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LAS VEGAS – A randomized controlled trial comparing a single postdelivery intravenous dose of antibiotic after operative delivery found that antibiotics nearly halved the risk for maternal infection.
For women who received a single dose of amoxicillin-clavulanic acid, the risk ratio was 0.58 for suspected or confirmed infection, compared with those who received an intravenous dose of saline solution (95% confidence interval, 0.49-0.69, P less than .001). Culture-confirmed systemic infections were similarly reduced by a risk ratio (RR) of 0.44 (95% CI, 0.22-0.89; P =.018).
Superficial and deep incisional infections were also significantly less likely in the women who had received antibiotics (RRs 0.53 and 0.46, respectively; P less than .001 for both). Although sepsis occurred in numerically fewer women who received antibiotics, the numbers were, overall, small and not statistically significant.
By 6 weeks after delivery, patients receiving antibiotics were less likely to have outpatient or home visits for perineal problems or concerns as well (P less than .001).
“This trial shows clear benefit of a single dose of prophylactic antibiotic after operative vaginal birth, and this should be introduced into routine practice,” said Marian Knight, MBChB, DPhil.
Dr. Knight presented findings of the randomized trial, dubbed ANODE, at a late-breaking abstract session of the meeting, which was sponsored by the Society for Maternal-Fetal Medicine. Dr. Knight, professor of maternal and child population health at the University of Oxford (England), explained that ANODE aimed to determine whether a single dose of prophylactic amoxicillin-clavulanic acid was clinically effective in preventing confirmed or suspected maternal infection after operative vaginal birth.
The study tips the scales in favor of the anti-infective properties of the single antibiotic dose after operative delivery, and comes at a time when unacceptable levels of maternal morbidity and mortality coexist with pressing worries about antibiotic resistance, Dr. Knight said.
The multicenter randomized, blinded, placebo-controlled trial was conducted at 27 sites in the United Kingdom between March 2016 and June 2018.
Women at the study sites who underwent operative delivery, whether by forceps or vacuum extraction, received either a single dose of intravenous amoxicillin-clavulanic acid (1 gm/200 mg), or a placebo dose of saline solution. Antibiotics were given in the window of 0 to 6 hours post-delivery.
The primary outcome measure was confirmed or suspected maternal infection within 6 weeks of delivery. Women were positive for infection if they were prescribed antibiotics for perineal wound infections, if they experienced endometrial or uterine infections, if they had urinary tract infections with “systemic features, or if they had other systemic infections. Other criteria for infection were culture-confirmed systemic infection, or endometritis by criteria established by the Centers for Disease Control and Prevention.
Dr. Knight and her colleagues used an intention-to-treat analysis that looked at the primary outcome as a risk ratio, with a 95% CI. Secondary outcomes, also presented as risk ratios, were considered with a 99% CI.
A total of 3,427 women were randomized. In all, 1,715 women in the active arm and 1,705 in the placebo arm were included in the outcomes analyses. Women were interviewed by telephone, they completed questionnaires, and they received a questionnaire by mail or completed one online. Slightly more than 1,500 women in each arm completed the phone interview, and nearly 1,300 in each arm completed the initial questionnaire.
The mean age was 30 years, and most of the participants (84%-87%) were white. Most were of normal weight, with a median body mass index at the initial prenatal visit of 25 kg/m2.
Though women with multiple pregnancies were included in the study, just 11 in the active arm and 9 in the placebo arm delivered twins. There were no triplets. Most women (76%-78%) were primiparous, and just 7%-8% of women had prior cesarean delivery.
The mode of operative delivery for most of the participants (63%-67%) was forceps, with all but 10 of the remaining women receiving vacuum extraction (the remaining 10 had spontaneous vaginal deliveries).
The reasons for instrumental delivery were approximately evenly divided between failure of labor to progress and fetal compromise.
Nearly 90% of the women – more than 1,500 in each study arm – received episiotomies, a figure that Dr. Knight said she found surprising. She noted that mediolateral incisions are the standard of care in the United Kingdom. Still, 29%-33% of the women experienced a tear, with most being second-degree tears. Third- and fourth-degree tears occurred in two women overall. Almost all of the women (99%) had their wounds sutured.
