TABLE 1.

Randomized controlled trials that assessed the use of antibiotics in women with clinical chorioamnionitis

First author, year (country)	Interventions (sample size)	Main outcome (definition)	Main findings
Intrapartum vs. postpartum treatment
Gibbs, 198899 (United States)	(1) Intrapartum treatment: ampicillin 2 g IV every 6 hours and gentamicin 1.5 mg/kg IV every 8 hours, beginning at the time of diagnosis of chorioamnionitis, until afebrile for approximately 48 hours (N=26) (2) Postpartum treatment: ampicillin 2 g IV every 6 hours and gentamicin 1.5 mg/kg IV every 8 hours immediately after cord clamping, until afebrile for approximately 48 hours (N=19) Patients delivered by cesarean section also received clindamycin 900 mg IV every 8 hours, beginning after cord clamping	Neonatal sepsis (bacteremia or death with a clinical diagnosis of sepsis and positive peripheral cultures) and pneumonia	Intrapartum treatment, as compared with immediate postpartum treatment, was associated with a significant decrease in the risk of neonatal pneumonia or sepsis (0.0% vs. 31.6%; RR 0.06, 95% CI 0.000.95; P = 0.046), mean neonatal hospital stay (3.8 days vs. 5.7 days; MD −1.9 days, 95% CI −0.4 to −3.4 days; P = 0.02), and mean maternal postpartum hospital stay (4.0 days vs. 5.0 days; MD −1.0 days, 95% CI 0.1 to −1.9 days; P = 0.04), and a non-significant reduction in the risk of neonatal sepsis (0.0% vs. 21.1%; RR 0.08, 95% CI 0.00–1.44; P = 0.09)
Intrapartum treatment
Scalambrino, 1989100 (Italy)	(1) Ampicillin/sulbactam 3 g IV every 6 hours for at least 72 h (N=11) (2) Cefotetan 2 g IV every 12 hours for at least 72 h (N=8)	Ineffective treatment (signs and symptoms and/or temperature curve remained unchanged or rose during the first 72 hours of treatment)	Treatment was effective in 100% of women in both antibiotic regimens
Maberry, 1991101 (United States)	(1) Ampicillin plus gentamicin (dual antibiotic regimen) (N=69) (2) Ampicillin plus gentamicin plus clindamycin (triple antibiotic regimen) (N=64) Dosage not reported. Antibiotics were administered for 24–48 hours after delivery and stopped if the patient remained afebrile	Endometritis	There were no significant differences between the dual antibiotic and triple antibiotic regimens in the risk of endometritis (14.5% vs. 7.8%; RR 1.86, 95% CI 0.67–5.14; P = 0.23) and neonatal sepsis (1.5% vs. 3.1%; RR 0.46, 95% CI 0.04–4.99; P = 0.53). The frequencies of other adverse neonatal outcomes did not significantly differ between the study groups
Locksmith, 2005102 (United States)	(1) Ampicillin 2 g IV every 6 hours plus gentamicin 5.1 mg/kg IV every 24 hours (once-daily dosing) (N=18) (2) Ampicillin 2 g IV every 6 hours plus gentamicin 120 mg IV followed by 80 mg IV every 8 hours (thrice-daily dosing) (N=20)	Maternal and umbilical cord serum peak gentamicin concentrations	Median maternal and umbilical cord serum peak gentamicin concentrations were higher with once-daily dosing compared with thrice-daily dosing. There were no significant differences between the once-daily and thrice-daily dosing groups in the risk of puerperal metritis (5.6% vs. 5.0%; RR 1.11, 95% CI 0.07–16.49; P = 0.94) and suspected neonatal sepsis (16.7% vs. 25.0%, RR 0.67, 95% CI 0.19–2.40; P = 0.54). The frequencies of other adverse maternal and neonatal outcomes did not significantly differ between the study groups
