FilmArray Respiratory Panel Research Articles

Rapid detection of respiratory organisms with the FilmArray respiratory panel in a large children\u2019s hospital in China

BackgroundRespiratory tract infections (RTIs) are the most common illness in children, and rapid diagnosis is required for the optimal management of RTIs, especially severe infections.MethodsNasopharyngeal swab or sputum specimens were collected from children aged 19 days to 15 years who were admitted to a hospital in Shanghai and diagnosed with RTIs. The specimens were tested with the FilmArray Respiratory Panel, a multiplex PCR assay that detects 16 viruses, Mycoplasma pneumoniae (M. pneumoniae), Bordetella pertussis (B. pertussis) and Chlamydophila pneumoniae (C. pneumoniae).ResultsAmong the 775 children studied, 626 (80.8%, 626/775) tested positive for at least one organism, and multiple organisms were detected in 198 (25.5%). Rhinoviruses/enteroviruses (25.5%, 198/775) were detected most often, followed by respiratory syncytial virus (19.5%, 151/775), parainfluenza virus 3 (14.8%, 115/775), influenza A or B (10.9%), adenovirus (10.8%), M. pneumoniae (10.6%) and B. pertussis (6.3%). The prevalence of organisms differed by age, and most of the viruses were more common in winter. Of the 140 children suspected of having pertussis, 35.0% (49/140) tested positive for B. pertussis.ConclusionsFilmArray RP allows the rapid simultaneous detection of a wide number of respiratory organisms, with limited hands-on time, in Chinese pediatric patients with RTIs.

Clinical impact of rapid molecular detection of respiratory pathogens in patients with acute respiratory infection

BackgroundAcute respiratory infections (ARI) are a leading cause of morbidity and mortality worldwide. There is a need to demonstrate the clinical impact of using the new, rapid and sensitive molecular assays in prospectively designed studies. ObjectivesTo study the impact on medical management of a rapid molecular assay in patients with respiratory infections. Study designA prospective, randomized, non-blinded study was performed in patients presenting to the Emergency Department during two respiratory seasons (2016–2017). Diagnosis was performed by FilmArray Respiratory Panel (FilmArray-RP) or by immunofluorescence assay (IFA). ResultsA total of 432 patients (156 children and 276 adults) were analyzed. Diagnosis with FilmArray-RP was associated with significant changes in medical management including withholding antibiotic prescriptions (OR:15.52, 95%CI:1.99–120.83 in adults and OR:12.23, 95%CI:1.56–96.09 in children), and reduction in complementary studies in children (OR:9.64, 95%CI:2.13–43.63) compared to IFA. Decrease in oseltamivir prescriptions was significantly higher in adults in the FilmArray-RP group (p = 0.042; OR:1.19, 95%CI:0.51-2.79) compared to adults managed with IFA. Diagnostic yield was significantly higher by FilmArray-RP (81%) than by IFA (31%)(p < 0.001). The median time from sample collection to reporting was 1 h 52 min by FilmArray-RP and 26 h by IFA (p < 0.001). ConclusionsThe high respiratory viruses’ detection rate and availability of results within two hours when using FilmArray-RP were associated with decreases in antibiotic prescriptions and complementary studies and more accurate use of oseltamivir.

Comparison of the Biofire FilmArray Respiratory Panel, Seegene AnyplexII RV16, and Argene for the detection of respiratory viruses

BackgroundRespiratory infections are common reasons for hospital admission, and are associated with enormous economic burden due to significant morbidity and mortality. The wide spectrum of microbial agents underlying the pathology renders the diagnosis of respiratory infections challenging. Molecular diagnostics offer an advantage to the current serological and culture-based methods in terms of sensitivity, coverage, hands-on time, and time to results. ObjectivesThis study aimed to compare the clinical performance of three commercial kits for respiratory viral detection. Study designThe performance of FilmArray Respiratory Panel, AnyplexII RV16, and Argene was compared using clinical respiratory samples (n = 224, comprising 189 nasopharyngeal swabs in Universal Transport Medium (UTM) and 35 endotracheal aspirates), based on common overlapping targets across the platforms. Influenza A “equivocal” and “no-subtype” samples by FilmArray were further compared to a laboratory-developed Influenza A/B test. Results and ConclusionsThe overall performance of all three platforms appeared to be comparable with regards to sensitivities (95.8–97.9%) and specificities (96.1–98.0%), detection of coinfections, and distinguishment of influenza from non-influenza cases. “Equivocal” and “no-subtype” samples by FilmArray mostly represented weak Influenza A by laboratory-developed test. Lower respiratory tract samples had comparable final-run success-rates and discordant-rates as compared to UTM. Coronavirus HKU1, which was not targeted by AnyplexII RV16, were detected as OC43. The expected test volume would be the main determinant for the selection of platform. Among the platforms, the FilmArray is the most automated but is of the lowest-throughput and has the highest reagent cost.

