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.

Improving neonatal mortality and morbidity - The ultimate aim of this work is to help reduce neonatal mortality in the long term, the major obstacle to Kenya achieving new sustainable development goal targets for health, and which results in over 40,000 lives lost per year in Kenya alone (21). This work will inform future efforts to test interventions that could reduce neonatal deaths by optimising infection prevention and control and antibiotic stewardship (IPC-ABS), so preventing hospital acquired infection, and reducing bacterial antibiotic resistance (BAR) in the highly vulnerable population of sick newborns.

Improving health system design and rational and effective use of resources - Health care provision is often not strategically planned or informed by evidence in low-income settings but rather is often influenced by powerful professional voices and market mechanisms that may be at odds with considerations of efficiency, equity and public health. This work seeks to begin a process that could inform medium and long term planning and implementation of critical aspects of IPC-ABS within health facilities that are seeing a rising number of users, as barriers to access are removed, and an increasing use of invasive technologies. These latter factors, combined with major human resource challenges, often result in high rates of HCAIs that increase costs and worsen patient outcomes. At the same time, inappropriate antibiotic use may hasten the emergence and broaden the spectrum of BAR. By addressing systematically the barriers to effective IPC-ABS and helping design contextually appropriate interventions to improve managerial, team and individual behaviours, this work will help the design of interventions that can help reduce such infections, prevent adverse outcomes and ameliorate BAR risks as part of improving patient safety.

Reducing population risk from bacterial antibiotic resistance -Reducing risks at the individual level will also help reduce risks in the population. Neonatal and other intensive or high dependency care units are hotspots for the emergence of BAR linked to the vulnerability of their patient populations, their prolonged hospital stays, high usage of antibiotics and concentration of invasive procedures. Those exiting such units may become colonised with resistant organisms and help spread these to other areas of facilities and into the community. Implementing effective IPC-ABS will help limit these risks.

Partnerships in research and capacity building - From its outset this research will engage policy makers, a wider set of stakeholders concerned with IPC-ABS and a set of professionals, managers and carers that influence policy implementation. This will improve research and promote the development of locally applicable intervention strategies for subsequent testing. Particularly worthy of note are strengthened linkages between The Kenyan Ministry of Health, researchers based in Kenya and those based in Oxford at the Department of Psychology and The Said Business School, who will link with potential collaborators at the University of Nairobi and Strathmore University. Our emphasis is on developing new disciplinary linkages and transferring skills to help build research capacity amongst young investigators in Kenya and absorptive capacity amongst policy makers and other partners.

Generalisable learning -The methods, results and approach we take will likely be of value across Kenya, East Africa and internationally. In particular, the tools to be developed or refined to evaluate IPC-ABS and the aim of identifying feasible, efficient and effective indicators of IPC-ABS practice will be of value. This formative work will support the development of intervention strategies that can then be tested helping to build an evidence base for how to improve IPC-ABS and reduce BAR going forwards.