Use of Azithromycin for the Prevention of Lung Injury in Mechanically Ventilated Preterm Neonates: A Randomized Controlled Trial

Abstract

<b><i>Introduction:</i></b> Macrolides have anti-inflammatory and immunomodulatory properties that give this class of antibiotics a role that differs from its classical use as an antibiotic, which opens new therapeutic possibilities. <b><i>Objective:</i></b> The aim of this study was to evaluate the anti-inflammatory effect of azithromycin in preventing mechanical ventilation (MV)-induced lung injury in very-low-birth-weight preterm neonates. <b><i>Methods:</i></b> This is a randomized, double-blind, placebo-controlled trial of preterm neonates who received invasive MV within 72 h of birth. Patients were randomized to receive intravenous azithromycin (at a dose of 10/mg/kg/day for 5 days) or placebo (0.9% saline) within 12 h of the start of MV. Two blood samples were collected (before and after intervention) for measurement of interleukins (ILs) and PCR for <i>Ureaplasma</i>. Patients were followed up throughout the hospital stay for the outcomes of death and broncho­pulmonary dysplasia defined as need for oxygen for a period of ≥28 days of life (registered at ClinicalTrials.gov, No. NCT03485703). <b><i>Results:</i></b> Forty patients were analyzed in the azithromycin group and 40 in the placebo group. Five days after the last dose, serum IL-2 and IL-8 levels dropped significantly in the azithromycin group. There was a significant reduction in the incidence of death and O₂ dependency at 28 days/death in azithromycin-treated patients regardless of the detection of <i>Ureaplasma</i> in blood. <b><i>Conclusions:</i></b> Azithromycin has anti-inflammatory effects, with a decrease in cytokines after 5 days of use and a reduction in death and O₂ dependency at 28 days/death in mechanically ventilated preterm neonates.