BioFire Diagnostics Research Articles

Potential Impact of Rapid Molecular Microbiologic Diagnosis for Mechanically Ventilated Children in Intensive Care With Suspected Pneumonia

Background: Lower respiratory tract infections (LRTIs) remain a leading cause of community-acquired and nosocomial infection in children and a common indication for antimicrobial use and intensive care admission. Determining the causative pathogen for LRTIs is difficult and traditional culture-based methods are labor- and time-intensive. Emerging molecular diagnostic tools may identify pathogens and detect antimicrobial resistance more quickly, to enable earlier targeted antimicrobial therapy. Methods: This is a single-center, prospective observational laboratory study evaluating the use of the Biofire FilmArray pneumonia panel (FA-PP) (BioFire Diagnostics, Salt Lake City, UT) for bronchoalveolar lavage specimens from mechanically ventilated children admitted with suspected or presumed pneumonia. We aimed to determine its feasibility and utility for identifying pathogens, antimicrobial resistance and its potential influence on antibiotic prescribing. Results: We analyzed 50 samples taken from 41 children with a median age of 6 months. Positive agreement between culture and FA-PP was 83% and negative agreement was 76%. Agreement between FA-PP (mecA/C or MREJ) and culture was high for methicillin-resistant Staphylococcus aureus. In 3 cases, extended-spectrum beta-lactamase-producing Gram-negative organisms were detected by culture and not FA-PP. Hypothetically, FA-PP results would have affected antimicrobial prescribing in approximately half the cases (24, 48%). Conclusions: FA-PP is a useful adjunct to traditional culture methods in mechanically ventilated children with LRTIs and may influence clinical decision-making regarding antibiotic escalation or stewardship.

Assessment of the FilmArray Gastrointestinal Pathogen PCR Panel at a Tertiary Cancer Center

Background: The FilmArray gastrointestinal (GI) pathogen panel (BioFire Diagnostics, Salt Lake City, UT) is a multiplex PCR assay for syndromic diagnosis of infectious gastroenteritis. This highly sensitive assay has been widely adopted as a preferred testing modality for infectious diarrhea among hospitalized patients. However, in the era of diagnostic stewardship, concerns have been raised that this approach risks unexpected findings of questionable significance. Following an increase in GI pathogen panel testing, the infection control department reviewed results among hospitalized patients at different stages of admission. Methods: From October 2022 to May 2023, we retrospectively reviewed all GI pathogen panels sent in a large tertiary cancer hospital. Count of tests ordered and positivity trends were studied by unit and organism among inpatients. We categorized an admission course into early (≤2 inpatient days) and late (≥3 inpatient days) stages and compared results across these stages. Finally, we compared reproducibility of multiple tests sent during a single admission. Results: From October 2022 to May 2023, a total of 2,763 tests were sent across the institution with 2,113 tests from inpatient units. Tests were most commonly sent on the Pediatrics and Hematology -Oncology inpatient units and together these units accounted for 60% of tests. These two units also had the highest rate of test positivity and together accounted for 60% of positive tests among hospitalized patients. The most frequently detected organisms were Norovirus (7%) and Enteropathogenic E. coli (3%) (Figure 1). Patients tested in the early stage of hospital admission were more likely to have a positive result for any target (93/509, 18.3%) compared to patients tested in the late stage (202/1604, 12.5%). Patients with a positive test in the early stage of admission were less likely to have a subsequent negative test (3/93, 3%) compared to patients who were positive in late stage of admission (39/202, 19.3% (Figure 2). Conclusions: Our findings suggest that the utility of the FilmArray GI PCR panel is highest in the early stages of a patient’s hospital admission. Testing of patients hospitalized ≥3 days is likely to be inappropriate. These findings support implementation of diagnostic stewardship standards on when syndromic testing for potentially infectious diarrhea is appropriate. Figure 1: FilmArray gastrointestinal pathogen PCR panel positivity by organism. Figure 2: FilmArray gastrointestinal pathogen PCR panel positivity by organism comparing early vs late stage of hospital admission.

The Evaluation of the BioFire FilmArray Meningitis/Encephalitis Panel for the Detection of Bacteria and Yeast in Cerebrospinal Fluid Specimens.

Background and objective Infectious meningitis and encephalitis are serious diseases that can have fatal consequences, especially in the case of bacterial meningitis. Molecular biology has made it possible to quickly introduce appropriate treatment. Our study aims to evaluate the FilmArrayMeningitis/Encephalitis Polymerase Chain Reaction (PCR) Panel (BioFire Diagnostics, Salt Lake City, Utah) implemented in our department compared to traditional methods. Material and methods This was a retrospective single-center study conducted in the Department of Bacteriology ofMohammed V Military Training Hospital, Rabat, for a period of four years. All cerebrospinal fluid (CSF) samples from patients with symptoms of meningitis or meningoencephalitis submitted to the laboratory for cytobacteriological analysis were included in the study. Conventional analysis has been compared with molecular biology. Results The overall agreement rate with FilmArray in our study was 86%. The sensitivity to Escherichia coli K1, Haemophilus influenzae, Neisseria meningitidis, Streptococcus agalactiae, and Streptococcus pneumoniae was 100%. And for Cryptococcus neoformans it was 83% in our study. Conclusion In summary, this technique can be used to diagnose bacterial meningitis more sensitively than with conventional techniques, while at the same time allowing a rapid and efficacious patient's treatment.