Lyell, 2010103 (United States)	(1) Ampicillin 2 grams IV every 6 hours for 4 doses total plus oncedaily gentamicin (5 mg/kg IV, then 2 placebo doses IV after 8 and 16 hours) (N=62) (2) Ampicillin 2 grams IV every 6 hours for 4 doses total plus thrice-daily gentamicin (2 mg/kg IV, then 1.5 mg/kg IV after 8 and 16 hours) (N=63) Patients delivered by cesarean section also received clindamycin 900 mg IV every 8 hours, for 3 doses total	Treatment success (resolution of chorioamnionitis after 16 hours of treatment without development of endometritis)	The frequency of treatment success did not significantly differ between the once-daily and thrice-daily gentamicin groups (93.6% vs. 88.9%; RR 1.05, 95% CI 0.94–1.17: P = 0.36). Once-daily gentamicin was noninferior to thrice-daily gentamicin because the range of risk difference (5.2% to 14.5%) fell within the predefined margin (15%). There were no significant differences between the study groups in the risk of endometritis (6.5% vs. 7.9%; RR 0.81, 95% CI 0.23–2.89; P = 0.75), neonatal sepsis (6.5% vs. 3.2%; RR 2.03, 95% CI 0.39–10.70; P = 0.40), and other adverse maternal and neonatal outcomes
Greenberg, 2015104 (United States)	(1) Ampicillin/sulbactam 3 g IV every 6 hours plus IV normal saline placebo dose every 8 hours until 24 hours postdelivery (N=43) (1) Ampicillin 2 g IV every 6 hours plus gentamicin 1.5 mg/kg IV every 8 hours until 24 hours postdelivery (N=49) Patients delivered by cesarean section also received clindamycin IV (dosage not reported) at the time of umbilical cord clamping, which was continued as part of the antibiotic regimen	Postpartum composite morbidity (any of the following: endometritis, sepsis, pneumonia, blood transfusion or ileus); postpartum infectious morbidity (any of the following: endometritis, sepsis, or pneumonia); and neonatal sepsis	There were no significant differences between the ampicillin/sulbactam and ampicillin plus gentamicin groups in the frequency of postpartum composite morbidity (0.0% vs. 12.2%; RR 0.09, 95% CI 0.01–1.51; P = 0.09), postpartum infectious morbidity (0.0% vs. 8.2%; RR 0.13, 95% CI 0.01–2.28; P = 0.16), and neonatal sepsis (2.3% vs. 4.1%; RR 0.57, 95% CI 0.05–6.07; P = 0.64)
Postpartum treatment
Berry, 1994105 (United States)	(1) Ampicillin 2 g IV plus gentamicin 2.0 mg/kg IV at the time of diagnosis of clinical chorioamnionitis. After vaginal delivery, ampicillin 2 g IV every 6 hours for 8 doses plus gentamicin 2.0 mg/kg IV every 8 hours for 6 doses (N=21) (2) Ampicillin 2 g IV plus gentamicin 2.0 mg/kg IV at the time of diagnosis of clinical chorioamnionitis. After vaginal delivery, normal saline on an identical dosing schedule (placebo) (N=17)	Treatment failure (temperature >38 °C after the first postpartum antibiotic or placebo dose)	There was no significant difference between the antibiotic and placebo groups in the frequency of treatment failure (4.8% vs. 5.9%, RR 0.81, 95% CI 0.05–12.01; P = 0.88). There were no cases of endometritis, wound infection, or sepsis
Chapman, 1997106 (United States)	(1) Ampicillin plus gentamicin during the intrapartum period (dosage not reported). After vaginal delivery, cefotetan 2 g IV single dose (N=55) (2) Ampicillin plus gentamicin during the intrapartum period (dosage not reported). After vaginal delivery, cefotetan 2 g IV every 12 hours for at least 48 h (N=54)	Interval from delivery to discharge and failed therapy (any of the following: (1) two temperatures ≥38 °C [single dose group] or ≥38.9 °C [multiple dose group] ≥4 hours apart; or (2) a single temperature ≥38.9 °C >4 hours after delivery [single dose group] or ≥38 °C >24 hours after delivery [multiple dose group]; or (3) postpartum readmission for endometritis)	There was no significant difference between the study groups in the frequency of failed therapy (10.9% vs. 3.7%; RR 2.95, 95% CI 0.62–13.96; P = 0.17). The median interval from delivery to discharge was 24 hours shorter in the single dose group (33 hours, range I6–190) than in the multiple dose group (57 hours, range 36–190) (P = 0.0001).
