Immunomodulators plus antibiotics delay preterm delivery after experimental intraamniotic infection in a nonhuman primate model.
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.
Gravett
Michael G
MG
Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, WA 98195-6460, USA. gravettm@u.washington.edu
Adams
Kristina M
KM
Sadowsky
Drew W
DW
Grosvenor
Alexandra R
AR
Witkin
Steven S
SS
Axthelm
Michael K
MK
Novy
Miles J
MJ
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
D000900:Anti-Bacterial Agents; D016207:Cytokines; D005938:Glucocorticoids; D007155:Immunologic Factors; D000667:Ampicillin; D003907:Dexamethasone; D020780:Matrix Metalloproteinase 9; D007213:Indomethacin