Anti-inflammatory effects of adjunctive macrolide treatment in adults hospitalized with influenza: A randomized controlled trial
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AbstractIntroduction: 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 laboratoryconfirmed
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 0e10); 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: b 0.037, 95%CI-0.067,-0.007, P ¼ 0.016; reduction from
baseline 83.4% vs 59.5%), CXCL8/IL-8 (b 0.018, 95%CI-0.037,0.000, P ¼ 0.056; 80.5% vs 58.0%), IL-
17 (b 0.064, 95%CI-0.117,-0.012, P ¼ 0.015; 74.0% vs 34.3%), CXCL9/MIG (b 0.010, 95%CI-0.020,0.000,
P ¼ 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 (b 0.463, 95%CI-1.297,0.371). Viral RNA
decline (P ¼ 0.777) and culture-negativity rates were unaffected. Additional ex vivo studies confirmed
reduced induction of IL-6 (P ¼ 0.017) and CXCL8/IL-8 (P ¼ 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 macrolidecontaining
regimen deserve further study.
Acceptance Date18/05/2017
All Author(s) ListNelson Lee, Chun-Kwok Wong, Martin C.W. Chan, Esther S.L. Yeung, Wilson W.S. Tam, Owen T.Y. Tsang, Kin-Wing Choi, Paul K.S. Chan, Angela Kwok, Grace C.Y. Lui, Wai-Shing Leung, Irene M.H. Yung, Rity Y.K. Wong, Catherine S.K. Cheung, David S.C. Hui
Journal nameAntiviral Research
Volume Number144
Pages48 - 56
LanguagesEnglish-United States
KeywordsMacrolide, Anti-inflammatory effects, Influenza

Last updated on 2020-06-08 at 02:38