Mitra, 1997107 (United States)	(1) Gentamicin 4 mg/kg IV every 24 hours plus clindamycin 1200 mg IV every 12 hours after delivery (N=65) (2) Gentamicin 1.33 mg/kg IV plus clindamycin 800 mg IV every 8 hours after delivery (N=66) There was no report on antibiotics used in the intrapartum period	Cure (an average temperature of ≤37.2 °C for 24 hours and the resolution of symptoms); failure (a persistently elevated temperature 72 hours after the initiation of antibiotic therapy, clinical deterioration, or the need for additional antibiotic or heparin therapy); and duration and cost of treatment	There were no significant differences between the two treatment groups in the frequency of cure (93.9% vs. 93.9%; RR 1.00, 95% CI 0.92–1.09; P = 0.98) and failure (6.1% vs. 6.1%, RR 1.02, 95% CI 0.27–3.89; P = 0.98). The group receiving once-daily gentamicin dosing with twice-daily clindamycin dosing had a shorter mean treatment duration (2.0 days) and a lower mean treatment cost (US $251) than the group receiving thrice-daily dosing of gentamicin and clindamycin (2.3 days and US $442, respectively; P = 0.04 and 0.0001, respectively)
Adashek, 1998108 (United States)	(1) Gentamicin plus clindamycin after vaginal delivery. Dosage and duration of treatment were not reported (N=127) (2) Placebo after vaginal delivery (N=123) There was no report on antibiotics used in the intrapartum period	Treatment failure (persistent fever after the third dose of the study drug or readmission for endomyometritis)	There was no significant difference between the antibiotic and placebo groups in the frequency of treatment failure (1.6% vs. 3.3%; RR 0.48, 95% CI 0.09–2.60; P = 0.40)
Turnquest, 1998109 (United States)	(1) Ampicillin 2 g IV every 6 hours. Preoperative gentamicin 2 mg/kg IV plus clindamycin 900 mg IV. After cesarean delivery, gentamicin 1.5 mg/kg IV plus clindamycin 900 mg IV every 8 hours until afebrile for a minimum of 24 hours (N=55) (2) Ampicillin 2 g IV every 6 hours. Preoperative gentamicin 2 mg/kg IV plus clindamycin 900 mg IV. No antibiotics after cesarean delivery (N=61)	Endometritis	There was no significant difference between the postoperative antibiotic and no postoperative antibiotic groups in the risk of endometritis (21.8% vs. 14.8%; RR 1.48, 95% CI 0.68–3.24; P=0.33). The frequencies of other adverse maternal and neonatal outcomes did not significantly differ between the study groups.
Edwards, 2003110 (United States)	(1) Ampicillin 2 g IV every 6 hours and gentamicin 1.5 mg/kg IV every 8 hours at the time of diagnosis of chorioamnionitis. After delivery, ampicillin 2 g IV plus gentamicin 1.5 mg/kg IV, single additional dose. Patients delivered by cesarean section received clindamycin 900 mg IV single dose at the time of umbilical cord clamping (N=151) (2) Ampicillin 2 g IV every 6 hours and gentamicin 1.5 mg/kg IV every 8 hours at the time of diagnosis of chorioamnionitis. After delivery, ampicillin 2 g IV every 6 hours plus gentamicin 1.5 mg/kg IV every 8 hours until afebrile and asymptomatic for 24 hours. Patients delivered by cesarean section received clindamycin 900 mg IV at the time of umbilical cord clamping, then every 8 hours until antibiotics were discontinued (N=141)	Treatment failure (a single temperature after the first postpartum dose of antibiotics ≥39.0 °C, or two temperatures ≥38.4 °C at least 4 hours apart)	There was no significant difference between the single antibiotic dose and the continued use of antibiotics groups continued antibiotic regimen and the single additional dose groups in the frequency of treatment failure (4.6% vs 3.5%; RR 1.31, 95% CI 0.42–4.02; P = 0.64). The frequencies of wound infection (0.7% vs. 1.3%) and pelvic abscess (0.0% vs. 0.7%) did not significantly differ between the study groups
Shanks, 2016111 (United States)	(1) Ampicillin 2 g IV every 6 hours and gentamicin 1.5 mg/kg IV every 8 hours until cesarean delivery, plus preoperative clindamycin 900 mg IV. After cesarean delivery, one additional dose of gentamicin 1.5 mg/kg IV and clindamycin 900 mg IV (N=41) (2) Ampicillin 2 g IV every 6 hours and gentamicin 1.5 mg/kg IV every 8 hours until cesarean delivery, plus preoperative clindamycin 900 mg IV. No antibiotics after cesarean delivery (N=39)	Endometritis	There was no significant difference in the frequency of endometritis between women who received one additional dose of antibiotics after cesarean delivery and those who did not receive postoperative antibiotics (9.8% vs. 7.7%; RR 1.27, 95% CI 0.30–5.31; P = .74). The frequency of wound infection (17.1% vs. 5.1%, P = .12) and median length of hospital stay (4 days vs. 4 days, P = .88) did not significantly differ between the study groups. Neonatal outcomes were similar between the two study groups
Goldberg, 2017112 (United States)	(1) Single antibiotic dose after vaginal delivery (N=23) (2) Antibiotics until afebrile for 24 hours after vaginal delivery (N=23) There was no report on antibiotics used in both intrapartum and postpartum periods	Endometritis	“There were no significant differences for length of stay and no participants experienced treatment failures requiring resumption of antibiotics for endometritis or fevers”

CI, confidence interval; IV, intravenously; MD, mean difference; RR, relative risk