Respiratory tract infections (RTIs) are a significant cause of morbidity and mortality worldwide, particularly during the winter months due to seasonal respiratory epidemics [
Compared to traditional tests such as direct fluorescence assays (DFA) and cell cultures, laboratory-developed polymerase chain reaction (PCR) tests have high sensitivity and specificity for the detection of respiratory pathogens, with shorter turnaround times (TAT) [
In this study, we undertook to describe the direct utility of the FilmArray RP as a POC test in our emergency department, which is known to manage a significant number of infectious diseases during the winter months due to seasonal respiratory epidemics among ED visitors. The aim of this study was to investigate the performance of the FilmArray RP system when utilized in a nonspecific test setting and with clinicians in a hands-on manner.
This single-center, open, observational study took place between October 2017 and February 2018 in Beijing Ditan Hospital (BJDH), affiliated with Capital Medical University, China. BJDH is a teaching hospital with 800 beds. As a specialized hospital for infectious diseases, we have a separate ED for patients with infectious diseases, and a large proportion of patients come to this ED for RTIs in winter. Participants were enrolled from the ED in BJDH, including patients with a fever or feeling feverish, or experiencing a cough, runny nose or stuffy nose, and fatigue or tiredness, who could be recruited directly from their first arrival at the ED, and possibly also presenting with vomiting or diarrhea. Patients were excluded if patients had experienced a fever for longer than 7 days or prescribed with antibiotics during the last 2 weeks, and we also excluded patients who presented in a state of unconsciousness, as well as those known to be HIV-infected. Written informed consent was obtained by the emergency department staff from the participants, or for children from the child’s parents or guardians. This study was approved by the Ethics Committee of BJDH.
The FilmArray RP was the first multiplex test implemented in the ED by clinical staff, so all clinical staff were educated about the manufacturer’s instructions by microbiology staff through personnel training on the operation of the FilmArray instrument. Clinical staff collected all the respiratory samples, consulting the standard operating procedure of clinical sample collection used in our hospital. Before the October start date of the study, all clinical staff undertook competency evaluations.
For the FilmArray RP assay, a nasopharyngeal swab for the respiratory sample was collected using a nylon flocked swab (Copan Diagnostics, Italy) at midturbinate, which was then placed in a viral transport medium (VTM, Copan Diagnostics) immediately. If respiratory virus detection was needed, the clinicians would take the nasopharyngeal swab from the patient’ nasopharynx for more than 5 seconds directly, and all results from the FilmArray RP assay were recorded in the statistics records. The clinicians performed the FilmArray could then give an antibiotic prescription according to the patient’s clinical manifestation, based on the results of the laboratory examination and the FilmArray RP assay. A trained assistant collected all clinical data and etiological information using a standard case report form and input this information into an electronic study database.
In this study, the FilmArray assay (FilmArray RP panel, BioFire Diagnostics, LLC, Salt Lake City, Utah) detected 20 targets of viral and atypical pathogens present in respiratory samples, including 17 respiratory viruses from the rhinovirus/enterovirus family (Rhino/Entero), respiratory syncytial virus (RSV), adenovirus (AdV), human metapneumovirus (hMPV), influenza B virus (Flu B), influenza A virus unsubtyped/H1/H3/2009H1 (Flu A/unsubtyped, Flu A/H1, Flu A/H3, and Flu A/2009H1), coronavirus 229E/HKU1/NL63/OC43 (Cov 229E, Cov HKU1, Cov NL63, and Cov OC43), parainfluenza 1/2/3/4 (PIV 1, PIV 2, PIV 3, and PIV 4), the bacterium
Patient demographic characteristics were collected, including age and gender. The clinical syndrome information included fever, cough, duration of symptoms, and if complicated with pneumonia. The clinical outcomes evaluated were antibiotic prescription and anti-influenza prescription. The data management software was Microsoft Excel 2015. All analyses in this study used IBM SPSS Statistics software v22.0 (StataCorp; USA) or Prism v6.0 (GraphPad Software; USA). The categorical variables of demographic and clinical characteristics and the clinical outcomes were shown in percentages and compared with Pearson’s chi-square test or Fisher’s exact test for differences. The white cell count, level of C-reactive protein, and lymphocytes were presented as a median (interquartile range). The differences in antimicrobials among groups with different pathogens detected were compared using Student's
Between 15 October 2016 and 31 February 2017, the study assessed 315 patients for eligibility, of whom 271 were eligible to participate. None of the participants withdrew from the study (Figure
Flowchart of study participants. The results from the detection of respiratory pathogens using the FilmArray respiratory panel.