Impact of Nasopharyngeal FilmArray Respiratory Panel Results on Antimicrobial Decisions in Hospitalized Patients.

Objective To determine whether results of the nasopharyngeal FilmArray respiratory panel (NP-FARP) influenced antibiotic decisions. Methods We reviewed the medical records of nonintensive care unit (ICU) inpatients that had an NP-FARP performed at our institution between June 2013 and June 2014. The inpatient records were reviewed 48 hours after the NP-FARP for the following data: demographic information; NP-FARP, serum procalcitonin, and methicillin-resistant Staphylococcus aureus nasal swab (MRSA NS) results; antibiotics prior and post-48 hours of the NP-FARP result; and the current immunosuppression status. Clinical outcome data were not obtained. Patients were categorized into those who had a positive (+) or a negative (−) NP-FARP. We further subdivided these two categories into groups A, B, and C based on the antibiotic modifications 48 hours after their NP-FARP result. Group A included patients who were never initiated on antimicrobial therapy. Patients whose antibiotics were discontinued or deescalated were placed in group B. Patients with antibiotic escalation or continuation without change constituted group C. We compared and analyzed groups A, B, and C in the (+) and (−) NP-FARP cohorts. Results A total of 545 patients were included. There were 143 (26%) patients with positive and 402 (74%) patients with negative NP-FARPs. Comparison of groups A, B, and C between those with a (+) and (−) NP-FARP were as follows: (+) A and (−) A, 28/143 (20%) and 84/402 (21%); (+) B and (−) B, 59/143 (41%) and 147/402 (37%); and (+) C and (−) C, 56/143 (39%) and 171/402 (43%), respectively. We found no statistically significant differences between groups (+) A versus (−) A, (+) B versus (−) B, and (+) C versus (−) C with respect to age, gender, MRSA NS result, procalcitonin result, or concurrent immunosuppression. Conclusion In non-ICU inpatients, NP-FARP alone or in combination with procalcitonin or MRSA NS did not influence antibiotic decisions during the study period.

Evaluation of FilmArray respiratory panel multiplex polymerase chain reaction assay for detection of pathogens in adult outpatients with acute respiratory tract infection.

Although viruses are the major pathogen that causes upper respiratory tract infection (URTI) and acute bronchitis, antibiotics have been prescribed. This was a prospective observational study in influenza epidemics that enrolled adult outpatients who visited a hospital with respiratory tract infection symptoms. In this study, we evaluated the usefulness of FilmArray respiratory panel (RP). Fifty patients were enrolled. FilmArray RP detected the pathogens in 28 patients. The common pathogens were influenza virus (n = 14), respiratory syncytial virus (n = 6), and human rhinovirus (n = 6). Of the 14 patients with influenza virus, 6 were negative for the antigen test. The physicians diagnosed and treated the patients without the result of FilmArray in this study. Of the patients with positive FilmArray RP, 9 were treated with antibiotics; however, bacteria were detected in only 3 patients. By implementing FilmArray RP, URTI and acute bronchitis would be precisely diagnosed, and inappropriate use of antibiotics can be reduced.

Age-related prevalence of common upper respiratory pathogens, based on the application of the FilmArray Respiratory panel in a tertiary hospital in Greece.

The FilmArray Respiratory Panel (FA-RP) is an FDA certified multiplex PCR that can detect 17 viruses and 3 bacteria responsible for upper respiratory tract infections, thus it is potentially useful to the assessment of the age-related prevalence of these pathogens.In this observational study, we retrospectively analyzed the results of all the respiratory samples, which had been processed during 1 year-period (November 2015 to November 2016) with the FA-RP, in the Central Laboratories of Hygeia & Mitera General Hospitals of Athens, Greece. In order to have an age-related distribution, the following age groups were implemented: (<2), (≥2, <5), (≥5, <10), (≥10, <18), (≥18, <45), (≥45, <65), and (≥65) years old.Among 656 respiratory samples tested, 362 (55%) were from male and 294 (45%) from female patients, while 356 (54.3%) were positive and 300 (45.7%) negative. In the first age-group (<2), 41/121 samples (33.9%) revealed human rhinovirus/enterovirus (HRV) and 16 (13.2%) adenovirus (Adv), followed by respiratory syncytial virus (RSV), coronavirus, human metapneumovirus (Hmpv), and parainfluenza viruses (PIV). In the age-group (≥2, <5), Adv predominated with 37/147 samples (25.2%), followed by HRV, RSV, coronavirus (all types), and influenza, Hmpv and PIV. In the age-group (≥5, <10), HRV was identified in 25/80 samples (31.3%), Adv in 18 (22.5%), influenza in 11 (13.8%), and Hmpv in 6 (7.5%). Influenza predominated in the age-group (≥10, <18), with 4/22 samples (18.2%), while in the remaining age-groups (≥18), HRV was the commonest isolated pathogen, 33/286 (11.5%), followed by influenza with 20 (7%) (influenza A H1-2009, 11/20).In our patient series, HRV seemed to prevail in most age-groups, followed by Adv, although Influenza was the second most frequent pathogen isolated in the age-groups (≥18). Moreover, increasing age corresponded to increasing possibility of having a negative sample, indicating that FilmArray may be more useful before adolescence.