Three serious adverse events were reported. One woman in the placebo arm required intensive care unit admission for severe sepsis, and another placebo participant required a transfusion after postpartum hemorrhage. One patient who received antibiotic had immediate diffuse itching and a swollen throat. However, antibiotic side effects were reported in only 2 of the 1,715 active arm participants, Dr. Knight said.
The competing concerns of maternal safety and antibiotic stewardship are weighed against a global backdrop of high maternal infection rates, Dr. Knight said. Sepsis causes 11% of global maternal deaths, a rate that drops to about 5% in higher-income nations. However, she pointed out, that figure rises to about 13% in the United States.
“For every woman that dies from pregnancy-related infection, a further 70 have severe infection and survive,” she said.
Known risk factors for infection include operative vaginal delivery and cesarean deliveries. For cesareans performed after the onset of labor, the adjusted odds ratio reaches 6.7 for severe infection, Dr. Knight said (PLoS Med. 2014;11:e1001672). A systematic review estimated that the rate for any infection following cesarean delivery approaches one in four women, she said (Cochrane Database Syst Rev. 2014 Oct 28;[10]:CD007482).
The same systematic review found that prophylactic antibiotics reduced incidence of wound infection, endometritis, and serious maternal wound infection after cesarean delivery (RR 0.40, 0.38, and 0.31, respectively).
For operative vaginal deliveries, however, a Cochrane review found one study of 393 women. Although no women given antibiotics developed endometritis compared with seven cases of endometritis in the no-antibiotics group for a RR of .07, the 95% confidence interval in the Cochrane analysis included zero, so the findings weren’t statistically significant. Hospital length of stay didn’t differ between the two groups (Cochrane Database Syst Rev. 2014 Oct 13;[10]:CD004455).
Citing this review, the United Kingdom’s Royal College of Gynecologists had concluded that evidence was insufficient to support routine antibiotic prophylaxis in operative deliveries. The American College of Obstetricians and Gynecologists make no mention of antibiotic prophylaxis or postdelivery infection in its guidelines for operative delivery, Dr. Knight said.
Since confirmed or suspected infection was still seen in 11% of women who received antibiotics, further analysis “is needed to investigate whether early administration, prenatal administration, or repeated administration is more likely to be effective,” she said. Women in the ANODE trial received their dose at a median of 3 hours after delivery.
“Until these analyses are completed, there is no indication for administration of more than a single dose of prophylactic antibiotic, or for predelivery administration,” she said.
Dr. Knight reported that ANODE was funded by the U.K.’s National Institute for Health Research. She reported that she had no conflicts of interest.
SOURCE: Knight M et al. Am J Obstet Gynecol. 2019 Jan;220;1:S685. Abstract LB 3.
LAS VEGAS – A randomized controlled trial comparing a single postdelivery intravenous dose of antibiotic after operative delivery found that antibiotics nearly halved the risk for maternal infection.
For women who received a single dose of amoxicillin-clavulanic acid, the risk ratio was 0.58 for suspected or confirmed infection, compared with those who received an intravenous dose of saline solution (95% confidence interval, 0.49-0.69, P less than .001). Culture-confirmed systemic infections were similarly reduced by a risk ratio (RR) of 0.44 (95% CI, 0.22-0.89; P =.018).
Superficial and deep incisional infections were also significantly less likely in the women who had received antibiotics (RRs 0.53 and 0.46, respectively; P less than .001 for both). Although sepsis occurred in numerically fewer women who received antibiotics, the numbers were, overall, small and not statistically significant.
By 6 weeks after delivery, patients receiving antibiotics were less likely to have outpatient or home visits for perineal problems or concerns as well (P less than .001).
“This trial shows clear benefit of a single dose of prophylactic antibiotic after operative vaginal birth, and this should be introduced into routine practice,” said Marian Knight, MBChB, DPhil.
Dr. Knight presented findings of the randomized trial, dubbed ANODE, at a late-breaking abstract session of the meeting, which was sponsored by the Society for Maternal-Fetal Medicine. Dr. Knight, professor of maternal and child population health at the University of Oxford (England), explained that ANODE aimed to determine whether a single dose of prophylactic amoxicillin-clavulanic acid was clinically effective in preventing confirmed or suspected maternal infection after operative vaginal birth.
