Project Details
Description
Maternal complications during pregnancy and childbirth are a global concern, resulting in high maternal mortality.1 Globally, an estimated 287,000 maternal deaths occurred in 2020, translating to 800 women dying daily from pregnancy and childbirth complications, equivalent to one every two minutes.2 Almost 95% of these deaths are in low-income and middle-income countries (LMICs), and about 70% of global maternal deaths are in Sub-Saharan Africa (SSA).2 In 2020, Nigeria alone accounted for almost 30% of all estimated global maternal deaths, with 82,000 annual deaths and 1,047 maternal deaths per 100,000 live births.2 This reflects the inequalities in accessing quality healthcare services during pregnancy, childbirth, and post-partum periods within the world's regions.
Post-partum hemorrhage, hypertensive disorders, and sepsis are the top three leading maternal complications, accounting for over half of maternal deaths worldwide.1 Maternal sepsis, an "organ dysfunction resulting from infection during pregnancy, childbirth, post-abortion or in the post-partum period," 3 is responsible for 10% of all global maternal deaths if not promptly diagnosed and treated.1,4,5 Maternal sepsis before and during childbirth has also been associated with neonatal complications such as neonatal sepsis and death.6–8 Neonatal sepsis is another significant cause of neonatal mortality,9,10 responsible for 10%-17% of neonatal deaths globally.9,11 Consistent with the global data, maternal and neonatal sepsis are among the leading causes of maternal and neonatal deaths in LMICs, particularly SSA9,12–14 and Nigeria.15–20 Beyond these deaths, women who experience peripartum infections face severe morbidities and long-term disabilities such as chronic pelvic pain, ectopic pregnancy, and secondary infertility.5,7 Also, the widespread and inappropriate prescription and use of antibiotics in women during labor and birth continue to contribute to the burden of antimicrobial resistance in LMICs.21–23 Thus, a need to prioritize maternal infection prevention in LMICs, as it poses a major threat to global health.
To reduce maternal deaths, the World Health Organization (WHO) in 2015 recommended the use of antibiotics around birth to prevent and treat maternal peripartum infection in five clinical situations: (1) women with group B streptococcus (GBS) colonization to prevent early neonatal GBS infection; (2) preterm pre-labor rupture of membranes (PPROM); (3) delivery by cesarean section (CS); (4) repair of third/fourth-degree perineal tear; and (5) manual placental removal.7 Several trials have widely used prophylactic antibiotics to prevent maternal sepsis during the peripartum period, especially for cesarean section.21,24–26 However, implementation gaps exist due to wide variation in clinical practice, dosing regimen, cost, limited antimicrobial availability and diagnostic capabilities, inappropriate antibiotic prescription, dispensing, consumption, and use contributing to the emergence and dissemination of antimicrobial resistance and side effects.21,23,27–30 Antibiotics such as cephalosporin and erythromycin have been recommended as antimicrobial prophylaxis for cesarean section and PPROM, respectively.31 However, there are notable deviations from this practice, with several examples of prolonged and multidrug regimens, higher adverse effects, poor compliance, and the emergence of antimicrobial resistance to gram-positive and gram-negative bacteria.21,32,33
Azithromycin, an inexpensive broad-spectrum macrolide antibiotic, is effective against gram-positive and gram-negative bacteria.34–36 responsible for maternal sepsis in SSA.37–42 Besides its broad-spectrum activity, its prolonged half-life, high-sustained antibiotic levels in placental tissues, ease of administration, decreased cost, better compliance and side effects, and pharmacokinetic profile make it an attractive agent than erythromycin 32,43 and preventing maternal infections during labor and delivery,34,44 PPROM,45 and planned cesarean delivery.46–48 These features make Azithromycin a suitable treatment to implement for vaginal deliveries. Azithromycin administered during pregnancy has reduced the risk of low birth weight and prematurity in malaria-endemic settings,34 and has been used to treat sexually transmitted infections, toxoplasmosis, and malaria.32,34 However, in a placebo-controlled randomized trial of 2,297 pregnant women given oral azithromycin (1g) at 16–24 and 28–32 week gestation in Southern Malawi, the findings do not support the use of antibiotics as routine prophylaxis to prevent preterm birth in high-risk populations.49 High-quality studies are therefore needed to assess the effect of azithromycin in pregnancy on neonatal complications.50 The effectiveness of oral azithromycin given during pregnancy and labor on stillbirth and skin and soft tissue infections in infants is ongoing in Mali and Fiji, respectively.51,52
