251 - Azithromycin eradicates Ureaplasma spp. colonisation and decreases pro-inflammatory cytokines in the respiratory tract of premature born infants without decreasing development of CLD

Publication Number: 251.3619

John Lowe, Cardiff University, Cardiff, Wales, United Kingdom; Ali F. Aboklaish, Cardiff University, Cardiff, Wales, United Kingdom; William J. Watkins, Cardiff University, Cardiff, Wales, United Kingdom; David J. Gallacher, Cardiff University, Cardiff, Wales, United Kingdom; Julian Marchesi, Imperial College London, London, England, United Kingdom; Sailesh Kotecha, Cardiff University, Cardiff, Wales, United Kingdom

Background: The mollicute, Ureaplasma spp., which often colonises the respiratory tract of preterm-born infants, is associated with the development of chronic lung disease of prematurity (CLD). In addition, pulmonary inflammation is also associated with the development of CLD. Our recent AZTEC trial of 796 preterm-born infants of < 30 weeks’ gestation did not show improved survival without development of CLD after ten-day early treatment with azithromycin when compared to placebo (Lowe et al. Lancet Respir Med. 2024;12:608-618).

Objective: As part of the AZTEC study, we assessed if azithromycin eradicated pulmonary colonisation of Ureaplasma spp and if pulmonary inflammation was decreased by azithromycin when compared to placebo treatment (Ethics approval: Wales REC2 18/WA/0199).

Design/Methods: qPCR was used to identify Ureaplasma spp. (U. urealyticum and U. parvum) in serial respiratory samples (endotracheal aspirates if invasively ventilated, otherwise nasopharyngeal aspirates) from randomised preterm-born infants at baseline, day 5, 10 and 14 of age. Ureaplasma culture was also performed for any positive qPCR results in the treatment group after treated had started. Proinflammatory cytokines were estimated using V-PLEX Human Cytokine 30-Plex Kit.

Results: Respiratory aspirate samples were available from 756 (95%) infants including 372 and 384 from the azithromycin and placebo groups respectively. Rates of CLD and death were similar between the two treatment groups. Overall, including baseline samples, the prevalence of Ureaplasma spp. was 25.8% (96/372) in the azithromycin group and 37.5% (144/384) in the placebo group. After treatment, the proportion of Ureaplasma-positive infants declined significantly in the azithromycin group when compared with the placebo group (15.6% vs 29.2%, p< 0.001). Importantly, no viable Ureaplasma spp. were detected by culture in any of the qPCR Ureaplasma-positive samples from the azithromycin group but were positive in the small number cultured from the placebo qPCR Ureaplasma spp. positive samples. As previously noted, pulmonary inflammatory cytokines (IL-1alpha, IL-1beta, IL-8, IL-12p70 and TNF-alpha) were significantly increased at 5 days of age in the placebo group but these were markedly decreased by azithromycin in the active treatment group.

Conclusion(s): In infants recruited to the AZTEC trial, azithromycin effectively eradicated Ureaplasma spp. from the respiratory tracts of preterm born infants and decreased lung inflammation by lowering proinflammatory cytokines. However, these positive effects of azithromycin did not translate into clinically decreased rates of CLD.