title: Maternal azithromycin therapy for Ureaplasma intraamniotic infection delays preterm delivery and reduces fetal lung injury in a primate model.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Beaverton, OR, USA. grigsbyp@ohsu.edu
authors.forename: Peta L
authors.initials: PL
authors.lastname: Grigsby
authors.forename: Miles J
authors.initials: MJ
authors.lastname: Novy
authors.forename: Drew W
authors.initials: DW
authors.lastname: Sadowsky
authors.forename: Terry K
authors.initials: TK
authors.lastname: Morgan
authors.forename: Mary
authors.initials: M
authors.lastname: Long
authors.forename: Ed
authors.initials: E
authors.lastname: Acosta
authors.forename: Lynn B
authors.initials: LB
authors.lastname: Duffy
authors.forename: Ken B
authors.initials: KB
authors.lastname: Waites
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D017963:Azithromycin / Q000008:administration & dosage*; D002821:Chorioamnionitis / Q000188:drug therapy* / Q000382:microbiology; D003907:Dexamethasone / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D005260:Female; D005315:Fetal Diseases / Q000517:prevention & control; D007213:Indomethacin / Q000008:administration & dosage; D055370:Lung Injury / Q000517:prevention & control*; D008253:Macaca mulatta; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D047928:Premature Birth / Q000517:prevention & control*; D016896:Treatment Outcome; D014509:Ureaplasma / Q000187:drug effects / Q000302:isolation & purification*; D016869:Ureaplasma Infections / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003907:Dexamethasone; D017963:Azithromycin; D007213:Indomethacin