Among critically ill COVID-19 patients, bacterial coinfections may occur, and timely appropriate therapy may be limited with culture-based microbiology due to turnaround time and diagnostic yield challenges (e.g. antibiotic pre-exposure). We performed a systematic review and meta-analysis of the impact of BioFire® FilmArray® Pneumonia Panel in detecting bacteria and clinical management among critically ill COVID-19 patients admitted to the ICU. Seven studies with 558 patients were included. Antibiotic use before respiratory sampling occurred in 28-79% of cases. The panel incidence of detections was 33% (95% CI 0.25 to 0.41, I2=32%) while culture yielded 18% (95% CI 0.02 to 0.45; I2=93%). The panel was associated with approximately a 1 and 2 day decrease in turnaround for identification and common resistance targets, respectively. The panel may be an important tool for clinicians to improve antimicrobial use in critically ill COVID-19 patients.

INTRODUCTION:Bone and Joint Infections (BJI) are medically important, costly and occur in native and prosthetic joints. Arthroplasties will increase significantly in absolute numbers over time as well as the incidence of Prosthetic Joint Infections (PJI). Diagnosis of BJI and PJI is sub-optimal. The available diagnostic tests have variable effectiveness, are often below standard in sensitivity and/or specificity, and carry significant contamination risks during the collection of clinical samples. Improvement of diagnostics is urgently needed.AREAS COVERED:We provide a narrative review on current and future diagnostic microbiology technologies. Pathogen identification, antibiotic resistance detection, and assessment of the epidemiology of infections via bacterial typing are considered useful for improved patient management. We confirm the continuing importance of culture methods and successful introduction of molecular, mass spectrometry-mediated and next-generation genome sequencing technologies. The diagnostic algorithms for BJI must be better defined, especially in the context of diversity of both disease phenotypes and clinical specimens rendered available.EXPERT OPINION:Whether interventions in BJI or PJI are surgical or chemo-therapeutic (antibiotics and bacteriophages included), prior sensitive and specific pathogen detection remains a therapy-substantiating necessity. Innovative tests for earlier and more sensitive and specific detection of bacterial pathogens in BJI are urgently needed.

Diagnostic testing is a critical tool to mitigate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, but molecular testing capacity remains limited. Rapid diagnostic tests (RDTs) that detect SARS-CoV-2 protein antigens (Ag) offer the potential to substantially expand testing capacity and to allow frequent, large-scale, population screening. Testing is simple, rapid (results generally available within 15 minutes), and applicable for diagnosis at point of care. However, implementation of Ag RDTs requires a detailed understanding of test performance and operational characteristics in each testing scenario and population being evaluated. Successful implementation of Ag RDTs on a large scale should combine testing with technical oversight and with clinical and public health infrastructure, and will require production at levels much higher than presently possible. In this commentary, we provide detailed considerations for Ag RDT assessment and use cases to encourage and enable broader manufacturing and deployment.

Testing for SARS-CoV-2 in symptomatic and asymptomatic patients is an important component of the multifaceted approach of managing the COVID-19 pandemic Determining how to best define testing strategies for different populations and incorporating these into broader infection prevention programs can be complex Many circumstances are not addressed by federal, local or professional guidelines This commentary describes various scenarios where testing of symptomatic or asymptomatic individuals for SARS-CoV-2 virus (antigen or RNA) can be of potential benefit Consideration to pre-test probability, risks of testing (impact of false-positive or false-negative results), testing strategy as well as action based on test results are explored Testing, regardless of setting, must be incorporated into overarching infection control plans which include use of personal protective equipment (e g , masks), physically distancing, and isolation when exposure is suspected

