Anti-inflammatory effects of adjunctive macrolide treatment in adults hospitalized with influenza: A randomized controlled trial.

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Anti-inflammatory effects of adjunctive macrolide treatment in adults hospitalized with influenza: A randomized controlled trial.

Antiviral Res. 2017 Aug;144:48-56

Authors: Lee N, Wong CK, Chan MCW, Yeung ESL, Tam WWS, Tsang OTY, Choi KW, Chan PKS, Kwok A, Lui GCY, Leung WS, Yung IMH, Wong RYK, Cheung CSK, Hui DSC

Abstract
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].

PMID: 28535933 [PubMed - indexed for MEDLINE]

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