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

Peta Grigsby, Miles J. Novy, Drew W. Sadowsky, Terry Morgan, Mary Long, Ed Acosta, Lynn B. Duffy, Ken B. Waites

Research output: Contribution to journalArticle

67 Citations (Scopus)

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 (107 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.

Original languageEnglish (US)
JournalAmerican Journal of Obstetrics and Gynecology
Volume207
Issue number6
DOIs
StatePublished - Dec 2012

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Ureaplasma Infections
Azithromycin
Lung Injury
Primates
Mothers
Amniotic Fluid
Macaca mulatta
Therapeutics
Ureaplasma
Chorioamnionitis
Premature Birth
Infection
Indomethacin
Placenta
Dexamethasone
Pneumonia
Fetus
Anti-Inflammatory Agents
Pharmacokinetics
Anti-Bacterial Agents

Keywords

  • antenatal antibiotic therapy
  • bronchopulmonary dysplasia/chronic lung disease
  • chorioamnionitis and mycoplasmas
  • fetal brain injury
  • preterm birth

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Maternal azithromycin therapy for Ureaplasma intraamniotic infection delays preterm delivery and reduces fetal lung injury in a primate model. / Grigsby, Peta; Novy, Miles J.; Sadowsky, Drew W.; Morgan, Terry; Long, Mary; Acosta, Ed; Duffy, Lynn B.; Waites, Ken B.

In: American Journal of Obstetrics and Gynecology, Vol. 207, No. 6, 12.2012.

Research output: Contribution to journalArticle

Grigsby, Peta ; Novy, Miles J. ; Sadowsky, Drew W. ; Morgan, Terry ; Long, Mary ; Acosta, Ed ; Duffy, Lynn B. ; Waites, Ken B. / Maternal azithromycin therapy for Ureaplasma intraamniotic infection delays preterm delivery and reduces fetal lung injury in a primate model. In: American Journal of Obstetrics and Gynecology. 2012 ; Vol. 207, No. 6.
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AB - 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 (107 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.

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