BioFire FilmArray Gastrointestinal Panel Research Articles

Utility of BioFire FilmArray Gastrointestinal Panel in the Diagnosis of Gastrointestinal Infections

Abstract Background Conventional diagnostic methods like culture and microscopy are time-consuming and have low diagnostic yield for gastrointestinal infections. New rapid molecular methods such as multiplex polymerase chain reaction (PCR) have recently been introduced for etiological diagnosis. The aim of this study was to evaluate the utility of the FilmArray gastrointestinal panel (GIP) in the diagnosis of gastrointestinal infections. Materials and Methods This is a retrospective study performed in the microbiology department of a tertiary care hospital. Stool samples were received and processed according to the manufacturer's instructions by FilmArray GIP. Stool culture and routine microscopy were also performed. Results The mean age of the 32 patients was 46 ± 24.2 years and with a male-to-female ratio of 1:1. Out of 32 stool samples received for testing by BioFire GIP, 23 samples (71.9%) were found to be positive for one or the other target. A total of 41 targets were detected from 23 positive patients, with predominant bacterial etiology (65.9%) followed by parasitic (31.7%) and viral (4.9%). Giardia lamblia was the most common (26.8%) target detected in all age groups. Additionally, in 56.5% of patients, more than one target was detected. The stool culture was positive in 2 of the 16 patients (12.5%). Conclusion The FilmArray GIP showed very good diagnostic performance compared with culture for the diagnosis of gastrointestinal infections. Further studies are needed to determine whether multiplex PCR improves patient outcomes and reduces costs.

Detection of multiple human enteropathogens in Norway rats (Rattus norvegicus) from an under-resourced neighborhood of Vancouver, British Columbia.

Urban Norway rats (Rattus norvegicus) can carry various human pathogens, and may be involved in pathogen propagation and transmission to humans. From January 31-August 14, 2021, a community outbreak of Shigella flexneri serotype 2a occurred among unhoused or poorly housed people in the Downtown Eastside neighborhood of Vancouver, British Columbia, Canada. The source could not be identified; however, patients reported contact with rats, and previous studies indicated transmission of rat-associated zoonotic pathogens among the unhoused or poorly housed residents of this neighborhood. The study objective was to determine if rats trapped in the outbreak area were carriers of Shigella spp. and other zoonotic enteric pathogens. From March 23-April 9, 2021, 22 rats were lethally trapped within the outbreak area. Colonic content was analyzed using the BioFire FilmArray Gastrointestinal (multiplex PCR) panel for human enteropathogens, which detected: Campylobacter spp. (9/22), Clostridioides difficile (3/22), Yersinia enterocolitica (5/22), Cryptosporidium spp. (8/22), Giardia duodenalis (5/22), Rotavirus A (1/22), enteroaggressive Escherichia coli (2/22), enteropathogenic E. coli (10/22), and Shigella spp. or enteroinvasive E. coli (EIEC) (3/22). An ipaH PCR assay was used for targeted detection of Shigella spp./EIEC, with five rats positive. Two samples contained insertion sites unique to S. flexneri isolated from the human outbreak. This study highlights the potential for rats to carry a broad range of human pathogens, and their possible role in pathogen maintenance and/or transmission.

Impact of Rapid Molecular Multiplex Gastrointestinal Pathogen Testing in Management of Children during a Shigella Outbreak.

Fecal culture for isolation and identification of Shigella may take days. The BioFire FilmArray Gastrointestinal (GI) panel (bioMérieux, France) is a PCR-based assay that detects enteric pathogens including Shigella/enteroinvasive Escherichia coli (EIEC) in about an hour. The aim of this study was to evaluate the impact of GI panel detection of Shigella in a pediatric emergency department (ED) during an outbreak. Stool samples from children with acute gastroenteritis were tested by the GI panel. Test results were either withheld in preintervention (PRE) or reported to clinicians/families in the postintervention (POST) period. The impact of the GI panel testing on patient management and outcomes was measured. Shigella/EIEC was identified by the GI panel in the PRE (n = 30) and POST (n = 21) phase. The GI panel detected more Shigella infections than did culture; six of 31 (19.4%) Shigella GI panel-positive patients who also had stool cultures were missed by culture. Azithromycin therapy was prescribed for 20% of subjects in the PRE phase and 71.4% of subjects in the POST phase (P < 0.001). Time from the clinical encounter until starting azithromycin therapy was shorter in the POST phase (n = 9), 8.25 h (range, 6.37 to 52.37 h), than in the PRE phase (n = 1), 72 h. Six subjects in the PRE phase visited additional providers compared with one in the POST phase. Prompt diagnosis of shigellosis with the GI panel may provide the opportunity for prompt antimicrobial therapy and avoid additional visits to providers due to early definitive diagnosis. Prompt diagnosis of Shigella at an ED visit may optimize patient management and reduce transmission.