Respiratory tract viral infections associated sepsis in patients with underlying liver disease: Viral sepsis an entity to look forward!

Sepsis remains a global health burden associated with significant morbidity and mortality. Bacteria are known to be the predominant pathogens in sepsis; however, viral etiologies in sepsis are still under diagnosed. Respiratory viral pathogens have been previously linked to sepsis, but the knowledge of incidence, disease burden and mortality of viral-induced sepsis remains limited. This study aimed at understanding the role of respiratory viral infections in the causation of sepsis in liver disease patients. In this retrospective study, the clinical records of liver disease patients with influenza-like illness, whose requests for respiratory viral testing were received from January 2019 to December 2022, were reviewed. Respiratory viruses were identified using FilmArray 2.0 respiratory panel (BioFire Diagnostics,Utah, USA). Of 1391 patients tested, a respiratory viral etiology was detected in 23%. The occurrence of sepsis was seen in 35%. Among these, isolated viral etiology with no other bacterial/fungal coinfection was found in 55% of patients. Rhinovirus/Enterovirus was found as the most common underlying viral etiology (23.4%). The sepsis prevalence was higher among patients with associated comorbidities (45%) and decompensated cirrhosis (84%). On multi-variable analysis, no factor was found independently associated with sepsis-related mortality. This study underlines the importance of isolated viral etiology in causation of sepsis among liver disease patients. Patients with comorbidities, older age and decompensated cirrhosis are at an increased risk of developing sepsis and are associated with poorer outcomes. Accurate and timely identification of the viral etiology in sepsis would prevent the misuse of antibiotics and improve overall patient care.

Prevalence and Predictors for Respiratory Viral Infections among Liver Disease Patients.

Respiratory viral infections (RVIs) cause significant hospitalizations every year. Also, RVIs caused by either influenza or noninfluenza group of viruses can have adverse outcomes, especially among immunosuppressed patients. Regular and timely supervision is needed for accurate etiological identification, to prevent inappropriate use of antibiotics in patients with nonbacterial etiology. This study aimed to identify the spectrum of RVIs and clinical characteristics among liver disease patients with influenza-like illness (ILI). In this study, medical records of patients with ILI, whose requests for respiratory viral testing came from September 2016 to December 2022 were retrospectively reviewed. Respiratory viruses were identified using FilmArray 2.0 respiratory panel (BioFire Diagnostics, USA). Of the 1,577 liver disease patients with ILI, the overall prevalence of RVI was 28% (n = 449). Infection by noninfluenza viruses (NIVs) was detected in 329 patients (73%), higher than those infected with influenza viruses. In multivariable logistic regression analysis, female gender [odds ratio (OR): 2.5, 95% confidence interval (CI): 1.5-4.2], infection with influenza B (OR: 3.3, 95% CI: 1.09-9.9) and decompensated cirrhosis (OR: 3.9, 95% CI: 1.7-8.5) were independent risk factors for mortality. Regarding seasonality, influenza peaked in monsoons and winters, whereas NIVs circulated throughout the year. Overall, this study adds new knowledge regarding the incidence of RVI and the distribution of respiratory viral etiologies among liver disease patients with ILI. The findings highlight that female gender, decompensated cirrhosis, and influenza B infection are independently associated with poor clinical outcomes. Early etiological identification of viral causes of ILI could aid in an enhanced understanding of the prevalence of ILI and the timely management of the patients. Respiratory viral infections can cause severe illness in individuals with underlying liver disease. Accurate diagnosis and risk stratification is crucial in mitigating the adverse health effects. Samal J, Prabhakar T, Prasad M, et al. Prevalence and Predictors for Respiratory Viral Infections among Liver Disease Patients. Euroasian J Hepato-Gastroenterol 2023;13(2):108-114.

Epidemiology and Clinical Characteristics of Adult Astrovirus Gastroenteritis in Metropolitan Washington DC, USA: 2016-2023