The WHO only recommends routine antibiotics prophylaxis for women undergoing operative vaginal birth.53 However, several studies have investigated using azithromycin to prevent maternal infections during vaginal delivery. A double-blind, placebo-controlled randomized trial among 829 mothers in Gambia showed that an oral dose of azithromycin (2g) administered during vaginal delivery reduced GBS, Staphylococcus aureus, and Streptococcus pneumoniae carriage in mothers and newborns by 60%,54 and also reduced maternal (occurrence of fever, mastitis, and widespread infections) and infant (skin and overall infections) infections by 60% and 24%, respectively up to eight weeks post-intervention.55 The study was conducted in a government facility without immediate access to emergency obstetric interventions and less frequent use of antibiotics in usual care.55 In a recent multi-country (Bangladesh, Democratic Republic of the Congo, Guatemala, India, Kenya, Pakistan, and Zambia), placebo-controlled, randomized trial involving 29,278 women, a single 2g oral dose of azithromycin before a vaginal delivery reduced the risk of maternal sepsis or death by 33% than placebo, but did not reduce the risk of sepsis or death in newborns.8 This maternal outcome was driven by a reduction in sepsis by 35%.8 Another recent multi-country double-blind, placebo-controlled, randomized clinical trial in Gambia and Burkina Faso among 11,983 women found that 2g of azithromycin administered orally during labor did not reduce neonatal sepsis or mortality.56 However, noninvasive infections during the subsequent four weeks were reduced for newborns (skin infections) and mothers (puerperal fever and mastitis) in the azithromycin group.56 Thus, the study did not support the routine introduction of oral intrapartum azithromycin to reduce neonatal sepsis or mortality.56 Conversely, a multicenter, three-group, double-blind, randomized controlled trial in Cameroun found that a single dose of oral azithromycin (1g) with or without 2g of amoxicillin for prolonged labor or rupture of membranes at term did not significantly reduce maternal peripartum or neonatal infection or death.57 This was attributed to lower-than-expected infection rates and the frequent use of antibiotics in routine care.57 The study was implemented in settings with a high level of care and adequate resources (i.e., access to emergency obstetric interventions, cesarean birth, antibiotics, and referral hospitals) and high antibiotic usage.57 Meanwhile, there are concerns about the potential harms of adding routine azithromycin for vaginal deliveries in LMICs, such as increased antimicrobial resistance, effects of changes to the maternal or neonatal microbiome, drug side effects, and costs, requiring further research.8,21 While studies have not established the significant associations between a single azithromycin dose and the development of antibiotic resistance, more research is required to investigate the effects of regular use of azithromycin prophylaxis during vaginal delivery.8
Evidence exists on the barriers and facilitators of implementing interventions to improve appropriate antibiotic use in LMICs.23 23 However, there is no evidence on factors that influence the effects and implementation of azithromycin use in vaginal delivery to inform its generalizability and replicability in other settings and contexts,8,34 and women's needs and perspectives to support updating the WHO recommendations for antibiotics to prevent maternal infection in LMICs, especially SSA.21,24,57 There is also no evidence on the best strategy to routinely implement azithromycin to prevent sepsis or death during vaginal delivery.
