Division of Infectious Diseases, Department of Medicine, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada.
Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada.
PLoS One. 2022 Mar 23;17(3):e0265493. doi: 10.1371/journal.pone.0265493. eCollection 2022.
The use of broad-spectrum antibiotics is widespread in patients with COVID-19 despite a low prevalence of bacterial co-infection, raising concerns for the accelerated development of antimicrobial resistance. Antimicrobial stewardship (AMS) is vital but there are limited randomized clinical trial data supporting AMS interventions such as prospective audit and feedback (PAF). High quality data to demonstrate safety and efficacy of AMS PAF in hospitalized COVID-19 patients are needed.
This is a prospective, multi-center, non-inferiority, pragmatic randomized clinical trial evaluating AMS PAF intervention plus standard of care (SOC) versus SOC alone. We include patients with microbiologically confirmed SARS-CoV-2 infection requiring hospital admission for severe COVID-19 pneumonia. Eligible ward beds and critical care unit beds will be randomized prior to study commencement at each participating site by computer-generated allocation sequence stratified by intensive care unit versus conventional ward in a 1:1 fashion. PAF intervention consists of real time review of antibacterial prescriptions and immediate written and verbal feedback to attending teams, performed by site-based AMS teams comprised of an AMS pharmacist and physician. The primary outcome is clinical status at post-admission day 15 measured using a 7-point ordinal scale. Patients will be followed for secondary outcomes out to 30 days. A total of 530 patients are needed to show a statistically significant non-inferiority, with 80% power and 2.5% one-sided alpha assuming standard deviation of 2 and the non-inferiority margin of 0.5.
This study protocol presents a pragmatic clinical trial design with small unit cluster randomization for AMS intervention in hospitalized COVID-19 that will provide high-level evidence and may be adopted in other clinical situations.
This study is being performed at the University of Alberta and is registered at ClinicalTrials.gov (NCT04896866) on May 17, 2021.
尽管 COVID-19 患者中细菌合并感染的发生率较低，但广谱抗生素的使用仍很广泛，这引发了人们对加速出现抗菌药物耐药性的担忧。抗菌药物管理（AMS）至关重要，但支持 AMS 干预措施（如前瞻性审核和反馈（PAF））的随机临床试验数据有限。需要高质量的数据来证明在住院 COVID-19 患者中实施 AMS PAF 的安全性和有效性。
这是一项前瞻性、多中心、非劣效性、实用随机临床试验，评估 AMS PAF 干预加标准治疗（SOC）与 SOC 单独治疗的效果。我们纳入因严重 COVID-19 肺炎需要住院治疗的微生物学确诊 SARS-CoV-2 感染患者。在每个参与地点，在研究开始前，将根据 ICU 与普通病房进行分层的计算机生成分配序列对符合条件的病房床位和重症监护病房床位进行随机分组，比例为 1:1。PAF 干预包括实时审核抗菌药物处方，并立即向主治团队提供书面和口头反馈，由基于现场的 AMS 团队进行，该团队由 AMS 药剂师和医生组成。主要结局是通过 7 分序数量表在入院后第 15 天测量的临床状态。将对患者进行次要结局随访至 30 天。假设标准偏差为 2，非劣效性边界为 0.5，需要 530 名患者才能显示出具有统计学意义的非劣效性，效能为 80%，单侧α值为 2.5%。
本研究方案提出了一种实用的临床研究设计，采用小单位集群随机化方法对住院 COVID-19 患者进行 AMS 干预，将提供高级别的证据，并可能在其他临床情况下采用。
该研究正在阿尔伯塔大学进行，于 2021 年 5 月 17 日在 ClinicalTrials.gov 注册（NCT04896866）。