Characterization of respiratory infection viruses in hospitalized children from Naples province in Southern Italy.

Most acute respiratory infections (ARIs) in children are due to viral etiology, and represent an important cause of mortality and morbidity in children <5 years old in developing countries. The pathogens that cause ARIs vary geographically and by season, and viruses serve a major role. In the present study, the distribution of the seven respiratory viruses that are more prevalent in Southern European countries were retrospectively analyzed in a Southern Italy Hospital, that centralizes pediatric diseases from the Naples province. Viruses were categorized by a FilmArray Respiratory Panel, and demonstrated no substantial differences in sex, age and seasonal viruses distribution. However, all the investigated viruses had a higher detection rate in the surrounding municipalities than in the metropolitan area of Naples. In recent years, the association between air pollution and respiratory infections has become an increasing public health concern. The data in this study support this association in the surrounding areas of Naples extensively contaminated by environmental toxic agents. In these areas, characterization of the epidemiology of ARIs is required to implement a prevention and control program.

Multicenter Evaluation of the ePlex Respiratory Pathogen Panel for the Detection of Viral and Bacterial Respiratory Tract Pathogens in Nasopharyngeal Swabs

ABSTRACTThe performance of the new ePlex Respiratory Pathogen (RP) panel (GenMark Diagnostics) for the simultaneous detection of 19 viruses (influenza A virus; influenza A H1 virus; influenza A 2009 H1 virus; influenza A H3 virus; influenza B virus; adenovirus; coronaviruses [HKU1, OC43, NL63, and 229E]; human rhinovirus/enterovirus; human metapneumovirus; parainfluenza viruses 1, 2, 3, and 4; and respiratory syncytial virus [RSV] [RSV subtype A and RSV subtype B]) and 2 bacteria (Mycoplasma pneumoniae and Chlamydia pneumoniae) was evaluated. Prospectively and retrospectively collected nasopharyngeal swab (NPS) specimens (n = 2,908) were evaluated by using the ePlex RP panel, with the bioMérieux/BioFire FilmArray Respiratory Panel (BioFire RP) as the comparator method. Discordance analysis was performed by using target-specific PCRs and bidirectional sequencing. The reproducibility of the assay was evaluated by using reproducibility panels comprised of 6 pathogens. The overall agreement between the ePlex RP and BioFire RP results was >95% for all targets. Positive percent agreement with the BioFire RP result for viruses ranged from 85.1% (95% confidence interval [CI], 80.2% to 88.9%) to 95.1% (95% CI, 89.0% to 97.9%), while negative percent agreement values ranged from 99.5% (95% CI, 99.1% to 99.7%) to 99.8% (95% CI, 99.5% to 99.9%). Additional testing of discordant targets (12%; 349/2,908) confirmed the results of ePlex RP for 38% (131/349) of samples tested. Reproducibility was 100% for all targets tested, with the exception of adenovirus, for which reproducibilities were 91.6% at low virus concentrations and 100% at moderate virus concentrations. The ePlex RP panel offers a new, rapid, and sensitive “sample-to-answer” multiplex panel for the detection of the most common viral and bacterial respiratory pathogens.

Laboratory Impact of Rapid Molecular Tests used for the Detection of Respiratory Pathogens

With outbreaks of new respiratory viruses such as the severe acute respiratory syndrome coronavirus and swine-origin influenza A/H1N1, the nucleic acid-based amplification test was introduced to identify causative agents. Multiplex PCR, which can simultaneously detect various respiratory pathogens, is currently used worldwide. Recently, a new type of multiplexed molecular test using a fully automated workflow system was developed, which was also adapted to our laboratory. In this study, we assessed improvements in laboratory practice brought about by the implementation of the rapid test for the detection of respiratory viruses. We investigated the number of routine and rapid tests conducted as well as the change in monthly test frequency of the routine test. We also analyzed the waiting time, turnaround time, and lead time for the routine and rapid tests. The Anyplex II RV16 detection kit (Seegene, Seoul, Korea) and Filmarray Respiratory Panel (BioFire Diagnostics, Inc., Salt Lake City, UT, USA) were used for the routine and rapid tests, respectively. Compared to the routine test, the rapid test significantly (p < 0.01) decreased the mean waiting time (1 hour 46 minutes), turnaround time (1 hour 45 minutes), and lead time (3 hours 32 minutes). After the implementation of the rapid test, the number of routine tests conducted was reduced over the 5-month period, from 13 times a month to 3 times a month. The implementation of the rapid test for the detection of respiratory viruses improved the diagnostic efficiency of the laboratory and greatly reduced lead time.

