Randomised trial of azithromycin to eradicate Ureaplasma in preterm infants
Rose Marie Viscardi1, Michael L Terrin2, Laurence S Magder2
1Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland, USA rviscard@som.umaryland.edu.
Insights
Azithromycin effectively eradicated Ureaplasma in preterm infants. This macrolide antibiotic improved Ureaplasma-free survival and reduced respiratory complications in neonates.
Area of Science:
- Neonatal intensive care
- Infectious diseases in neonates
- Respiratory medicine
Background:
- Ureaplasma colonization is common in preterm infants.
- Ureaplasma is associated with bronchopulmonary dysplasia and mortality.
- Limited data exist on antibiotic efficacy for Ureaplasma eradication in neonates.
Purpose of the Study:
- To evaluate the efficacy of azithromycin in eradicating Ureaplasma from the respiratory tract of preterm infants.
- To assess the impact of Ureaplasma eradication on neonatal outcomes.
Main Methods:
- Phase IIb, randomized, double-blind, placebo-controlled trial.
- Involved 121 preterm infants (24-28 weeks gestation) across seven NICUs.
- Infants received either intravenous azithromycin or placebo for 3 days.
Main Results:
- Azithromycin significantly improved Ureaplasma-free survival (92% vs. 61%).
- Azithromycin effectively eradicated Ureaplasma in all treated infants.
- Reduced rates of bronchopulmonary dysplasia-free survival were observed in infants with lower respiratory tract Ureaplasma colonization treated with azithromycin.
Conclusions:
- A 3-day azithromycin regimen is effective in eradicating respiratory tract Ureaplasma colonization in preterm infants.
- Azithromycin demonstrates potential in reducing Ureaplasma-related morbidities in neonates.
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.
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