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A Multicomponent Intervention to Improve Maternal Infection Outcomes. BACKGROUND: Maternal infection and sepsis are major causes of maternal death and severe illness worldwide, particularly in low- and middle-income countries. Inconsistent implementation of evidence-based recommendations for infection prevention and management and delays in detection and treatment of maternal sepsis contribute to the number of preventable deaths. METHODS: We conducted a cluster-randomized trial to assess a multicomponent intervention, the Active Prevention and Treatment of Maternal Sepsis (APT-Sepsis) program. This program was designed to support health care providers in achieving three goals: adherence to World Health Organization (WHO) hand-hygiene standards; adoption of evidence-based practices for maternal infection prevention and management; and early detection of sepsis and use of the FAST-M (fluids, antibiotics, source control, transfer if required, and monitoring) treatment bundle. Usual care was provided in the control group, along with dissemination of guidelines. The primary outcome was a composite of infection-related maternal death, infection-related near-miss event (events in which women survived a life-threatening complication), or severe infection-related illness (deep surgical-site, deep perineal, or body-cavity infection) among women who were pregnant or had recently been pregnant. RESULTS: We randomly assigned 59 health facilities (where 431,394 women gave birth during the trial) in Malawi and Uganda to the intervention group (30 clusters) or the usual-care group (29 clusters). A primary-outcome event occurred in 1.4% of the patients in the intervention group and in 1.9% of those in the usual-care group (risk ratio, 0.68; 95% confidence interval, 0.55 to 0.83; P<0.001). This effect was generally consistent between countries and among facilities of difference sizes and was sustained over time. CONCLUSIONS: Implementation of the APT-Sepsis program led to a significantly lower risk of a composite of infection-related maternal death, infection-related near-miss event, or severe infection-related illness than usual care. (Funded by the Joint Global Health Trials scheme and others; APT-Sepsis ISRCTN number, ISRCTN42347014.).

The APT-Sepsis trial was a multi-country, two-arm parallel cluster-randomized trial with a baseline control phase. The intervention was delivered at the health facility level (clusters), targeting the behaviors of healthcare providers and systems within the facilities. There was a baseline phase of at least 6 months in all participating facilities, during which they provided usual care. At completion of the baseline phase, facilities were randomly assigned in a 1:1 ratio to receive the trial intervention or continue providing usual care for 12 months. A transition period of 3 months allowed for training of champions and embedding of the intervention into hospital systems; data from this period were not included in the effectiveness analysis. Malawi sites were randomized between November 6, 2023 and January 8, 2024, and Uganda sites between January 8, 2024 and March 4, 2024.

tion period of 3 months allowed for training of champions and embedding of the intervention into hospital systems; data from this period were not included in the effectiveness analysis. Malawi sites were randomized between November 6, 2023 and January 8, 2024, and Uganda sites between January 8, 2024 and March 4, 2024. A minimization algorithm generated by an independent statistician was used to ensure balance between facilities allocated to the intervention and control groups within each country. Minimization factors were the number of live births per cluster per week (categorized in tertiles) and the proportion of births with the composite primary outcome (categorized by median split) during the baseline phase. Facilities were allocated sequentially. A random element was incorporated so each facility was given the allocation that would minimize the imbalance with 90% probability, or the other allocation with 10% probability. A mixed-methods process evaluation explored additional implementation outcomes of acceptability, feasibility, mechanisms of change and cost (as part of a formal economic evaluation).