Studies have recommended aligning implementation strategies with improvement approaches and healthcare systems' existing culture, infrastructure, and practices to effectively integrate evidence-based interventions into routine practice.58,59 Implementation strategies are methods or techniques used to enhance the adoption, implementation, and sustainability of an evidence-based intervention.60 Plan-Do-Study-Act (PDSA), an intervention in improvement science, is used as an implementation strategy in implementation science to quickly identify issues, determine necessary changes, measure the impact of those changes, and make an informed plan for improvement.58,61–64 They are widely used to improve quality healthcare delivery in routine practices and address barriers and needed changes in implementation and outcome efforts within local contexts and LMICs, including Nigeria.58,61,63,65–68 This is given to its iterative nature of assessing change through a structured experimental learning approach.63,66 However, there is no evidence of how the PDSA process can be applied to pragmatic trials and healthcare providers' (HCPs) perceptions of their use to facilitate the integration of evidence-based interventions into their everyday care processes. 61
Maternal complications during pregnancy and childbirth are a global concern, resulting in high maternal mortality.1 Globally, an estimated 287,000 maternal deaths occurred in 2020, translating to 800 women dying daily from pregnancy and childbirth complications, equivalent to one every two minutes.2 Almost 95% of these deaths are in low-income and middle-income countries (LMICs), and about 70% of global maternal deaths are in Sub-Saharan Africa (SSA).2 In 2020, Nigeria alone accounted for almost 30% of all estimated global maternal deaths, with 82,000 annual deaths and 1,047 maternal deaths per 100,000 live births.2 This reflects the inequalities in accessing quality healthcare services during pregnancy, childbirth, and post-partum periods within the world's regions.
Post-partum hemorrhage, hypertensive disorders, and sepsis are the top three leading maternal complications, accounting for over half of maternal deaths worldwide.1 Maternal sepsis, an "organ dysfunction resulting from infection during pregnancy, childbirth, post-abortion or in the post-partum period," 3 is responsible for 10% of all global maternal deaths if not promptly diagnosed and treated.1,4,5 Maternal sepsis before and during childbirth has also been associated with neonatal complications such as neonatal sepsis and death.6–8 Neonatal sepsis is another significant cause of neonatal mortality,9,10 responsible for 10%-17% of neonatal deaths globally.9,11 Consistent with the global data, maternal and neonatal sepsis are among the leading causes of maternal and neonatal deaths in LMICs, particularly SSA9,12–14 and Nigeria.15–20 Beyond these deaths, women who experience peripartum infections face severe morbidities and long-term disabilities such as chronic pelvic pain, ectopic pregnancy, and secondary infertility.5,7 Also, the widespread and inappropriate prescription and use of antibiotics in women during labor and birth continue to contribute to the burden of antimicrobial resistance in LMICs.21–23 Thus, a need to prioritize maternal infection prevention in LMICs, as it poses a major threat to global health.
To reduce maternal deaths, the World Health Organization (WHO) in 2015 recommended the use of antibiotics around birth to prevent and treat maternal peripartum infection in five clinical situations: (1) women with group B streptococcus (GBS) colonization to prevent early neonatal GBS infection; (2) preterm pre-labor rupture of membranes (PPROM); (3) delivery by cesarean section (CS); (4) repair of third/fourth-degree perineal tear; and (5) manual placental removal.7 Several trials have widely used prophylactic antibiotics to prevent maternal sepsis during the peripartum period, especially for cesarean section.21,24–26 However, implementation gaps exist due to wide variation in clinical practice, dosing regimen, cost, limited antimicrobial availability and diagnostic capabilities, inappropriate antibiotic prescription, dispensing, consumption, and use contributing to the emergence and dissemination of antimicrobial resistance and side effects.21,23,27–30 Antibiotics such as cephalosporin and erythromycin have been recommended as antimicrobial prophylaxis for cesarean section and PPROM, respectively.31 However, there are notable deviations from this practice, with several examples of prolonged and multidrug regimens, higher adverse effects, poor compliance, and the emergence of antimicrobial resistance to gram-positive and gram-negative bacteria.21,32,33