Abstract Introduction/Objective Astrovirus gastroenteritis is commonly studied in children but not adults. Detection of astrovirus on PCR panels allows for characterization of infected patients. Here, we investigate the epidemiology and clinical characteristics of adult astrovirus infections at our institution. Methods/Case Report Stool specimens tested between 01/2016-03/2023 on a gastrointestinal PCR panel (BioFire Diagnostics, Salt Lake City, UT) were analyzed. Chart abstraction was performed to collect patient demographics, laboratory results, clinical presentation and management for patients positive for astrovirus. Fisher Exact Test and 95% Confidence Intervals were calculated where appropriate. Results (if a Case Study enter NA) Overall positivity rate of astrovirus was 0.6% (34/5053) with highest (1.02%) in 2018 and none in 2020. The mean age was 32 years old (range:18-52 yo) with majority being Caucasian (56%) and female (56%). Symptoms included diarrhea (100%), abdominal pain (92%), vomiting (47%), and fever (35%). Comparing patients in age group 30-39 years versus other age groups, vomiting (21% vs 65%, p=0.0173) and fever (40% vs 67%, p=0.717) were less prevalent. More females had abdominal pain (95% vs 87%, p=0.6) while more males had fever (47% vs 26%, p=0.3) although insignificant. Average period of diarrhea was 3 days (range:1-10 days). 23.5% of patients had increased monocytes (CI 0.29-1.92 x 103/µl), and 29.4% showed decreased lymphocytes (CI 0.29-1.10 x 103/µl). Peak seasons were late winter to spring (February-April). All patients were immunocompetent except one (HIV+). Gastrointestinal co-infections included toxigenic E. coli (12%), C. difficile (6%), Campylobacter (3%), Norovirus (3%), Salmonella (3%) and Stronglyloides (3%). In all 34 patients, clinicians acknowledged detection of astrovirus and discharged patients without antibiotics. Conclusion To our knowledge, this is the first case series on adult astrovirus infections from the D.C. area. We report novel findings about adult astrovirus gastroenteritis that are different from observations in children. PCR can rapidly diagnose viral gastroenteritis and can reduce inappropriate antibiotic administration.

1687. Unprecedented Outbreak of Invasive group A Streptococcus Infections in Children - Colorado, October 2022 to March 2023

Abstract Background Since the fall of 2022, we have observed a sharp rise in pediatric invasive group A Streptococcus (iGAS) hospitalizations in Colorado, similar to trends reported in other countries. Methods From October 2022 – March 2023, iGAS cases were prospectively identified in patients hospitalized at Children’s Hospital Colorado and medical charts were systematically reviewed. iGAS was defined as isolation of GAS from a sterile site (confirmed case) or a non-sterile site with clinically consistent disease (probable). Using laboratory specimen records, we compared the number of patients with sterile site GAS-positive cultures across three time periods: Pre-COVID-19 (Jan 2015 – Mar 2020), COVID-19 pandemic (Apr 2020 – Sep 2022), and Outbreak (Oct 2022 – Mar 2023). Results Among the 81 iGAS cases identified during the outbreak (Table 1), median age was 6 years old; 64% of patients were male and 69% were previously healthy. 33% of patients required pediatric intensive care unit (PICU) admission, and two patients died. iGAS was more commonly associated with upper respiratory infection (URI) symptoms (63%) than isolated sore throat (5%) or trauma/skin findings (15%). The most common clinical manifestations were head and neck infections (37%), musculoskeletal infections (32%) and pneumonia (20%). 11% had toxic shock syndrome and 4% had necrotizing fasciitis. Lab findings associated with PICU admission were bandemia, leukopenia and higher CRP values. Disease severity and treatment varied by clinical manifestation (Table 2). There were more iGAS cases during the outbreak (average 10.0/month) compared to pre-pandemic years (3.8/month over the same period) and during the pandemic (1.2/month over the same period) (Figure 1). Conclusion We report an unprecedented outbreak of iGAS in pediatric patients in Colorado, with case numbers close to triple the pre-pandemic baseline at our hospital. The timing and high proportion of cases with associated URI symptoms suggest a link to the recent surges in respiratory viruses, although iGAS cases have continued to persist past the peak of respiratory season. Invasive GAS can be severe and evolve rapidly; there are important clinical and laboratory features that may help in earlier identification of children who are critically ill. Disclosures Samuel R. Dominguez, MD, PhD, Biofire Diagnostics: Advisor/Consultant|Biofire Diagnostics: Grant/Research Support|Cobio Diagnostics: Board Member|Karius: Advisor/Consultant|Pfizer: Grant/Research Support

98. Resurgence of Invasive Group A Streptococcal Disease in Utah Children

Abstract Background Streptococcus pyogenes (GAS) is a common cause of non-invasive mucosal infections in childhood as well as life-threatening invasive infections. Since 1997, emm1 has been the most common emm type associated with invasive GAS (iGAS) in the US. Apparent increases in iGAS have been reported in several countries during the winter of 2022-23. We sought to characterize changing clinical and molecular epidemiology of iGAS disease in Utah children before and after the emergence of COVID-19. Methods We retrospectively identified children 0-18 years with iGAS treated at Primary Children’s Hospital (Salt Lake City, Utah) from 2018- 2023. Cases were identified through the laboratory database. Electronic health record review confirmed that cases met the CDC definition of iGAS and streptococcal toxic shock syndrome (STSS). We abstracted demographics, disease classification and outcomes (Table). Comparisons were made across years. GAS isolates underwent whole genome sequencing for emm type determination. Results From 1/2018 to 3/2023, we identified 141 cases of iGAS. Case numbers ranged from 6/yr (2021) to 39 (2019). The highest number of cases by quarter was seen in Q1 2023 (Figure). We observed a marked decrease in iGAS from Q1 2020 through Q3 2022 followed by a steep increase, coinciding with surges in RSV and influenza. Demographics were similar across the study period. 60% of iGAS cases were in males. Complicated pneumonia and head/neck infections predominated. iGAS associated with STSS appeared higher post-pandemic (4/73 [5%] cases in 2018-19 vs. 8/51 [16%] in 2022-23 [OR = 3.2; 95% CI 0.8-15]). The majority of STSS (7/12; 57%) was associated with complicated pneumonia. Clinical outcomes were comparable pre- and post-pandemic. emm types were available for 49/51 (96%) of isolates in 2022-23. emm1 and emm12 were associated with 67% of iGAS disease (emm1 n = 16 [33%]; emm12 n = 17 [35%]). Conclusion After a marked drop in iGAS infections in children during the COVID-19 pandemic in Utah there was a resurgence of iGAS starting in late 2022 and early 2023, modestly exceeding pre-pandemic levels. emm1 and emm12 predominated in the surge. Further analysis of disease severity and molecular epidemiology are in progress. Disclosures Kwabena Krow Ampofo, MD, Merck: Advisor/Consultant|Merck: Grant/Research Support Andrew T. Pavia, MD, GlaxoSmith Kline: Advisor/Consultant|Sanofi: Advisor/Consultant Anne J. Blaschke, MD, PhD, BioFire Diagnostics: Grant/Research Support|BioFire Diagnostics: I have IP owned by the U. of Utah licensed to BioFire and receive royalties. I have been a consultant and received grant support as well.|Merck and Company, Inc.: Advisor/Consultant

