The combination of oseltamivir with azithromycin does not show additional benefits over oseltamivir monotherapy in mice infected with influenza A(H1N1)pdm2009 virus

Fage, Clément; Pizzorno, Andrés; Rhéaume, Chantal; Abed, Yacine; Boivin, Guy

doi:10.1002/jmv.24911

Cited by 10 publications

(7 citation statements)

References 27 publications

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“…Moreover, mice displayed less weight loss, less airway inflammation and lower mortality [41]. In contrast, a combination therapy of oseltamivir-azithromycin compared to oseltamivir monotherapy did not provide additional benefits in mice infected with influenza [64]. However, this study had several limitations.…”

Section: Effects On Virus-induced Ardsmentioning

confidence: 87%

“…First of all, the study designs differed significantly in terms of dosing and treatment duration. FAGE et al [64] only applied a single dose of azithromycin on day 3 post-inoculation. Viral titres were reduced but the combined therapy of azithromycin and oseltamivir did not improve survival probably due to the fact that severe lung injury had already occurred on day 3.…”

Section: Effects On Virus-induced Ardsmentioning

confidence: 99%

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Antibiotics as immunomodulators: a potential pharmacologic approach for ARDS treatment

et al. 2021

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First described in the mid-1960s, acute respiratory distress syndrome (ARDS) is a life-threatening form of respiratory failure with an overall mortality rate of approximately 40%. Despite significant advances in the understanding and treatment of ARDS, no substantive pharmacologic therapy has proven to be beneficial, and current management continues to be primarily supportive. Beyond their antibacterial activity, several antibiotics such as macrolides and tetracyclines exert pleiotropic immunomodulatory effects that might be able to rectify the dysregulated inflammatory response present in patients with ARDS. This review aims to provide an overview of preclinical and clinical studies that describe the immunomodulatory effects of antibiotics in ARDS. Moreover, the underlying mechanisms of their immunomodulatory properties will be discussed. Further studies are necessary to investigate their full therapeutic potential and to identify ARDS phenotypes which are most likely to benefit from their immunomodulatory effects.

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Section: Effects On Virus-induced Ardsmentioning

confidence: 87%

Section: Effects On Virus-induced Ardsmentioning

confidence: 99%

Antibiotics as immunomodulators: a potential pharmacologic approach for ARDS treatment

et al. 2021

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“…43 However, the effect was not sustained, and not associated with a change in virus-induced weight loss, a sensitive measurement of influenza pathology. Another study found AZM reduced lung viral titres at day 6 post infection, though the effects were not additive to that achieved with oseltamivir in terms of survival, viral titres or cytokine levels, 46 and so these data remain conflicting. 47 In a separate influenza study, AZM decreased total leukocyte accumulation in lung tissue and BAL, with the largest reduction being in neutrophils, and associated with decreased inflammatory mediators.…”

Section: Mechanism Of Effects In Influenza Amentioning

confidence: 99%

Azithromycin in viral infections

Oliver

Hinks

2020

Reviews in Medical Virology

106

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Summary Azithromycin (AZM) is a synthetic macrolide antibiotic effective against a broad range of bacterial and mycobacterial infections. Due to an additional range of anti‐viral and anti‐inflammatory properties, it has been given to patients with the coronaviruses SARS‐CoV or MERS‐CoV. It is now being investigated as a potential candidate treatment for SARS‐CoV‐2 having been identified as a candidate therapeutic for this virus by both in vitro and in silico drug screens. To date there are no randomised trial data on its use in any novel coronavirus infection, although a large number of trials are currently in progress. In this review, we summarise data from in vitro, murine and human clinical studies on the anti‐viral and anti‐inflammatory properties of macrolides, particularly AZM. AZM reduces in vitro replication of several classes of viruses including rhinovirus, influenza A, Zika virus, Ebola, enteroviruses and coronaviruses, via several mechanisms. AZM enhances expression of anti‐viral pattern recognition receptors and induction of anti‐viral type I and III interferon responses. Of relevance to severe coronavirus‐19 disease (COVID‐19), which is characterised by an over‐exuberant innate inflammatory response, AZM also has anti‐inflammatory properties including suppression of IL‐1beta, IL‐2, TNF and GM‐CSF. AZM inhibits T cells by inhibiting calcineurin signalling, mammalian target of rapamycin activity and NFκB activation. AZM particularly targets granulocytes where it concentrates markedly in lysosomes, particularly affecting accumulation, adhesion, degranulation and apoptosis of neutrophils. Given its proven safety, affordability and global availability, tempered by significant concerns about antimicrobial stewardship, there is an urgent mandate to perform well‐designed and conducted randomised clinical trials.

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“…44,45 Conversely, Fage C et al concluded that the inclusion of AZI in the combination therapy provided no additional clinical or antiviral benefits over oseltamivir monotherapy in their experimental murine models infected with influenza A. 46 In summary, most experimental and clinical studies investigating the effects of macrolide antibiotics against influenza viruses (mostly type A) were focused on CLA. Even if potential direct and indirect mechanisms by which CLA may works against this virus have been reported, actually the clinical evidence is not strong enough to conclude for any significant medical effect of this antibiotic in flu patients, as summarized in Table 3.…”

Section: Influenza Virusesmentioning

confidence: 99%

“…concluded that the inclusion of AZI in the combination therapy provided no additional clinical or antiviral benefits over oseltamivir monotherapy in their experimental murine models infected with influenza A. 46 …”

Section: Macrolides In Viral Diseasesmentioning

confidence: 99%

Clinical evidences on the antiviral properties of macrolide antibiotics in the COVID-19 era and beyond

Poddighe

Aljofan

2020

Antivir Chem Chemother

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Macrolides are a large group of antibiotics characterised by the presence of a macro-lactone ring of variable size. The prototype of macrolide antibiotics, erythromycin was first produced by Streptomyces and associated species more than half a century ago; other related drugs were developed. These drugs have been shown to have several pharmacological properties: in addition to their antibiotic activity, they possess some anti-inflammatory properties and have been also considered against non-bacterial infections. In this review, we analysed the available clinical evidences regarding the potential anti-viral activity of macrolides, by focusing on erythromycin, clarithromycin and azithromycin. Overall, there is no significant evidences so far that macrolides might have a direct benefit on most of viral infections considered in this review (RSV, Influenza, coronaviruses, Ebola and Zika viruses). However, their clinical benefit cannot be ruled out without further and focused clinical studies. Macrolides may improve the clinical course of viral respiratory infections somehow, at least through indirect mechanisms relying on some and variable anti-inflammatory and/or immunomodulatory effects, in addition to their well-known antibacterial activity.

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The combination of oseltamivir with azithromycin does not show additional benefits over oseltamivir monotherapy in mice infected with influenza A(H1N1)pdm2009 virus

Cited by 10 publications

References 27 publications

Antibiotics as immunomodulators: a potential pharmacologic approach for ARDS treatment

Antibiotics as immunomodulators: a potential pharmacologic approach for ARDS treatment

Azithromycin in viral infections

Clinical evidences on the antiviral properties of macrolide antibiotics in the COVID-19 era and beyond

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