Evaluation of Allplex Respiratory Panel 1/2/3 Multiplex Real-Time PCR Assays for the Detection of Respiratory Viruses with Influenza A Virus subtyping

The Allplex Respiratory Panel 1/2/3 (All16) is a multiplex PCR assay for detecting 16 respiratory viruses with influenza A virus (FluA) subtyping, and the first clinical assay based on multiple detection temperatures. We compared the results between All16 and Anyplex II RV16 (Any16) in 426 clinical samples. Samples showing discrepancies between the two tests were further tested using monoplex PCR. FluA subtyping based on the hemagglutinin type results of All16, which yielded H1, H3, and non-H1/H3, was compared with the results of the BioFire FilmArray respiratory panel. The positive and negative percent agreements and kappa value for each virus between All16 and Any16 ranged from 54.5-100.0%, 84.7-100.0%, and 0.57-1.00, respectively. FluA subtype results from All16 for 26 samples were consistent with those from FilmArray. Good agreement was observed between the two methods, except when analyzing human enterovirus (kappa value 0.70), and the All16 showed reliable FluA subtyping results. For parainfluenza virus 3, the All16 was more sensitive than Any16. When testing 28 samples simultaneously, the mean test time and hands-on time were 4.3 and 0.5 hours, respectively in All16. In conclusion, All16 showed reliable performance, but further studies are needed regarding human enterovirus analysis.

Feasibility and Validation of Viral Respiratory Disease Surveillance in a Combat Theater Using the Filmarray Respiratory Panel

BackgroundViral respiratory infections are a significant threat to deployed military units. Pathogen-based surveillance may be hampered by limitations in trained personnel in theater, difficulty with specimen shipment, and technical issues with equipment maintenance. In this project, we evaluated the performance of the FilmArray respiratory panel at military clinics in Afghanistan and compare results to testing performed in the United States.MethodsParticipants were recruited after presenting at military clinics at Bagram Airfield (BAF), Afghanistan, in 2013–2014 with fever (≥38° C) and respiratory symptoms (cough, dyspnea, chest pain, and/or sore throat). General medical laboratory staff at BAF were trained to operate the FilmArray; nasopharyngeal swabs were obtained and tested in-theater using the FilmArray respiratory panel (Biofire Diagnostics, Salt Lake City, UT). Samples were then shipped to the USAFSAM Applied Technology Center in 50% RNALater (Qiagen, Valencia, CA) without dry ice and then retested using the same panel. Selected influenza isolates then underwent sequencing to evaluate for potential novel circulating strains.Results29 specimens underwent testing. A virus was identified on FilmArray in 22/29 specimens at BAF and 24/29 specimens at USAFSAM, of whom 17/29 had influenza A. Positive results between BAF and USAFSAM were concordant in all cases; 2 of the negative results at BAF were identified as having influenza A and rhinovirus, respectively. Among those with influenza A, all but one had undergone seasonal influenza vaccination. 5 influenza isolates then underwent sequencing; 2 were A(H1N1pdm09) consistent with the predominant 2012–2013 strain, while 3 were A(H3N2) viruses with HA mutations that differed from those in the 2013–2014 vaccine strain. No resistance-associated neuraminidase mutations were identified.ConclusionSurveillance using the FilmArray system is effective and feasible in theater by general laboratory staff. H1N1 and H3N2 influenza A viruses predominated in this sample of acute respiratory infections in a deployed military setting despite high vaccination rates. The use of the RNALater preservative is an effective method for specimen transport without requiring a cold chain and may facilitate biosurveillance in remote settings.Disclosures All authors: No reported disclosures.

Acute Flaccid Myelitis Cases Presenting During a Spike in Respiratory Enterovirus D68 Circulation: Case Series From a Single Pediatric Referral Center.