The study tips the scales in favor of the anti-infective properties of the single antibiotic dose after operative delivery, and comes at a time when unacceptable levels of maternal morbidity and mortality coexist with pressing worries about antibiotic resistance, Dr. Knight said.
The multicenter randomized, blinded, placebo-controlled trial was conducted at 27 sites in the United Kingdom between March 2016 and June 2018.
Women at the study sites who underwent operative delivery, whether by forceps or vacuum extraction, received either a single dose of intravenous amoxicillin-clavulanic acid (1 gm/200 mg), or a placebo dose of saline solution. Antibiotics were given in the window of 0 to 6 hours post-delivery.
The primary outcome measure was confirmed or suspected maternal infection within 6 weeks of delivery. Women were positive for infection if they were prescribed antibiotics for perineal wound infections, if they experienced endometrial or uterine infections, if they had urinary tract infections with “systemic features, or if they had other systemic infections. Other criteria for infection were culture-confirmed systemic infection, or endometritis by criteria established by the Centers for Disease Control and Prevention.
Dr. Knight and her colleagues used an intention-to-treat analysis that looked at the primary outcome as a risk ratio, with a 95% CI. Secondary outcomes, also presented as risk ratios, were considered with a 99% CI.
A total of 3,427 women were randomized. In all, 1,715 women in the active arm and 1,705 in the placebo arm were included in the outcomes analyses. Women were interviewed by telephone, they completed questionnaires, and they received a questionnaire by mail or completed one online. Slightly more than 1,500 women in each arm completed the phone interview, and nearly 1,300 in each arm completed the initial questionnaire.
The mean age was 30 years, and most of the participants (84%-87%) were white. Most were of normal weight, with a median body mass index at the initial prenatal visit of 25 kg/m2.
Though women with multiple pregnancies were included in the study, just 11 in the active arm and 9 in the placebo arm delivered twins. There were no triplets. Most women (76%-78%) were primiparous, and just 7%-8% of women had prior cesarean delivery.
The mode of operative delivery for most of the participants (63%-67%) was forceps, with all but 10 of the remaining women receiving vacuum extraction (the remaining 10 had spontaneous vaginal deliveries).
The reasons for instrumental delivery were approximately evenly divided between failure of labor to progress and fetal compromise.
Nearly 90% of the women – more than 1,500 in each study arm – received episiotomies, a figure that Dr. Knight said she found surprising. She noted that mediolateral incisions are the standard of care in the United Kingdom. Still, 29%-33% of the women experienced a tear, with most being second-degree tears. Third- and fourth-degree tears occurred in two women overall. Almost all of the women (99%) had their wounds sutured.
Three serious adverse events were reported. One woman in the placebo arm required intensive care unit admission for severe sepsis, and another placebo participant required a transfusion after postpartum hemorrhage. One patient who received antibiotic had immediate diffuse itching and a swollen throat. However, antibiotic side effects were reported in only 2 of the 1,715 active arm participants, Dr. Knight said.
The competing concerns of maternal safety and antibiotic stewardship are weighed against a global backdrop of high maternal infection rates, Dr. Knight said. Sepsis causes 11% of global maternal deaths, a rate that drops to about 5% in higher-income nations. However, she pointed out, that figure rises to about 13% in the United States.
“For every woman that dies from pregnancy-related infection, a further 70 have severe infection and survive,” she said.
Known risk factors for infection include operative vaginal delivery and cesarean deliveries. For cesareans performed after the onset of labor, the adjusted odds ratio reaches 6.7 for severe infection, Dr. Knight said (PLoS Med. 2014;11:e1001672). A systematic review estimated that the rate for any infection following cesarean delivery approaches one in four women, she said (Cochrane Database Syst Rev. 2014 Oct 28;[10]:CD007482).
The same systematic review found that prophylactic antibiotics reduced incidence of wound infection, endometritis, and serious maternal wound infection after cesarean delivery (RR 0.40, 0.38, and 0.31, respectively).
