Infection Prevention and Control and Antibiotic Stewardship to Avert Antibiotic Resistance in High-Risk Populations from Resource-Poor Settings Global under-5 deaths have halved in the last 20 years(1). However, reduction in the neonatal mortality rate has lagged greatly behind other advances, and now contributes over 40% of all child mortality in many countries (1). Yet, prior research in low and middle income countries (LMICs) suggests sick newborns often do not receive the interventions they need to ensure their disability free survival.  Infections are estimated to cause 40% of all neonatal deaths in LMICs (2), where the burden health care-associated infections (HCAIs) is also up to 20 times higher than in industrialised countries (3)  and where antibiotic resistant HCAIs are rapidly increasing (4) due to increases in antibiotic use, rising rates of hospitalisation, and high prevalence HCAIs (5) not matched with increases in hospital resources and measures to prevent these. Resistant infections often lead to longer hospitalizations (6), thus increasing opportunity for transmission to other inpatients in care, and subsequent transmission into the community following hospital discharge. The potential societal impact of bacterial antibiotic resistance (BAR) infections in sick newborns in LMICs, is reflected in the 58,000 deaths attributable to antibiotic resistant neonatal sepsis in India alone (5) compared to the 23,000 deaths each year across all population age groups in the United States (7).  The much-needed attention to improve newborn health, has triggered multiple stakeholders to propose the 'Every Newborn: an action plan to end preventable deaths' (8), which seeks to improve the quality of care to ultimately end preventable newborn deaths. HCAIs, reflect breakdown in infection prevention and control (IPC) measures, which combined with injudicious use of antibiotics contribute to emergence of resistant HCAIs in neonatal units (9), and are the most frequent preventable adverse event in healthcare delivery worldwide (3). Intervention bundles comprising behavioural, environmental and antibiotic stewardship components (10), could prevent many HCAIs (11-13), and improved provision of high-quality, basic care in resource-limited hospitals could deliver up to a 71% reduction in neonatal mortality (14,15).  Initiatives to improve quality and safety in healthcare, however, too often result in limited changes for the better and are often hard to replicate in new contexts (16). In this pump-priming grant, we seek to address key formative stages of the MRC framework for complex interventions (17,18) by generating contextual knowledge of the health system traits and behaviours that need to be understood prior to formulation and implementation of behavioural/integrated interventions to attain best IPC and antibiotic stewardship (IPC-ABS) practice required to reduce HCAIs and BAR in resource-limited healthcare facilities delivering care to sick newborns. In our approach, we draw from elements of the theory of change (ToC) (19,20), by first identifying the desired long-term goals and then working back from these to identify all the conditions that must be in place for the goals to occur. This proposed pump-priming grant includes research that aims to: a. Facilitate the development of appropriate, evidence based interventions based on a critical analysis of the policy, organisational and practice environments and current management, team and individual behaviours relevant to IPC-ABS, aimed at limiting BAR in high-risk populations in Kenyan facilities; b. Help identify context-appropriate clinical and performance indicators for use in monitoring and evaluation of IPC-ABS interventions; c. Highlight challenges in the uptake of policy into effective IPC-ABS practice; d. Increase capability and motivation to limit BAR and improve safety in hospitals; e. Initiate a process of building research capacity around IPC-ABS in Kenya.  We expect proposed interventions to be generalizable to other inpatient settings in East African hospitals that share similar challenges. The Global Challenges Research Fund (GCRF) supports cutting-edge research to address challenges faced by developing countries. The fund addresses the UN sustainable development goals. It aims to maximise the impact of research and innovation to improve lives and opportunity in the developing world.