Abstract Background The initial focus of the US public health response to coronavirus disease 2019 (COVID-19) was the implementation of numerous social distancing policies. While COVID-19 was the impetus for imposing these policies, it is not the only respiratory disease affected by their implementation. This study aimed to assess the impact of social distancing policies on non–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) respiratory pathogens typically circulating across multiple US states. Methods Linear mixed-effect models were implemented to explore the effects of 5 social distancing policies on non-SARS-CoV-2 respiratory pathogens across 9 states from January 1 through May 1, 2020. The observed 2020 pathogen detection rates were compared week by week with historical rates to determine when the detection rates were different. Results Model results indicate that several social distancing policies were associated with a reduction in total detection rate, by nearly 15%. Policies were associated with decreases in pathogen circulation of human rhinovirus/enterovirus and human metapneumovirus, as well as influenza A, which typically decrease after winter. Parainfluenza viruses failed to circulate at historical levels during the spring. The total detection rate in April 2020 was 35% less than the historical average. Many of the pathogens driving this difference fell below the historical detection rate ranges within 2 weeks of initial policy implementation. Conclusions This analysis investigated the effect of multiple social distancing policies implemented to reduce transmission of SARS-CoV-2 on non-SARS-CoV-2 respiratory pathogens. These findings suggest that social distancing policies may be used as an impactful public health tool to reduce communicable respiratory illness.

Testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in symptomatic and asymptomatic patients is an important component of the multifaceted approach of managing the coronavirus disease 2019 pandemic. Determining how to best define testing strategies for different populations and incorporating these into broader infection prevention programs can be complex. Many circumstances are not addressed by federal, local, or professional guidelines. This commentary describes various scenarios in which testing of symptomatic or asymptomatic individuals for SARS-CoV-2 virus (antigen or ribonucleic acid) can be of potential benefit. Consideration to pretest probability, risks of testing (impact of false-positive or false-negative results), testing strategy, as well as action based on test results are explored. Testing, regardless of setting, must be incorporated into overarching infection control plans, which include use of personal protective equipment (eg, masks), physically distancing, and isolation when exposure is suspected.

Uptake of existing diagnostics to identify infections more accurately could minimize unnecessary antibiotic use and decrease the growing threat of antibiotic resistance. The Infectious Diseases Society of America (IDSA) and the Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria (PACCARB) agree that, to improve uptake of existing diagnostics, healthcare providers, health systems, and payors all need better clinical and economic outcomes data to support use of diagnostic tests over empiric use of antibiotics, providers need better tools and education about diagnostic tests, and diagnostics developers need federal funding in the absence of a viable diagnostics market. Recommendations from PACCARB and the IDSA are amplified. Incentives for—and challenges to—diagnostics research, development, and uptake are summarized. Advocacy opportunities are given for infectious disease professionals to join the fight against antimicrobial resistance.

Diagnostic testing is a critical tool to mitigate the SARS-CoV-2 pandemic, but molecular testing capacity remains limited Rapid diagnostic tests (RDTs) that detect SARS-CoV-2 protein antigens (Ag) offer the potential to substantially expand testing capacity and to allow frequent, large scale population screening Testing is simple, rapid (results generally available within 15 minutes), and applicable for diagnosis at point of care However, implementation of Ag RDTs requires a detailed understanding of test performance and operational characteristics in each testing scenario and population being evaluated Successful implementation of Ag RDTs on a large scale should combine testing with technical oversight and with clinical and public health infrastructure, and will require production at levels much higher than presently possible In this commentary, we provide detailed considerations for Ag RDT assessment and use cases to encourage and enable broader manufacturing and deployment