582. Comparing Broad-range PCR Testing and The Biofire® FilmArray® Pneumonia (PN) Panel in the Diagnosis of Bacterial Pneumonia

Abstract Background Given the low sensitivity of conventional microbial isolation methods for identifying respiratory pathogens in bacterial pneumonia, target-specific syndromic multiplex real-time PCR panels have been used in conjunction with culture methods to improve diagnostic yield. Additionally, broad-range polymerase chain reaction (BR-PCR) targeting bacterial 16s rRNA conserved region has shown higher sensitivity with certain specimen types, so we sought to evaluate the clinical performance of BR-PCR performed on bronchoalveolar lavage (BAL) specimens in comparison to The Biofire® FilmArray® Pneumonia (PN) Panel (BioFire Diagnostics, Salt Lake City, UT, USA). Methods A retrospective chart review was performed on all BAL specimens that had both a PN panel test and BR-PCR performed from January 2020 to May 2022 at all Indiana University affiliated hospitals. The PN panel test was performed in-house as per laboratory protocol, while BR-PCR was performed in a reference laboratory. Outcomes assessed included turn-around times (TAT), sensitivity and specificity of BR-PCR and clinical impact, if any. Results A total of 68 BAL specimens from 53 patients were identified (83% of patients were immunocompromised). Percent positivity for the PN panel was 19% and that of BR-PCR was 18%. With the PN panel used as the gold standard, the sensitivity and specificity of BR-PCR was 85% and 98%, respectively. Only one respiratory organism was detected by BR-PCR but not by the PN panel, and it was not considered pathogenic or to have a significant clinical impact. The median TAT for the PN panel was 2.1 hours (1.8, 3.2) versus 7.8 days (6.9, 10.4) for BR-PCR. Conclusion In our cohort of patients, BR-PCR testing was not superior to the Biofire® FilmArray® Pneumonia (PN) Panel when used to detect certain bacterial etiologies of pneumonia. Additionally, faster TAT for the panel test has the potential to enhance antimicrobial stewardship practices by enabling better antibiotic utilization. Adjunctive BR-PCR testing may be useful for clinical care when conventional testing is negative and patients are at risk for a variety of potential pathogens, including fungi. Disclosures All Authors: No reported disclosures

1691. Use of multiplex PCR in pleural effusion: a case series study in a pediatric reference center in Colombia

Abstract Background The microbiological diagnosis of pleural effusion (PE) is largely based on methods of classical microbiology. Culture-based methods allow for testing of bacterial susceptibility tests, but these methods take time and frequently have false negative results. We describe the utility of multiplex PCR in pleural fluid for the diagnosis of complicated pneumonia in children using a commercial platform for respiratory samples. Methods We conducted a case series of children with complicated pneumonia by PE, empyema or necrotizing pneumonia. Pleural fluid was sent for laboratory to culture, cytochemical and molecular biology testing analysis between 2021 and 2022 in a reference children hospital in Bogotá, Colombia. We used BIOFIRE® FILMARRAY® Pneumonia Panel plus (BioFire Diagnostics, Salt Lake City, Utah). The results were strictly analyzed by a multidisciplinary team. Any change in patient’s therapeutics was decided by this group. Results We identified 17 samples that were processed for multiplex-PCR from 16 patients (Table 1). Median age was 3 years (IQR 2-4 years). Pleural empyema was the most common presentation (7/17, 41%), followed by free pleural effusion (6/17, 35%) and necrotizing pneumonia with empyema (4/17, 23,5%). Pathogens were documented in 16 out of 17 (94%) molecular panels performed. Streptococcus pneumoniae was detected in 11/17 (64.7%) multiplex PCR tests, adenovirus was detected in 7/17 (41.1%), and H. influenzae in 2/17 (11.7%) tests. Pneumococcus was isolated in classical cultures in 4 patients (23.5%), of which only one was in pleural fluid. Changes in antibiotic management in 9/17 (52.9%) of the patients. In 5 patients, there was an increase in the antibiotic spectrum, and in 4 patients, there was a decrease in it. Conclusion Although the use of this multiplex PCR device is not approved by the FDA for use in pleural fluid samples (off-label), this case series described its usefulness and importance in contexts where there is no other approved PCR technology for these samples. Disclosures All Authors: No reported disclosures

A Summer of Fevers and Fussiness: Eighteen Infants Admitted With Parechovirus Meningitis.

