Maternal Administration of Solithromycin, a New, Potent, Broad-Spectrum Fluoroketolide Antibiotic, Achieves Fetal and Intra-Amniotic Antimicrobial Protection in a Pregnant Sheep Model

The Human Ureaplasma Species as Causative Agents of Chorioamnionitis

“…The transplacental transfer of solithromycin was significantly higher than that reported for other macrolides, including azithromycin, and a maternal intravenous infusion resulted in sustained therapeutic concentrations within maternal plasma, fetal plasma, and amniotic fluid for Ͼ12 h (302). In vitro, solithromycin has potent activity against human clinical Ureaplasma isolates (303,304), in addition to a range of other important pathogens (305)(306)(307)(308)(309).…”

“…Recent research efforts have evaluated a new, broad-spectrum fluoroketolide, solithromycin, in pregnant sheep and demonstrated that a single maternal dose can deliver therapeutic concentrations to both the fetus and the amniotic fluid (302). The transplacental transfer of solithromycin was significantly higher than that reported for other macrolides, including azithromycin, and a maternal intravenous infusion resulted in sustained therapeutic concentrations within maternal plasma, fetal plasma, and amniotic fluid for Ͼ12 h (302).…”

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

“…The ovine placenta differs both structurally and metabolically from the human placenta (54). In the sheep, SOLI is metabolized to form two bioactive metabolites at a significantly higher rate than in the human; these metabolites accumulate in the AF and likely contribute to its extended antimicrobial activity (37). We did not analyze the concentrations of AZ and SOLI in AF, maternal blood, and fetal blood, so we were unable to determine the extent of transfer and accumulation of the parent drugs and their metabolites in the various compartments.…”

“…It should, however, be noted that in the present study, we did not assess the rate at which each treatment modality resolved intrauterine U. parvum infection. It is possible that the superior maternal-fetal transfer of SOLI (37) and its greater potency against U. parvum may mean that a SOLI-based treatment regimen will allow for more rapid resolution of intrauterine infection relative to the results with AZ treatment. As rapid resolution of intrauterine U. parvum infection is likely to limit inflammation-associated injury to the fetus and reduce the risk of inflammation-driven PTB, further studies to assess the U. parvum clearance rate achieved with each agent are warranted.…”

“…At 120 days of GA, animals were randomly assigned to receive one of the following treatments (all maternal IV drug regimens were 10 mg/kg of maternal weight, every 24 h for 4 days): (i) maternal IV SOLI with a single IA injection of vehicle given with the first IV injection (IV-only SOLI), (ii) maternal IV SOLI with a single IA SOLI injection (0.14 mg/kg of fetal weight) (IVϩIA SOLI), (iii) maternal IV AZ and a single IA injection of vehicle (IV-only AZ), (iv) maternal IV AZ and a single IA AZ injection (1.4 mg/kg of fetal weight) (IVϩIA AZ), or (v) maternal IV and single IA injections of vehicle (control). The dosages of AZ and SOLI used were derived from our previous pharmacokinetic studies in pregnant sheep (15,37). In a previous study, 3 of 16 chronically catheterized fetuses administered IA SOLI at 1.4 mg/kg of estimated fetal weight died, with autopsy revealing bloody ascites and hepatomegaly.…”