This pragmatic, clinical trial is the first, to our knowledge, to report on the performance of FilmArray RP panel for directly using in ED for outpatients by clinical staffs, on the outcomes including analysis of signal pathogen detected, analysis of co-pathogens 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, that yielded a detected rate of 72.6 % with a positive result in 270 passed specimens. Although, the PCR instrument was operated by clinical staff, only one of all samples failed. As the three groups divided by age in the analysis of signal pathogen detected, the group of ≤ 16 years had the highest positive rate of 81.6 %, followed by group of ≥ 50 years (66.7 %) and group of 16 - 49 years had the lowest positive of 65.8%. The trend of low detection rate of respiratory viral pathogens in adults is consistent with previous studies, Christine M. et al. have shown that with the increasing of age the positive rates with FilmArray RP panel are decreasing, and other studies with multiplex respiratory pathogens PCR also reported lower detected rates in the population of adults[3, 21, 22]. However, the whole detected rate in this study which resuls from the clinical staffs’ operation is higher than other studies in which all diagnosis with FilmArray RP panel, including the study of respiratory pathogens at tertiary care medical centers (age of 5 days to 91 years), ED or urgent care of pediatric patients, ward-based operating with in-patient and out-patient medical areas[7, 22-24]. It is possible that ED-based POC testing has a shorten time from sample collection to perform a FilmArray run than testing in specific tests settings. It is also possibly relating to the difference of time and sample size, the characters of age distribution of participants.
We noted the difference of detected number of respiratory pathogens in the result with a signal pathogen detected. Flu A was the most detected viral pathogen in three groups, Liu et al., Qian et al. and Jin et al. similarly observed that Flu A was the most detected pathogen in RTI in winter in their studies [16, 25, 26]. Rhino/Entero and RSV was the predominant virus for all age group but far more less than the most detected Flu A [19, 27]. Rhinovirus is a common virus of all seasons, as we all know, peaks of rhinovirus infections are well documented around September, a low positive rate of rhinovirus may be associated with the tendency of the doctors in ED to enroll patients with severe symptoms, because of the purchase price of a FilmArray RP panel is very expensive [3, 21].
M. pneumoniae was observed in three groups, and the positive rates of the children group and the old adult group are higher than that of group 16 - 49 years, in China, M. pneumoniae is reported as one of the most common pathogen of patients with CAP and it is an unexpected result in our study [25, 28]. With an overall detected rate of 4.1 % in the participants of 270, further revealing the diagnostic performance of FilmArray RP panel in ED’s application. B. pertussis cases were detected only in group ≤ 16 years with a positive rate of 7.9 % in 114 patients, at present, the using of culture and serology methods in diagnosis of pertussis are the only choice in China, FilmArray RP panel may help to manage the patient with suspected pertussis since it is difficult to identify other kinds respiratory pathogens for which often cause similar clinical symptoms like pertussis [29]. No C. pneumoniae case was detected in our study, the location of Beijing has a lowest incidence of reported C. pneumonia in the entire China with an incidence of 0.40 % and 2.97 % by Chen et al. and Zhao et al. respectively [30, 31].
Respiratory pathogens more than one were co-detected in 16.7 % of the 270 specimens in this study, unlikely, Jin et al. reported 25.5 % co-detected of patients from children aged 19 days to 15 years with RTI by FilmArray Respiratory Panel [16]. However, in adult, studies reported lower rates of approximately around 10 % and 15.9 % [19, 21]. For each Respiratory pathogen of co-detected, the largest proportion of which included RSV (17.3 %) and B. pertussis (17.3 %), and Flu A was the second common pathogen with a low positive rate (16.3 %) than that in the analysis of signal detected. Because of there was no laboratory testing for respiratory viral pathogens (except for Flu A and Flu B) at our hospital, the detections of multiplex respiratory organisms may be the most unexpected result for the clinical staffs in our ED, fully illustrating the value of FilmArray RP panel as a tool of POC testing in clinical department.
We found that patients whose detected with Flu A and Flu B received significantly lower antibiotic prescriptions and more anti-influenza prescriptions than who had a positive result of non-Flu A/B viral pathogen or with a negative result for all pathogens. The detection of a positive result for viral pathogen contributes to decrease the usage of antibiotic in patients with RTI in ED, which suggested that the using of FilmArray RP panel may be a good tool for reducing antibiotic prescriptions in outpatients with RTI. However, there was no evidence for significant decrease for the anti-influence prescriptions usage between non-Flu A/B viral pathogen detected patients and non-pathogen detected patients. Through without influenza A or B virus identified, the doctors were more likely to prescribe anti-influenza drugs for outpatients in winter season, this notice may be a hit for preventing inappropriate prescriptions of anti-influenza [32]. As for the effects of respiratory viral pathogens results on antimicrobial prescriptions rates including antibiotic and anti-influenza have been reported for mixed findings by previous studies, however, in our study, multiplex pathogens PCR system of FilmArray has shown the potential ability of reducing unnecessary antimicrobial prescriptions.
According the results of 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 non-pathogen detected group respectively. Antibiotic prescription rates were significantly different among the three groups ( c2 = 37.1, P < 0.001), with the highest rate of 50.0 % in non-pathogen detected patients in table 4. Between patients with non-Flu A/B virus pathogen detected and those who with non-pathogen detected there was significant difference about antibiotic prescription rates ( 28.8 % and 51.4 %, respectively, [ c2 = 8.2, P < 0.001]).The difference of anti-influenza prescription rates were also significant in three group ( c2 = 98.8, P < 0.001), with those detected with Flu A or Flu B receiving the most prescriptions ( 71.6 %). Anti-influenza prescription rates were no difference between patients with non-Flu A/B virus pathogen detected and those with non-pathogen detected (3.1 % and 8.1 %, respectively, [ c2 = 1.8, P = 0.194]). More detailed information is shown in Table 4.
However, there are numbers of limitations in this study. First, our study was a single-centre study and results from multicentre 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 the high cost of FilmArray RP panel we choose to implement our study only in a single winter season and we dose not own data from a complete year. Fourth, the study was conducted in ED which is special for infectious diseases other than general ED that including clinical staffs facing more kinds of diseases. Finally, the utility of FilmArray respiratory panel in the emergency department needs further evaluation in multicentre studies and more patients in ED.