For operative vaginal deliveries, however, a Cochrane review found one study of 393 women. Although no women given antibiotics developed endometritis compared with seven cases of endometritis in the no-antibiotics group for a RR of .07, the 95% confidence interval in the Cochrane analysis included zero, so the findings weren’t statistically significant. Hospital length of stay didn’t differ between the two groups (Cochrane Database Syst Rev. 2014 Oct 13;[10]:CD004455).
Citing this review, the United Kingdom’s Royal College of Gynecologists had concluded that evidence was insufficient to support routine antibiotic prophylaxis in operative deliveries. The American College of Obstetricians and Gynecologists make no mention of antibiotic prophylaxis or postdelivery infection in its guidelines for operative delivery, Dr. Knight said.
Since confirmed or suspected infection was still seen in 11% of women who received antibiotics, further analysis “is needed to investigate whether early administration, prenatal administration, or repeated administration is more likely to be effective,” she said. Women in the ANODE trial received their dose at a median of 3 hours after delivery.
“Until these analyses are completed, there is no indication for administration of more than a single dose of prophylactic antibiotic, or for predelivery administration,” she said.
Dr. Knight reported that ANODE was funded by the U.K.’s National Institute for Health Research. She reported that she had no conflicts of interest.
SOURCE: Knight M et al. Am J Obstet Gynecol. 2019 Jan;220;1:S685. Abstract LB 3.
LAS VEGAS – A randomized controlled trial comparing a single postdelivery intravenous dose of antibiotic after operative delivery found that antibiotics nearly halved the risk for maternal infection.
For women who received a single dose of amoxicillin-clavulanic acid, the risk ratio was 0.58 for suspected or confirmed infection, compared with those who received an intravenous dose of saline solution (95% confidence interval, 0.49-0.69, P less than .001). Culture-confirmed systemic infections were similarly reduced by a risk ratio (RR) of 0.44 (95% CI, 0.22-0.89; P =.018).
Superficial and deep incisional infections were also significantly less likely in the women who had received antibiotics (RRs 0.53 and 0.46, respectively; P less than .001 for both). Although sepsis occurred in numerically fewer women who received antibiotics, the numbers were, overall, small and not statistically significant.
By 6 weeks after delivery, patients receiving antibiotics were less likely to have outpatient or home visits for perineal problems or concerns as well (P less than .001).
“This trial shows clear benefit of a single dose of prophylactic antibiotic after operative vaginal birth, and this should be introduced into routine practice,” said Marian Knight, MBChB, DPhil.
Dr. Knight presented findings of the randomized trial, dubbed ANODE, at a late-breaking abstract session of the meeting, which was sponsored by the Society for Maternal-Fetal Medicine. Dr. Knight, professor of maternal and child population health at the University of Oxford (England), explained that ANODE aimed to determine whether a single dose of prophylactic amoxicillin-clavulanic acid was clinically effective in preventing confirmed or suspected maternal infection after operative vaginal birth.
The study tips the scales in favor of the anti-infective properties of the single antibiotic dose after operative delivery, and comes at a time when unacceptable levels of maternal morbidity and mortality coexist with pressing worries about antibiotic resistance, Dr. Knight said.
The multicenter randomized, blinded, placebo-controlled trial was conducted at 27 sites in the United Kingdom between March 2016 and June 2018.
Women at the study sites who underwent operative delivery, whether by forceps or vacuum extraction, received either a single dose of intravenous amoxicillin-clavulanic acid (1 gm/200 mg), or a placebo dose of saline solution. Antibiotics were given in the window of 0 to 6 hours post-delivery.
The primary outcome measure was confirmed or suspected maternal infection within 6 weeks of delivery. Women were positive for infection if they were prescribed antibiotics for perineal wound infections, if they experienced endometrial or uterine infections, if they had urinary tract infections with “systemic features, or if they had other systemic infections. Other criteria for infection were culture-confirmed systemic infection, or endometritis by criteria established by the Centers for Disease Control and Prevention.
Dr. Knight and her colleagues used an intention-to-treat analysis that looked at the primary outcome as a risk ratio, with a 95% CI. Secondary outcomes, also presented as risk ratios, were considered with a 99% CI.