Background: In 2014, enterovirus D68 (EV-D68) was responsible for an outbreak of severe respiratory illness in children, with 1,153 EV-D68 cases reported across 49 states. Despite this, there is no commercial assay for its detection in routine clinical care. BioFire (R) Syndromic Trends (Trend) is an epidemiological network that collects, in near real-time, deidentified. BioFire test results worldwide, including data from the BioFire (R) Respiratory Panel (RP). Objectives: Using the RP version 1.7 (which was not explicitly designed to differentiate EV-D68 from other picornaviruses), we formulate a model, Pathogen Extended Resolution (PER), to distinguish EV-D68 from other human rhinoviruses/enteroviruses (RV/EV) tested for in the panel. Using PER in conjunction with Trend, we survey for historical evidence of EVD68 positivity and demonstrate a method for prospective real-time outbreak monitoring within the network. Study design: PER incorporates real-time polymerase chain reaction metrics from the RPRV/EV assays. Six institutions in the United States and Europe contributed to the model creation, providing data from 1,619 samples spanning two years, confirmed by EV-D68 gold-standard molecular methods. We estimate outbreak periods by applying PER to over 600,000 historical Trend RP tests since 2014. Additionally, we used PER as a prospective monitoring tool during the 2018 outbreak. Results: The final PER algorithm demonstrated an overall sensitivity and specificity of 87.1% and 86.1%, respectively, among the gold-standard dataset. During the 2018 outbreak monitoring period, PER alerted the research network of EV-D68 emergence in July. One of the first sites to experience a significant increase, Nationwide Children's Hospital, confirmed the outbreak and implemented EV-D68 testing at the institution in response. Applying PER to the historical Trend dataset to determine rates among RP tests, we find three potential outbreaks with predicted regional EV-D68 rates as high as 37% in 2014, 16% in 2016, and 29% in 2018. Conclusions: Using PER within the Trend network was shown to both accurately predict outbreaks of EV-D68 and to provide timely notifications of its circulation to participating clinical laboratories

Abstract Background Classical methods to identify causes of community acquired, healthcare and ventilator associated pneumonia can be insensitive and slow, leading to unnecessary or inappropriate antimicrobial therapy. The BioFire® FilmArray® Pneumonia plus Panel (PNplus) detects 15 bacteria (in semi-quantitative log bin values from 10^4 to > 10^7), 7 antibiotic resistance markers (mecA/C/MREJ, CTX-M, KPC, VIM, IMP, NDM, OXA-48 like), 3 atypical bacteria (AB), and 8 viral classes directly from bronchoalveolar lavage (BAL)-like and sputum-like specimens (including endotracheal aspirates) in about 1 hr. This study compared PNplus results to standard of care testing (SOC). Methods 2476 samples (1234 BAL-like; 1242 sputum-like) were tested at 52 laboratories from 13 European countries and Israel by PNplus and SOC. SOC varied by site and physician prescription. Pathogen detection rates were compared. PNplus bin values and SOC descriptive or numerical quantities were evaluated for 1297 bacterial detections. Results 13 samples (0.5%) gave invalid PNplus results. 3278 bacteria in PNplus were detected by PNplus and/or SOC. SOC detected 1878 bacteria (57.1%) compared to 3128 bacteria (95.8%) for PNplus (p=< 0.0001). SOC detected 73 AB (70.9%) and 134 viruses (21.1%), PNplus detected 93 AB (90.3%) and 618 viruses (97.9%) (p=< 0.0001). Mean number of analytes/sample detected by PNplus and SOC were 1.99 and 1.44, respectively. PNplus bin values were less than SOC, equal to SOC or greater than SOC in 5.9%, 25.4% and 69.6% of results, respectively. PNplus values were on average > 1 log than SOC values (58.5% 1-2 logs; 11.0% 3-4 logs). PNplus identified 98.2% of MRSA and SOC 55.6%. All gram-negative resistance markers were detected at least once. PNplus and SOC results were fully concordant (positive or negative) or partially concordant for 49.1% and 26.4% of samples, respectively. Conclusion PNplus detected significantly more potential pathogens than SOC. Lack of routine SOC viral testing was a missed opportunity to define the cause of pneumonia. Semi-quantification may assist in understanding the significance of the pathogens detected. Pathogen and resistance marker detection in about 1 hr could dramatically impact antimicrobial use and enhance patient outcomes. Disclosures Christine C. Ginocchio, PhD, MT(ASCP), bioMerieux (Employee)bioMerieux (Employee, Shareholder) Barbara Mauerhofer, Pharmacist, bioMerieux (Employee) Cory Rindlisbacher, n/a, BioFire Diagnostics (Employee) Carolina Garcia, BS, bioMerieux (Employee)

The clinical signs and symptoms of acute respiratory tract infections (RTIs) are not pathogen specific. Highly sensitive and specific nucleic acid amplification tests have become the diagnostic reference standard for viruses, and translation of bacterial assays from basic research to routine clinical practice represents an exciting advance in respiratory medicine. Most recently, molecular diagnostics have played an essential role in the global health response to the novel coronavirus pandemic. How best to use newer molecular tests for RTI in combination with clinical judgment and traditional methods can be bewildering given the plethora of available assays and rapidly evolving technologies. Here, we summarize the current state of the art with respect to the diagnosis of viral and bacterial RTIs, provide a practical framework for diagnostic decision making using selected patient-centered vignettes, and make recommendations for future studies to advance the field.