To define the presentation, spectrum of illness, and outcomes in infants with parechovirus (PeV) meningitis admitted to our inpatient general pediatrics service during a spike in incidence of admissions in summer 2022. This study is a retrospective case series of all patients aged 3 months and younger discharged from our institution with a CSF BioFire (BioFire Diagnostics, Salt Lake City, UT) FilmArray Polymerase Chain Reaction Meningitis/Encephalitis Panel result positive for PeV between January 1 and September 19, 2022. We collected and analyzed clinical and demographic data. Eighteen infants with PeV meningitis were admitted within our time frame, with 8 (44%) of the admissions occurring in July. Patients' mean age was 28.7 days and mean length of stay was 50.5 hours. Although all had a history of fever, only 72% were febrile on presentation. Laboratory findings showed a procalcitonin of less than 0.5 ng/mL in 86% of the 14 patients who had it drawn and no cerebrospinal fluid (CSF) pleocytosis in 83% of the patients who had CSF cell counts sent. Neutropenia was present in 17%. Although 89% of infants were given initial antibiotics, antibiotics were discontinued in 63% once their CSF panel returned positive for PeV, and in all by 48 hours. Infants hospitalized with PeV meningitis were febrile and fussy, but experienced uncomplicated hospital stays without neurological deficits. Parechovirus meningitis must be considered as a common cause of acute viral meningitis in young infants even without CSF pleocytosis. This study, although limited in scope and follow-up, can potentially assist in the diagnosis and treatment of PeV meningitis at other institutions.

Is Kawasaki Disease Caused by a Respiratory Virus?

Kawasaki disease is characterized by high fever, rash, cervical lymphadenopathy, conjunctival injection, oral mucous membrane changes and swelling of the extremities followed by skin sloughing. Despite >50 years of study, no bacterial, viral or other infectious agent has been consistently associated with the illness. The lockdown and social distancing for COVID-19 in March 2020 led to a marked decrease in respiratory virus circulation. This provided an "experiment of nature" to determine whether Kawasaki disease would decline in parallel. Discharge ICD-10 diagnosis codes were obtained from the Vizient Clinical Data Base for Kawasaki disease and respiratory viruses, and analyzed for the age group < 5 years. Weekly respiratory virus positivity data were also obtained from BioFire Diagnostics. Common enveloped respiratory viruses declined precipitously from April 2020 through March 2021 to levels at or below historical seasonal minimum levels. Kawasaki Disease declined about 40% compared with 2018-2019, which is distinctly different from the pattern seen for the enveloped respiratory viruses. Strong seasonality was seen for Kawasaki disease as far back as 2010, and correlated most closely with respiratory syncytial virus, human metapneumovirus and less so with influenza virus suggesting there is a baseline level of Kawasaki disease activity that is heightened during yearly respiratory virus activity but that remains at a certain level even in the near total absence of respiratory viruses. The striking decrease in enveloped respiratory viruses after lockdown and social distancing was not paralleled by a comparable decrease in Kawasaki disease incidence, suggesting a different epidemiology.

Whole-exome sequencing shows no specific mutation in ovarian teratoma of NMDAR-antibody encephalitis (P5-5.003)

<h3>Objective:</h3> To investigate mutations specific to the N-methyl-D-aspartate receptor (NMDAR)-associated teratoma to reveal the autoimmunity mechanism <h3>Background:</h3> N-methyl-D-aspartate receptor (NMDAR)-antibody encephalitis is the most common form of autoimmune encephalitis, about 40% of which is caused by ovarian teratoma. However, it is unknown why only a small population of ovarian teratoma causes the autoimmunity while the majority of the teratoma don’t. This study aimed to investigate any driver mutations specific to the NMDAR-associated teratoma to reveal the autoimmunity mechanism. <h3>Design/Methods:</h3> We included 17 ovarian teratomas derived from 15 patients with NMDAR-antibody encephalitis and 18 control ovarian teratoma from 30 patients without encephalitis. All the samples were genotyped by the SureSelect V6-Post Exome Capture kit (Agilent, CA, USA). The exome data were analyzed with R version 4.06 (Vienna, Austria) and the MUTALISK program (National cancer center, Goyang-si, Korea). <h3>Results:</h3> The two groups with and without NMDAR-antibody encephalitis had a mean age of 23.9 and 24.4 years, respectively. The average teratoma size was smaller in the group with encephalitis (3.0±2.1 cm vs 10.9±2.1, respectively). With the criteria lower than 1% of allele frequency with 1000 genome phase 3 (1000Gp3) and the Exome Aggregation Consortium (ExAC), 34 exomes were passed in our samples. Of these, no exome showed significantly different mutations between the groups of teratoma with and without NMDAR-antibody encephalitis. From the MUTALISK analysis, there was no significant difference in the mutation pattern signature in exomes between the two groups. <h3>Conclusions:</h3> This study shows that there is no difference in the mutation profile in protein-coding genes between the ovarian teratoma causing NMDAR-antibody encephalitis and the control teratoma. This result implies that post-transcriptional immune pathogeneses are involved in the autoimmune recognition of ovarian teratoma with NMDAR-antibody encephalitis. <b>Disclosure:</b> Dr. Jang has nothing to disclose. Dr. Ahn has nothing to disclose. Mr. Lee has nothing to disclose. Prof. PARK has nothing to disclose. Prof. Lee has nothing to disclose. Prof. Chu has nothing to disclose. Dr. Lee has nothing to disclose. Prof. Won has nothing to disclose. Prof. Lee has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Advanced Neural Technologies. Prof. Lee has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biofire Diagnostics. Prof. Lee has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Prof. Lee has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for GC pharma. The institution of Prof. Lee has received research support from GC pharma.