531. Clinical Evaluation of the BioFire® FilmArray® Gastrointestinal (GI) Panel for use with Rectal Swab Specimens in Cary-Blair Media

Abstract Background The BioFire® FilmArray® Gastrointestinal (GI) Panel provides results for 22 bacterial, viral, and protozoan pathogens responsible for GI infection in about an hour. This test is indicated for use with stool specimens in Cary-Blair media (SCB) as a specimen type. For many patients, a stool sample can be difficult to provide during a single clinic visit, potentially delaying diagnosis and treatment. Rectal swabs in Cary-Blair (RSCB; an off-label sample type) are a more convenient and faster specimen type to collect, as collection can occur during a patient’s healthcare visit. The purpose of this study was to assess the performance of the GI Panel when testing RSCB compared to SCB. Methods Paired SCB and RSCB specimens were collected from outpatient subjects with signs of GI infection and tested in parallel using the GI Panel. All detections were confirmed using culture (for some bacterial analytes) and PCR/sequencing. Performance of the GI Panel in RSCB versus SCB specimen types was assessed using the ratios (RSCB/SCB) of sensitivities and false positive rates (FPR). Positive percent agreement (PPA) and negative percent agreement (NPA) for the GI Panel test in RSCB compared to SCB were also evaluated. Results A total of 299 paired SCB and RSCB specimens were collected and tested with the GI Panel. Detections for 17 of the 22 analytes on the GI Panel were observed in both specimen types. When comparing results from RSCB and SCB specimen types, the overall ratio of sensitivity was 0.86 and the overall ratio of FPR was 0.31. Further, overall PPA was 76.6% and overall NPA was 99.8%. Conclusion Overall, the GI Panel is sensitive and specific for the rapid detection of many of the organisms responsible for GI infection when using either specimen type, however RSCB specimens have a lower diagnostic yield (i.e. fewer detections) compared to SCB. As a result, GI Panel performance for the RSCB is characterized as less sensitive compared to performance for SCB specimens. Acknowledging these limitations, the convenience and time-to-result benefits of the RSCB specimen type may aid in the effective diagnosis and management of GI infection in outpatient settings. The BioFire FilmArray GI Panel is not cleared or approved for use with rectal swabs in Cary-Blair. Disclosures Jared Goos, PhD, bioMerieux: Employee|bioMerieux: Stocks/Bonds Crissy Neff, n/a, bioMerieux: Employee|bioMerieux: Stocks/Bonds Kristen Holmberg, n/a, bioMerieux: Employee Annie Lyons, n/a, bioMerieux: Employee Nicole Monroe, Dr. sc. nat., bioMerieux: Employee Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, F(AAM), BioFire: Grant/Research Support|Luminex: Grant/Research Support Kimberle Chapin, MD, Cepheid: Employee Bradley A. Connor, MD, BioMerieux: Advisor/Consultant Cynthia Andjelic, PhD, bioMerieux: Employee.

Clinical impact of biofire gastrointestinal panel testing for hospitalised children with acute gastroenteritis.

To investigate the clinical impact of BioFire FilmArray Gastrointestinal Panel (FGP) testing in real-life diarrhoeal episodes of hospitalised paediatric patients. Children hospitalised between October 2018 and September 2020 for whom stool specimens for FGP were submitted at the clinician's discretion were retrospectively observed. For each episode, demographics, clinical information and stool tests were collected. The clinical impact for each case was evaluated by changing the antibiotic prescription, following the result of the FGP testing. Out of 140 diarrhoeal episodes, 25 pathogens were found in 24 cases using conventional methods, whereas, FGP testing identified 75 pathogens in 56 cases (p< 0.05). The pathogens more frequently identified by FGP testing were Campylobacter, Shigella, Rotavirus, Giardia lamblia and Cryptosporidium. The clinical impact of FGP testing was observed in 17/140 (12%) diarrhoeal episodes, and higher rates in previously healthy (19%) and solid organ-transplanted children (15%). We found that using FGP testing for hospitalised children with diarrhoeal episodes could increase pathogen identification and impact clinical decisions, especially in healthy and transplant patients.