Purpose Many patients with suspected meningitis do not require hospitalization yet are admitted, often resulting in unnecessary care and additional cost. We assessed the possible economic impact of a rapid multiplex test for suspected adult community-acquired meningitis/encephalitis. Methods A model simulated diagnosis, clinical decisions, resource use/costs of standard of care (SOC) and two cerebrospinal fluid (CSF) testing strategies using the FDA-cleared BioFire® FilmArray® System (FA) which provides results in approximately one hour. Results Pathogens detected by FA caused approximately 74% of cases, 97% of which would be accurately diagnosed with FA. False positives and false negatives more often led to extended/unnecessary admission than inappropriate discharge/missed admission. Mean cost per case ranged from 16829 to 20791. A strategy of testing all suspected cases yielded greater savings (2213/case) than testing only those with abnormal CSF (812/case) and both were less expensive than SOC. Conclusion This economic analysis demonstrates that FA can inform more appropriate clinician decisions resulting in cost savings with greater economic benefits achievable with syndromic testing of all cases, rather than SOC or targeted syndromic testing.

Background: Large epidemiologic studies evaluating the etiologies, management decisions and outcomes of infants and children with meningitis and encephalitis in the United States are lacking. Methods: Children 0–17 years of age with meningitis or encephalitis as assessed by International Classification of Diseases, Ninth Revision, codes available in the Premier Healthcare Database during 2011–2014 were analyzed. Results: Six thousand six hundred sixty-five patients with meningitis or encephalitis were identified; 3030 (45.5%) were younger than 1 year of age, 295 (4.4%) were 1–2 years of age, 1460 (21.9%) were 3–9 years of age, and 1880 (28.2%) were 10–17 years of age. Etiologies included enterovirus (58.4%), unknown (23.7%), bacterial (13.0%), noninfectious (3.1%), herpes simplex virus (1.5%), other viruses (0.7%), arboviruses (0.5%) and fungal (0.04%). The majority of patients were male [3847 (57.7%)] and healthy [6094 (91.4%)] with no reported underlying conditions. Most underwent a lumbar puncture in the emergency department [5363 (80%)] and were admitted to the hospital [5363 (83.1%)]. Antibiotic therapy was frequent (92.2%) with children younger than 1 year of age with the highest rates (97.7%). Antiviral therapy was less common (31.1%). Only 539 (8.1%) of 6665 of patients received steroids. Early administration of adjunctive steroids was not associated with a reduction in mortality ( P = 0.266). The overall median length of stay was 2 days. Overall mortality rate (0.5%) and readmission rates (<1%) was low for both groups. Conclusion: Meningitis and encephalitis in infants and children in the United States are more commonly caused by viruses and are treated empirically with antibiotic therapy and antiviral therapy in a significant proportion of cases. Adjunctive steroids are used infrequently and are not associated with a benefit in mortality.

