Repeated maternal intramuscular or intraamniotic erythromycin incompletely resolves intrauterine Ureaplasma parvum infection in a sheep model of pregnancy

Am J Obstet Gynecol. 2014 Aug;211(2):134.e1-9. doi: 10.1016/j.ajog.2014.02.025. Epub 2014 Feb 28.

Abstract

Objective: Ureaplasma spp are the most commonly isolated microorganisms in association with preterm birth. Maternal erythromycin administration is a standard treatment for preterm prelabor rupture of membranes. There is little evidence of its effectiveness in eradicating Ureaplasma spp from the intrauterine cavity and fetus. We used a sheep model of intrauterine Ureaplasma spp infection to investigate the efficacy of repeated maternal intramuscular and intraamniotic erythromycin treatment to eradicate such an infection.

Study design: Thirty ewes with singleton pregnancies received an intraamniotic injection of 10(7) color change units of erythromycin-sensitive Ureaplasma parvum serovar 3 at 55 days' gestation. At 116 days' gestation, 28 ewes with viable fetuses were randomized to receive (1) intraamniotic and maternal intramuscular saline solution treatment (n = 8), (2) single intraamniotic and repeated maternal intramuscular erythromycin treatment (n = 10), or (3) single maternal intramuscular and repeated intraamniotic erythromycin treatment (n = 10). Fetuses were surgically delivered at 125 days' gestation. Treatment efficacy was assessed by culture, quantitative polymerase chain reaction, and histopathologic evaluation.

Results: Animals treated with intraamniotic erythromycin had significantly less viable U parvum serovar 3 in the amniotic fluid at delivery. However, neither combination of maternal intramuscular and intraamniotic erythromycin treatment successfully cleared U parvum serovar 3 from the amniotic fluid or fetal tissues. Three de novo erythromycin-resistant U parvum isolates were identified in erythromycin-treated animals.

Conclusion: Erythromycin treatment, given both to the ewe and into the amniotic cavity, fails to eradicate intrauterine and fetal U parvum serovar 3 infection and may lead to development of erythromycin resistant U parvum.

Keywords: Ureaplasma parvum; erythromycin; infection; preterm birth; sheep.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amnion
  • Amniotic Fluid / microbiology
  • Animals
  • Anti-Bacterial Agents / administration & dosage*
  • Chorion / metabolism
  • Chorion / microbiology
  • Chorion / pathology
  • DNA, Bacterial / blood
  • Drug Administration Schedule
  • Erythromycin / administration & dosage*
  • Female
  • Injections
  • Injections, Intramuscular
  • Interleukins / metabolism
  • Liver / metabolism
  • Lung / metabolism
  • Models, Animal
  • Pregnancy
  • Pregnancy Complications, Infectious / drug therapy*
  • RNA, Bacterial / blood
  • Random Allocation
  • Serum Amyloid A Protein / metabolism
  • Sheep
  • Skin / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Ureaplasma / genetics
  • Ureaplasma / isolation & purification
  • Ureaplasma Infections / drug therapy*

Substances

  • Anti-Bacterial Agents
  • DNA, Bacterial
  • Interleukins
  • RNA, Bacterial
  • Serum Amyloid A Protein
  • Tumor Necrosis Factor-alpha
  • Erythromycin