Last update and review: June 7, 2020.
Azithromycin is a macrolide antibiotic with immunomodulatory properties that has shown benefit in inflammatory lung disease.
Azithromycin is a part of UK’s national clinical trials RECOVERY program that aims to identify treatments that may be beneficial for people hospitalized with suspected or confirmed COVID-19.
RECOVERY’s protocols for different drugs have multiple flaws and may have been designed with an intention to give negative results.
However, the information on azithromycin contained in the RECOVERY’s documentation as well as referenced literature are of interest. We published them below.
RECOVERY trials protocol (1):
Azithromycin:
Azithromycin is a macrolide antibiotic. In addition to their antimicrobial properties, the macrolide antibiotics are known to have immunomodulatory activity. The mechanism of immunomodulation includes decreased production of pro-inflammatory cytokines and inhibition of neutrophil activation. 38-40 Macrolides are widely used both in infectious pneumonia due to their antimicrobial activity and in chronic inflammatory lung disease due to the immunomodulatory effects. 41 Azithromycin is preferred over other macrolides because data suggest it has stronger immunomodulatory effects than other macrolides. 40 The use of macrolides in influenza-associated pneumonia has been associated with a faster reduction in inflammatory cytokines and, in combination with naproxen, decreased mortality. 42-44 Observational studies in MERS-CoV have not demonstrated a mortality benefit of macrolide use. 45 Macrolides have not been evaluated in severe betacoronavirus infections in randomised controlled trials. The safety of macrolides is well established.
(The trial protocol for the UK’s RECOVERY trials)
Azithromycin 500mg by mouth (or nasogastric tube) or intravenously once daily for 10 days.
Selected references:
1. RANDOMISED EVALUATION OF COVID-19 THERAPY (RECOVERY). Available at https://www.recoverytrial.net/files/recovery-protocol-v6-0-2020-05-14.pdf
Accessed on June 7, 2020.
The following numeration starts from 38 as in the original RECOVERY protocols description.
38. Kanoh S, Rubin BK. Mechanisms of action and clinical application of macrolides as immunomodulatory medications. Clin Microbiol Rev 2010;23:590 -615.
39. Shinkai M, Henke MO, Rubin BK. Macrolide antibiotics as immunomodulatory medications: proposed mechanisms of action. Pharmacol Ther 2008;117:393-405.
40. Zimmermann P, Ziesenitz VC, Curtis N, Ritz N. The Immunomodulatory Effects of Macrolides-A Systematic Review of the Underlying Mechanisms. Front Immunol 2018;9:302.
41. Spagnolo P, Fabbri LM, Bush A. Long-term macrolide treatment for chronic respiratory disease. Eur Respir J 2013;42:239-51.
42. Hui DS, Lee N, Chan PK, Beigel JH. The role of adjuvant immunomodulatory agents for treatment of severe influenza. Antiviral Res 2018;150:202-16.
43. Lee N, Wong CK, Chan MCW, et al. Anti-inflammatory effects of adjunctive macrolide treatment in adults hospitalized with influenza: A randomized controlled trial. Antiviral Res 2017;144:48-56.
44. Hung IFN, To KKW, Chan JFW, et al. Efficacy of Clarithromycin-Naproxen-Oseltamivir Combination in the Treatment of Patients Hospitalized for Influenza A(H3N2) Infection: An Open -label Randomized, Controlled, Phase IIb/III Trial. Chest 2017;151:1069-80.
45. Arabi YM, Deeb AM, Al-Hameed F, et al. Macrolides in critically ill patients with Middle East Respiratory Syndrome. Int J Infect Dis 2019;81:184-90.
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