Unusual Combination of Gastrointestinal Pathogens Detected by Multiplex PCR

Abstract Introduction/Objective Infectious gastroenteritis (IGE) is a common but complex entity which is a major cause of global morbidity and mortality. IGE is caused by a wide range of etiologic agents such as viruses, bacteria, and parasites. In the United States there are approximately 373 million of IGE cases per year. Most cases of IGE resolve without identification of a specific pathogen. Multiplex molecular assays allow identification of multiple possible pathogens with rapid turnaround time and increased sensitivity, facilitating to formulate an effective treatment plan and control measures. Methods/Case Report We present a case of a pediatric patient with no significant past medical history who has been having runny stools that have progressively worsened in the last 3 months and 2 days history of bloody stools with mucus before emergency room presentation. She had no fever, vomiting, joint pain, oral ulcer, and rash. Physical exam showed that the patient appeared well, nontoxic, and vital signs were within normal limit. Copious rhinorrhea was noted. She was at 50th percentile for age on the growth chart. Family denied any recent travel or sick contacts however stated that all the family members have been on well water. Complete blood count was obtained and showed a platelet count of 669 x 10(3)/mcL and WBC of 16.6 x 10(3)/mcL with differential showing absolute lymphocytosis, absolute monocytosis and absolute eosinophilia. Biofire FilmArray gastrointestinal panel performed on the stool detected Giardia lamblia, Campylobacter, Shiga-like toxin producing E. coli and Adenovirus F 40/41. Repeat of the panel per protocol detected the same four pathogens. Results (if a Case Study enter NA) N/A. Conclusion This case report highlights the significance of detecting multiple causative pathogens. While long term watery diarrhea may guide clinicians to malabsorptive process and the use of well water to Giardia, a sensitive and specific multiplex assay can detect all the pathogens involved in the disease process and greatly simplify the treatment plan for patients. This unusual combination of pathogens can explain the unique symptomology of the patient including long term watery diarrhea, recent bloody diarrhea as well as copious rhinorrhea and failure to thrive.

The Efficacy of the BioFire FilmArray Gastrointestinal Panel to Reduce Hospital Costs Associated With Contact Isolation: A Pragmatic Randomized Controlled Trial.

Background: Molecular syndromic panels can rapidly detect common pathogens responsible for acute gastroenteritis in hospitalized patients. Their impact on both patient and healthcare system outcomes is uncertain compared to conventional stool testing. This randomized trial evaluates the impact of molecular testing on in-hospital resource utilization compared to conventional stool testing.Methods: Hospitalized patients with acute diarrheal illness were randomized 1:1 to either conventional or molecular stool testing with the BioFire FilmArray gastrointestinal panel (FGP). The primary outcome was the duration of contact isolation, and secondary outcomes included other in-hospital resource utilization such as diagnostic imaging and antimicrobial use.Results: A total of 156 patients were randomized. Randomization resulted in a balanced allocation of patients across all three age strata (<18, 18-69, ≥70 years old). The proportion of positive stools was 20.5% vs 29.5% in the control and FGP groups, respectively (p=0.196). The median duration of contact isolation was 51 hours (interquartile range [iqr] 66) and 69 hours (iqr 81) in the conventional and FGP groups, respectively (p=0.0513). There were no significant differences in other in-hospital resource utilization between groups.Conclusions: There were no differences in in-hospital resource utilization observed between the FGP and conventional stool testing groups.

Alternative Causes of Infectious Diarrhea in Patients with Negative Tests for Clostridoides Difficile.

Hospitalized patients with diarrhea who have a negative Clostridoides difficile (C. difficile) test are not routinely evaluated for alternative causes of infectious diarrhea. This study assessed for potential infectious causes of diarrhea in hospitalized patients with an order for repeat C. difficile toxin enzyme immunoassay (tEIA) testing after an initial tEIA test was negative. For patients age ