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Background There is limited data on antibiotic treatment in hospitalized neonates in low- and middle-income countries (LMICs). We aimed to describe patterns of antibiotic use, pathogens, and clinical outcomes, and to develop a severity score predicting mortality in neonatal sepsis to inform future clinical trial design. Methods and findings Hospitalized infants A total of 3,204 infants were enrolled, with median birth weight of 2,500 g (IQR 1,400 to 3,000) and postnatal age of 5 days (IQR 1 to 15). 206 different empiric antibiotic combinations were started in 3,141 infants, which were structured into 5 groups based on the World Health Organization (WHO) AWaRe classification. Approximately 25.9% (n = 814) of infants started WHO first line regimens (Group 1-Access) and 13.8% (n = 432) started WHO second-line cephalosporins (cefotaxime/ceftriaxone) (Group 2-'Low' Watch). The largest group (34.0%, n = 1,068) started a regimen providing partial extended-spectrum beta-lactamase (ESBL)/pseudomonal coverage (piperacillin-tazobactam, ceftazidime, or fluoroquinolone-based) (Group 3-'Medium' Watch), 18.0% (n = 566) started a carbapenem (Group 4-'High' Watch), and 1.8% (n = 57) a Reserve antibiotic (Group 5, largely colistin-based), and 728/2,880 (25.3%) of initial regimens in Groups 1 to 4 were escalated, mainly to carbapenems, usually for clinical deterioration (n = 480; 65.9%). A total of 564/3,195 infants (17.7%) were blood culture pathogen positive, of whom 62.9% (n = 355) had a gram-negative organism, predominantly Klebsiella pneumoniae (n = 132) or Acinetobacter spp. (n = 72). Both were commonly resistant to WHO-recommended regimens and to carbapenems in 43 (32.6%) and 50 (71.4%) of cases, respectively. MRSA accounted for 33 (61.1%) of 54 Staphylococcus aureus isolates. Overall, 350/3,204 infants died (11.3%; 95% CI 10.2% to 12.5%), 17.7% if blood cultures were positive for pathogens (95% CI 14.7% to 21.1%, n = 99/564). A baseline NeoSep Severity Score had a C-index of 0.76 (0.69 to 0.82) in the validation sample, with mortality of 1.6% (3/189; 95% CI: 0.5% to 4.6%), 11.0% (27/245; 7.7% to 15.6%), and 27.3% (12/44; 16.3% to 41.8%) in low (score 0 to 4), medium (5 to 8), and high (9 to 16) risk groups, respectively, with similar performance across subgroups. A related NeoSep Recovery Score had an area under the receiver operating curve for predicting death the next day between 0.8 and 0.9 over the first week. There was significant variation in outcomes between sites and external validation would strengthen score applicability. Conclusion Antibiotic regimens used in neonatal sepsis commonly diverge from WHO guidelines, and trials of novel empiric regimens are urgently needed in the context of increasing antimicrobial resistance (AMR). The baseline NeoSep Severity Score identifies high mortality risk criteria for trial entry, while the NeoSep Recovery Score can help guide decisions on regimen change. NeoOBS data informed the NeoSep1 antibiotic trial (ISRCTN48721236), which aims to identify novel first- and second-line empiric antibiotic regimens for neonatal sepsis. Trial registration ClinicalTrials.gov, (NCT03721302)., Author(s): Neal J. Russell 1,*, Wolfgang Stöhr 2, Nishad Plakkal 3, Aislinn Cook 1, James A. Berkley 4,5,6, Bethou Adhisivam 3, Ramesh Agarwal 7, Nawshad Uddin Ahmed 8, Manica Balasegaram [...]

Background: In low- and -middle-income countries (LMICs) like Tanzania, the competency of healthcare providers critically influences the quality of pediatric care. To address this, we introduced PACE (Pediatric Acute Care Education), an adaptive e-learning program tailored to enhance provider competency in line with Tanzania's national guidelines for managing seriously ill children. Adaptive e-learning presents a promising alternative to traditional in-service education, yet optimal strategies for its implementation in LMIC settings remain to be fully elucidated., Objectives: This study aimed to (1) evaluate the initial implementation of PACE in Mwanza, Tanzania, using the constructs of Normalization Process Theory (NPT), and (2) provide insights into its feasibility, acceptability, and scalability potential., Methods: A mixed-methods approach was employed across three healthcare settings in Mwanza: a zonal hospital and two health centers. NPT was utilized to navigate the complexities of implementing PACE. Data collection involved a customized NoMAD survey, focus groups and in-depth interviews with healthcare providers., Results: The study engaged 82 healthcare providers through the NoMAD survey and 79 in focus groups and interviews. Findings indicated high levels of coherence and cognitive participation, demonstrating that PACE is well-understood and resonates with existing healthcare goals. Providers expressed a willingness to integrate PACE into their practice, distinguishing it from existing educational methods. However, challenges related to resources and infrastructure, particularly affecting collective action, were noted. The short duration of the study limited the assessment of reflexive monitoring, though early indicators point towards the potential for PACE's long-term sustainability., Conclusion: This study offers vital insights into the feasibility and acceptability of implementing PACE in a Tanzanian context. While PACE aligns well with healthcare objectives, addressing resource and infrastructure challenges is crucial for its successful and sustainable implementation. Furthermore, the study underscores the value of NPT as a framework in guiding implementation processes, with broader implications for implementation science and pediatric acute care in LMICs., Competing Interests: Competing interests BR and MB are compensated by Area 9 Lyceum as Senior Learning Architect and Medical Director, respectively. Additional Declarations REDCap Database. Study data were collected and managed using REDCap electronic data capture tools hosted at Stanford University.71,72 REDCap (Research Electronic Data Capture) is a secure, web-based software platform designed to support data capture for research studies, providing 1) an intuitive interface for validated data capture; 2) audit trails for tracking data manipulation and export procedures; 3) automated export procedures for seamless data downloads to common statistical packages; and 4) procedures for data integration and interoperability with external sources. The Stanford REDCap platform (http://redcap.stanford.edu) is developed and operated by the Stanford Medicine Research IT team. The REDCap platform services at Stanford are subsidized by a) the Stanford School of Medicine Research Office, and b) the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through grant UL1 TR001085. Area9 Rhapsode™ meets the requirements for full GDPR compliance including encryption, data security, and ‘forget me’. Use of ChatGPT: We employed ChatGPT in two ways: 1) to edit and revise manuscripts for clarity, to ensure adherence to writing standards (such as STROBE, SRQR) and to format manuscripts, tables, and figures; and 2) to conduct preliminary data screening/monitoring using de-identified exported from our data from our REDCap databases. All statistical results and conclusions in this manuscript are confirmed by a biostatistician or member of the author group. Patient and public involvement. This research was done without patient involvement. Patients were not invited to comment on the study design and were not consulted to develop patient-relevant outcomes or interpret the results. Patients were not invited to contribute to the writing or editing of this document for readability or accuracy.