The prophylactic use of macrolides to prevent chronic lung disease (CLD) in premature infants is not supported by the evidence, a randomised controlled trial shows.  

Based on the results and those from other smaller trials, the authors say caution is required when prescribing azithromycin for the prevention of CLD, as the use of antibiotics in this vulnerable population is associated with increased morbidity, mortality, and antibiotic microbial resistance. 

The AZTEC trial [link here] was a multicentre, double-blind, randomised, placebo-controlled trial conducted in 28 neonatal intensive care units in the UK. Eligibility criteria included the need for invasive or non-invasive respiratory support for at least two hours within 72 hours of birth.  Preterm infants born at less than 30 weeks gestation received either a 10-day regimen of azithromycin (20 mg/kg per day for three days, followed by 10 mg/kg for the subsequent seven days) or a placebo.

The research team saw no difference between the groups, with 166 (42%) of 394 infants in the azithromycin group and 179 (45%) of 402 infants in the placebo group having the primary outcome of survival without moderate or severe CLD.  

Ureaplasma spp colonisation did not affect the primary outcome and azithromycin treatment did not affect secondary outcomes, including rates of death, corticosteroid use, the need for invasive or non-invasive ventilation. 

Rates of retinopathy of prematurity were lower in surviving infants in the intervention group, but not when death was included in the outcome.

“Our results are consistent with other smaller studies which do not support the routine prophylactic use of macrolides to decrease rates of CLD, despite convincing evidence of eradicating pulmonary Ureaplasma spp with the azithromycin dose used in our study,” the authors concluded. 

Writing in an accompanying editorial (link here) Dr Abdul Razak from the Department of Paediatrics, Monash University, Melbourne, Australia said that while the immediate findings from the AZTEC trial did not advocate for using azithromycin in preterm infants; it was crucial to await additional long-term data and additional analyses. 

“That said, CLD is a multifaceted condition that is influenced not only by perinatal infections such as Ureaplasma spp, but also by various other factors, and simply administering azithromycin might not adequately address the intricate interplay of factors associated with CLD. There will almost certainly never be a single solution—neither golden nor silver—to reduce or prevent CLD,” he added.