Azithromycin, an inexpensive broad-spectrum macrolide antibiotic, is effective against gram-positive and gram-negative bacteria.34–36 responsible for maternal sepsis in SSA.37–42 Besides its broad-spectrum activity, its prolonged half-life, high-sustained antibiotic levels in placental tissues, ease of administration, decreased cost, better compliance and side effects, and pharmacokinetic profile make it an attractive agent than erythromycin 32,43 and preventing maternal infections during labor and delivery,34,44 PPROM,45 and planned cesarean delivery.46–48 These features make Azithromycin a suitable treatment to implement for vaginal deliveries. Azithromycin administered during pregnancy has reduced the risk of low birth weight and prematurity in malaria-endemic settings,34 and has been used to treat sexually transmitted infections, toxoplasmosis, and malaria.32,34 However, in a placebo-controlled randomized trial of 2,297 pregnant women given oral azithromycin (1g) at 16–24 and 28–32 week gestation in Southern Malawi, the findings do not support the use of antibiotics as routine prophylaxis to prevent preterm birth in high-risk populations.49 High-quality studies are therefore needed to assess the effect of azithromycin in pregnancy on neonatal complications.50 The effectiveness of oral azithromycin given during pregnancy and labor on stillbirth and skin and soft tissue infections in infants is ongoing in Mali and Fiji, respectively.51,52
The WHO only recommends routine antibiotics prophylaxis for women undergoing operative vaginal birth.53 However, several studies have investigated using azithromycin to prevent maternal infections during vaginal delivery. A double-blind, placebo-controlled randomized trial among 829 mothers in Gambia showed that an oral dose of azithromycin (2g) administered during vaginal delivery reduced GBS, Staphylococcus aureus, and Streptococcus pneumoniae carriage in mothers and newborns by 60%,54 and also reduced maternal (occurrence of fever, mastitis, and widespread infections) and infant (skin and overall infections) infections by 60% and 24%, respectively up to eight weeks post-intervention.55 The study was conducted in a government facility without immediate access to emergency obstetric interventions and less frequent use of antibiotics in usual care.55 In a recent multi-country (Bangladesh, Democratic Republic of the Congo, Guatemala, India, Kenya, Pakistan, and Zambia), placebo-controlled, randomized trial involving 29,278 women, a single 2g oral dose of azithromycin before a vaginal delivery reduced the risk of maternal sepsis or death by 33% than placebo, but did not reduce the risk of sepsis or death in newborns.8 This maternal outcome was driven by a reduction in sepsis by 35%.8 Another recent multi-country double-blind, placebo-controlled, randomized clinical trial in Gambia and Burkina Faso among 11,983 women found that 2g of azithromycin administered orally during labor did not reduce neonatal sepsis or mortality.56 However, noninvasive infections during the subsequent four weeks were reduced for newborns (skin infections) and mothers (puerperal fever and mastitis) in the azithromycin group.56 Thus, the study did not support the routine introduction of oral intrapartum azithromycin to reduce neonatal sepsis or mortality.56 Conversely, a multicenter, three-group, double-blind, randomized controlled trial in Cameroun found that a single dose of oral azithromycin (1g) with or without 2g of amoxicillin for prolonged labor or rupture of membranes at term did not significantly reduce maternal peripartum or neonatal infection or death.57 This was attributed to lower-than-expected infection rates and the frequent use of antibiotics in routine care.57 The study was implemented in settings with a high level of care and adequate resources (i.e., access to emergency obstetric interventions, cesarean birth, antibiotics, and referral hospitals) and high antibiotic usage.57 Meanwhile, there are concerns about the potential harms of adding routine azithromycin for vaginal deliveries in LMICs, such as increased antimicrobial resistance, effects of changes to the maternal or neonatal microbiome, drug side effects, and costs, requiring further research.8,21 While studies have not established the significant associations between a single azithromycin dose and the development of antibiotic resistance, more research is required to investigate the effects of regular use of azithromycin prophylaxis during vaginal delivery.8
Evidence exists on the barriers and facilitators of implementing interventions to improve appropriate antibiotic use in LMICs.23 23 However, there is no evidence on factors that influence the effects and implementation of azithromycin use in vaginal delivery to inform its generalizability and replicability in other settings and contexts,8,34 and women's needs and perspectives to support updating the WHO recommendations for antibiotics to prevent maternal infection in LMICs, especially SSA.21,24,57 There is also no evidence on the best strategy to routinely implement azithromycin to prevent sepsis or death during vaginal delivery.
