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支气管扩张症患者气道细菌负荷与吸入抗生素反应。

Airway Bacterial Load and Inhaled Antibiotic Response in Bronchiectasis.

机构信息

1 Respiratory Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.

2 Biomedical Research Institute Sant Pau, Barcelona, Spain.

出版信息

Am J Respir Crit Care Med. 2019 Jul 1;200(1):33-41. doi: 10.1164/rccm.201809-1651OC.

Abstract

The principal underlying inhaled antibiotic treatment in bronchiectasis is that airway bacterial load drives inflammation, and therefore antibiotic treatment will reduce symptoms. To determine the relationship between bacterial load and clinical outcomes, assess the stability of bacterial load over time, and test the hypothesis that response to inhaled antibiotics would be predicted by baseline bacterial load. We performed three studies. Studies 1 and 2 were prospective studies including adults with bronchiectasis. Study 3 was a analysis of a randomized trial of inhaled aztreonam. patients were divided into low (<10 cfu/g), moderate (10-10 cfu/g), and high bacterial load (≥10 cfu/g) using quantitative sputum culture. Bacterial load was a stable trait associated with worse quality of life and more airway inflammation in studies 1, 2, and 3. In study 3, patients with high bacterial load showed an improvement in the primary endpoint (Quality of Life-Bronchiectasis-Respiratory Symptoms Score at Week 4) in favor of aztreonam (mean difference of 9.7 points; 95% confidence interval, 3.4-16.0;  = 0.003). The proportion of patients who achieved an increase above the minimum clinically important difference was higher in the aztreonam group at Week 4 (63% vs. 37%;  = 0.01) and at Week 12 (62% vs. 38%;  = 0.01) only in high bacterial load patients. Improvement of quality of life with inhaled aztreonam was only evident in patients with high bacterial load. Bacterial load may be a useful biomarker of severity of disease and treatment response.

摘要

支气管扩张症中主要的吸入抗生素治疗的基本原理是气道细菌负荷驱动炎症,因此抗生素治疗将减轻症状。为了确定细菌负荷与临床结果之间的关系,评估细菌负荷随时间的稳定性,并检验假设即吸入抗生素的反应将通过基线细菌负荷来预测。我们进行了三项研究。研究 1 和 2 是包括支气管扩张症成人患者的前瞻性研究。研究 3 是对吸入妥布霉素随机试验的分析。患者根据定量痰培养分为低细菌负荷(<10 cfu/g)、中细菌负荷(10-10 cfu/g)和高细菌负荷(≥10 cfu/g)。在研究 1、2 和 3 中,细菌负荷是一种与生活质量较差和气道炎症更多相关的稳定特征。在研究 3 中,高细菌负荷患者在主要终点(第 4 周时的生活质量-支气管扩张症-呼吸症状评分)中显示出对妥布霉素有利的改善(平均差异为 9.7 分;95%置信区间,3.4-16.0;=0.003)。在第 4 周(63%对 37%;=0.01)和第 12 周(62%对 38%;=0.01),只有在高细菌负荷患者中,妥布霉素组达到最小临床重要差异以上的患者比例更高。吸入妥布霉素改善生活质量仅在高细菌负荷患者中明显。细菌负荷可能是疾病严重程度和治疗反应的有用生物标志物。

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