What is the role of azithromycin (Zithromax) in treating COVID-19?

Azithromycin Should Not Be Used for COVID-19 Treatment

Azithromycin should NOT be used for the treatment of COVID-19 in the absence of suspected or confirmed bacterial co-infection, as multiple randomized trials demonstrate no benefit in mortality, length of hospital stay, clinical status, or disease deterioration. 1

Evidence Against Azithromycin in COVID-19

• The European Respiratory Society (ERS) provides a conditional recommendation against offering azithromycin to hospitalized patients with COVID-19 in the absence of bacterial infection 1
• Pooled data from multiple randomized trials show no difference in mortality (OR 1.02,95% CI 0.69–1.49) when azithromycin is used for COVID-19 treatment 1
• The RECOVERY trial results, which were not included in the ERS meta-analysis but support their recommendation, demonstrated no benefit of azithromycin in COVID-19 patients 1
• The PRINCIPLE trial found no justification for routine use of azithromycin for reducing time to recovery or risk of hospitalization for people with suspected COVID-19 in the community 2
• The ATOMIC2 trial showed that in patients with mild-to-moderate COVID-19 managed without hospital admission, adding azithromycin to standard care did not reduce the risk of subsequent hospital admission or death 3

Potential Harms of Inappropriate Azithromycin Use

• Widespread use of azithromycin during the pandemic raises significant antimicrobial resistance concerns 4
• Although adverse events were not increased in COVID-19 patients in clinical trials, long-term concerns about antimicrobial resistance should be considered 1
• When combined with hydroxychloroquine, there was an increased number of adverse events (39.3%) compared to standard care (22.6%) 1
• Azithromycin can cause QT prolongation, especially when combined with other medications, potentially leading to cardiac complications 4

Appropriate Context for Antibiotic Use in COVID-19

• Bacterial co-infection is reported infrequently in COVID-19 patients, with systematic reviews suggesting <10% of patients isolate a bacterial pathogen 1, 4
• Antibiotics should be reserved only for patients with proven or strongly suspected bacterial co-infection 1, 4
• The Cochrane review concluded that in relation to the evidence for azithromycin and in the context of antimicrobial resistance, antibiotics should not be used for treatment of COVID-19 outside well-designed RCTs 5

Clinical Decision Algorithm

1. For patients with confirmed COVID-19 without evidence of bacterial infection:

   • Do NOT prescribe azithromycin 1, 4
   • Focus on supportive care and evidence-based COVID-19 treatments 4

2. For COVID-19 patients with suspected bacterial co-infection:

   • Obtain appropriate cultures when possible 4
   • Consider targeted antibiotic therapy based on local resistance patterns 1
   • Discontinue antibiotics if bacterial infection is ruled out 4

Common Pitfalls to Avoid

• Using azithromycin as a routine treatment for COVID-19 despite evidence showing no benefit 1, 2
• Combining azithromycin with hydroxychloroquine, which increases risk of adverse events without clinical benefit 1
• Prescribing antibiotics for viral infections without evidence of bacterial co-infection, contributing to antimicrobial resistance 1, 4
• Relying on small, non-randomized studies or case reports suggesting benefit, rather than larger randomized controlled trials showing no benefit 6, 7, 5

Despite some early enthusiasm and small studies suggesting potential benefit 6, 7, high-quality evidence from multiple randomized controlled trials consistently demonstrates that azithromycin does not improve outcomes in COVID-19 patients and should not be used outside the context of bacterial co-infection.