h facility was given the allocation that would minimize the imbalance with 90% probability, or the other allocation with 10% probability. A mixed-methods process evaluation explored additional implementation outcomes of acceptability, feasibility, mechanisms of change and cost (as part of a formal economic evaluation). The trial was approved by the University of Liverpool, the WHO Ethics Review Committee, the College of Medicine Research Ethics Committee in Malawi, the Infectious Diseases Institute Research Ethics Committee and Uganda National Council for Science and Technology in Uganda. Patients were not individually consented as the intervention was delivered to healthcare providers, and the components were considered best practice. Agreement for participation was obtained at a national and facility level. Trial oversight and monitoring were provided by a trial steering committee and an independent data monitoring committee. Patient and Public Involvement groups provided advice on trial design and materials, how best to engage the public and on study-related messaging. The first and last author, and the trial statisticians from the Liverpool Clinical Trials Centre vouch for the accuracy and completeness of the data and for the fidelity of the trial to the protocol, available with the full text of this article at NEJM.org.

how best to engage the public and on study-related messaging. The first and last author, and the trial statisticians from the Liverpool Clinical Trials Centre vouch for the accuracy and completeness of the data and for the fidelity of the trial to the protocol, available with the full text of this article at NEJM.org. Health facilities in Malawi and Uganda, with at least 1500 births per year, providing comprehensive obstetric care (able to perform cesarean births and provide blood transfusions) were eligible. Participation was subject to a trial-specific readiness assessment process, that ensured the availability of basic site prerequisites such as a water supply and electricity. Facilities were widely spread geographically in both countries.

re (able to perform cesarean births and provide blood transfusions) were eligible. Participation was subject to a trial-specific readiness assessment process, that ensured the availability of basic site prerequisites such as a water supply and electricity. Facilities were widely spread geographically in both countries. APT-Sepsis is a multi-component intervention delivered as an integrated program (Figure 1), aiming to help providers achieve three goals: 1) perform hand-hygiene according to the WHO 5 moments of hand hygiene approach, with the correct technique,19 2) follow WHO recommendations on infection prevention and management during and after pregnancy, including the evidence-based use of antibiotics for prophylaxis and treatment of common maternal infections, and the correct preparation of the skin and vagina with antiseptic solution prior to cesarean surgery,20 and 3) detect sepsis early and initiate the FAST-M treatment bundle (fluids, antibiotics, source identification and control, assessment of the need for transfer to a higher level of care, and monitoring of the woman and baby) when sepsis is suspected. A standardized observation chart that provided clear thresholds for triggering the bundle was used for all patients in the intervention facilities. Intervention components were derived using an iterative process of evidence synthesis, international expert consensus and optimization through multi-site pilot studies and mixed-methods evaluation.25–27

rt that provided clear thresholds for triggering the bundle was used for all patients in the intervention facilities. Intervention components were derived using an iterative process of evidence synthesis, international expert consensus and optimization through multi-site pilot studies and mixed-methods evaluation.25–27 Implementation strategies were developed from a behavior change perspective28 and include the following key components: hospital leadership engagement; program champions selected from existing facility staff; multi-disciplinary training with comprehensive training materials; implementation tools (eg FAST-M checklist); and performance feedback with dashboards and quarterly visits (Figure 1; details in the Supplementary Appendix). Key resources such as antibiotics were obtained by both the intervention and control sites through their usual procurement pathways. Additional soap and alcohol hand rub were provided to intervention group facilities if needed. A small number of thermometers and blood pressure machines were also supplied on one occasion to any site if not adequate at the site readiness assessment. The control facilities continued with usual care and were provided with the relevant WHO and national guidelines on hand hygiene and maternal infection prevention and treatment that informed the APT-Sepsis program (passive guideline dissemination). After the study ended, the APT-Sepsis intervention was rolled out to all the sites that had been allocated to usual care.

