Favorable Impact of Azithromycin on Icu Patients with Covid-19: Insights from the First Wave Using Japanese Database

Azithromycin has favorable effects on critical respiratory diseases owing to its antimicrobial and anti-inflammatory effects. During the early stages of the coronavirus disease 2019 (COVID-19) pandemic, azithromycin was frequently used before specific treatments were developed. However, the effectiveness of the treatment has not been well verified. We retrospectively investigated its intravenous administration's effect in severe/critical COVID-19 patients using Japan's national administrative database during the first wave in Japan (February to April 2020). Patients were categorized based on receiving intravenous azithromycin within 3 days of hospitalization. The overlap weighting method with estimated propensity scores was used to reduce bias. Among 830 severe/critical COVID-19 patients, 148 received azithromycin (17.8%), and 682 did not (82.2%). After adjustment, the use of azithromycin was associated with a shorter duration of intensive-care unit (ICU) management (-3.48 days, 95% CI: -4.59 to -2.38). On the other hand, other endpoints, including mortality rates, duration of mechanical ventilation, and hospital stay, did not suggest associations. Then, we focused on the ICU patients. In 115 ICU patients, 27 (23.5%) were treated with intravenous azithromycin, and 88 (76.5%) were not. After adjustment, azithromycin was associated with favorable outcomes, including reduced in-hospital mortality (odds ratio [OR], 0.45, 95% CI: 0.22 to 0.92) and 30-day mortality (OR, 0.46, 95% CI: 0.22 to 0.94). Additionally, the use of azithromycin was linked to a shorter duration of ICU management (-2.94 days, 95% CI: -5.15 to -0.73). These results suggest that intravenous azithromycin has favorable effects on severe/critical COVID-19 patients requiring ICU management.