General characteristics of enrolled patients.
Pathogen detected | Nonpathogen detected | |
---|---|---|
Male gender | 53.1% (104/196) | 55.4% (41/74) |
No. (%) of patients of age | ||
≤16 years | 93 (47.4) | 21 (28.4) |
16–49 years | 73 (37.2) | 38 (51.4) |
≥50 years | 30 (15.4) | 15 (20.4) |
No. (%) of patients of prescription during the last 2 weeks | ||
Antibiotic used | 10 (5.1) | 6 (8.1) |
Anti-influenza used | 6 (3.1) | 7 (10.8) |
No. (%) of patients of fever | 119 (60.7) | 60 (81.1) |
No. (%) of patients of coughing | 121 (61.7) | 62 (83.8) |
Duration of symptoms (days)a | 2.3 (1–2) | 3.4 (2–3) |
Complicated with pneumonia (%) | 40 (20.4) | 24 (32.4) |
White cell count (×109/L)a | 8.5 (4.52–9.40) | 9.28 (4.05–11.86) |
C-reactive protein (mg/L)a | 16.70 (2.40–19.30) | 28.86 (7.40–34.83) |
Lymphocytes (×109/L)a | 4.64 (1.26–5.73) | 3.03 (0.91–1.75) |
aMedian (IQR). Duration of symptoms: the time from patients had symptoms to visit the emergency department.
Overall, 151 (55.9%) of the 270 patients had a signal pathogen detected (Table
Prevalence of respiratory pathogens signal detected in different age groups.
Result | ≤16 years | 16–49 years | ≥50 years | Total | ||||
---|---|---|---|---|---|---|---|---|
No. | Prevalence (%, | No. | Prevalence (%, | No. | Prevalence (%, | No. | Prevalence (%, | |
Not detected | 21 | 18.4 | 38 | 34.2 | 15 | 33.3 | 74 | 27.4 |
Rhino/Entero | 6 | 5.3 | 7 | 6.3 | 4 | 8.9 | 17 | 6.3 |
RSV | 8 | 7.0 | 7 | 6.3 | 2 | 4.4 | 17 | 6.3 |
AdV | 1 | 0.9 | 1 | 0.9 | 0 | 0.0 | 2 | 0.7 |
hMPV | 0 | 0.0 | 2 | 1.8 | 0 | 0.0 | 2 | 0.7 |
Flu B | 2 | 1.8 | 2 | 1.8 | 2 | 4.4 | 6 | 2.2 |
FluA/H1 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 |
FluA/H3 | 16 | 14.0 | 22 | 19.8 | 12 | 26.7 | 50 | 18.5 |
FluA/2009 H1 | 8 | 7.0 | 7 | 6.3 | 0 | 0.0 | 15 | 5.6 |
Flu A unsubtyped | 2 | 1.8 | 7 | 6.3 | 2 | 4.4 | 11 | 4.1 |
Flu A total | 26 | 22.8 | 36 | 32.4 | 14 | 31.1 | 76 | 28.1 |
Cov 229E | 0 | 0.0 | 1 | 0.9 | 2 | 4.4 | 3 | 1.1 |
Cov HKU1 | 0 | 0.0 | 1 | 0.9 | 0 | 0.0 | 1 | 0.4 |
Cov NL63 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 |
Cov OC43 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 |
Cov total | 0 | 0.0 | 2 | 1.8 | 2 | 4.4 | 4 | 1.5 |
PIV1 | 2 | 1.8 | 0 | 0.0 | 0 | 0.0 | 2 | 0.7 |
PIV2 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 |
PIV3 | 3 | 2.6 | 0 | 0.0 | 1 | 2.2 | 4 | 1.5 |
PIV4 | 0 | 0.0 | 1 | 0.9 | 0 | 0.0 | 1 | 0.4 |
PIV total | 5 | 4.4 | 1 | 0.9 | 1 | 2.2 | 7 | 2.6 |
0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | |
6 | 5.3 | 3 | 2.7 | 2 | 4.4 | 11 | 4.1 | |
9 | 7.9 | 0 | 0.0 | 0 | 0.0 | 9 | 3.3 |
Rhino/Entero: rhinovirus/enterovirus; RSV
The highest prevalence of targeted pathogens in the three age groups was Flu A: the prevalence of Flu A in the groups ≤16 years, 16–49 years, and ≥50 years was 22.8%, 32.4%, and 31.1%, respectively. More specifically, the highest rate of Flu A from three distinguishable subtypes was FluA/H3 in all three age groups, with a rate of 26.7% in the group ≥50 years, followed by 19.8% in the group aged 16–49 years and 14.0% in the group ≤16 years. The other respiratory pathogens, such as Rhino/Entero (6.3%), RSV (6.3%), Flu B (2.2%), Cov (1.5%),
Among 270 patients, 45 had two or more respiratory pathogens codetected, with a rate of 16.7%. Among the 45 patients with codetected respiratory pathogens, 40 were codetected with dual pathogens, accounting for the majority of the sample. Four patients had triple pathogens codetected, and one had quadruple pathogens codetected. Rhino/Entero codetected with
