Critically Ill, Pneumonia
Conditions
Keywords
infection, antimicrobial, antibiotics, multidrug resistant organisms, antibiotic stewardship, intensive care
Brief summary
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.
Detailed description
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.
Interventions
DIAGNOSTIC_TESTFA Pneumonia Panel
A single BioFire® FilmArray® Pneumonia Panel assay will be performed on a respiratory clinical specimen.
Sponsors
Chinese University of Hong Kong
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
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
Intervention model description
Pilot, randomized, controlled open-label trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time interval to appropriate antimicrobial therapy | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time interval to pathogen detection | 7 days | Defined as the time interval (hours) between culture or FA Pneumonia Panel sampling time to reporting time that confirmed the presence (with sensitivity pattern) or absence any causative pathogens from the tracheal aspirate or BAL sample taken after randomization. |
| Duration of antimicrobial therapy between FA Pneumonia Panel guided and standard care group | 28 days | Defined as the duration (hours) of antimicrobial therapy given after randomization until hospital discharge |
| Proportion of patients on broad-spectrum antibiotics at 48 hours after randomization | 48 hours | Defined as the proportion of patients who are prescribed carbapenem, tigecycline, ceftolozane-tazobactam, ceftaroline, ceftazidime/avibactam, linezolid, vancomycin, daptomycin, aztreonam or cefiderocol at 48 hours after randomization. |
| Ventilator free days | 28 days | Defined as the number of days free from mechanical ventilation 28 days after randomization. |
| Vasopressor free days | 28 days | Defined as the number of days free from vasopressor therapy 28 days after randomization. |
| ICU length of stay | 28 days | Defined as the duration (days) of ICU length of stay |
| 28-day mortality | 28 days | Defined as the all-cause mortality rate on or before 28 days after randomization |
| Proportion of patients with appropriate antimicrobial therapy at 48 hours after randomization | 48 hours | Defined as the proportion of patients with appropriate antimicrobial therapy at 48 hours after randomization as determined by the antimicrobial stewardship review panel |
| Proportion of patients who require re-initiation or escalation of antimicrobial therapy after 48 hours of discontinuation or de-escalation | 7 days | Defined as the proportion of patients who required restart or escalation of antimicrobial therapy after discontinuation or de-escalation after ≥ 48 hours |
Countries
Hong Kong
Outcome results
None listed