Lung Protection with Azithromycin in the Preterm Infant and the Role of Ureaplasma and Mycoplasma in the Development of Bronchopulmonary Dysplasia

Bronchopulmonary Dysplasia (BPD)is a ventilator-induced lung injury found primarily in extremely low birth weight infants. BPD is characterized by pulmonary fibrosis and arrest of lung development. It results when volutrauma and barotrauma from positive pressure ventilation trigger the inflammatory cascade. BPD is a major cause of death and prolonged pulmonary disability in the extremely low birth weight population. Preliminary data indicates a trend toward lower incidence and severity of BPD in preterm infants treated with azithromycin, a macrolide antibiotic with anti-inflammatory properties. The objectives of this project are to: 1. Demonstrate shorter duration of mechanical ventilation and decreased incidence of BPD with prophylactic administration of azithromycin in extremely low birth weight infants requiring mechanical ventilation. 2. Clarify the role of mycoplasma and urea plasma in the development of BPD. 3. Demonstrate a decrease in the inflammatory mediator NF-kB in tracheal lavage fluid with prophylactic azithromycin administration in infants requiring mechanical ventilation. The project will be randomized and double-blinded. Infants with birth weight < 1250 grams and requiring mechanical ventilation will be eligible for enrollment. Infants will be enrolled within 12 hours of beginning mechanical ventilation and will be randomized to receive either 6 weeks of azithromycin or placebo. Tracheal aspirates for mycoplasma/ureaplasma cultures and for ureaplasma PCR will be collected on admission weekly thereafter until extubation. Tracheal aspirates for NF-kB will also be collected weekly until extubation. Duration of ventilation, presence of BPD, need for post-natal steroids, and incidence of other infectious and inflammatory conditions, including necrotizing enterocolitis and sepsis, will be compared between groups.