title: Immunomodulators plus antibiotics delay preterm delivery after experimental intraamniotic infection in a nonhuman primate model.
abstract: OBJECTIVE
  The purpose of this study was to determine whether treatment with ampicillin together with dexamethasone and indomethacin delays preterm birth that is induced by intraamniotic group B Streptococcus in a nonhuman primate model.
  
  
  METHODS
  After contraction onset that was induced by group B Streptococcus (10(6) colony-forming units/mL), chronically instrumented rhesus macaques received either no treatment (controls; n = 6); ampicillin (n = 4); or ampicillin + dexamethasone + indomethacin (n = 5). Outcomes included the interval from contraction onset until delivery and concentrations of amniotic fluid inflammatory mediators.
  
  
  RESULTS
  Mean interval from contraction onset until delivery was 33 +/- 8.7 hours in controls, 82 +/- 28.0 hours with ampicillin (P = .18, vs controls), and 213 +/- 50.8 hours with ampicillin + dexamethasone + indomethacin (P = .004, vs controls). Ampicillin eradicated group B Streptococcus; however, uterine activity, amniotic fluid cytokines, prostaglandins, and matrix metalloproteinase-9 remained elevated. Ampicillin + dexamethasone + indomethacin suppressed interleukin-1beta, tumor necrosis factor-alpha, and prostaglandins E2 and F2alpha but did not alter matrix metalloproteinase expression or chorioamnionitis.
  
  
  CONCLUSIONS
  The combination of ampicillin + dexamethasone + indomethacin suppressed inflammation and significantly prolonged gestation.
authors.affiliation: Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, WA 98195-6460, USA. gravettm@u.washington.edu
authors.forename: Michael G
authors.initials: MG
authors.lastname: Gravett
authors.forename: Kristina M
authors.initials: KM
authors.lastname: Adams
authors.forename: Drew W
authors.initials: DW
authors.lastname: Sadowsky
authors.forename: Alexandra R
authors.initials: AR
authors.lastname: Grosvenor
authors.forename: Steven S
authors.initials: SS
authors.lastname: Witkin
authors.forename: Michael K
authors.initials: MK
authors.lastname: Axthelm
authors.forename: Miles J
authors.initials: MJ
authors.lastname: Novy
mesh_terms: D000650:Amnion / Q000382:microbiology; D000653:Amniotic Fluid / Q000737:chemistry / Q000382:microbiology; D000667:Ampicillin / Q000627:therapeutic use*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002585:Cesarean Section; D002821:Chorioamnionitis; D002823:Chorion / Q000382:microbiology; D016207:Cytokines / Q000032:analysis; D003907:Dexamethasone / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000627:therapeutic use*; D007213:Indomethacin / Q000627:therapeutic use*; D008253:Macaca mulatta; D020780:Matrix Metalloproteinase 9 / Q000737:chemistry; D007752:Obstetric Labor, Premature / Q000517:prevention & control*; D011247:Pregnancy
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D005938:Glucocorticoids; D007155:Immunologic Factors; D000667:Ampicillin; D003907:Dexamethasone; D020780:Matrix Metalloproteinase 9; D007213:Indomethacin