nd were provided with the relevant WHO and national guidelines on hand hygiene and maternal infection prevention and treatment that informed the APT-Sepsis program (passive guideline dissemination). After the study ended, the APT-Sepsis intervention was rolled out to all the sites that had been allocated to usual care. The primary outcome was infection-related maternal death or severe morbidity. This was defined as a composite of infection-related maternal mortality, infection-related maternal “near-miss” events, and severe infection (deep surgical-site, deep perineal or body-cavity infection) during pregnancy, childbirth or within 42 days of pregnancy ending, at any time up to 28 days of discharge (whichever occurred first). Outcome definitions are provided in the Supplementary appendix. WHO criteria for near-miss were modified to ensure ascertainment would not be influenced by the intervention. Modified CDC criteria were used to define deep surgical site infection, deep perineal/labial/vaginal tear infection, and reproductive tract or body cavity infection within 30 days after the procedure or birth. For maternal mortality and near-miss events, attribution to maternal infection was assessed based on review of the full clinical record by the site-based clinical data collector and by the central country clinical team. If there was discordance in assessments, or if uncertainty in the causation was recorded by either group, the case was adjudicated by a separate case classification committee blinded to site allocation.

eview of the full clinical record by the site-based clinical data collector and by the central country clinical team. If there was discordance in assessments, or if uncertainty in the causation was recorded by either group, the case was adjudicated by a separate case classification committee blinded to site allocation. Secondary outcomes included: individual components of the primary composite outcome; stillbirth; early neonatal death (infection-related and total); maternal mortality (any cause); maternal near-miss (any cause); and maternal severe acute respiratory infections. Clinical outcomes were recorded by study staff, independent of the implementation team. Clinical areas were monitored at each site and objective, structured reporting conducted daily in the baseline and post-randomization phases; identification of outcomes involved active case finding, chart review and site records assessment. Additional secondary outcomes, related to Implementation, included: compliance with hand hygiene; correct antibiotic prophylaxis at cesarean section; complete vital sign recording; and compliance with maternal sepsis management bundle. These were measured quarterly during the intervention phase in both intervention and usual care facilities.

tcomes, related to Implementation, included: compliance with hand hygiene; correct antibiotic prophylaxis at cesarean section; complete vital sign recording; and compliance with maternal sepsis management bundle. These were measured quarterly during the intervention phase in both intervention and usual care facilities. We calculated that at least 60 clusters (a minimum of 30 in Malawi and 30 in Uganda) would be required for the trial to have 95% power, with 2 sided p < 0.05, to detect a 25% relative reduction in the composite primary outcome from 3% to 2.25%. This calculation adjusted for clustering, (assuming an intra-cluster correlation (ICC) of 0.03 (range: 0.001 to 0.05) and variation in clustering over time, assuming a cluster autocorrelation of 0.97 (range: 0.9 to 1.0). The original sample size calculations were based on an intervention period of 20 months. A pre-specified re-estimation of the sample size was conducted once the intra-cluster correlation, baseline event rate and number of participants per cluster was known from the baseline phase. This demonstrated an ICC of 0.02 and a larger than expected number of participants per cluster. Based on these findings, shortening the intervention was expected to have minimal effect on power, and the independent data monitoring committee and trial steering committee recommended a revised intervention period of 12 months. A full sample-size justification is provided in the trial protocol. All analyses were performed according to the intention-to-treat principle. There were no interim analyses during the trial.

We calculated that at least 60 clusters (a minimum of 30 in Malawi and 30 in Uganda) would be required for the trial to have 95% power, with 2 sided p < 0.05, to detect a 25% relative reduction in the composite primary outcome from 3% to 2.25%. This calculation adjusted for clustering, (assuming an intra-cluster correlation (ICC) of 0.03 (range: 0.001 to 0.05) and variation in clustering over time, assuming a cluster autocorrelation of 0.97 (range: 0.9 to 1.0). The original sample size calculations were based on an intervention period of 20 months. A pre-specified re-estimation of the sample size was conducted once the intra-cluster correlation, baseline event rate and number of participants per cluster was known from the baseline phase. This demonstrated an ICC of 0.02 and a larger than expected number of participants per cluster. Based on these findings, shortening the intervention was expected to have minimal effect on power, and the independent data monitoring committee and trial steering committee recommended a revised intervention period of 12 months. A full sample-size justification is provided in the trial protocol. All analyses were performed according to the intention-to-treat principle. There were no interim analyses during the trial. In the primary analysis, we used generalized linear mixed effects models incorporating a constrained baseline approach. For this, both baseline and post-randomization timepoints were included as outcomes, but the treatment effect was constrained to be zero in the baseline phase. We used binomial distribution and logit link, with robust standard errors, followed by marginal standardization to estimate risk ratios and risk differences. Cluster and cluster by period were included as random effects, with country, and the categorical minimization factor of facility size included as covariates. The second minimization factor (proportion of births with the composite primary outcome) was not included as it was already in the model as the outcome variable.

