Infection Prevention and Control and Antibiotic Stewardship to Avert Antibiotic Resistance in High-Risk Populations from Resource-Poor Settings

在过去20年中，全球5岁以下儿童死亡人数减少了一半(1)。然而，新生儿死亡率的降低远远落后于其他进展，现在在许多国家，新生儿死亡率占所有儿童死亡率的40%以上(1)。然而，先前在低收入和中等收入国家（LMICs）进行的研究表明，患病的新生儿往往得不到确保其无残疾生存所需的干预措施。在低收入和中等收入国家，感染估计占所有新生儿死亡的40%(2)，在这些国家，卫生保健相关感染（hcai）的负担也比工业化国家高出20倍(3)，而且抗生素耐药性hcai正在迅速增加(4)，原因是抗生素使用的增加、住院率的上升以及hcai的高患病率(5)与医院资源和预防措施的增加不匹配。耐药感染通常导致更长的住院时间(6)，从而增加了传播给其他住院患者的机会，并在出院后随后传播到社区。细菌抗生素耐药性（BAR）感染对中低收入国家患病新生儿的潜在社会影响，反映在仅印度就有58,000例死亡可归因于抗生素耐药性新生儿败血症(5)，而美国每年所有人口年龄组的死亡人数为23,000例(7)。对改善新生儿健康的迫切关注促使多个利益攸关方提出了“每个新生儿：终结可预防死亡的行动计划”(8)，该计划寻求改善护理质量，最终终结可预防的新生儿死亡。hcai反映了感染预防和控制（IPC）措施的失败，加上不明智地使用抗生素，导致新生儿病房出现耐药hcai(9)，并且是世界范围内医疗保健服务中最常见的可预防不良事件(3)。包括行为、环境和抗生素管理组成部分的一揽子干预措施（10）可以预防许多hcai(11-13)，并且在资源有限的医院改善提供高质量的基本护理可以将新生儿死亡率降低71%（14,15）。然而，改善医疗保健质量和安全的举措往往导致有限的改善，而且往往难以在新的情况下复制（16）。在这项泵启动拨款中，我们寻求解决复杂干预MRC框架的关键形成阶段（17,18），通过产生在制定和实施行为/综合干预措施之前需要了解的卫生系统特征和行为的背景知识，以实现最佳IPC和抗生素管理（IPC- abs）实践，以减少资源有限的医疗机构向患病新生儿提供护理的hcai和BAR。在我们的方法中，我们从变化理论（ToC）（19,20）的元素中得出结论，首先确定期望的长期目标，然后从这些目标中回过头来确定实现目标必须具备的所有条件。这项提议的激励拨款包括旨在：b.基于对与ipcc - abs相关的政策、组织和实践环境以及当前管理、团队和个人行为的批判性分析，促进制定适当的、基于证据的干预措施，旨在限制肯尼亚设施中高风险人群的BAR；帮助确定适合具体情况的临床和绩效指标，用于监测和评价IPC-ABS干预措施；强调将政策纳入ipcc - abs有效实践的挑战；提高能力和动力，限制BAR和改善医院安全；在肯尼亚启动围绕ipcc - abs的研究能力建设进程。我们希望建议的干预措施可以推广到东非医院中面临类似挑战的其他住院环境。

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.