Studies have recommended aligning implementation strategies with improvement approaches and healthcare systems' existing culture, infrastructure, and practices to effectively integrate evidence-based interventions into routine practice.58,59 Implementation strategies are methods or techniques used to enhance the adoption, implementation, and sustainability of an evidence-based intervention.60 Plan-Do-Study-Act (PDSA), an intervention in improvement science, is used as an implementation strategy in implementation science to quickly identify issues, determine necessary changes, measure the impact of those changes, and make an informed plan for improvement.58,61–64 They are widely used to improve quality healthcare delivery in routine practices and address barriers and needed changes in implementation and outcome efforts within local contexts and LMICs, including Nigeria.58,61,63,65–68 This is given to its iterative nature of assessing change through a structured experimental learning approach.63,66 However, there is no evidence of how the PDSA process can be applied to pragmatic trials and healthcare providers' (HCPs) perceptions of their use to facilitate the integration of evidence-based interventions into their everyday care processes. 61
Post-partum hemorrhage, hypertensive disorders, and sepsis are the top three leading maternal complications, accounting for over half of maternal deaths worldwide.1 Maternal sepsis, an "organ dysfunction resulting from infection during pregnancy, childbirth, post-abortion or in the post-partum period," 3 is responsible for 10% of all global maternal deaths if not promptly diagnosed and treated.1,4,5 Maternal sepsis before and during childbirth has also been associated with neonatal complications such as neonatal sepsis and death.6–8 Neonatal sepsis is another significant cause of neonatal mortality,9,10 responsible for 10%-17% of neonatal deaths globally.9,11 Consistent with the global data, maternal and neonatal sepsis are among the leading causes of maternal and neonatal deaths in LMICs, particularly SSA9,12–14 and Nigeria.15–20 Beyond these deaths, women who experience peripartum infections face severe morbidities and long-term disabilities such as chronic pelvic pain, ectopic pregnancy, and secondary infertility.5,7 Also, the widespread and inappropriate prescription and use of antibiotics in women during labor and birth continue to contribute to the burden of antimicrobial resistance in LMICs.21–23 Thus, a need to prioritize maternal infection prevention in LMICs, as it poses a major threat to global health.
To reduce maternal deaths, the World Health Organization (WHO) in 2015 recommended the use of antibiotics around birth to prevent and treat maternal peripartum infection in five clinical situations: (1) women with group B streptococcus (GBS) colonization to prevent early neonatal GBS infection; (2) preterm pre-labor rupture of membranes (PPROM); (3) delivery by cesarean section (CS); (4) repair of third/fourth-degree perineal tear; and (5) manual placental removal.7 Several trials have widely used prophylactic antibiotics to prevent maternal sepsis during the peripartum period, especially for cesarean section.21,24–26 However, implementation gaps exist due to wide variation in clinical practice, dosing regimen, cost, limited antimicrobial availability and diagnostic capabilities, inappropriate antibiotic prescription, dispensing, consumption, and use contributing to the emergence and dissemination of antimicrobial resistance and side effects.21,23,27–30 Antibiotics such as cephalosporin and erythromycin have been recommended as antimicrobial prophylaxis for cesarean section and PPROM, respectively.31 However, there are notable deviations from this practice, with several examples of prolonged and multidrug regimens, higher adverse effects, poor compliance, and the emergence of antimicrobial resistance to gram-positive and gram-negative bacteria.21,32,33
Azithromycin, an inexpensive broad-spectrum macrolide antibiotic, is effective against gram-positive and gram-negative bacteria.34–36 responsible for maternal sepsis in SSA.37–42 Besides its broad-spectrum activity, its prolonged half-life, high-sustained antibiotic levels in placental tissues, ease of administration, decreased cost, better compliance and side effects, and pharmacokinetic profile make it an attractive agent than erythromycin 32,43 and preventing maternal infections during labor and delivery,34,44 PPROM,45 and planned cesarean delivery.46–48 These features make Azithromycin a suitable treatment to implement for vaginal deliveries. Azithromycin administered during pregnancy has reduced the risk of low birth weight and prematurity in malaria-endemic settings,34 and has been used to treat sexually transmitted infections, toxoplasmosis, and malaria.32,34 However, in a placebo-controlled randomized trial of 2,297 pregnant women given oral azithromycin (1g) at 16–24 and 28–32 week gestation in Southern Malawi, the findings do not support the use of antibiotics as routine prophylaxis to prevent preterm birth in high-risk populations.49 High-quality studies are therefore needed to assess the effect of azithromycin in pregnancy on neonatal complications.50 The effectiveness of oral azithromycin given during pregnancy and labor on stillbirth and skin and soft tissue infections in infants is ongoing in Mali and Fiji, respectively.51,52