BackgroundIn 2014, a global outbreak of Enterovirus D68 (EV-D68) caused severe respiratory disease and was associated with an increase in acute flaccid myelitis (AFM) cases. Despite heightened surveillance, both EV-D68 detection and AFM reporting dropped in 2015. As AFM reporting increased in 2016, we sought to better understand AFM and EV-D68 epidemiology at our institution.MethodsChart review of clinical presentation and workup was conducted on patients meeting the case definition for AFM for 2015-16. To determine EV-D68 prevalence at CHLA, samples positive for Rhinovirus/Enterovirus (RV/EV) by FilmArray® Respiratory Panel (FA-RP) in September 2016 were screened for EV-D68 by RT-PCR. Results were compared with a research algorithm developed within the FilmArray®Trend epidemiology software. After establishing accurate EV-D68 prediction, the algorithm was used on historic FA-RP assays to measure EV-D68 prevalence at CHLA in 2015 and 2016.Results7 patients with a median age of 3.3 years and no significant past medical history presented with AFM between July 15 - October 15, 2016, while none were identified in 2015. All had acute onset patchy weakness involving mostly the upper limbs and grey matter involvement on MRI. 6/7 reported fever/upper respiratory infection prior to AFM onset. CSF from 7/7 was negative by FilmArray®meningitis/encephalitis Panel and 2/7 were positive for EBV DNA. Further work up on CSF and blood were negative. 4/7 (57.1%) patients were RV/EV positive from respiratory samples and 3 were confirmed as EV-D68 by RT-PCR. IVIG was given in 7/7 cases. Patients were discharged after an average of 8.8 (4.8-13.6) days. The FilmArray Trend monitoring revealed that during the time of AFM presentation in 2016, 226/778 patients tested for respiratory viruses by the FA-RP were positive for RV/EV. Of those, 29.2% (66/226) were positive for EV-D68 compared with 0.02% (2/224) over the same period in 2015.ConclusionAs shown by CDC surveillance data, we saw a resurgence of AFM cases in 2016 compared with 2015. All 7 patients identified were previously healthy and had persistent weakness at discharge. Cases were accompanied by increases in circulating respiratory EV-D68. Further investigation of the correlation between EV-D68 resurgence and AFM is warranted.Disclosures L. Meyers, BioFire Diagnostics: Employee, Salary. J. Jones, Biofire Diagnostics LLC: Employee, Salary. J. Dien Bard, BioFire: Consultant and Investigator, Research grant and Speaker honorarium.

Impact of a Pharmacist-Driven Respiratory Viral Panel Stewardship Program on Antibiotic Exposure Within a Multicenter Community Health System

BackgroundStrategies to ensure optimal use of multiplex polymerase chain reaction (mPCR) testing results for antimicrobial stewardship in acute respiratory infections remain to be elucidated. This study sought to assess the impact of pharmacist intervention (by means of prospective feedback to prescribers) on overall antibiotic exposure in patients with viral-positive mPCR Respiratory Viral Panel (RVP) laboratory test results.MethodsThis retrospective cohort study included patients ≥18 years of age admitted to an acute care hospital with a viral-positive nasopharyngeal FilmArray Respiratory Panel test result receiving antibiotics for a suspected respiratory tract infection. Immunocompromised patients, patients with RVP samples from bronchiolar lavage, patients in the intensive care unit when samples were obtained, and patients receiving antibiotics for non-respiratory infections were excluded. Antibiotic exposure days, antibiotic discontinuation at 72 hours, and culture-positive bacterial superinfection were compared in two cohorts of patients, before and after the rollout of an educational pharmacist RVP stewardship initiative.ResultsMedian antibiotic exposure days did not differ between the pre- and post-intervention groups (6 days vs. 7 days, P = 0.20). Antibiotic discontinuation at 72 hours was significantly lower in the post-intervention group (38% vs. 25%, P = 0.02). More patients in the post-intervention group had positive bacterial respiratory cultures (2.7% vs. 10%, P = 0.007) and chest radiographs suggestive of pneumonia (34.7% vs. 46%, P = 0.05). Patients with peak serum procalcitonin levels <0.25 ng/mL were more likely to have antibiotics discontinued at 72 hours than those with peak levels ≥0.25 ng/mL (36% vs. 0%, P = 0.02).ConclusionAn antimicrobial stewardship initiative by pharmacists among patients with viral-positive RVP results did not appear to impact antibiotic exposure days. Serum procalcitonin levels appeared to influence antibiotic discontinuation decisions. Alternative strategies for maximizing the antimicrobial stewardship impact of RVP testing should be explored.Disclosures All authors: No reported disclosures.