Cluster and cluster by period were included as random effects, with country, and the categorical minimization factor of facility size included as covariates. The second minimization factor (proportion of births with the composite primary outcome) was not included as it was already in the model as the outcome variable. We analyzed the treatment effect on the primary outcome in prespecified subgroups, according to country, facility size, and months post-implementation. Subgroup analyses were carried out by including a treatment group by subgroup interaction parameter in the regression model and reporting adjusted treatment effects with 95% confidence intervals [CI]. Secondary outcomes were analyzed using the same methods as the primary outcome. Implementation outcomes from the quarterly visits in each facility were analyzed using mixed effect repeated measures linear regression with country and facility size included as covariates. There was no prespecified plan to adjust for multiplicity in tests of secondary outcomes. The widths of the 95% confidence intervals around point estimates have not been adjusted for multiplicity and should not be used to infer definitive treatment effects.

Health facilities in Malawi and Uganda, with at least 1500 births per year, providing comprehensive obstetric care (able to perform cesarean births and provide blood transfusions) were eligible. Participation was subject to a trial-specific readiness assessment process, that ensured the availability of basic site prerequisites such as a water supply and electricity. Facilities were widely spread geographically in both countries.

APT-Sepsis is a multi-component intervention delivered as an integrated program (Figure 1), aiming to help providers achieve three goals: 1) perform hand-hygiene according to the WHO 5 moments of hand hygiene approach, with the correct technique,19 2) follow WHO recommendations on infection prevention and management during and after pregnancy, including the evidence-based use of antibiotics for prophylaxis and treatment of common maternal infections, and the correct preparation of the skin and vagina with antiseptic solution prior to cesarean surgery,20 and 3) detect sepsis early and initiate the FAST-M treatment bundle (fluids, antibiotics, source identification and control, assessment of the need for transfer to a higher level of care, and monitoring of the woman and baby) when sepsis is suspected. A standardized observation chart that provided clear thresholds for triggering the bundle was used for all patients in the intervention facilities. Intervention components were derived using an iterative process of evidence synthesis, international expert consensus and optimization through multi-site pilot studies and mixed-methods evaluation.25–27

The primary outcome was infection-related maternal death or severe morbidity. This was defined as a composite of infection-related maternal mortality, infection-related maternal “near-miss” events, and severe infection (deep surgical-site, deep perineal or body-cavity infection) during pregnancy, childbirth or within 42 days of pregnancy ending, at any time up to 28 days of discharge (whichever occurred first). Outcome definitions are provided in the Supplementary appendix. WHO criteria for near-miss were modified to ensure ascertainment would not be influenced by the intervention. Modified CDC criteria were used to define deep surgical site infection, deep perineal/labial/vaginal tear infection, and reproductive tract or body cavity infection within 30 days after the procedure or birth. For maternal mortality and near-miss events, attribution to maternal infection was assessed based on review of the full clinical record by the site-based clinical data collector and by the central country clinical team. If there was discordance in assessments, or if uncertainty in the causation was recorded by either group, the case was adjudicated by a separate case classification committee blinded to site allocation.