Respiratory viral infections are associated with a wide range of acute syndromes and infectious disease processes in children and adults worldwide. Many viruses are implicated in these infections, and these viruses are spread largely via respiratory means between humans but also occasionally from animals to humans. This article is an American Society for Microbiology (ASM)-sponsored Practical Guidance for Clinical Microbiology (PGCM) document identifying best practices for diagnosis and characterization of viruses that cause acute respiratory infections and replaces the most recent prior version of the ASM-sponsored Cumitech 21 document, Laboratory Diagnosis of Viral Respiratory Disease, published in 1986. The scope of the original document was quite broad, with an emphasis on clinical diagnosis of a wide variety of infectious agents and laboratory focus on antigen detection and viral culture. The new PGCM document is designed to be used by laboratorians in a wide variety of diagnostic and public health microbiology/virology laboratory settings worldwide. The article provides guidance to a rapidly changing field of diagnostics and outlines the epidemiology and clinical impact of acute respiratory viral infections, including preferred methods of specimen collection and current methods for diagnosis and characterization of viral pathogens causing acute respiratory tract infections. Compared to the case in 1986, molecular techniques are now the preferred diagnostic approaches for the detection of acute respiratory viruses, and they allow for automation, high-throughput workflows, and near-patient testing. These changes require quality assurance programs to prevent laboratory contamination as well as strong preanalytical screening approaches to utilize laboratory resources appropriately. Appropriate guidance from laboratorians to stakeholders will allow for appropriate specimen collection, as well as correct test ordering that will quickly identify highly transmissible emerging pathogens.

Ventilator-associated pneumonia (VAP) is one of the most commonly encountered hospital-acquired infections worldwide, and one of the major contributors to an over mortality in critically ill patients. Initial empirical antimicrobial therapy is often broad-spectrum. Fast identification and quantification of microorganisms is of great importance to enable early effective targeted antimicrobial treatment. This trial compares the performance of the new BioFire® Pneumonia Panel (BPP) with quantitative conventional culture (CC) and an independent real-time quantitative molecular-based method (MM), in Intensive Care Unit (ICU) patients with VAP suspicion. Bronchoalveolar lavage (BAL) specimens from 120 patients with suspected VAP, enrolled at four different French ICUs, during January to November 2013, were analysed by CC, following microbiological standard procedures, by BPP and MM. A total of 15 bacterial targets, commonly detected by the three methods, were analysed for concordance above an agreed threshold for positivity. While every step is fully integrated, from specimen-to-results (BPP), bacterial DNA was extracted from each sample on the NucliSENS easyMAG® Platform, and real-time polymerase chain reactions were run in an ABI 7500 Dx thermocycler (MM). A total of 117 different BAL specimens were processed. Positive culture was obtained for 65.8% of BAL, while positive detections were observed in 79.4% with BPP and 75.4% with independent MM. Fourteen different species were detected by the three methods, with majority of the bacteria being S. aureus, P. aeruginosa, and H. influenzae. Overall concordance performance between BPP and CC was 89.0% (83.1%–94.9%) positive percentage agreement (PPA) and 95.9% (95.0%–96.9%) negative percentage agreement (NPA). Overall concordance between BPP and MM was 97.1% (93.8%–100.3%) PPA and 96.6% (95.6%–97.6%) NPA. Following discrepancy analyses overall performance increased to 95.3% (91.2–99.3%) PPA when comparing BPP to CC. The new BioFire® Pneumonia Panel provides reliable quantitative microbiological data in BAL specimens, in only 65 minutes, which can lead to more appropriate management of VAP suspected patients in the ICU. RUO products used in this study have not been evaluated by the FDA or other regulatory agencies for In Vitro Diagnostic use. A. Iannello, bioMérieux: Employee, Salary. C. Dubost, bioMérieux: Employee, Salary. C. Weber, bioMérieux: Employee, Salary. C. Alberti-Segui, bioMérieux: Employee, Salary. C. Mousset, bioMérieux: Employee, Salary. C. Ginocchio, bioMérieux: Employee, Salary. M. Rogatcheva, BioFire: Employee, Salary. V. Moucadel, bioMérieux: Employee, Salary. J. Yugueros-Marcos, bioMérieux: Employee, Salary.

ObjectiveTo determine the associated costs related to the diagnosis and treatment of meningitis and encephalitis (ME) in adult patients in the USA.MethodsA retrospective observational study design was used to assess the use and costs of diagnostic tests and antimicrobial treatment and the total hospitalization costs for adult patients with suspected ME, who received a lumbar puncture procedure during an emergency department visit or during the first two service days of an inpatient stay. Related costs were calculated by timing of lumbar puncture performed and infectious etiology.ResultsA total 26 429 adult patients with suspected ME diagnosed between 2011 and 2014 were included in the study. The mean hospitalization cost was $15 572 ± 27 168, with antimicrobial medication cost of $1144 ± 4052 and laboratory test cost of $210 ± 244. The total visit cost increased with delayed lumbar puncture procedure, intensive care unit stay, and if the etiology was fungi, arbovirus, or bacteria.ConclusionsHigher diagnostic and treatment costs are associated with a delayed lumbar puncture procedure, the etiological agent, and the requirement for an intensive care unit stay.

