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Immunomodulators plus antibiotics delay preterm delivery after experimental intraamniotic infection in a nonhuman primate model

2007; Elsevier BV; Volume: 197; Issue: 5 Linguagem: Inglês

10.1016/j.ajog.2007.03.064

1097-6868

Michael G. Gravett, Kristina M. Adams Waldorf, Drew W. Sadowsky, Alexandra Grosvenor, Steven S. Witkin, Michael K. Axthelm, Miles J. Novy,

Neonatal Respiratory Health Research

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 F2α but did not alter matrix metalloproteinase expression or chorioamnionitis. Conclusion The combination of ampicillin + dexamethasone + indomethacin suppressed inflammation and significantly prolonged gestation. 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. 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. 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 F2α but did not alter matrix metalloproteinase expression or chorioamnionitis. The combination of ampicillin + dexamethasone + indomethacin suppressed inflammation and significantly prolonged gestation.