Randomised trial of azithromycin to eradicate Ureaplasma in preterm infants

Abstract

Objective To test whether azithromycin eradicates Ureaplasma from the respiratory tract in preterm infants. Design Prospective, phase IIb randomised, double-blind, placebo-controlled trial. Setting Seven level III–IV US, academic, neonatal intensive care units (NICUs). Patients Infants 24⁰–28⁶ weeks’ gestation (stratified 24⁰–26⁶; 27⁰–28⁶ weeks) randomly assigned within 4 days following birth from July 2013 to August 2016. Interventions Intravenous azithromycin 20 mg/kg or an equal volume of D5W (placebo) every 24 hours for 3 days. Main outcome measures The primary efficacy outcome was Ureaplasma-free survival. Secondary outcomes were all-cause mortality, Ureaplasma clearance, physiological bronchopulmonary dysplasia (BPD) at 36 weeks’ postmenstrual age, comorbidities of prematurity and duration of respiratory support. Results One hundred and twenty-one randomised participants (azithromycin: n=60; placebo: n=61) were included in the intent-to-treat analysis (mean gestational age 26.2±1.4 weeks). Forty-four of 121 participants (36%) were Ureaplasma positive (azithromycin: n=19; placebo: n=25). Ureaplasma-free survival was 55/60 (92% (95% CI 82% to 97%)) for azithromycin compared with 37/61 (61% (95% CI 48% to 73%)) for placebo. Mortality was similar comparing the two treatment groups (5/60 (8%) vs 6/61 (10%)). Azithromycin effectively eradicated Ureaplasma in all azithromycin-assigned colonised infants, but 21/25 (84%) Ureaplasma-colonised participants receiving placebo were culture positive at one or more follow-up timepoints. Most of the neonatal mortality and morbidity was concentrated in 21 infants with lower respiratory tract Ureaplasma colonisation. In a subgroup analysis, physiological BPD-free survival was 5/10 (50%) (95% CI 19% to 81%) among azithromycin-assigned infants with lower respiratory tract Ureaplasma colonisation versus 2/11 (18%) (95% CI 2% to 52%) in placebo-treated infants. Conclusion A 3-day azithromycin regimen effectively eradicated respiratory tract Ureaplasma colonisation in this study. Trial registration number NCT01778634.