When you have a patient who requests a Z-pack for what is almost certainly an acute viral respiratory infection, you probably respond internally or externally (possibly both) that antibiotics do not treat viruses. But could there be some effect on their symptoms, or the viral infection itself, that is not part of the common discussion when it comes to such things? We know that azithromycin is an antibiotic, but it turns out that azithromycin actually has some activity in the viral arena. This absolutely shocked me. The question is, does it matter?
To wit…
- In vitro studies show azithromycin reduces rhinovirus replication and release.
- Another in vitro study on respiratory cells from lung transplant patients found azithromycin reduces rhinovirus-associated cellular inflammation.
- Kids with coronavirus (the pre-COVID, old-school coronavirus) had reduced viral load with azithromycin.
- In enterovirus-infected mice, azithromycin improved survival.
- Patients infected with influenza a who were given azithromycin had reduced interleukins 6, 8, 17, tumor necrosis factor, and CRP, indicating anti-inflammatory properties in flu patients.
- This study, however, did not show improved clinical outcomes with azithromycin.
- Another study using a similar methodology did not see any change in inflammatory markers but had a slight improvement in sore throat and fever resolution in the azithromycin group.
- A 2009 paper found that azithromycin did not improve disease course in hospitalized infants with a respiratory synovial virus. There has been signal of clarithromycin decreasing hospitalization in patients with severe RSV, but the preponderance of data are fairly consistent that there is no benefit in hospital stay, length of illness, or oxygen utilization.
Selective poison
Every medication is a selective poison and azithromycin poisons a lot of stuff: interleukin beta production, PGE2 synthesis, tumor necrosis factor, cytokine expression, it slows membrane trafficking towards lysosomes, and inhibits the fluid phase of endocytosis of macromolecules. Suffice it to say, there’s a lot going on here.
When we see these changes in inflammatory markers or in vitro decreased viral loads, it isn’t far-fetched. By extension, it frankly wouldn’t be far-fetched if this drug improved resolution and severity of illness in viral upper respiratory infections. When it comes to the flu, an illness with cytokine dysregulation, a medication such as azithromycin, with its immunomodulatory and anti-inflammatory effects, looks very tasty.
Bottom line
It’s pretty clear that something happens when a patients take this drug. It’s even possible that they may even have a sense of feeling better. I can’t refute that. My assumption is that their cold or acute sinusitis improves despite their taking an antibiotic, but maybe there is something subtle afoot that is as yet unmeasured. Unfortunately, the data to date do not show observable clinical outcome benefits with azithromycin and viral infections.
References
- Oliver, Madeleine E., and Timothy SC Hinks. “Azithromycin in viral infections.” Reviews in medical virology 31.2 (2021): e2163. Link
- Pradhan S, Madke B, Kabra P, Singh AL. Anti-inflammatory and Immunomodulatory Effects of Antibiotics and Their Use in Dermatology. Indian J Dermatol. 2016 Sep-Oct;61(5):469-81. doi: 10.4103/0019-5154.190105. PMID: 27688434; PMCID: PMC5029230. Link
- Kneyber, Martin CJ, et al. “Azithromycin does not improve disease course in hospitalized infants with respiratory syncytial virus (RSV) lower respiratory tract disease: a randomized equivalence trial.” Pediatric pulmonology 43.2 (2008): 142-149. Link
- Kong M, Zhang WW, Sewell K, et al. Azithromycin Treatment vs Placebo in Children With Respiratory Syncytial Virus–Induced Respiratory Failure: A Phase 2 Randomized Clinical Trial. JAMA Netw Open. 2020;3(4) Link
- Farley, Rebecca, et al. “Antibiotics for bronchiolitis in children under two years of age.” Cochrane Database of Systematic Reviews 10 (2014). Link
- Khoshnood, Saeed, et al. “Antiviral effects of azithromycin: A narrative review.” Biomedicine & Pharmacotherapy 147 (2022): 112682. Link
- Lee, Nelson, et al. “Anti-inflammatory effects of adjunctive macrolide treatment in adults admitted to hospital with influenza: an open-label, randomised controlled trial.” The Lancet 390 (2017): S2 Link
- Kakeya, Hiroshi, et al. “Efficacy of combination therapy with oseltamivir phosphate and azithromycin for influenza: a multicenter, open-label, randomized study.” PLoS One 9.3 (2014): e91293. Link
- Ling, Kak‐Ming, et al. “Azithromycin reduces airway inflammation induced by human rhinovirus in lung allograft recipients.” Respirology 24.12 (2019): 1212-1219. Link
- Kevin Antoine Brown, Bradley Langford, Kevin L Schwartz, Christina Diong, Gary Garber, Nick Daneman, Antibiotic Prescribing Choices and Their Comparative C. Difficile Infection Risks: A Longitudinal Case-Cohort Study, Clinical Infectious Diseases, Volume 72, Issue 5, 1 March 2021, Pages 836–844, Link
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