MOG antibody-associated encephalitis in adult: clinical phenotypes and outcomes (P13-5.020)

<h3>Objective:</h3> We investigated the clinical characteristics and outcomes of myelin oligodendrocyte glycoprotein (MOG) antibody-associated autoimmune encephalitis (MOGAE) in adult patients. <h3>Background:</h3> Although MOG antibody-associated disease (MOGAD) can be associated with autoimmune encephalitis, the clinical features and outcomes of MOGAE in adults are largely unknown. <h3>Design/Methods:</h3> From an institutional cohort, we analyzed adult patients with MOGAE followed-up for more than one year. Disease severity was assessed using the modified Rankin scale (mRS) and Clinical Assessment Scales in Autoimmune Encephalitis (CASE) scores. Immunotherapy profiles, outcomes, and disease relapses were evaluated along with serial brain MRI data. <h3>Results:</h3> A total of 40 patients were enrolled and categorized into cortical encephalitis (18 patients), limbic encephalitis (LE, 5 patients), and acute disseminated encephalomyelitis (ADEM, 17 patients). 80.0% of patients achieved good clinical outcomes (mRS 0–2) and 40.0% relapsed. The LE subtype was associated with an older onset age (<i>P</i>=0.004) and poor clinical outcomes (<i>P</i>=0.014) than the other subtypes but with a low rate of relapse (0.0%). 21/25 (84.0%) relapse attacks were associated with an absence or short (≤6 months) immunotherapy maintenance. On MRI, the development of either diffuse cerebral or medial temporal atrophy within the first six-month was correlated with poor outcomes. MOG-antibody was co-present with anti-N-methyl-D-aspartate receptor (NMDAR)-antibody in 13 patients, in whom atypical clinical presentation (cortical encephalitis or ADEM, <i>P&lt;</i>0.001) and disease relapse (46.2% vs. 0.0%, <i>P&lt;</i>0.001) were more frequent compared to conventional NMDAR encephalitis without MOG-Ab. <h3>Conclusions:</h3> Outcomes are different according to the three phenotypes in MOGAE. Short immunotherapy maintenance is associated with relapse, and brain atrophy was associated with poor outcomes. Patients with dual antibodies of NMDAR and MOG have a high relapse rate. <b>Disclosure:</b> Prof. Lee has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Advanced Neural Technologies. Prof. Lee has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biofire Diagnostics. Prof. Lee has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Prof. Lee has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for GC pharma. The institution of Prof. Lee has received research support from GC pharma. Prof. Kim has received intellectual property interests from a discovery or technology relating to health care. Prof. Chu has nothing to disclose. Prof. Lee has nothing to disclose. Woo-jin Lee has nothing to disclose.

Evaluation of BioFire® FilmArray® Pneumonia Panel in Bronchoalveolar Lavage Samples From Immunocompromised Patients With Suspected Pneumonia.

Objectives Immunocompromised patients, specifically those with solid organ transplants or cancer on chemotherapy, are at particularly high risk of severe pneumonia and opportunistic infections. In select patients, bronchoalveolar lavage (BAL) is performed to provide high-quality samples for analysis. We compare BioFire® FilmArray® Pneumonia Panel (BioFire Diagnostics,Salt Lake City, Utah, United States), a multiplex polymerase chain reaction (PCR) assay, with standard of care diagnostics in BAL samples from immunocompromised patients to identify opportunities for this test to affect clinical decision making. Methods Patients hospitalized with pneumonia based on clinical and radiographic findings who underwent evaluation with bronchoscopybetween May 2019 to January 2020 were reviewed. Among those patients undergoing bronchoscopy, those who were immunocompromised were selected for inclusion in the study. BAL specimens submitted to the microbiology laboratory were chosen based onas part of the internal validation of the panel in comparison with sputum culture at our hospitals.We compared the outcomes of the multiplex PCR assay with traditional culture methods and evaluated the role of PCR assay in de-escalating antimicrobial therapy. Results Twenty-four patients were identified for testing with the multiplex PCR assay. Of the 24 patients, 16 were immunocompromised, all with solid or hematological malignancy or a history of organ transplant. Seventeen individual BAL samples from the 16 patients were reviewed. BAL culture results and the multiplex PCR assay were in agreement in 13 samples (76.5%). In four cases, the multiplex PCR assay identified a possible causative pathogen not detected by standard workup. The median time to de-escalation of antimicrobials was three days (interquartile range (IQR) 2-4) from the day of collection of the BAL samples. Conclusions Studies have established the additive role of multiplex PCR testing in addition to traditional diagnostic tools like sputum culture in diagnosing the etiology of pneumonia. Limited data exist specifically looking at immunocompromised patients, in whom a timely and accurate diagnosis is particularly important. There is a potential benefit for performing multiplex PCR assays as an additive diagnostic tool in BAL samples for these patients.

