Ureaplasma urealyticum, erythromycin and respiratory morbidity in high-risk preterm neonates. Randomised trial of erythromycin on the development of chronic lung disease in preterm infants.
We investigated colonization with Ureaplasma urealyticum (Uu) in infants <30 weeks gestation and assessed the relationship to other risk factors influencing respiratory morbidity, plus the effect of treatment with erythromycin. Ventilated preterm infants [n = 155; median GA 26 (23-29) weeks] were cultured for Uu in endotracheal aspirate and nasopharynx. Colonized infants were randomly assigned to treatment with erythromycin 40 mg/kg/d, intravenously or orally. The rate of colonization was 29/155 (19%) and the Uu-colonized infants had lower mean gestational ages than the culture-negative infants (25 vs 26 weeks). For the colonized infants PROM (48% vs 12%), chorioamnionitis in the mother (46% vs 17%) and vaginal delivery (71% vs 29%) were more common. More colonized infants needed supplemental oxygen at 36 weeks' postconceptual age (p < 0.05). Erythromycin treatment was effective in reducing colonization with negative control cultures in 12/14 (86%) of treated infants. No significant differences were found between the colonized treated infants (n = 14) and those not treated (n = 14) in time with supplemental oxygen. Oxygen requirement at 36 weeks was related to lower gestational age, late appearance of PDA, late onset sepsis and signs of chorioamnionitis in the mother. We conclude that the Uu colonization is related to increasing immaturity, the presence of prolonged rupture of membranes, signs of chorioamnionitis and vaginal delivery. Treatment with erythromycin reduced colonization but did not significantly alter length of time with supplemental oxygen. To determine if erythromycin given from birth reduces the inflammatory response and the incidence and severity of chronic lung disease.
                Seventy five infants less than 30 weeks of gestation and ventilated from birth for lung disease were randomly assigned to receive erythromycin intravenously for 7 days or to no treatment. Ureaplasma urealyticum was detected in tracheal secretions by culture and polymerase chain reaction. Differential cell counts were obtained from bronchoalveolar lavage fluid collected daily for 5 days and concentrations of the cytokines interleukins IL-1 beta and IL-8, and tumour necrosis factor alpha (TNF-alpha) were measured. Chronic lung disease (CLD) was defined as oxygen dependency at 36 weeks of gestation.
                Nine infants (13%) were positive for U urealyticum. The inflammatory cytokines in the lungs increased over the first 5 days of life in all babies, but no association was found between their concentrations and the development of CLD. Those treated with erythromycin showed no significant differences from the non-treated group in the differential cell counts or concentrations of the cytokines. The two groups had a similar incidence of CLD. Babies infected with U urealyticum did not have a more pronounced cytokine response than those without infection. Chorioamnionitis was associated with significantly higher concentrations of IL-1 beta and IL-8 on admission: these babies had less severe acute lung disease and developed significantly less CLD.
                U urealyticum in the trachea was not associated with an increased inflammatory response in preterm infants. Erythromycin did not reduce the incidence or severity of CLD.
Current evidence does not demonstrate a reduction in CLD/death when intubated preterm infants are treated with erythromycin prophylactically before U. urealyticum culture/PCR results are known or when Ureaplasma colonized, intubated preterm infants are treated with erythromycin. However, a true benefit could easily have been missed with the small sample sizes in the two eligible studies. The studies were greatly underpowered to detect uncommon adverse effects such as pyloric stenosis. Additional controlled trials are required to determine whether antibiotic therapy of Ureaplasma reduces CLD and/or death in intubated preterm infants.