Prevalence of respiratory pathogens in the copathogens detected groups.
In the 45 cases with codetected respiratory pathogens, the total number of detected pathogens was 98; RSV and
According to the results of the FilmArray RP panel, 98, 98, and 74 patients were assigned to the Flu A/B virus detected group, non-Flu A/B virus pathogen detected group, and nonpathogen detected group, respectively. Antibiotic prescription rates were significantly different among the three groups (
Antimicrobial prescription rates among patients.
No. (%) of patients with | Total | |||||
---|---|---|---|---|---|---|
Flu A/B | Non-Flu A/B viral pathogen | Nonpathogen | ||||
Total patients included | 97 | 52 | 74 | 223 | ||
Antibiotic prescription | 9 (9.3) | 15 (28.8) | 38 (51.4) | 62 (27.8) | 37.1 | <0.001 |
Oseltamivir prescription | 70 (72.2) | 6 (11.5) | 4 (5.4) | 80 (35.9) | 98.8 | <0.001 |
This pragmatic clinical trial is the first, to our knowledge, to report on the performance of the FilmArray RP panel for direct use in an ED for outpatients by clinical staff, in terms of outcomes including the analysis of the signal pathogen detected, analysis of copathogens detected, and antimicrobial prescription rates. After clinical staff training and personnel training, 271 specimens were detected over the winter season using the automated nested multiplex PCR system for pathogen detection, yielding a detection rate of 72.6% and a positive result in 270 specimens. Although the PCR instrument was operated by clinical staff, only one sample failed. When the three groups were divided by age in the analysis of signal pathogen detection, the group ≤16 years had the highest positive rate of 81.6%, followed by the group ≥50 years (66.7%), and the group aged 16–49 years had the lowest positive rate of 65.8%. The trend of low detection rates of respiratory viral pathogens in adults is consistent with previous studies; Christine et al. showed that with increasing age, the positive rates obtained with the FilmArray RP panel decrease, and other studies using multiplex respiratory pathogen PCR have also reported lower detection rates in adults [
We also note here differences in the detected number of respiratory pathogens in results where a signal pathogen was detected. Flu A was the most detected viral pathogen in all three groups; Liu et al., Qian et al., and Jin et al. similarly observed that Flu A was the most detected pathogen in RTIs in winter in their studies [
More than one respiratory pathogen was codetected in 16.7% of the 270 specimens in this study. Li et al. reported a rate of 25.5% codetected patients from among children aged 19 days to 15 years with RTIs when using the FilmArray Respiratory Panel [
We found that patients detected with Flu A and Flu B received significantly lower antibiotic prescriptions and more anti-influenza prescriptions than those who had a positive result for non-Flu A/B viral pathogens or had a negative result for all pathogens. The detection of a positive result for viral pathogens contributed to a decrease in the usage of antibiotics in patients with RTIs in ED, which suggested that the use of the FilmArray RP panel may be helpful in reducing antibiotic prescriptions in outpatients with RTIs. However, there was no evidence for a significant decrease in anti-influenza prescription usage between non-Flu A/B viral pathogen detected patients and nonpathogen detected patients. For those without influenza A or B virus identified, the clinicians were more likely to prescribe anti-influenza drugs for outpatients in the winter season, suggesting the prevention of inappropriate prescriptions of anti-influenza medications needs further attention [
