Maternal intravenous administration of azithromycin results in significant fetal uptake in a sheep model of second trimester pregnancy

Matthew W Kemp, Yuichiro Miura, Matthew S Payne, Alan H Jobe, Suhas G Kallapur, Masatoshi Saito, Sarah J Stock, O Brad Spiller, Demelza J Ireland, Nobuo Yaegashi, Michael Clarke, Dorothee Hahne, Jennifer Rodger, Jeffrey A Keelan, John P Newnham

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

OBJECTIVE: Treatment of intrauterine infection is likely key to preventing a significant proportion of preterm deliveries before 32 weeks' gestation. Azithromycin (AZ) may be an effective antimicrobial in pregnancy; however, few gestation-appropriate data are available to inform the design of AZ-based treatment regimens in early pregnancy. We aimed to determine whether a single intraamniotic AZ dose, or repeated maternal IV AZ doses, would safely yield therapeutic levels of AZ in an 80 d gestation (term=150 d) ovine fetus.

STUDY DESIGN: 50 sheep carrying single pregnancies at 80 d gestation were randomised to receive either: I: single intraamniotic AZ administration; or II: 12-hourly maternal intravenous AZ administration. Amniotic fluid, maternal plasma and fetal AZ concentrations were determined over a 5 d treatment regimen. Markers of liver injury and amniotic fluid inflammation were measured to assess fetal injury in response to drug exposure.

RESULTS: Single intraamniotic administration yielded significant amniotic fluid and fetal lung AZ accumulation. In contrast, repeated maternal intravenous administration achieved high levels of AZ accumulation in the fetal lung and liver and a statistically significant increase in fetal plasma concentration at 120 h. There was no evidence of fetal injury in response to drug exposure.

CONCLUSIONS: These data suggest that: I: repeated maternal IV AZ dosing yields substantial fetal tissue uptake, although fetal plasma levels remain low; II: transfer of AZ from the amniotic fluid is lower than that of transplacental transfer; and III: and exposure to high concentrations of AZ did not elicit overt changes in fetal white blood cell counts, amniotic fluid monocyte chemoattractant protein-1 concentration or hepatotoxicity, all consistent with an absence of fetal injury.

Original languageEnglish
Pages (from-to)6581-6591
JournalAntimicrobial Agents and Chemotherapy
Volume56
DOIs
Publication statusPublished - 25 Aug 2014

Fingerprint

Dive into the research topics of 'Maternal intravenous administration of azithromycin results in significant fetal uptake in a sheep model of second trimester pregnancy'. Together they form a unique fingerprint.

Cite this