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. Study Design: After contraction onset that was induced by group B Streptococcus (10⁶ 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-1β, tumor necrosis factor-α, and prostaglandins E₂ and F_2α but did not alter matrix metalloproteinase expression or chorioamnionitis. Conclusion: The combination of ampicillin + dexamethasone + indomethacin suppressed inflammation and significantly prolonged gestation.