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.
- ureaplasma parvum
- ureaplasma urealyticum
- bronchopulmonary dysplasia
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Correction notice This paper has been updated since it was published online. Author Namasivayam Ambalavanan’s first and last name were reversed and this has now been corrected.
Contributors RV, MLT, LSM and NLD had full access to all of the data in the study and take responsibility for the integrity of the data and accuracy of the data analysis. Study concept and design: RV, MLT, LSM and NDE. Acquisition, analysis or data interpretation: all authors. Drafting of the manuscript: RV, MLT and LSM. Critical revision of the manuscript: all authors. Statistical Analysis: RV, MLT, LSM and NLD. Obtained funding: RV, MLT, LSM, SJD, PD, DAK, KBW, AN and NDE. Study supervision: RV, MLT, SJD, PD, DAK, AN, DJT, J-HW and KBW.
Funding This study was funded by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (R01 HD067126). NICHD had no role in the design and conduct of the study; data collection, management, analysis, and interpretation; preparation, review, or approval prior to submission of the manuscript.
Disclaimer The views expressed in this publication are those of the authors and not necessarily the views of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
Competing interests None declared.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available in a public, open access repository. Deidentified data analysis file, study protocol and statistical analysis plan will be accessible on the NICHD Data and Specimen Hub (URL pending).
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