Evaluation of BioFire Filmarray panel for respiratory pathogens: a demographic and clinical analysis in Istanbul, Turkey

We aimed to analyze the distribution of respiratory pathogens(RP) detected by a multiplex PCR-based method (BioFire Diagnostics, USA) among patients with suspected respiratory tract infections (RTI) and to evaluate the demographic, clinical and radiological characteristics of infected individuals . RP were detected in 1621/6376 (25.4%) of the samples in the years 2018-2020. Rhinovirus/enterovirus (RV/EV) were the most commonly detected pathogens (38.1%) followed by influenza A and B viruses (21%) and parainfluenza virus (PIV) (9.5%). Single pathogen was detected in 1361 (84%) and multi pathogens in 260 (16%) of 1621 samples. At least one comorbidity was present in 379 (30.5%) of the patients. Fever was the most common sign followed by cough and dyspnea. Thorax CT was present in 426 of 1243 RP positive patients (34.3%). Any radiological findings was found significantly related for a specific pathogen. No medication was given to 52.9% whereas antibiotics in 35.7% and antivirals in 3.8% of the patients. Film Array panel as a multiplex PCR test is not used rationally in our hospital and results were not dramatically improve management of RTI. A better communication between clinician and microbiologist is required for efficient use of laboratory and rational use of antimicrobials.

Evaluation of the Biofire Filmarray pneumonia panel for the detection of bacterial respiratory pathogens and antimicrobial resistance genes in endotracheal aspirate specimens

Background: Rapid detection of the causative agents is essential for determining the appropriate treatment for patients with lower respiratory tract infections. We evaluated the performance of the Biofire FilmArray pneumonia panel (FA-PE; BioFire Diagnostics, USA) in the identification of bacterial pathogens and antibiotic resistance genes in endotracheal aspirate specimens. Methods: A total of 43 non-duplicated endotracheal aspirates were included in this study. The performance of the FA-PE was assessed using the routine culture method as the reference standard. Results: The FA-PE demonstrated 92.9% sensitivity and 79.3% specificity for the identification of 15 bacterial targets compared to routine bacterial culture. Four antimicrobial resistance genes in 43 specimens were detected by the FA-PE. The most frequently detected resistance genes were mecA/C and SCCmec in three specimens, followed by CTX-M in one specimen. Conclusion: The FA-PE offers a rapid diagnostic method for lower respiratory tract infections. It may be useful at the early stage of pneumonia, before routine culture and antimicrobial susceptibility results are available.

1318. Etiology of Infectious Conjunctivitis in Children: A Multi-Center Case-Controlled Study

Abstract Background Acute infectious conjunctivitis (AIC) is a common pediatric infection affecting one in eight children annually. The etiology of AIC is poorly understood but important to inform treatment and return to school recommendations. Additionally, the association of bacteria isolated from the conjunctiva with the development of clinical AIC is not well defined. We aimed to determine the bacterial and viral causes of AIC in children. Methods Patients age 6 months-18 years with AIC at Denver Health (Denver, CO) and Marshfield Clinic (Marshfield, WI) from 2019-2021 were included. Age-matched healthy and upper respiratory infection (URI) controls without conjunctivitis were enrolled within 30 days of each case. Patients had a conjunctival flocked swab (Eswab®, Copan Diagnostics) obtained. Nucleic acids were extracted using the NucliSENS® easyMAG® system (Quidel, San Diego, CA) per manufacturer’s instructions. Multiplex RT-PCR for S.pneumoniae, H.influenzae, M.catarrhalis, S.aureus , and 11 respiratory viruses were completed using Lyra® (Quidel, San Diego, CA) and AnDiaTec® assay kits (Quidel Germany GmbH, Kornwestheim, Germany, Table). Nucleic acid amplification and detection was completed on the Applied Biosystems® (ABI) 7500 Fast Dx Real-Time PCR Instrument. Odds ratios were computed for each organism. Results A total of 78 cases and 71 controls (33 healthy, 38 URI) were included (Table). Bacteria were detected in 59 (75.6%) cases and 36 (50.7%) of controls (OR 14.3; 4.7,33.7). Respiratory viruses were infrequently detected (cases 2, 2.6%; controls 6, 8.5%), including in the pre-pandemic period. Of bacteria detected in cases, H.influenzae was the most common (56.4%) and had the highest association with conjunctivitis (OR 11.8; 4.8, 29.1) followed by M.catarrhalis (35.9% cases, OR 2.5; 1.2, 5.3). S.pneumoniae was detected more often in controls than cases (33.8% v 26.9%). Conclusion H.influenzae is likely the most important pathogen associated with AIC in children. Though data have suggested marginal benefit of antibiotic treat for conjunctivitis overall, studies specifically looking at benefit by organism would advance the field. A rapid diagnostic test for H.influenzae and possibly M.catarrhalis could help direct antibiotic treatment to children most likely to benefit. Disclosures Samuel R. Dominguez, MD PhD, Biofire DIagnostics: Advisor/Consultant|Biofire DIagnostics: Grant/Research Support|DiaSorin Molecular: Advisor/Consultant|Karius: Advisor/Consultant|Pfizer: Grant/Research Support.