The WHO only recommends routine antibiotics prophylaxis for women undergoing operative vaginal birth.53 However, several studies have investigated using azithromycin to prevent maternal infections during vaginal delivery. A double-blind, placebo-controlled randomized trial among 829 mothers in Gambia showed that an oral dose of azithromycin (2g) administered during vaginal delivery reduced GBS, Staphylococcus aureus, and Streptococcus pneumoniae carriage in mothers and newborns by 60%,54 and also reduced maternal (occurrence of fever, mastitis, and widespread infections) and infant (skin and overall infections) infections by 60% and 24%, respectively up to eight weeks post-intervention.55 The study was conducted in a government facility without immediate access to emergency obstetric interventions and less frequent use of antibiotics in usual care.55 In a recent multi-country (Bangladesh, Democratic Republic of the Congo, Guatemala, India, Kenya, Pakistan, and Zambia), placebo-controlled, randomized trial involving 29,278 women, a single 2g oral dose of azithromycin before a vaginal delivery reduced the risk of maternal sepsis or death by 33% than placebo, but did not reduce the risk of sepsis or death in newborns.8 This maternal outcome was driven by a reduction in sepsis by 35%.8 Another recent multi-country double-blind, placebo-controlled, randomized clinical trial in Gambia and Burkina Faso among 11,983 women found that 2g of azithromycin administered orally during labor did not reduce neonatal sepsis or mortality.56 However, noninvasive infections during the subsequent four weeks were reduced for newborns (skin infections) and mothers (puerperal fever and mastitis) in the azithromycin group.56 Thus, the study did not support the routine introduction of oral intrapartum azithromycin to reduce neonatal sepsis or mortality.56 Conversely, a multicenter, three-group, double-blind, randomized controlled trial in Cameroun found that a single dose of oral azithromycin (1g) with or without 2g of amoxicillin for prolonged labor or rupture of membranes at term did not significantly reduce maternal peripartum or neonatal infection or death.57 This was attributed to lower-than-expected infection rates and the frequent use of antibiotics in routine care.57 The study was implemented in settings with a high level of care and adequate resources (i.e., access to emergency obstetric interventions, cesarean birth, antibiotics, and referral hospitals) and high antibiotic usage.57 Meanwhile, there are concerns about the potential harms of adding routine azithromycin for vaginal deliveries in LMICs, such as increased antimicrobial resistance, effects of changes to the maternal or neonatal microbiome, drug side effects, and costs, requiring further research.8,21 While studies have not established the significant associations between a single azithromycin dose and the development of antibiotic resistance, more research is required to investigate the effects of regular use of azithromycin prophylaxis during vaginal delivery.8
Evidence exists on the barriers and facilitators of implementing interventions to improve appropriate antibiotic use in LMICs.23 23 However, there is no evidence on factors that influence the effects and implementation of azithromycin use in vaginal delivery to inform its generalizability and replicability in other settings and contexts,8,34 and women's needs and perspectives to support updating the WHO recommendations for antibiotics to prevent maternal infection in LMICs, especially SSA.21,24,57 There is also no evidence on the best strategy to routinely implement azithromycin to prevent sepsis or death during vaginal delivery.
Studies have recommended aligning implementation strategies with improvement approaches and healthcare systems' existing culture, infrastructure, and practices to effectively integrate evidence-based interventions into routine practice.58,59 Implementation strategies are methods or techniques used to enhance the adoption, implementation, and sustainability of an evidence-based intervention.60 Plan-Do-Study-Act (PDSA), an intervention in improvement science, is used as an implementation strategy in implementation science to quickly identify issues, determine necessary changes, measure the impact of those changes, and make an informed plan for improvement.58,61–64 They are widely used to improve quality healthcare delivery in routine practices and address barriers and needed changes in implementation and outcome efforts within local contexts and LMICs, including Nigeria.58,61,63,65–68 This is given to its iterative nature of assessing change through a structured experimental learning approach.63,66 However, there is no evidence of how the PDSA process can be applied to pragmatic trials and healthcare providers' (HCPs) perceptions of their use to facilitate the integration of evidence-based interventions into their everyday care processes. 61
Maternal complications during pregnancy and childbirth are a global concern, resulting in high maternal mortality.1 Globally, an estimated 287,000 maternal deaths occurred in 2020, translating to 800 women dying daily from pregnancy and childbirth complications, equivalent to one every two minutes.2 Almost 95% of these deaths are in low-income and middle-income countries (LMICs), and about 70% of global maternal deaths are in Sub-Saharan Africa (SSA).2 In 2020, Nigeria alone accounted for almost 30% of all estimated global maternal deaths, with 82,000 annual deaths and 1,047 maternal deaths per 100,000 live births.2 This reflects the inequalities in accessing quality healthcare services during pregnancy, childbirth, and post-partum periods within the world's regions.
