Azithromycin in Outpatient COVID-19: Not Recommended

I am not going to belabor this too much but we should stop using azithromycin in the community setting for COVID-19. The rationale for this recommendation was based on an article that was published on 4 March 2021 in the Lancet. The article is titled “azithromycin for community treatment of suspected COVID-19 in people at increased risk of an adverse clinical course in the UK (PRINCIPLE): a randomized, controlled, open label, adaptive platform trial. I recommend that you read this article for yourself as it is free for you to download and do not trust me.

As in intensive care physician, I do not have much of a say in what clinicians do in the outpatient setting to treat their patients with COVID-19. I do feel it is about most importance to start therapies sooner in the course of their infection as the consequences of patients reaching the level of inflammation that leads them to be hospitalized is extremely high. I wish we had better treatments to mitigate hospitalizations. Unfortunately, azithromycin does not appear to be one of those treatments based on these data. I definitely have to tip my hat to the authors of this paper and the entire group that collaborated to perform in this trial.

The first question that many people ask themselves when looking at utilizing azithromycin, an antibiotic, is how in the world with this work against a virus? Well, it turns out that there are in vitro studies which suggest that is azithromycin could potentially work against the virus that causes Covid. The article goes into further detail as to how it could interfere with intracellular SARS-CoV-2 activity and replication. I am not going to go into this during this review. In addition, azithromycin has been known to have the ability to reduce the levels of pro inflammatory cytokines such as interleukin six. Unfortunately, trails looking azithromycin in the inpatient setting have sadly been negative.

This is an outpatient study that looked at individuals who were at risk of the deleterious effects of COVID-19. This means patients who are age 65 or over and patients who were 50 years and older who had at least one comorbidity. These patients had not been feeling well for 14 days or less. The exact details of patient selection are noted in the article. The randomized these patients into two groups. The intervention group received azithromycin 500 mg once daily for three days plus usual care versus the control group receiving only usual care.

I am personally a fan of their original primary outcome which was hospitalization or death within 28 days. The authors had to change the primary outcome because their calculations and up under powering the study. That being the case, they developed co-primary and points of time to first self-reported recovery within 28 days along with hospitalization or death within 28 days. In total, it appears as if they were able to recruit 1323 patients into the study.

Unfortunately, the primary outcome did not reach statistical significance. There was no difference in time to report his recovery. There was no difference in hospitalization or death at 28 days. This is regardless of the patient population that was explored when subgroup analysis was conducted. The authors took the time to analyze different sub groups based on the age, comorbidities, duration of illness, and symptoms severity score. The authors did a great job looking at different secondary outcomes of which none obtained statistical significance. One of the pieces of information that can be teased out of these secondary outcomes include the fact that approximately 1% of patients in both the azithromycin group and the usual care group ended up in the intensive care unit.

All in all, the authors report that “our findings show that azithromycin should not be used routinely to treat COVID-19 in the community in older adults, in the absence of additional indications”. This is disappointing as we are looking for additional tools for our arsenal to defeat this virus and avoid hospitalization. This well conduct a study shows that azithromycin is not that tool. Let us hope that we could find one soon.

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Link to Article

Cite this post as: Eddy J. Gutierrez, “Azithromycin in Outpatient COVID-19: Not Recommended”, eddyjoemd blog, March 5, 2021. Available at:

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