2147. Multi-modal Quality Improvement Study to Reduce C. difficile Detection and Infections in Hospitalized Children

Abstract Background Our institution identified rising rates of Clostridiodes difficile (C. difficile) results and infections, which coincided in part with the introduction of gastrointestinal panels (GIP) testing. We aimed to reduce the rate of positive C. difficile results and hospital-acquired infections (HAI) by 20%. Methods We engaged key stakeholders to identify key drivers, develop interventions, and evaluate outcomes through several plan-do-study-act cycles. We conducted a multi-modal intervention that involved 1) provider education, 2) C. difficile clinical pathway development, 3) improved preventative cleaning measures, and 4) electronic medical record (EMR)-based GIP changes including a) added option for GIP with or without C. difficile (run on same testing platform, but C. difficile results were suppressed if not ordered), and b) built in testing restrictions with optional approval process (Table 1). Our population included all hospitalized children (&amp;lt; 18 years old) who had a stool test performed at a large quaternary-care children’s hospital over 30 months (2018-2020). Our primary outcomes were 1) rate of C. difficile positive results and 2) C. difficile HAI rates (defined as a positive test and symptom onset on or after day three of admission; adjudicated in real-time as part of routine surveillance) per 10,000 patient-days (PDs). Our process measure was the rate of testing capable of detecting C. difficile per 10,000 PDs. As a balancing measure, we evaluated the proportion of suppressed results that were ultimately released based on judgement of a infectious disease specialist who monitored these results in real-time for 7 months. Results We identified 2,001 stool tests performed for 1,982 encounters (Table 2). After education and EMR-based changes, we found special cause variation with a 44% decrease in the rate of positive C. difficile results and 55% decrease in HAI rates (Figures 1,2). There was a 44% decrease in testing for C. difficile, and only 2% (2/89) of suppressed results were ultimately released based on expert monitoring. The majority of patients (76%) with suppressed C. difficile results had a coinfection or were &amp;lt; 1 old. Conclusion Education coupled with EMR-based testing changes resulted in an impactful and sustained decrease in C. difficile detection and HAI rates. Disclosures Samuel R. Dominguez, MD PhD, Biofire DIagnostics: Advisor/Consultant|Biofire DIagnostics: Grant/Research Support|DiaSorin Molecular: Advisor/Consultant|Karius: Advisor/Consultant|Pfizer: Grant/Research Support.

874. Diagnostic Stewardship of Gastrointestinal Multiplex PCR Panels in Hospitalized Children

Abstract Background The introduction of multiplex gastrointestinal panels (GIP) led to increased rates of children with stool testing, high rates of negative results, and no change in clinical outcomes for most children. We aimed to reduce overall stool testing and stool testing with negative results by 20%. Methods We engaged stakeholders and implemented multi-modal interventions including 1) education and development of a clinical pathway to guide testing, and 2) electronic medical record (EMR)-based testing changes including built in stool testing restrictions with optional approval process (Table 1), and quantification of stool caliber in the EMR by nursing using the validated Bristol Stool Scale (BSS). We included all hospitalized children who had stool testing performed at a large children’s hospital over 30 months (2018–2020). Outcomes included the rate of stool tests and negative stool results per 10,000 patient-days. We evaluated rates of BSS documentation and GIPs performed for children hospitalized for &amp;gt; 96 hours as process measures. Balancing measures included the percent of ordered tests that were restricted, and percent of initially restricted tests that were approved. We compared the rate of actionable results (bacteria or parasite identified) between initially restricted but ultimately approved tests and non-restricted tests. Results There were 2,001 tests performed for 1,982 encounters (Table 2). After interventions, we found special cause variation with a 29% sustained decrease in the rate of stool testing and a 28% decrease in the rate of negative stool results (Figures 1,2). The rate of use of BSS was 81% and was sustained. There was a 33% decrease in the number of GIPs performed for children hospitalized for &amp;gt;96 hours. 34% of ordered stool tests per month were restricted, and this did not change over time. 56% of initially restricted tests were ultimately approved with no change over time, and these tests had a lower rate of actionable results compared to non-restricted tests (25 vs 34%, p=0.02). Conclusion Education coupled with EMR-based testing restrictions resulted in reduced rates of overall stool testing and low-value stool testing. Sustained ordering of restricted tests over time suggests that EMR-decision support is needed and likely cannot be removed. Disclosures Samuel R. Dominguez, MD PhD, BioFire Diagnostics: Advisor/Consultant|BioFire Diagnostics: Grant/Research Support|Karius: Advisor/Consultant|Pfizer: Grant/Research Support.