Post-partum hemorrhage, hypertensive disorders, and sepsis are the top three leading maternal complications, accounting for over half of maternal deaths worldwide.1 Maternal sepsis, an "organ dysfunction resulting from infection during pregnancy, childbirth, post-abortion or in the post-partum period," 3 is responsible for 10% of all global maternal deaths if not promptly diagnosed and treated.1,4,5 Maternal sepsis before and during childbirth has also been associated with neonatal complications such as neonatal sepsis and death.6–8 Neonatal sepsis is another significant cause of neonatal mortality,9,10 responsible for 10%-17% of neonatal deaths globally.9,11 Consistent with the global data, maternal and neonatal sepsis are among the leading causes of maternal and neonatal deaths in LMICs, particularly SSA9,12–14 and Nigeria.15–20 Beyond these deaths, women who experience peripartum infections face severe morbidities and long-term disabilities such as chronic pelvic pain, ectopic pregnancy, and secondary infertility.5,7 Also, the widespread and inappropriate prescription and use of antibiotics in women during labor and birth continue to contribute to the burden of antimicrobial resistance in LMICs.21–23 Thus, a need to prioritize maternal infection prevention in LMICs, as it poses a major threat to global health.
To reduce maternal deaths, the World Health Organization (WHO) in 2015 recommended the use of antibiotics around birth to prevent and treat maternal peripartum infection in five clinical situations: (1) women with group B streptococcus (GBS) colonization to prevent early neonatal GBS infection; (2) preterm pre-labor rupture of membranes (PPROM); (3) delivery by cesarean section (CS); (4) repair of third/fourth-degree perineal tear; and (5) manual placental removal.7 Several trials have widely used prophylactic antibiotics to prevent maternal sepsis during the peripartum period, especially for cesarean section.21,24–26 However, implementation gaps exist due to wide variation in clinical practice, dosing regimen, cost, limited antimicrobial availability and diagnostic capabilities, inappropriate antibiotic prescription, dispensing, consumption, and use contributing to the emergence and dissemination of antimicrobial resistance and side effects.21,23,27–30 Antibiotics such as cephalosporin and erythromycin have been recommended as antimicrobial prophylaxis for cesarean section and PPROM, respectively.31 However, there are notable deviations from this practice, with several examples of prolonged and multidrug regimens, higher adverse effects, poor compliance, and the emergence of antimicrobial resistance to gram-positive and gram-negative bacteria.21,32,33
Azithromycin, an inexpensive broad-spectrum macrolide antibiotic, is effective against gram-positive and gram-negative bacteria.34–36 responsible for maternal sepsis in SSA.37–42 Besides its broad-spectrum activity, its prolonged half-life, high-sustained antibiotic levels in placental tissues, ease of administration, decreased cost, better compliance and side effects, and pharmacokinetic profile make it an attractive agent than erythromycin 32,43 and preventing maternal infections during labor and delivery,34,44 PPROM,45 and planned cesarean delivery.46–48 These features make Azithromycin a suitable treatment to implement for vaginal deliveries. Azithromycin administered during pregnancy has reduced the risk of low birth weight and prematurity in malaria-endemic settings,34 and has been used to treat sexually transmitted infections, toxoplasmosis, and malaria.32,34 However, in a placebo-controlled randomized trial of 2,297 pregnant women given oral azithromycin (1g) at 16–24 and 28–32 week gestation in Southern Malawi, the findings do not support the use of antibiotics as routine prophylaxis to prevent preterm birth in high-risk populations.49 High-quality studies are therefore needed to assess the effect of azithromycin in pregnancy on neonatal complications.50 The effectiveness of oral azithromycin given during pregnancy and labor on stillbirth and skin and soft tissue infections in infants is ongoing in Mali and Fiji, respectively.51,52