A retrospective cohort study design was used to assess the use and costs of diagnostic tests, medication, and total hospitalization costs for pediatric patients with suspected meningitis/encephalitis who received a lumbar puncture (LP) procedure. Related costs were calculated by timing of LP performed and infectious etiology for infants (<1 year) and children (1-17 years). A total of 3030 infants and 3635 children with suspected ME diagnosed between 2011 and 2014 were included in the study. The mean hospitalization cost for infants and children was $12,759 and $11,119, respectively, with medication and laboratory test costs of $834 and $1771 for infants and $825 and $855 for children, respectively. Total visit cost increased with delayed LP procedure, ICU stay, and if the etiology was viral (other than enterovirus or arbovirus) or bacterial. Higher diagnostic and treatment costs were associated with delayed LP procedure, etiologic agent, and ICU stay.

Influenza viruses infect millions of people each year, leading to several hundred thousand hospitalizations and thousands of deaths annually in the US. Early antiviral therapy reduces illness duration, complications, and mortality associated with influenza. Yet, antivirals are consistently used at a suboptimal rate. Patients with positive influenza diagnostic testing results are more likely to receive antiviral therapy and less likely to be prescribed unnecessary antibiotics. Thus, access to reliable influenza testing in both ambulatory and inpatient settings is critical to facilitate both optimal patient outcomes and antimicrobial stewardship. Recently, the first point-of-care (POC)7 molecular diagnostic test was cleared by the US Food and Drug Administration (FDA) for the detection of influenza. At the same time, concerns about the performance of commonly used rapid antigen tests, particularly the test sensitivity, led to modified regulatory requirements for these devices. The landscape of influenza diagnostics is rapidly evolving, and clinical laboratorians are certain to face pressure regarding new testing modalities. In this article, 5 experts that span the continuum of influenza diagnosis from the clinical laboratory to industry to public health and regulatory agencies discuss recent advances and ongoing challenges in influenza diagnostics. During influenza season, how does rapid influenza diagnostic testing affect clinical management and clinical workflows? Neil Anderson: During influenza season, most infected individuals will present to 1 of 2 places: an outpatient clinic or an emergency department (ED). These initial interactions with the healthcare system are often very brief. During this short amount of time, clinicians must make many decisions. Should the patient be given antibiotics, antivirals, or neither? Should the patient be admitted? Given the overlap in symptomatology of different respiratory pathogens, these questions can be very difficult to answer on presentation alone. In this situation, a rapid influenza diagnostic test is an essential component of patient management …