BioFire FilmArray Decreases Infection Control Isolation Times by 4 days in ICU, BMT and Respiratory Wards

BackgroundNovel, rapid, syndromic testing of patients presenting with respiratory infections has the potential to improve patient access and care by decreasing time to diagnosis. BioFire FilmArray (BioFire Diagnostics, bioMerieux) is a cartridge-based, multiplex PCR platform capable of detecting 17 viral and 3 bacterial targets in one hour. This study assessed the impact of implementing this technology on the duration of infection control isolation.MethodsA randomized control trial in a 900-bed tertiary-care academic hospital was conducted between December 2016 and January 2017. Fifty consecutive samples of patients with respiratory infections on our ICU, BMT and Respiratory wards to received either BioFire FilmArray Respiratory Panel (BF) diagnostic testing or our routine diagnostic testing (RO) consisting of an influenza A/B/RSV PCR (in-house) followed by Luminex NxTag Respiratory Pathogen Panel that was batched at a reference lab. Five patient charts with missing data were excluded from analysis. Statistical analysis was completed using RStudio Version 1.0.136 – © 2009–2016 RStudio, Inc.ResultsPatients randomized to the BF arm remained on respiratory isolation precautions on average (42.3 ± 72.9 hours) over 100 hours less than patients randomized to the routine arm (151.3 ± 151.8 hours) (95% CI: 35.6–184.4 hours, P = 0.0052).ConclusionImplementing the BioFire FilmArray Respiratory Panel decreased infection control isolation time by approximately 4 days compared with routine testing; further study is warranted to determine the impact of this technology on patient outcomes and cost benefit. Table 1: Mean Hours in Respiratory Isolation is Statistically Significantly Decreased with BioFire FilmArray Respiratory Panel Arm N Mean (hours) SD (hours) Median (hours) 95% CI* P value* BioFire24 42.3 72.9 8.2 35.6–184.4 0.005253 Routine21152.3151.867.0*Welch two-sample t-test (assumed unequal variance), significance set at p≤0.05Figure 1The majority of patients randomized to receive BioFire testing were in respiratory isolation for less than 50 hours.Disclosures T. Wong, bioMerieux: Investigator, Research grant A. Stefanovic, bioMerieux: Investigator, Research grant E. Bryce, bioMerieux: Investigator, Research grant J. M. Grant, bioMerieux: Investigator, Research grant D. Roscoe, bioMerieux: Investigator, Research grant

The Impact of Biofire Filmarray Respiratory Panel on Antibiotic Usage in the Emergency Department at an Academic Medical Center

BackgroundBiofire respiratory panel is a multiplex PCR test designed to detect 17 pathogens within 1 hour. It has greater sensitivity, specificity, and number of pathogens detected compared with older testing methods. The aim of this research was to evaluate the impact of Biofire respiratory panel on antibiotic usage in the emergency department (ED) of an academic medical center.MethodsThis was an observational chart review. Patients with positive RSV or influenza rapid antigen test or PCR test, and patients with a positive Biofire test were included. RSV or influenza tests were reviewed from July to December 2015, and Biofire tests were reviewed from July to December 2016. The primary outcome was to evaluate the duration of antibiotic therapy in patients with viral respiratory infections diagnosed with RSV and influenza rapid antigen and PCR testing compared with Biofire viral respiratory panel. Secondary outcomes included virus type, antibiotic prescription rates on discharge, number of addmissions, procalcitonin levels, and oseltamivir usage.ResultsIn 2016, 67% (105/155) of biofire tests were positive. The most common pathogen was rhinovirus and enterovirus (42%). Of the positive results, 23/105 (22%) received antibiotics with 6 patients having antibiotics discontinued within 72 hours. Another 6 patients had bacterial coinfections. A total of 18/105 (17%) received antibiotic prescriptions on discharge. Median days of therapy (DOT) in hospital was 1 day and median DOT for prescriptions was 8.5 days. There were 5 procalcitonin tests and no oseltamivir usage. Overall 38/105 (36%) patients were admitted to inpatient. In 2015, 3% (20/1313) of RSV (14) and influenza (6) rapid antigen and PCR tests were positive. A total of 5/20 (25%) patients received antibiotics, with 3/20 (15%) patients receiving a prescription for outpatient antibiotics. Median DOT in the hospital was 3 days and median DOT for prescriptions was 10 days. There were 2 procalcitonin tests and 2 cases used oseltamivir. Overall 19 patients were admitted.ConclusionAntibiotics are witheld in the majority of patients with positive Biofire testing. Most patients were treated with supportive care measures only. Biofire continues to be a useful tool to identify candidates for antibiotic avoidance in the ED at our institution.Disclosures All authors: No reported disclosures.

Human Adenovirus (HAdV) Viremia in Immunocompetent Children with HAdV Infection in Respiratory Specimens: Does Viremia Predict Severity of Illness?

