Azithromycin in COVID-19: Can It Promote Drug

What did researchers find about azithromycin and airway bacteria?

The study, published in Nature Microbiology, analyzed nasal samples from hospitalized adults, including 366 who received azithromycin. Researchers detected increased expression of genes associated with resistance to macrolide, lincosamide and streptogramin antibiotics. Some changes appeared after approximately one day and persisted beyond a week. [Study findings](https://www.nature.com/articles/s41564-026-02285-8)

The observational design cannot establish causation, and nasal samples may not reflect lung bacteria. Participants were enrolled before widespread vaccination. Detecting resistance-gene activity also does not establish that an individual developed a resistant infection or experienced treatment failure. [Study limitations](https://www.nature.com/articles/s41564-026-02285-8)

Does azithromycin improve outcomes for patients with COVID-19?

Azithromycin attracted interest early in the pandemic because, alongside its antibacterial effects, it can influence inflammatory responses. That biological rationale did not translate into better outcomes in the RECOVERY comparison, published in The Lancet in 2021. Among 7,763 hospitalized patients, mortality at 28 days was approximately 22% in both treatment groups. Researchers also found no significant improvement in hospital discharge or the combined outcome of invasive ventilation or death among patients initially not receiving invasive ventilation. [RECOVERY results](https://www.thelancet.com/article/S0140673621001495/pdf)

The CDC reports that almost 80% of patients hospitalized with COVID-19 received antibiotics between March and October 2020. Distinguishing viral illness from bacterial pneumonia was difficult, while staffing shortages, prolonged admissions and greater use of invasive devices also contributed to resistance risks. These historical figures describe pandemic practice; they are not estimates of prescribing today. The practical implication is to connect antibiotic treatment to a suspected bacterial infection rather than the COVID-19 diagnosis alone. [CDC assessment](https://www.cdc.gov/antimicrobial-resistance/data-research/threats/covid-19.html)

When should someone with COVID-19 receive antibiotics?

WHO's June 2025 clinical management guideline recommends against starting antibiotics empirically in non-severe COVID-19 when suspicion of bacterial infection is low. It also suggests avoiding empirical antibiotics in severe COVID-19 under the same condition, although that recommendation is conditional. Empirical treatment means prescribing before the responsible bacterium has been established. These recommendations do not prohibit prompt antibiotics when bacterial pneumonia or another serious bacterial infection is suspected. [WHO guidance](https://www.who.int/publications/i/item/B09467)

Diagnosis requires more than an isolated inflammatory blood test. NICE advises considering examination findings alongside investigations such as chest imaging and respiratory or blood samples; a high C-reactive protein level alone cannot distinguish bacterial pneumonia from COVID-19. For hospitalized patients receiving antibiotics, NICE recommends review within 24–48 hours, or when results become available, and narrowing treatment when appropriate. This reassessment helps clinicians match the medicine to the infection while limiting unnecessary exposure. [NICE prescribing guidance](https://www.nice.org.uk/guidance/ng191/chapter/6-Identifying-and-managing-co-infections)