:呼吸道症状严重程度评分降低≥50%;序贯器官衰竭评估评分降低≥30%以及降钙素原(PCT)动力学有良好变化(定义为PCT降低≥80%或PCT<0.25 ng/mL)中的任何一项。在这项探索性事后分析中,比较了两个治疗组在按人口统计学特征、合并症、CAP严重程度、基线实验室检查结果和皮质类固醇联合使用区分的亚组中复合主要终点的达成情况。还分析了克拉霉素治疗对所有亚组中机械通气(MV)需求的影响。

结果

加用克拉霉素显著提高了所有亚组中达到主要终点的患者比例,并在所研究的37个亚组中的19个亚组中降低了MV需求。例如,CURB-65评分≥2的安慰剂治疗患者中有32.7%达到主要终点,克拉霉素治疗患者中有67%达到主要终点(P<0.0001),而分别有18.8%和7.4%的患者需要MV(P=0.022)。当添加到SoC中时,单独添加皮质类固醇在临床上不如单独使用克拉霉素有利。

结论

在ACCESS试验中,在SoC基础上加用克拉霉素可实现早期临床抗炎反应,并降低住院CAP患者亚组中MV的需求。

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