We calculated that at least 60 clusters (a minimum of 30 in Malawi and 30 in Uganda) would be required for the trial to have 95% power, with 2 sided p < 0.05, to detect a 25% relative reduction in the composite primary outcome from 3% to 2.25%. This calculation adjusted for clustering, (assuming an intra-cluster correlation (ICC) of 0.03 (range: 0.001 to 0.05) and variation in clustering over time, assuming a cluster autocorrelation of 0.97 (range: 0.9 to 1.0). The original sample size calculations were based on an intervention period of 20 months. A pre-specified re-estimation of the sample size was conducted once the intra-cluster correlation, baseline event rate and number of participants per cluster was known from the baseline phase. This demonstrated an ICC of 0.02 and a larger than expected number of participants per cluster. Based on these findings, shortening the intervention was expected to have minimal effect on power, and the independent data monitoring committee and trial steering committee recommended a revised intervention period of 12 months. A full sample-size justification is provided in the trial protocol. All analyses were performed according to the intention-to-treat principle. There were no interim analyses during the trial.

A total of 83 health facilities were identified and underwent initial assessment for eligibility (Fig. S1). Of these, 33 facilities in Malawi and 38 facilities in Uganda proceeded to a readiness assessment and baseline data collection. Three facilities in Malawi and nine in Uganda were then excluded for the following reasons: they did not manage patients with severe infections or sepsis within the facility, they no longer met the eligibility criteria or, in Malawi, the maximum number of facilities were already included (Fig. S1). A total of 59 facilities underwent randomization, with 30 assigned to the intervention group (15 in Malawi and 15 in Uganda) and 29 to usual care (15 and 14, respectively). Following randomization, all sites received the planned intervention, and completed the study. There were a total of 431,394 women with live births during the study (190,500 in the baseline phase and 240,894 in the intervention phase, Table 1.) Facility characteristics and resource availability appeared generally similar between intervention and control groups at baseline; availability was low for some key resources. (Table 1). Table S1 summarizes the representativeness of the study population.

A total of 59 facilities underwent randomization, with 30 assigned to the intervention group (15 in Malawi and 15 in Uganda) and 29 to usual care (15 and 14, respectively). Following randomization, all sites received the planned intervention, and completed the study. There were a total of 431,394 women with live births during the study (190,500 in the baseline phase and 240,894 in the intervention phase, Table 1.) Facility characteristics and resource availability appeared generally similar between intervention and control groups at baseline; availability was low for some key resources. (Table 1). Table S1 summarizes the representativeness of the study population. The primary outcome occurred in 1752 of 124,298 women (1.4%) in the intervention group and in 2208 of 116,596 (1.9%) in the usual care group (risk ratio, 0.68; 95% CI, 0.55 to 0.83; P<0.001) (Table 2 and S2). This effect appeared generally consistent between countries (Fig. 3 and Table S4) and across small, medium and large facilities. The incidence of the primary outcome in the intervention group progressively decreased following randomization, with a mean rate of 2.4% at baseline, 2% in the first month following implementation and completion of the transition phase, and 0.9% in the final month of the study. The effect size correspondingly increased from the first month (risk ratio, 0.92; 95% CI, 0.68 to 1.25) to the final month of the intervention phase (risk ratio, 0.53; 95% CI, 0.35 to 0.80) (Fig. 3, and Table S4).

following implementation and completion of the transition phase, and 0.9% in the final month of the study. The effect size correspondingly increased from the first month (risk ratio, 0.92; 95% CI, 0.68 to 1.25) to the final month of the intervention phase (risk ratio, 0.53; 95% CI, 0.35 to 0.80) (Fig. 3, and Table S4). Components of the primary outcome are shown in Table 2. The reduction in the primary composite outcome appeared largely driven by the effect of the intervention on severe infection-related morbidity (incidence 1.35% in the intervention group and 1.80% in the usual care group; risk ratio, 0.68; 95% CI, 0.55 to 0.84). Stillbirth was recorded in 2.13% of total births in the intervention group and 1.95% in the usual care group (risk ratio, 0.90; 95% CI, 0.73 to 1.10) Neonatal deaths were recorded in 2.16% and 2.37%, respectively (risk ratio, 0.88; 95% CI, 0.73 to 1.04); these were attributable to infection in 0.66% and 0.53%, respectively (risk ratio, 0.86; 95% CI, 0.57 to 1.30)(Tables 2 and S2). The intervention was associated with improvements in the prespecified implementation outcomes targeted to the three goals of the intervention (Table 2). Mean hand hygiene compliance (Goal 1) was 33% in the intervention sites compared to 15% in the usual care sites (mean difference 14%; 95% CI 10% to 19%).

