Antoine Giraud1,2, Marie-Julie Allard3, Mariela Segura4, Frédéric Roche5, Hugues Patural5,6, Guillaume Sébire3. 1. Child Neurology Division, Department of Pediatrics, McGill University, Montreal, Québec, Canada, antoine.giraud@univ-st-etienne.fr. 2. EA 4607 SNA EPIS, Université de Lyon, Université Jean Monnet, Saint-Étienne, France, antoine.giraud@univ-st-etienne.fr. 3. Child Neurology Division, Department of Pediatrics, McGill University, Montreal, Québec, Canada. 4. Department of Infectiology and Microbiology, Faculté de Médecine Vétérinaire, Université de Montréal, Saint-Hyacinthe, Québec, Canada. 5. EA 4607 SNA EPIS, Université de Lyon, Université Jean Monnet, Saint-Étienne, France. 6. Neonatal Intensive Care Unit, Centre Hospitalier Universitaire de Saint-Étienne, Saint-Étienne, France.
Abstract
BACKGROUND: Antibiotic therapy during preterm labor with intact membranes has been associated with an increased risk of neonatal death. OBJECTIVES: Using an established rat model of group B Streptococcus (GBS)-induced chorioamnionitis, we hypothesized that ampicillin treatment increases placental inflammation, as shown in other bacterial infections. METHODS: At gestational day 19, 19 Lewis dams were intraperitoneally (i.p.) inoculated by 108 CFU of β-hemolytic serotype Ia GBS (strain #16955 susceptible to ampicillin). Dams were treated i.p. with either 200 mg/kg of ampicillin (n = 9) or 0.9% saline (n = 10) at 48 and 60 h post-GBS inoculation. Cesarean sections were performed 72 h post-GBS inoculation. RESULTS: Ampicillin treatment was associated with an increased number of polymorphonuclear cells (PMN) infiltrating the decidua (mean 1,536 vs. 532 PMN/mm2; p < 0.001) and a higher placental concentration of IL-1β (mean 26.4 vs. 7.9 pg/mg; p < 0.01) compared to saline-treated dams. These effects were observed in dams without GBS bacteremia. Conversely, ampicillin treatment was associated with a decreased placental concentration of proinflammatory cytokines in dams with GBS bacteremia. CONCLUSIONS: Ampicillin increases placental inflammation in a rat model of GBS-induced chorioamnionitis without bacteremia. This proinflammatory effect of ampicillin could be due to bacterial lysis. Our findings do not query the intrapartum antibiotic prophylaxis against GBS disease. They pave the way for future preclinical studies combining anti-inflammatory treatments and antibiotic therapy for GBS-induced chorioamnionitis.
BACKGROUND: Antibiotic therapy during preterm labor with intact membranes has been associated with an increased risk of neonatal death. OBJECTIVES: Using an established rat model of group B Streptococcus (GBS)-induced chorioamnionitis, we hypothesized that ampicillin treatment increases placental inflammation, as shown in other bacterial infections. METHODS: At gestational day 19, 19 Lewis dams were intraperitoneally (i.p.) inoculated by 108 CFU of β-hemolytic serotype Ia GBS (strain #16955 susceptible to ampicillin). Dams were treated i.p. with either 200 mg/kg of ampicillin (n = 9) or 0.9% saline (n = 10) at 48 and 60 h post-GBS inoculation. Cesarean sections were performed 72 h post-GBS inoculation. RESULTS:Ampicillin treatment was associated with an increased number of polymorphonuclear cells (PMN) infiltrating the decidua (mean 1,536 vs. 532 PMN/mm2; p < 0.001) and a higher placental concentration of IL-1β (mean 26.4 vs. 7.9 pg/mg; p < 0.01) compared to saline-treated dams. These effects were observed in dams without GBS bacteremia. Conversely, ampicillin treatment was associated with a decreased placental concentration of proinflammatory cytokines in dams with GBS bacteremia. CONCLUSIONS:Ampicillin increases placental inflammation in a rat model of GBS-induced chorioamnionitis without bacteremia. This proinflammatory effect of ampicillin could be due to bacterial lysis. Our findings do not query the intrapartum antibiotic prophylaxis against GBS disease. They pave the way for future preclinical studies combining anti-inflammatory treatments and antibiotic therapy for GBS-induced chorioamnionitis.