BackgroundThe interpretation of HAdV PCR from upper respiratory tract (RT) specimens can be challenging due to prolonged low grade viral shedding. We hypothesized that HAdV detection in the blood (viremia) is more common in acute HAdV infection with high respiratory viral burden (VB) compared with those with low VB in the RT. We sought to determine the frequency of HAdV viremia in immunocompetent children who have detectable HAdV in the RT.MethodsWe prospectively identified + HAdV in RT specimens from emergency department or inpatients using semi-quantitative real-time PCR (Ct <40) or multiplex respiratory viral PCR (FILMARRAY RESPIRATORY PANEL v1.7) and prospectively collected available whole blood from 8/2013 to 2/2015. Blood was considered positive for HAdV if Ct was <40 in whole blood. We compared virologic, including HAdV type from the RT and blood, and clinical characteristics between viremic and non-viremic groups using Mann–Whitney or chi-square as appropriate.ResultsThere were 196 unique patients with + HAdV in RT specimens as well as available blood for PCR (median age=1.3 years old). Blood and RT samples were obtained on the same calendar day in 78% of patients. Among these 196 patients, 163 (83%) were hospitalized and 58 (36%) were admitted to PICU. HAdV was detected in the blood in 33% of patients. Upper respiratory tract infections were more common (P = 0.026) and the duration of fever at the time of enrollment was longer in the viremia group (3 vs. 2 days, P = 0.043). There was no difference in ICU admission between two groups. Coinfections with bacterial pathogens from sterile sites were only found in the non-viremic group (4%); these included S. aureus or pneumococcal bacteremia, E. coli urinary tract infections, or pneumococcal pneumonia. HAdV VB in RT were significantly higher in the viremia group (Ct median 25.01 vs.. 36.38, P < 0.0001). Species C was more predominant in the viremia group compared with non C (A, B/E, D, F) (P = 0.018). RT type was 100% concordant with blood type.ConclusionHAdV viremia is relatively common in immunocompetent children with HAdV infection in the RT. Subjects with viremia had significantly higher VB in the RT, but this didn’t seem to be correlated with disease severity. HAdV viremia may be useful tool to add further evidence of acute HAdV infection.Disclosures A. Leber, BioFIre Diagnostics: Research Contractor and Scientific Advisor, Research support, Speaker honorarium and Travel expenses

A Cloud Based Epidemiology Network to Investigate Geographical Dynamics of Respiratory Disease

Background Real-time data collection of respiratory disease is important for understanding the spatiotemporal dynamics of disease transmission in the US. Healthcare professionals use tools such as FluView to help identify local pathogen circulation; however, these tools are limited to syndromic surveillance, and track a limited set of pathogens. Understanding respiratory disease dynamics requires 1) a large, pathogen rich data set 2) geographically dispersed data sources, and 3) fine temporal resolution. Here we utilize FilmArray® Trend, a research epidemiology system containing exported data from FilmArray® Respiratory Panel (RP) tests, to investigate geographic patterns of 20 common pathogens.Methods Over 6,000,000 individual pathogen assays from 19 clinical sites were exported to the Trend database from 2013 to present. Trend data were smoothed and normalized to produce the time series of pathogen incidence. A cross-correlation analysis was performed to compare sites to one another and determine offset of pathogen incidence. The results were plotted on a map of the US with visual indicators of correlation strength and directional movement as defined by cross-correlation lag values.ResultsThe respiratory pathogens detected by the FilmArray RP test show a diverse set of spatial and temporal behaviors Most striking was the spread of the virus Coronavirus OC43, and Respiratory Syncytial Virus (RSV), with RSV traveling from east coast sites to west coast sites across the US over 20 days. In contrast Parainfluenza virus 3 (PIV3) shows a small cross-correlation lag across all of the Trend sites during the regular summer season, indicating near simultaneous onset of detection nationwide. A localized cluster of PIV3 in the winter of 2016 was observed in the midwest and west, identifying the significance of localized regional trends.Conclusion FilmArray Trend shows great promise in deciphering spatiotemporal dynamics of these common respiratory pathogens. This system can identify localized outbreaks and directional movement of pathogens over time. Future work with finer geographic distribution of contributing sites will aide in making conclusions regarding spatial dynamics of all 20 RP pathogens. Other pathogen transmission models may also be explored using this data set.Disclosures C. Cook, BioFire Diagnostics: Employee, Salary. A. Wallin, BioFire Defense: Employee, Salary. A. Faucett, BioFire Diagnostics: Employee, Salary. L. Meyers, BioFire Diagnostics: Employee, Salary

Surveillance of upper respiratory infections using a new multiplex PCR assay compared to conventional methods during the influenza season in Taiwan