Stillbirth was recorded in 2.13% of total births in the intervention group and 1.95% in the usual care group (risk ratio, 0.90; 95% CI, 0.73 to 1.10) Neonatal deaths were recorded in 2.16% and 2.37%, respectively (risk ratio, 0.88; 95% CI, 0.73 to 1.04); these were attributable to infection in 0.66% and 0.53%, respectively (risk ratio, 0.86; 95% CI, 0.57 to 1.30)(Tables 2 and S2). The intervention was associated with improvements in the prespecified implementation outcomes targeted to the three goals of the intervention (Table 2). Mean hand hygiene compliance (Goal 1) was 33% in the intervention sites compared to 15% in the usual care sites (mean difference 14%; 95% CI 10% to 19%). Appropriate antibiotic prophylaxis was appropriately administered prior to cesarean section (Goal 2) in 74% and 58% of patients, respectively (mean difference 15%; 95% CI 4% to 26%). Several measures related to Goal 3 also supported primary outcomes findings; for example, complete observations at admission in 48% vs 15%, respectively (mean difference 32%; 95% CI 25% to 40%) and, among patients with suspected sepsis, antibiotics administered within 1 hour in 44% vs 38%, respectively (mean difference 8%; 95% CI -3% to 19%).

The primary outcome occurred in 1752 of 124,298 women (1.4%) in the intervention group and in 2208 of 116,596 (1.9%) in the usual care group (risk ratio, 0.68; 95% CI, 0.55 to 0.83; P<0.001) (Table 2 and S2). This effect appeared generally consistent between countries (Fig. 3 and Table S4) and across small, medium and large facilities. The incidence of the primary outcome in the intervention group progressively decreased following randomization, with a mean rate of 2.4% at baseline, 2% in the first month following implementation and completion of the transition phase, and 0.9% in the final month of the study. The effect size correspondingly increased from the first month (risk ratio, 0.92; 95% CI, 0.68 to 1.25) to the final month of the intervention phase (risk ratio, 0.53; 95% CI, 0.35 to 0.80) (Fig. 3, and Table S4). Components of the primary outcome are shown in Table 2. The reduction in the primary composite outcome appeared largely driven by the effect of the intervention on severe infection-related morbidity (incidence 1.35% in the intervention group and 1.80% in the usual care group; risk ratio, 0.68; 95% CI, 0.55 to 0.84). Stillbirth was recorded in 2.13% of total births in the intervention group and 1.95% in the usual care group (risk ratio, 0.90; 95% CI, 0.73 to 1.10) Neonatal deaths were recorded in 2.16% and 2.37%, respectively (risk ratio, 0.88; 95% CI, 0.73 to 1.04); these were attributable to infection in 0.66% and 0.53%, respectively (risk ratio, 0.86; 95% CI, 0.57 to 1.30)(Tables 2 and S2).

