Maternal Intravenous Treatment with Either Azithromycin or Solithromycin Clears Ureaplasma parvum from the Amniotic Fluid in an Ovine Model of Intrauterine Infection

Yuichiro Miura, Matthew S Payne, Jeffrey A Keelan, Andres Noe, Sean Carter, Rory Watts, Owen B Spiller, Alan H Jobe, Suhas G Kallapur, Masatoshi Saito, Sarah J Stock, John P Newnham, Matthew W Kemp

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Abstract / Description of output

OBJECTIVES: Intrauterine infection with Ureaplasma spp. is strongly associated with preterm birth and adverse neonatal outcomes. We assessed whether combined intra-amniotic (IA) and maternal intravenous (IV) treatment with one of two candidate antibiotics, azithromycin (AZ) or solithromycin (SOLI), would eradicate intrauterine Ureaplasma parvum (UP) infection in a sheep model of pregnancy.

STUDY DESIGN: Sheep with singleton pregnancies received an IA injection of UP serovar 3 at 85 d gestational age (GA). At 120 d GA, animals (n=5-8/group) received either: I: maternal IV SOLI with a single IA vehicle injection; II: maternal IV SOLI with a single IA SOLI injection; III: maternal IV AZ and a single IA vehicle injection; IV: maternal IV AZ and a single IA AZ injection; or V: maternal IV and single IA vehicle injections (control). Lambs were surgically delivered at 125 d GA. Treatment efficacy was assessed by UP culture, quantitative PCR, ELISA and histopathology.

RESULTS: Amniotic fluid (AF) from all control animals contained culturable UP. AF, lung, and chorioamnion from all AZ or SOLI-treated animals (IV-only or IV + IA) were negative for culturable UP. Relative to control: expression of IL-1β, IL-6, IL-8 and MCP-2 in fetal skin was significantly decreased in the IV SOLI (I: ) group; MCP-1 protein concentration in the amniotic fluid was significantly increased in the IV + IA SOLI (II: ) group; and there was no significant difference in histological inflammation scoring of lung or chorioamnion among the five groups.

CONCLUSIONS: In the present study, treatment with either AZ or SOLI (IV-only or IV + IA) effectively eradicated macrolide-sensitive UP from the AF. There was no discernable difference in antibiotic therapy efficacy between IV-only and IV + IA treatment regimens, relative to control.

Original languageEnglish
JournalAntimicrobial Agents and Chemotherapy
DOIs
Publication statusPublished - 30 Jun 2014

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