Maternal azithromycin therapy for Ureaplasma intraamniotic infection delays preterm delivery and reduces fetal lung injury in a primate model

Am J Obstet Gynecol. 2012 Dec;207(6):475.e1-475.e14. doi: 10.1016/j.ajog.2012.10.871. Epub 2012 Oct 23.

Abstract

Objective: We assessed the efficacy of a maternal multidose azithromycin (AZI) regimen, with and without antiinflammatory agents to delay preterm birth and to mitigate fetal lung injury associated with Ureaplasma parvum intraamniotic infection.

Study design: Long-term catheterized rhesus monkeys (n = 16) received intraamniotic inoculation of U parvum (10(7) colony-forming U/mL, serovar 1). After contraction onset, rhesus monkeys received no treatment (n = 6); AZI (12.5 mg/kg, every 12 h, intravenous for 10 days; n = 5); or AZI plus dexamethasone and indomethacin (n = 5). Outcomes included amniotic fluid proinflammatory mediators, U parvum cultures and polymerase chain reaction, AZI pharmacokinetics, and the extent of fetal lung inflammation.

Results: Maternal AZI therapy eradicated U parvum intraamniotic infection from the amniotic fluid within 4 days. Placenta and fetal tissues were 90% culture negative at delivery. AZI therapy significantly delayed preterm delivery and prevented advanced fetal lung injury, although residual acute chorioamnionitis persisted.

Conclusion: Specific maternal antibiotic therapy can eradicate U parvum from the amniotic fluid and key fetal organs, with subsequent prolongation of pregnancy, which provides a therapeutic window of opportunity to effectively reduce the severity of fetal lung injury.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Azithromycin / administration & dosage*
  • Chorioamnionitis / drug therapy*
  • Chorioamnionitis / microbiology
  • Dexamethasone / administration & dosage
  • Drug Therapy, Combination
  • Female
  • Fetal Diseases / prevention & control
  • Indomethacin / administration & dosage
  • Lung Injury / prevention & control*
  • Macaca mulatta
  • Polymerase Chain Reaction
  • Pregnancy
  • Premature Birth / prevention & control*
  • Treatment Outcome
  • Ureaplasma / drug effects
  • Ureaplasma / isolation & purification*
  • Ureaplasma Infections / drug therapy*
  • Ureaplasma Infections / microbiology

Substances

  • Anti-Bacterial Agents
  • Anti-Inflammatory Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Dexamethasone
  • Azithromycin
  • Indomethacin