The WHO only recommends routine antibiotics prophylaxis for women undergoing operative vaginal birth.53 However, several studies have investigated using azithromycin to prevent maternal infections during vaginal delivery. A double-blind, placebo-controlled randomized trial among 829 mothers in Gambia showed that an oral dose of azithromycin (2g) administered during vaginal delivery reduced GBS, Staphylococcus aureus, and Streptococcus pneumoniae carriage in mothers and newborns by 60%,54 and also reduced maternal (occurrence of fever, mastitis, and widespread infections) and infant (skin and overall infections) infections by 60% and 24%, respectively up to eight weeks post-intervention.55 The study was conducted in a government facility without immediate access to emergency obstetric interventions and less frequent use of antibiotics in usual care.55 In a recent multi-country (Bangladesh, Democratic Republic of the Congo, Guatemala, India, Kenya, Pakistan, and Zambia), placebo-controlled, randomized trial involving 29,278 women, a single 2g oral dose of azithromycin before a vaginal delivery reduced the risk of maternal sepsis or death by 33% than placebo, but did not reduce the risk of sepsis or death in newborns.8 This maternal outcome was driven by a reduction in sepsis by 35%.8 Another recent multi-country double-blind, placebo-controlled, randomized clinical trial in Gambia and Burkina Faso among 11,983 women found that 2g of azithromycin administered orally during labor did not reduce neonatal sepsis or mortality.56 However, noninvasive infections during the subsequent four weeks were reduced for newborns (skin infections) and mothers (puerperal fever and mastitis) in the azithromycin group.56 Thus, the study did not support the routine introduction of oral intrapartum azithromycin to reduce neonatal sepsis or mortality.56 Conversely, a multicenter, three-group, double-blind, randomized controlled trial in Cameroun found that a single dose of oral azithromycin (1g) with or without 2g of amoxicillin for prolonged labor or rupture of membranes at term did not significantly reduce maternal peripartum or neonatal infection or death.57 This was attributed to lower-than-expected infection rates and the frequent use of antibiotics in routine care.57 The study was implemented in settings with a high level of care and adequate resources (i.e., access to emergency obstetric interventions, cesarean birth, antibiotics, and referral hospitals) and high antibiotic usage.57 Meanwhile, there are concerns about the potential harms of adding routine azithromycin for vaginal deliveries in LMICs, such as increased antimicrobial resistance, effects of changes to the maternal or neonatal microbiome, drug side effects, and costs, requiring further research.8,21 While studies have not established the significant associations between a single azithromycin dose and the development of antibiotic resistance, more research is required to investigate the effects of regular use of azithromycin prophylaxis during vaginal delivery.8
Evidence exists on the barriers and facilitators of implementing interventions to improve appropriate antibiotic use in LMICs.23 23 However, there is no evidence on factors that influence the effects and implementation of azithromycin use in vaginal delivery to inform its generalizability and replicability in other settings and contexts,8,34 and women's needs and perspectives to support updating the WHO recommendations for antibiotics to prevent maternal infection in LMICs, especially SSA.21,24,57 There is also no evidence on the best strategy to routinely implement azithromycin to prevent sepsis or death during vaginal delivery.
Studies have recommended aligning implementation strategies with improvement approaches and healthcare systems' existing culture, infrastructure, and practices to effectively integrate evidence-based interventions into routine practice.58,59 Implementation strategies are methods or techniques used to enhance the adoption, implementation, and sustainability of an evidence-based intervention.60 Plan-Do-Study-Act (PDSA), an intervention in improvement science, is used as an implementation strategy in implementation science to quickly identify issues, determine necessary changes, measure the impact of those changes, and make an informed plan for improvement.58,61–64 They are widely used to improve quality healthcare delivery in routine practices and address barriers and needed changes in implementation and outcome efforts within local contexts and LMICs, including Nigeria.58,61,63,65–68 This is given to its iterative nature of assessing change through a structured experimental learning approach.63,66 However, there is no evidence of how the PDSA process can be applied to pragmatic trials and healthcare providers' (HCPs) perceptions of their use to facilitate the integration of evidence-based interventions into their everyday care processes. 61
| Status | Active |
|---|---|
| Effective start/end date | 14/11/24 → … |