A total of 3,427 women were randomized. In all, 1,715 women in the active arm and 1,705 in the placebo arm were included in the outcomes analyses. Women were interviewed by telephone, they completed questionnaires, and they received a questionnaire by mail or completed one online. Slightly more than 1,500 women in each arm completed the phone interview, and nearly 1,300 in each arm completed the initial questionnaire.
The mean age was 30 years, and most of the participants (84%-87%) were white. Most were of normal weight, with a median body mass index at the initial prenatal visit of 25 kg/m2.
Though women with multiple pregnancies were included in the study, just 11 in the active arm and 9 in the placebo arm delivered twins. There were no triplets. Most women (76%-78%) were primiparous, and just 7%-8% of women had prior cesarean delivery.
The mode of operative delivery for most of the participants (63%-67%) was forceps, with all but 10 of the remaining women receiving vacuum extraction (the remaining 10 had spontaneous vaginal deliveries).
The reasons for instrumental delivery were approximately evenly divided between failure of labor to progress and fetal compromise.
Nearly 90% of the women – more than 1,500 in each study arm – received episiotomies, a figure that Dr. Knight said she found surprising. She noted that mediolateral incisions are the standard of care in the United Kingdom. Still, 29%-33% of the women experienced a tear, with most being second-degree tears. Third- and fourth-degree tears occurred in two women overall. Almost all of the women (99%) had their wounds sutured.
Three serious adverse events were reported. One woman in the placebo arm required intensive care unit admission for severe sepsis, and another placebo participant required a transfusion after postpartum hemorrhage. One patient who received antibiotic had immediate diffuse itching and a swollen throat. However, antibiotic side effects were reported in only 2 of the 1,715 active arm participants, Dr. Knight said.
The competing concerns of maternal safety and antibiotic stewardship are weighed against a global backdrop of high maternal infection rates, Dr. Knight said. Sepsis causes 11% of global maternal deaths, a rate that drops to about 5% in higher-income nations. However, she pointed out, that figure rises to about 13% in the United States.
“For every woman that dies from pregnancy-related infection, a further 70 have severe infection and survive,” she said.
Known risk factors for infection include operative vaginal delivery and cesarean deliveries. For cesareans performed after the onset of labor, the adjusted odds ratio reaches 6.7 for severe infection, Dr. Knight said (PLoS Med. 2014;11:e1001672). A systematic review estimated that the rate for any infection following cesarean delivery approaches one in four women, she said (Cochrane Database Syst Rev. 2014 Oct 28;[10]:CD007482).
The same systematic review found that prophylactic antibiotics reduced incidence of wound infection, endometritis, and serious maternal wound infection after cesarean delivery (RR 0.40, 0.38, and 0.31, respectively).
For operative vaginal deliveries, however, a Cochrane review found one study of 393 women. Although no women given antibiotics developed endometritis compared with seven cases of endometritis in the no-antibiotics group for a RR of .07, the 95% confidence interval in the Cochrane analysis included zero, so the findings weren’t statistically significant. Hospital length of stay didn’t differ between the two groups (Cochrane Database Syst Rev. 2014 Oct 13;[10]:CD004455).
Citing this review, the United Kingdom’s Royal College of Gynecologists had concluded that evidence was insufficient to support routine antibiotic prophylaxis in operative deliveries. The American College of Obstetricians and Gynecologists make no mention of antibiotic prophylaxis or postdelivery infection in its guidelines for operative delivery, Dr. Knight said.
Since confirmed or suspected infection was still seen in 11% of women who received antibiotics, further analysis “is needed to investigate whether early administration, prenatal administration, or repeated administration is more likely to be effective,” she said. Women in the ANODE trial received their dose at a median of 3 hours after delivery.
“Until these analyses are completed, there is no indication for administration of more than a single dose of prophylactic antibiotic, or for predelivery administration,” she said.
Dr. Knight reported that ANODE was funded by the U.K.’s National Institute for Health Research. She reported that she had no conflicts of interest.
SOURCE: Knight M et al. Am J Obstet Gynecol. 2019 Jan;220;1:S685. Abstract LB 3.
REPORTING FROM THE PREGNANCY MEETING