Randomised trial of azithromycin to eradicate Ureaplasma in preterm infants

Arch Dis Child Fetal Neonatal Ed. 2020 Nov;105(6):615-622. doi: 10.1136/archdischild-2019-318122. Epub 2020 Mar 13.

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.

Keywords: bronchopulmonary dysplasia; neonatology; prematurity; ureaplasma parvum; ureaplasma urealyticum.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / therapeutic use*
  • Azithromycin / administration & dosage
  • Azithromycin / pharmacokinetics
  • Azithromycin / therapeutic use*
  • Bronchopulmonary Dysplasia / etiology
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Gestational Age
  • Humans
  • Infant, Extremely Premature
  • Infant, Newborn
  • Infant, Premature, Diseases / drug therapy*
  • Intensive Care Units, Neonatal
  • Intention to Treat Analysis
  • Male
  • Prospective Studies
  • Respiratory Tract Infections / complications
  • Respiratory Tract Infections / drug therapy*
  • Risk Factors
  • Ureaplasma Infections / complications
  • Ureaplasma Infections / drug therapy*

Substances

  • Anti-Bacterial Agents
  • Azithromycin

Associated data

  • ClinicalTrials.gov/NCT01778634