Procalcitonin to Reduce Antibiotic Use in Pediatric Pneumonia (P-RAPP)

项目摘要/摘要 尽管病毒是幼儿社区获得性肺炎(CAP)的主要原因，但抗生素 是为大多数CAP儿童开的处方。过度使用抗生素对社会和个人都有很大的影响 后果，包括促进抗菌素耐药性、抗生素相关副作用和严重 并发症。降钙素原(PCT)是一种生物标志物，在细菌感染患者中升高，但 在病毒感染中通常不会升高。低PCT水平已被证明具有很高的负面预测 CAP患儿典型细菌检测的价值。同样，PCT算法减少了抗生素 不会增加成人和儿童的不良事件；然而，临床医生可能对使用PCT犹豫不决， 由于门诊儿童避免使用抗生素的临床疗效具有低危和低危的临床特点 尚未对PCT水平进行评估。这项工作的总体目标是检验低风险的假设 接受安慰剂治疗的CAP和PCT水平为0.25 ng/mL的门诊儿童也有类似的情况 对于那些使用抗生素治疗的人，临床反应更少，不良反应更少，通过大规模、多学科的 机构随机试验(RCT)。鉴于进行这种性质的区域现金转移的复杂性，总体上 R34的目标是评估和最终确定研究人群、试验程序和研究结果 在通过一项试点试验评估研究可行性的同时，为今后开展这项区域合作研究提供了必要的支持。 具体目标1是完善和最终确定研究对象、结果、程序、工具和培训 一项研究CAP低危儿童抗生素需求的试验材料。作为家长和临床医生 投入对“无抗生素”战略的成功至关重要，我们将执行定性的半结构化 与关键利益相关者进行访谈，并使用Delphi方法与儿科CAP专家小组进行改进 并最终确定研究对象、程序和结果。我们还将对可靠性和可行性进行评估 使用移动视频聊天技术评估患有CAP的儿童的临床反应，我们将 在未来的RCT中发挥杠杆作用。具体目标2是通过以下方式实施和确定所有研究程序的可行性 在CAP和PCT水平为0.25的低风险儿童中进行阿莫西林与安慰剂的三点试点试验 纳克/毫升。我们将在3个参与地点招收36名儿童并将其随机分组。这一试点试验将提供必要的 计划大规模最终试验的数据，包括对促进者和研究障碍的评估 参与，估计入学率和流失率，评估研究程序和干预措施- 世界设定，并确定遵从率。此外，我们还将展示收集成果的能力 对未来的随机对照试验很重要，包括临床反应、症状缓解、不良事件和生活质量。 随后的大规模随机对照试验将具有重大意义，因为它将明确解决抗生素是否对 患有CAP的低风险儿童，代表着从经验性转变为对现状的创新性偏离 针对所有患有CAP的儿童采取有针对性的方法使用抗生素。

PROJECT SUMMARY/ABSTRACT Although viruses are the leading cause of community-acquired pneumonia (CAP) in young children, antibiotics are prescribed for most children with CAP. Antibiotic overuse has substantial societal and individual consequences, including promotion of antimicrobial resistance, antibiotic-associated side effects and severe complications. Procalcitonin (PCT) is a biomarker that is increased in patients with bacterial infections but is not typically elevated in viral infections. A low PCT level has been shown to have a high negative predictive value for detection of typical bacteria in children with CAP. Similarly, PCT algorithms have decreased antibiotic use without increasing adverse events in adults and children; however, clinicians may be hesitant to use PCT, as the clinical efficacy of avoiding antibiotics in outpatient children with low-risk clinical characteristics and low PCT levels has not been evaluated. The overall objective of this work is to test the hypothesis that low-risk children managed as outpatients with CAP and PCT levels <0.25 ng/mL treated with placebo have similar clinical response to those treated with antibiotics, with fewer adverse effects, through a large-scale, multi- institutional randomized trial (RCT). Given the complexities of conducting an RCT of this nature, the overall objective of this R34 is to evaluate and finalize the study population, trial procedures and study outcomes necessary for the development of this future RCT, while assessing study feasibility through a pilot trial. Specific Aim 1 is to refine and finalize the study population, outcomes, procedures, instruments and training materials for a trial examining the need for antibiotics in low-risk children with CAP. As parent and clinician input is critical to the success of a “no antibiotics” strategy, we will perform qualitative semi-structured interviews with key stakeholders and use Delphi methodology with a panel of pediatric CAP experts to refine and finalize the study population, procedures and outcomes. We will also evaluate the reliability and feasibility of using mobile video chat technology to evaluate the clinical response of children with CAP, which we will leverage in the future RCT. Specific Aim 2 is to implement and establish feasibility of all study procedures by conducting a 3-site pilot trial of amoxicillin vs placebo in low-risk children with CAP and PCT levels <0.25 ng/mL. We will enroll and randomize 36 children at 3 participating sites. This pilot trial will provide necessary data to plan the large-scale definitive trial, including assessment of facilitators and barriers of study participation, estimating enrollment and attrition rates, evaluating study procedures and interventions in a real- world setting, and determining adherence rates. In addition, we will demonstrate the ability to collect outcomes important to the future RCT, including clinical response, symptom resolution, adverse events and quality of life. The subsequent large RCT will be significant, as it will definitively address whether antibiotics are beneficial in low-risk children with CAP, representing an innovative departure from the status quo by shifting from empirical antibiotic use for all children with CAP to a targeted approach.