Introduction

− Macrolides can ameliorate inflammation in respiratory diseases, providing clinical benefits. Data in influenza is lacking.

Method

− A randomized, open-label, multicenter trial among adults hospitalized for laboratory-confirmed influenza was conducted. Study treatments of oseltamivir and azithromycin (500 mg/day), or oseltamivir alone, both for 5 days, were allocated at 1:1 ratio. The primary outcome was plasma cytokine/chemokine concentration change over time (Day 0–10); secondary outcomes were viral load and symptom score changes. Generalized Estimating Equation (GEE) models were used to analyze longitudinal data.

Results

− Fifty patients were randomized to the oseltamivir-azithromycin or oseltamivir groups, with comparable baseline characteristics (age, 57 ± 18 years; A/H3N2, 70%), complications (72%), and viral load. Pro-inflammatory cytokines IL-6 (GEE: β −0.037, 95%CI-0.067,-0.007, P = 0.016; reduction from baseline −83.4% vs −59.5%), CXCL8/IL-8 (β −0.018, 95%CI-0.037,0.000, P = 0.056; −80.5% vs −58.0%), IL-17 (β −0.064, 95%CI-0.117,-0.012, P = 0.015; −74.0% vs −34.3%), CXCL9/MIG (β −0.010, 95%CI-0.020,0.000, P = 0.043; −71.3% vs −56.0%), sTNFR-1, IL-18, and CRP declined faster in the oseltamivir-azithromycin group. There was a trend toward faster symptom resolution (β −0.463, 95%CI-1.297,0.371). Viral RNA decline (P = 0.777) and culture-negativity rates were unaffected. Additional ex vivo studies confirmed reduced induction of IL-6 (P = 0.017) and CXCL8/IL-8 (P = 0.005) with azithromycin.

Conclusion

− We found significant anti-inflammatory effects with adjunctive macrolide treatment in adults with severe influenza infections. Virus control was unimpaired. Clinical benefits of a macrolide-containing regimen deserve further study.

[ClinicalTrials.gov NCT01779570]

中文翻译：

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大环内酯辅助治疗对流感住院的成年人的抗炎作用：一项随机对照试验

介绍

−大环内酯类药物可减轻呼吸道疾病的炎症，提供临床益处。缺乏流感数据。

方法

−在因实验室确诊的流感住院的成年人中进行了一项随机，开放标签的多中心试验。分配5天的奥司他韦和阿奇霉素（500毫克/天）或单独使用奥司他韦的研究治疗药物按1：1的比例分配。主要结果是血浆细胞因子/趋化因子浓度随时间变化（第0-10天）；次要结果是病毒载量和症状评分变化。广义估计方程（GEE）模型用于分析纵向数据。

结果

−将50例患者随机分为奥司他韦-阿奇霉素或奥司他韦组，具有可比较的基线特征（年龄57±18岁； A / H3N2为70％），并发症（72％）和病毒载量。促炎细胞因子IL-6（GEE：β-0.037，95％CI-0.067，-0.007，P = 0.016;从基线降低-83.4％vs  -59.5％），CXCL8 / IL-8（β-0.018，95 ％CI-0.037,0.000，P = 0.056; -80.5％vs -58.0％ ），IL-17（β-0.064，95％CI-0.117，-0.012，P = 0.015; -74.0％vs  -34.3％）， CXCL9 / MIG（β-0.010，95％CI-0.020,0.000，P = 0.043; -71.3％vs oseltamivir-azithromycin组的sTNFR-1，IL-18和CRP下降幅度为-56.0％。有一种趋势，症状缓解更快（β-0.463，95％CI-1.297,0.371）。病毒RNA下降（P = 0.777）和培养阴性率不受影响。进一步的体外研究证实，阿奇霉素对IL-6（P = 0.017）和CXCL8 / IL-8（P = 0.005）的诱导作用降低。

结论

−我们发现大环内酯辅助治疗对严重流感感染的成年人具有显着的抗炎作用。病毒控制不受损害。含大环内酯类方案的临床益处值得进一步研究。

[ClinicalTrials.gov NCT01779570]