Abstract Background Antimicrobial-resistant (AMR) bacteria are a rising healthcare concern and are associated with an estimated five-fold increase in mortality for infected patients. Correct treatment requires antimicrobial susceptibility knowledge, but standard testing methods require multiple days for an accurate phenotype. Rapid identification of AMR immediately after blood culture positivity could potentially improve health outcomes, lower economic cost, prevent the spread of multidrug-resistant outbreaks and assist with antimicrobial stewardship goals. Methods The BioFire® Antimicrobial Resistance (AMR) Panel is a research use only multiplex-nested PCR system with 47 assays for 30 genes conferring resistance to cephalosporins, carbapenems, aminoglycosides, and fluoroquinolones which can be found in E. coli, K. pneumoniae, P. aeruginosa, A. baumannii, and E. cloacae complex. We tested 86 residual positive blood culture samples collected from Primary Children’s Hospital, University of Utah Hospital and Huntsman Cancer Hospital with the BioFire AMR Panel. Molecular genotypic results were compared with phenotypic susceptibility information for each blood culture specimen to confirm resistance detections. Results Of the 86 samples tested, there were 33 cultures phenotypically resistant (beyond intrinsic resistance) to at least one antibiotic class targeted by the panel. BioFire AMR Panel identified resistance to gentamicin, cefoxitin, all penicillins tested, and ciprofloxacin with 100% positive predictive value (PPV). For tobramycin, ceftazidime, and ceftriaxone, the PPV was greater than 85%. Carbapenem resistance was not detected, likely due to the low number of resistant organisms present in our patient population. Conclusion The BioFire AMR Panel provides identification of genetic AMR determinants in a rapid, easy-to-use system that accurately correlates with phenotypic data for specific antimicrobials. Studies will continue to test additional clinical samples at various geographical locations to further evaluate the relationship between genotypic and phenotypic resistance assessment. Data presented is from an assay that has not been cleared or approved by US FDA or other regulatory agencies for in vitro diagnostic use. Disclosures S. Marxreiter, NIH NIAID: Grant Investigator, Research grant. BioFire Diagnostics, LLC: Employee, Salary. E. Lo, BioFire Diagnostics, LLC: Employee, Salary. NIH NIAID: Grant Investigator, Research grant. C. Oswald, BioFire Diagnostics, LLC: Employee, Salary. NIH NIAID: Grant Investigator, Research grant. A. Hopper, Primary Children’s Hospital: Investigator, Research grant. B. Barr, Primary Children’s Hospital: Grant Investigator, Research grant. J. A. Daly, Primary Children’s Hospital: Grant Investigator, Research grant. University of Utah: Grant Investigator, Research grant. C. C. Ginocchio, Biomerieux: Employee, Salary. R. Crisp, BioFire Diagnostics, LLC: Employee, Salary. A. Hemmert, BioFire Diagnostics, LLC: Employee, Salary. NIH NIAID: Grant Investigator, Research grant.

Background: Health care and public health professionals rely on accurate, real-time monitoring of infectious diseases for outbreak preparedness and response. Early detection of outbreaks is improved by systems that are comprehensive and specific with respect to the pathogen but are rapid in reporting the data. It has proven difficult to implement these requirements on a large scale while maintaining patient privacy. Objective: The aim of this study was to demonstrate the automated export, aggregation, and analysis of infectious disease diagnostic test results from clinical laboratories across the United States in a manner that protects patient confidentiality. We hypothesized that such a system could aid in monitoring the seasonal occurrence of respiratory pathogens and may have advantages with regard to scope and ease of reporting compared with existing surveillance systems. Methods: We describe a system, BioFire Syndromic Trends, for rapid disease reporting that is syndrome-based but pathogen-specific. Deidentified patient test results from the BioFire FilmArray multiplex molecular diagnostic system are sent directly to a cloud database. Summaries of these data are displayed in near real time on the Syndromic Trends public website. We studied this dataset for the prevalence, seasonality, and coinfections of the 20 respiratory pathogens detected in over 362,000 patient samples acquired as a standard-of-care testing over the last 4 years from 20 clinical laboratories in the United States. Results: The majority of pathogens show influenza-like seasonality, rhinovirus has fall and spring peaks, and adenovirus and the bacterial pathogens show constant detection over the year. The dataset can also be considered in an ecological framework; the viruses and bacteria detected by this test are parasites of a host (the human patient). Interestingly, the rate of pathogen codetections, on average 7.94% (28,741/362,101), matches predictions based on the relative abundance of organisms present. Conclusions: Syndromic Trends preserves patient privacy by removing or obfuscating patient identifiers while still collecting much useful information about the bacterial and viral pathogens that they harbor. Test results are uploaded to the database within a few hours of completion compared with delays of up to 10 days for other diagnostic-based reporting systems. This work shows that the barriers to establishing epidemiology systems are no longer scientific and technical but rather administrative, involving questions of patient privacy and data ownership. We have demonstrated here that these barriers can be overcome. This first look at the resulting data stream suggests that Syndromic Trends will be able to provide high-resolution analysis of circulating respiratory pathogens and may aid in the detection of new outbreaks.