tetano
Editor, Senior Moderator
Antiviral Res. 2017 May 20. pii: S0166-3542(17)30141-9. doi: 10.1016/j.antiviral.2017.05.008. [Epub ahead of print]
[h=1]Anti-inflammatory effects of adjunctive macrolide treatment in adults hospitalized with influenza: A randomized controlled trial.[/h] Lee N[SUP]1[/SUP], Wong CK[SUP]2[/SUP], Chan MCW[SUP]3[/SUP], Yeung ESL[SUP]4[/SUP], Tam WWS[SUP]5[/SUP], Tsang OTY[SUP]6[/SUP], Choi KW[SUP]7[/SUP], Chan PKS[SUP]8[/SUP], Kwok A[SUP]3[/SUP], Lui GCY[SUP]9[/SUP], Leung WS[SUP]6[/SUP], Yung IMH[SUP]9[/SUP], Wong RYK[SUP]10[/SUP], Cheung CSK[SUP]9[/SUP], Hui DSC[SUP]11[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]INTRODUCTION:[/h] - Macrolides can ameliorate inflammation in respiratory diseases, providing clinical benefits. Data in influenza is lacking.
[h=4]METHOD:[/h] - 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.
[h=4]RESULTS:[/h] - 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.
[h=4]CONCLUSION:[/h] - 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].
Copyright ? 2017. Published by Elsevier B.V.
[h=4]KEYWORDS:[/h] Anti-inflammatory effects; Influenza; Macrolide
PMID: 28535933 DOI: 10.1016/j.antiviral.2017.05.008
[h=1]Anti-inflammatory effects of adjunctive macrolide treatment in adults hospitalized with influenza: A randomized controlled trial.[/h] Lee N[SUP]1[/SUP], Wong CK[SUP]2[/SUP], Chan MCW[SUP]3[/SUP], Yeung ESL[SUP]4[/SUP], Tam WWS[SUP]5[/SUP], Tsang OTY[SUP]6[/SUP], Choi KW[SUP]7[/SUP], Chan PKS[SUP]8[/SUP], Kwok A[SUP]3[/SUP], Lui GCY[SUP]9[/SUP], Leung WS[SUP]6[/SUP], Yung IMH[SUP]9[/SUP], Wong RYK[SUP]10[/SUP], Cheung CSK[SUP]9[/SUP], Hui DSC[SUP]11[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]INTRODUCTION:[/h] - Macrolides can ameliorate inflammation in respiratory diseases, providing clinical benefits. Data in influenza is lacking.
[h=4]METHOD:[/h] - 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.
[h=4]RESULTS:[/h] - 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.
[h=4]CONCLUSION:[/h] - 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].
Copyright ? 2017. Published by Elsevier B.V.
[h=4]KEYWORDS:[/h] Anti-inflammatory effects; Influenza; Macrolide
PMID: 28535933 DOI: 10.1016/j.antiviral.2017.05.008