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

在过去的20年里，全球5岁以下儿童死亡人数减少了一半(1)。然而，新生儿死亡率的下降大大落后于其他进步，目前在许多国家占所有儿童死亡率的40%以上(1)。然而，低收入和中等收入国家(LMICs)的先前研究表明，患病新生儿通常没有得到确保其无残疾生存所需的干预措施。感染估计导致了LMICs所有新生儿死亡的40%(2)，那里的卫生保健相关感染(HCAI)负担也比工业化国家高20倍(3)，而且由于抗生素使用的增加、住院率的上升以及HCAI的高发(5)医院资源和预防措施的增加，耐药HCAI正在迅速增加(4)。耐药感染往往导致更长的住院时间，从而增加传播给其他住院病人的机会，并在出院后随后传播到社区。细菌抗生素耐药性(BAR)感染对LMICs患病新生儿的潜在社会影响反映在仅印度就有5.8万人死于抗生素耐药新生儿败血症(5)，而美国所有人口年龄组每年的死亡人数为2.3万人(7)。改善新生儿健康是迫切需要关注的问题，这引发了多个利益相关者提出“每个新生儿：结束可预防死亡的行动计划”(8)，该计划旨在提高护理质量，最终结束可预防的新生儿死亡。HCAI，反映了感染预防和控制(IPC)措施的崩溃，再加上抗生素的不当使用，导致新生儿病房出现耐药HCAI(9)，是全世界医疗保健提供中最常见的可预防的不良事件(3)。由行为、环境和抗生素管理部分组成的干预捆绑(10)可以预防许多HCAI(11-13)，在资源有限的医院改善提供高质量的基本护理可以使新生儿死亡率降低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，而且往往很难在新的背景下复制(16)。在这项泵启动赠款中，我们寻求解决复杂干预措施(17，18)的MRC框架的关键形成阶段，方法是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，以实现减少HCAI所需的最佳IPC和抗生素管理(IPC-ABS)实践，并阻止资源有限的医疗机构向患病新生儿提供护理。在我们的方法中，我们借鉴了变革理论(TOC)(19，20)的要素，首先确定了所需的长期目标，然后从这些目标出发，确定了实现这些目标所必须具备的所有条件。这项拟议的泵启动赠款包括研究，目的是：a.根据对政策、组织和实践环境以及与IPC-ABS相关的当前管理、团队和个人行为的批判性分析，促进制定适当的循证干预措施，旨在限制肯尼亚设施中高危人群的禁忌；b.帮助确定用于监测和评估IPC-ABS干预措施的适合背景的临床和绩效指标；c.突出在将政策纳入有效的IPC-ABS实践方面的挑战；d.提高限制禁忌的能力和动力，并改善医院的安全性；E.在肯尼亚启动围绕IPC-ABS的研究能力建设进程。我们预计，拟议的干预措施将推广到东非医院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.