title: Maternal intravenous treatment with either azithromycin or solithromycin clears Ureaplasma parvum from the amniotic fluid in an ovine model of intrauterine infection.
abstract: Intrauterine infection with Ureaplasma spp. is strongly associated with preterm birth and adverse neonatal outcomes. We assessed whether combined intraamniotic (IA) and maternal intravenous (IV) treatment with one of two candidate antibiotics, azithromycin (AZ) or solithromycin (SOLI), would eradicate intrauterine Ureaplasma parvum infection in a sheep model of pregnancy. Sheep with singleton pregnancies received an IA injection of U. parvum serovar 3 at 85 days of gestational age (GA). At 120 days of GA, animals (n=5 to 8/group) received one of the following treatments: (i) maternal IV SOLI with a single IA injection of vehicle (IV SOLI only); (ii) maternal IV SOLI with a single IA injection of SOLI (IV+IA SOLI); (iii) maternal IV AZ and a single IA injection of vehicle (IV AZ only); (iv) maternal IV AZ and a single IA injection of AZ (IV+IA AZ); or (v) maternal IV and single IA injection of vehicle (control). Lambs were surgically delivered at 125 days of GA. Treatment efficacies were assessed by U. parvum culture, quantitative PCR, enzyme-linked immunosorbent assay, and histopathology. Amniotic fluid (AF) from all control animals contained culturable U. parvum. AF, lung, and chorioamnion from all AZ- or SOLI-treated animals (IV only or IV plus IA) were negative for culturable U. parvum. Relative to the results for the control, the levels of expression of interleukin 1β (IL-1β), IL-6, IL-8, and monocyte chemoattractant protein 2 (MCP-2) in fetal skin were significantly decreased in the IV SOLI-only group, the MCP-1 protein concentration in the amniotic fluid was significantly increased in the IV+IA SOLI group, and there was no significant difference in the histological inflammation scoring of lung or chorioamnion among the five groups. In the present study, treatment with either AZ or SOLI (IV only or IV+IA) effectively eradicated macrolide-sensitive U. parvum from the AF. There was no discernible difference in antibiotic therapy efficacy between IV-only and IV+IA treatment regimens relative to the results for the control.
authors: School of Women's and Infants' Health, The University of Western Australia, Perth, Western Australia, Australia.
authors: Yuichiro
authors: Y
authors: Miura
authors: School of Women's and Infants' Health, The University of Western Australia, Perth, Western Australia, Australia.
authors: Matthew S
authors: MS
authors: Payne
authors: School of Women's and Infants' Health, The University of Western Australia, Perth, Western Australia, Australia.
authors: Jeffrey A
authors: JA
authors: Keelan
authors: School of Women's and Infants' Health, The University of Western Australia, Perth, Western Australia, Australia.
authors: Andres
authors: A
authors: Noe
authors: School of Women's and Infants' Health, The University of Western Australia, Perth, Western Australia, Australia.
authors: Sean
authors: S
authors: Carter
authors: School of Women's and Infants' Health, The University of Western Australia, Perth, Western Australia, Australia.
authors: Rory
authors: R
authors: Watts
authors: Department of Child Health, School of Medicine, Cardiff University, Cardiff, United Kingdom.
authors: Owen B
authors: OB
authors: Spiller
authors: Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Centre, University of Cincinnati, School of Medicine, Cincinnati, Ohio, USA.
authors: Alan H
authors: AH
authors: Jobe
authors: Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Centre, University of Cincinnati, School of Medicine, Cincinnati, Ohio, USA.
authors: Suhas G
authors: SG
authors: Kallapur
authors: Division of Perinatal Medicine, Tohoku University Hospital, Sendai, Japan.
authors: Masatoshi
authors: M
authors: Saito
authors: MRC Centre for Reproductive Health, University of Edinburgh, United Kingdom.
authors: Sarah J
authors: SJ
authors: Stock
authors: School of Women's and Infants' Health, The University of Western Australia, Perth, Western Australia, Australia.
authors: John P
authors: JP
authors: Newnham
authors: School of Women's and Infants' Health, The University of Western Australia, Perth, Western Australia, Australia matthew.kemp@uwa.edu.au.
authors: Matthew W
authors: MW
authors: Kemp
mesh_terms: D061605:Administration, Intravenous / Q000379:methods; D000653:Amniotic Fluid / Q000187:drug effects* / Q000382:microbiology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017963:Azithromycin / Q000494:pharmacology*; D018932:Chemokine CCL2 / Q000378:metabolism; D054412:Chemokine CCL8 / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000187:drug effects; D007378:Interleukins / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D018942:Macrolides / Q000494:pharmacology*; D011014:Pneumonia / Q000378:metabolism; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D012756:Sheep; D014230:Triazoles / Q000494:pharmacology*; D014509:Ureaplasma / Q000187:drug effects*; D016869:Ureaplasma Infections / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D018932:Chemokine CCL2; D054412:Chemokine CCL8; D007378:Interleukins; D018942:Macrolides; D014230:Triazoles; D017963:Azithromycin; C547755:solithromycin