ObjectivesTo improve diagnosis as part of laboratory surveillance in Taiwan, influenza-like illness (ILI) surveillance was conducted using a new multiplex PCR assay (FilmArray) and the results compared to those of conventional methods The study was performed during the winter months. MethodsThroat swabs from patients with an ILI presenting to physicians in sentinel practices were collected during the 2016–2017 influenza season. ResultsA total of 52 samples tested positive by FilmArray Respiratory Panel. Forty percent were influenza A virus, and subtype H3N2 virus was the major epidemic strain. However, nearly 60% of ILI cases seen at sentinel sites were caused by non-influenza pathogens. The results of the FilmArray assay and cell culture were identical, and this assay was more sensitive than a rapid influenza diagnostic test. Genetic analyses revealed new influenza A H3N2 variants belonging to a novel subclade 3C.2a2. ConclusionsThe FilmArray assay facilitates urgent testing and laboratory surveillance for common viral and bacterial respiratory pathogens. This study demonstrated the use of a highly sensitive assay using clinical samples that is feasible for application worldwide. This may lead to an increased rate of diagnosis of viral infections and to improved patient outcomes, and in particular to a reduction in the overuse of antibiotics and antivirals.

Effect of genomic drift of influenza PCR tests

BackgroundNucleic acid amplification assays have become the method of choice for influenza (Flu) testing due to superior accuracy and faster turnaround time. Although assays are designed to detect highly conserved genomic targets, mutations can influence test sensitivity. Most of the circulating viruses in the United States during the 2014–2015 season were associated with significant genetic drift; however, the effect on testing was unknown. Objectives and study designWe compared the performance of Prodesse ProFlu+/ProFAST+ (PFlu/PFAST), FilmArray Respiratory Panel (RP), cobas® Influenza A/B test (cIAB), and Xpert® Flu (Xpt) in a retrospective analysis of consecutive nasopharyngeal specimens received for a two-week period during the winter of 2015. Furthermore, limits of detection (LOD) were determined with six isolates of Flu. ResultsOf the 275 specimens, 63 were positive for FluA by PFAST, 60 were positive by RP, 58 were positive by cIAB and 52 were positive by Xpt. Only a subset of 135 specimens was tested by PFlu, of which 32 were positive. The sensitivity/specificity for PFAST, RP, cIAB, Xpt and PFlu was 100/99.1%, 96.7/99.5%, 91.8/99.1%, 85.2%/100%, and 75.6%/98.9%, respectively. LOD analyses demonstrated assay performance variations were strain associated. Specifically, PFlu’s and cIAB’s LODs were higher with A/Texas/50/2012-like and A/Switzerland/9715293/2013-like strains, while Xpt’s highest LOD was with the Swiss strain. ConclusionsStrain-associated assay performance variation is known to occur with other Flu test methods; hence, it is not surprising that such variation would be observed with molecular tests. Careful monitoring and reporting for strain-associated variances are warranted for all test methods.

Molecular point-of-care testing for respiratory viruses versus routine clinical care in adults with acute respiratory illness presenting to secondary care: a pragmatic randomised controlled trial protocol (ResPOC)

BackgroundRespiratory viruses are associated with a huge socio-economic burden and are responsible for a large proportion of acute respiratory illness in hospitalised adults. Laboratory PCR is accurate but takes at least 24 h to generate a result to clinicians and antigen-based point-of-care tests (POCT) lack sensitivity. Rapid molecular platforms, such as the FilmArray Respiratory Panel, have equivalent diagnostic accuracy to laboratory PCR and can generate a result in 1 h making them deployable as POCT. Molecular point-of-care testing for respiratory viruses in hospital has the potential to improve the detection rate of respiratory viruses, improve the use of influenza antivirals and reduce unnecessary antibiotic use, but high quality randomised trials with clinically relevant endpoints are needed.MethodsThe ResPOC study is a pragmatic randomised controlled trial of molecular point-of-care testing for respiratory viruses in adults with acute respiratory illness presenting to a large teaching hospital in the United Kingdom. Eligible participants are adults presenting with acute respiratory illness to the emergency department or the acute medicine unit. Participants are allocated 1:1 by internet-based randomisation service to either the intervention of a nose and throat swab analysed immediately on the FilmArray Respiratory Panel as a POCT or receive routine clinical care. The primary outcome is the proportion of patients treated with antibiotics. Secondary outcomes include turnaround time, virus detection, neuraminidase inhibitor use, length of hospital stay and side room use. Analysis of the primary outcome will be by intention-to-treat and all enrolled participants will be included in safety analysis.DiscussionMultiple novel molecular POCT platforms for infections including respiratory viruses have been developed and licensed in the last few years and many more are in development but the evidence base for clinical benefit above standard practice is minimal. This randomised controlled trial aims to close this evidence gap by generating high quality evidence for the clinical impact of molecular POCT for respiratory viruses in secondary care and to act as an exemplar for future studies of molecular POCT for infections. This study has the potential to change practice and improve patient care for patients presenting to hospital with acute respiratory illness.Trial registrationThis study was registered with ISRCTN, number ISRCTN90211642, on 14th January 2015.