According to the results of the FilmArray RP panel, 98, 98, and 74 patients were assigned to the Flu A/B virus detected group, non-Flu A/B virus pathogen detected group, and nonpathogen detected group, respectively. Antibiotic prescription rates were significantly different among the three groups (
However, there are a number of limitations in this study. First, our study was a single-center study, and results from multicenter need to be reported for verifying. Second, another possible limitation of our study is the bias from age among participants, as we all know, young children in which infected with RTI have a totally different percentages of respiratory pathogenic spectra. Third, because of the high cost of the FilmArray RP panel, we choose to implement our study only in a single winter season and we do not have access data covering a complete year. Fourth, the study was conducted in an ED which is specialized for infectious diseases, rather than general ED that included clinical staff facing a range of diseases. Finally, the utility of the FilmArray respiratory panel in the emergency department needs further evaluation in multicenter studies and with more patients in EDs.
We tested respiratory pathogens in patients with RTIs in an ED using the FilmArray respiratory panel undertaken by clinical staff, for the first time in China. We found that the FilmArray, an automated nested multiplex diagnostic PCR system, was a rapid and simple tool for clinical staff to utilize in a nonspecific test setting. The multiplex diagnostic system significantly increased the rate of respiratory pathogen detection, and clinical staff from the ED performed the FilmArray RP testing without too many “Invalid” results, suggesting that this diagnostic system has potential for use in many divergent clinical settings. Based on the results of the FilmArray RP panel, the unnecessary usage of antibiotic prescriptions and anti-influenza prescriptions in patients with nondetected pathogens may be reduced when they present to an ED.
FilmArray respiratory panel
Respiratory tract infections
Emergency department
Community-acquired pneumonia
Direct fluorescence assays
Turnaround time
Point of care
Beijing Ditan Hospital
C-reactive protein
Human immunodeficiency virus
Viral transport media.
All major data generated or analyzed during this study were included in this article.
This study was approved by the Ethics Committee of Beijing Ditan Hospital, with the reference 2017ZX10103004.
After informing the patients regarding the usage of samples and the aims of detection, written informed consent was obtained from each patient.
The funders had no role in the development or implementation of the research, analysis of results, or preparation of the manuscript.
There are no conflicts of interest.
YSY and WLH were responsible for conception and design of the study; WF, YD, and GGJ organized the database and had useful suggestions on the clinical significance of this case report; WLS, LD, and XDH contributed to the imaging diagnosis; YSY contributed to the molecular diagnostic experiments and wrote the first draft of the manuscript; WLH revised the discussion. All authors have read and approved the manuscript.
This study was supported by the National Major Science and Technology Project for the Control and Prevention of Major Infectious Diseases of China (2017ZX10103004) and Beijing Hospital Authority Project (DFL20191802).