ntion group and 1.95% in the usual care group (risk ratio, 0.90; 95% CI, 0.73 to 1.10) Neonatal deaths were recorded in 2.16% and 2.37%, respectively (risk ratio, 0.88; 95% CI, 0.73 to 1.04); these were attributable to infection in 0.66% and 0.53%, respectively (risk ratio, 0.86; 95% CI, 0.57 to 1.30)(Tables 2 and S2). The intervention was associated with improvements in the prespecified implementation outcomes targeted to the three goals of the intervention (Table 2). Mean hand hygiene compliance (Goal 1) was 33% in the intervention sites compared to 15% in the usual care sites (mean difference 14%; 95% CI 10% to 19%). Appropriate antibiotic prophylaxis was appropriately administered prior to cesarean section (Goal 2) in 74% and 58% of patients, respectively (mean difference 15%; 95% CI 4% to 26%). Several measures related to Goal 3 also supported primary outcomes findings; for example, complete observations at admission in 48% vs 15%, respectively (mean difference 32%; 95% CI 25% to 40%) and, among patients with suspected sepsis, antibiotics administered within 1 hour in 44% vs 38%, respectively (mean difference 8%; 95% CI -3% to 19%).

In this cluster randomized trial, implementation of the Active Prevention and Treatment of Maternal Sepsis (APT-Sepsis) program resulted in a significant reduction in infection-related maternal mortality or severe morbidity compared to usual care in pregnant or recently pregnant women. This benefit was driven by the reduction in deep surgical or perineal site, or body cavity infection with the intervention, was consistent across countries and facility size, and was sustained throughout the trial. The scale of the trial, including government and non-government facilities of different sizes, supports the generalizability of the findings to health facilities providing comprehensive obstetric care. The intervention also covered the continuum of pregnancy-related infections, including in early pregnancy or following abortions. The intervention involved the provision of relatively few additional resources beyond what was generally available within the hospital systems, suggesting feasibility beyond the trial setting. For example, minimal equipment was provided, and site champions were not paid for this extra role.

ancy or following abortions. The intervention involved the provision of relatively few additional resources beyond what was generally available within the hospital systems, suggesting feasibility beyond the trial setting. For example, minimal equipment was provided, and site champions were not paid for this extra role. Results for implementation outcomes suggested improvement at intervention sites across all three program goals. However, adherence was incomplete; this was not unexpected given that the program did not address broader health system challenges (eg staffing shortages, inadequate sinks for handwashing, limited antibiotic availability). The observed clinical benefit despite modest changes in some implementation measures may reflect the simultaneous targeting of multiple points in the pathway to maternal sepsis and adverse outcomes. A recent trial demonstrated that azithromycin prophylaxis before all vaginal births reduced maternal sepsis,29 but this practice has not been routinely implemented owing to concerns regarding antimicrobial resistance.30 Our intervention reduced maternal infection with targeted use of antibiotics together with non-pharmacological changes in care.

that azithromycin prophylaxis before all vaginal births reduced maternal sepsis,29 but this practice has not been routinely implemented owing to concerns regarding antimicrobial resistance.30 Our intervention reduced maternal infection with targeted use of antibiotics together with non-pharmacological changes in care. The trial has several limitations. The multicomponent nature of the intervention precludes attribution of the effect to individual elements. Microbiological data were not available, preventing pathogen-specific diagnosis or resistance profiling. As study staff identifying outcomes were not blinded to group allocation, and there is subjectivity in identifying the relatedness of outcomes to infection, bias is possible. However, clinical outcomes were identified using objective criteria and collected daily by trained staff not involved in implementation. Identification of outcomes after hospital discharge required that the patient return for care, so underreporting is possible, but less likely given the serious nature of these outcomes. Extending this intervention to other countries and setting may require partnering with national ministries of health, as we did, to facilitate uptake of the intervention, and adapting materials and processes to ensure they are culturally and contextually appropriate. Further work is needed to evaluate patient and provider experience, behavior changes and cost-effectiveness of the intervention.

ering with national ministries of health, as we did, to facilitate uptake of the intervention, and adapting materials and processes to ensure they are culturally and contextually appropriate. Further work is needed to evaluate patient and provider experience, behavior changes and cost-effectiveness of the intervention. In summary, implementation of the APT-sepsis program substantially reduced the risk of the primary outcome of infection-related mortality and severe morbidity. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.