Azithromycin through the Lens of the COVID-19 Treatment

Abstract

Azithromycin has become famous in the last two years, not for its main antimicrobial effect, but for its potential use as a therapeutic agent for COVID-19 infection. Initially, there were some promising results that supported its use, but it has become clear that scientific results are insufficient to support such a positive assessment. In this review we will present all the literature data concerning the activity of azithromycin as an antimicrobial, an anti-inflammatory, or an antivirus agent. Our aim is to conclude whether its selection should remain as a valuable antivirus agent or if its use simply has an indirect therapeutic contribution due to its antimicrobial and/or immunomodulatory activity, and therefore, if its further use for COVID-19 treatment should be interrupted. This halt will prevent further antibiotic resistance expansion and will keep azithromycin as a valuable anti-infective therapeutic agent.

Revealing the drivers of antibiotic resistance trends inStreptococcus pneumoniaeamidst the 2020 COVID-19 pandemic: Insights from mathematical modeling

“…Due to reductions in primary care consultations in 2020, 26 European countries reported an estimated average decrease of 18.3% in overall antibiotic consumption, aligning with the global trend of reduced antibiotic prescriptions compared to 2019 (Högberg et al, 2021). On the other hand, frequent prescribing of azithromycin, a macrolide antibiotic initially hypothesized to be effective in COVID-19 treatment, has raised concerns for pandemic-associated antimicrobial overuse or misuse and may have exacerbated AMR during and following the first wave of the pandemic (Clancy et al, 2020; Knight et al, 2021; Kournoutou and Dinos, 2022; Langford et al, 2021; PRINCIPLE Trial Collaborative Group, 2021; Rusic et al, 2021). There are still uncertainties about pneumococcal ecology and the evolutionary processes that enable the robust coexistence of strains sensitive and resistant to antibiotics.…”

The Association between Previous Antibiotic Consumption and SARS-CoV-2 Infection: A Population-Based Case-Control Study

“…Azithromycin is well-known for its considerable effects on the immune system [ 29 , 30 , 46 ]. Its confirmed immunomodulatory effects include reduced production of pro-inflammatory cytokines such as interleukins-8 (IL-8), IL-6, tumor necrotic factor alpha (TNF-α) and matrix metalloproteinases.…”

“…Its confirmed immunomodulatory effects include reduced production of pro-inflammatory cytokines such as interleukins-8 (IL-8), IL-6, tumor necrotic factor alpha (TNF-α) and matrix metalloproteinases. Azithromycin also modulates macrophage and T-helper functions, causes alterations in autophagy and reduces oxidative stress [ 29 , 30 , 46 ]. Because of its profound immunomodulatory effects, azithromycin has been proposed for the prevention and treatment of asthma and other inflammatory conditions [ 29 , 30 ].…”

“…Furthermore, previous studies also reported antiviral activities of azithromycin, probably by inhibiting the endosome acidification during viral replication and affecting the un-coating step of viral infection [ 29 , 47 ]. Because of these properties, and as inflammation plays a major role in the severity of COVID-19, azithromycin has been suggested as a treatment for this infection, alone or with hydroxychloroquine [ 29 , 46 ], but several studies did not document efficacy of azithromycin in patients with COVID-19 and it is currently not recommended as a treatment for the disease. We have found that previous consumption of azithromycin is associated with reduced odds of SARS-CoV-2 infection.…”

“…It should be noted that azithromycin has an excellent tissue penetration and it accumulates within tissues and cells, particularly macrophages, with tissue concentrations about 50-fold greater than plasma concentration [ 29 , 41 ]. Its biologic half-life is long, estimated at 35–40 h in humans administered a single dose of 500 mg [ 29 , 46 ].…”