Impact of Rapid Pathogen Detection in ICU Patients With Suspected Pneumonia on Antimicrobial Therapy: a Pilot, Randomized, Controlled Open-label Feasibility Trial (IRISPAT-1)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Time interval to appropriate antimicrobial therapy
研究概览
简要总结
The goal of this intervention trial is to determine the feasibility, safety, and potential impact of rapid respiratory pathogen detection by FA Pneumonia Panel on antibiotic therapy in mechanically ventilated critically ill patients with suspected pneumonia.
Participants will randomized to either have an urgent BioFire FA Pneumonia Panel assay performed or recieve standard of care to guide antimicrobial therapy and treatment of pneumonia.
详细描述
Pneumonia is the most common cause of sepsis requiring admission to the intensive care unit (ICU). Molecular pathogen detection techniques such as polymerase chain reaction (PCR) may help optimize antimicrobial therapy. Its utility for diagnosing respiratory viral infections such as influenza is well established, and was an essential diagnostic tool during the coronavirus 2019 (COVID-19) pandemic. However, its use remains limited for bacterial pathogens. The rationale to use PCR based bacterial detection to facilitate antibiotic stewardship is threefold. First, it may shorten the time to pathogen detection. Second, it has improved sensitivity over conventional culture techniques, particularly for pathogens that are difficult to culture. Third, it can detect resistant genes to inform antimicrobial sensitivity. Taken together, utilization of bacterial PCR may shorten time to appropriate antimicrobial therapy and minimize injudicious use of broad-spectrum antimicrobials in patients who do not have infection from MDRO.
The BioFire® FilmArray® Pneumonia Panel (FA Pneumonia Panel) is a PCR based in vitro assay which rapidly identifies 8 viral and 18 bacterial common pathogens in tracheal aspirate and bronchoalveolar lavage (BAL) samples. Clinical studies showed that FA Pneumonia Panel on BAL specimens have sensitivity of 75 to 100% and specificity of >91% for the pathogens tested. Retrospective analysis suggests utilizing FA Pneumonia Panel may facilitate discontinuation or de-escalation of antimicrobials in 48% of patients with an average reduction of 6 antibiotic days. However, currently there are no randomized controlled trials that assessed the efficacy of FA Pneumonia Panel on improving antimicrobial stewardship.
Addition of FA Pneumonia Panel to standard care should shorten time to pathogen and resistance detection, enhance sensitivity over conventional microbiological cultures and shorten time to appropriate antimicrobial therapy by reducing over-narrow and over-broad coverage. Robust clinical trials are now needed to test these hypotheses. We propose to conduct a pilot, randomized, controlled open-label trial designed to determine the feasibility, safety, and potential impact of rapid respiratory pathogen detection by FA Pneumonia Panel on antibiotic therapy in 40 mechanically ventilated critically ill patients with suspected pneumonia.
The goal is to determine the feasibility, safety, and potential impact of rapid respiratory pathogen detection by BioFire FilmArray Pneumonia Panel on antimicrobial therapy in 40 mechanically ventilated critically ill patients with suspected pneumonia.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
The antimicrobial stewardship review panel consisted of a microbiologist, an infectious diseases specialist and an intensive care physician that were blinded to study group allocation. At the study conclusion, the panel reviewed the clinical notes, imaging, laboratory data, conventional microbiological culture and FA Pneumonia Panel results to determine diagnosis, causative respiratory pathogen and appropriateness of antimicrobial therapy for each patient. A clinical diagnosis of pneumonia could be established even if a causative respiratory pathogen was not identified. Alternatively, non-infective diagnoses such as pulmonary oedema or secondary acute respiratory distress syndrome were attributed as the cause of respiratory failure if pneumonia was not present.
Appropriate antimicrobial therapy was defined as use of the narrowest spectrum antimicrobial agent relative to the pathogen's sensitivity pattern. For patients who are considered not to have respiratory infection after retrosp
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •adult (≥18 years old) ICU patients
- •mechanical ventilation
- •new antibiotic prescription within 24 hours for suspected community acquired, healthcare or ventilator associated pneumonia
- •suspected pneumonia is defined as any of purulent sputum, cough, fever, shortness of breath, hypoxia, hypercapnia or abnormal white cell count AND chest infiltrates on imaging
- •need for antibiotics other than suspected respiratory infection
- •aspiration pneumonia
- •suspected pneumonia due to tuberculosis
- •known respiratory pathogens within 7 days prior to randomization
- •given empirical antimicrobials for suspected Stenotrophomonas infection
- •lack of sufficient respiratory samples for culture and FA Pneumonia Panel
- •not expected to survive beyond 48 hours
- •limitation of therapy prior to recruitment
- •prisoners
- •allergy to antibiotics
- •immunosuppression from long term steroid of at least 5 mg/day or chemotherapy or HIV or haematological disease
- •pregnancy
排除标准
- 未提供
研究组 & 干预措施
FA Pneumonia Panel Guided Group
Patients in the FA Pneumonia Panel guided group will have a BioFire® FilmArray® Pneumonia Panel assay performed as soon as possible but within 24 hours of new antibiotic prescription for suspected respiratory infection in addition to all the investigations performed in standard care. Based on the rapid test results, antimicrobial therapy will be adjusted according to a pre-determined treatment algorithm and antimicrobial guidelines. The treatment algorithm and antimicrobial guidelines were based on the latest hospital antibiogram, procalcitonin protocol, and consensus recommendations from microbiologists, infectious disease experts and intensive care physicians at our hospital. The treating clinical team will also be given the standard microbiological culture with sensitivity results when available. The treating clinical team may override the pre-determined antimicrobial algorithm for any clinical reason at any time and the rationale will be recorded.
干预措施: FA Pneumonia Panel (Diagnostic Test)
Standard Care Group
Patients in the standard care group will receive antimicrobial therapy guided by conventional microbiological cultures and standardized procalcitonin protocol. Choice of antimicrobial agent is based on use of the narrowest-spectrum antimicrobial agent possible according to culture sensitivity. Current standard investigations for any patient mechanically ventilated for suspected pneumonia in our ICU includes two sets of blood cultures, alternative day procalcitonin, respiratory specimen of tracheal aspirate or bronchoalveolar lavage for bacterial gram stain and cultures, respiratory viral PCR and urine streptococcus and legionella antigen. FA Pneumonia Panel will be performed from concurrent respiratory samples in the standard care group at the end of the study and the results will not be used by the treating clinical team for treatment decisions. Blinded results will only be available to the antimicrobial review panel for outcome assessment.
结局指标
主要结局
Time interval to appropriate antimicrobial therapy
时间窗: 7 days
Defined as the time interval (hours) from time of randomization to earliest time that appropriate antimicrobial therapy is achieved as determined by the antimicrobial stewardship review panel.
次要结局
- Proportion of patients with appropriate antimicrobial therapy at 48 hours after randomization(48 hours)
- Ventilator free days(28 days)
- Time interval to pathogen detection(7 days)
- Proportion of patients who require re-initiation or escalation of antimicrobial therapy after 48 hours of discontinuation or de-escalation(7 days)
- Duration of antimicrobial therapy between FA Pneumonia Panel guided and standard care group(28 days)
- Vasopressor free days(28 days)
- ICU length of stay(28 days)
- 28-day mortality(28 days)
- Proportion of patients on broad-spectrum antibiotics at 48 hours after randomization(48 hours)
研究者
Lowell Ling
Clinical Assistant Professor
Chinese University of Hong Kong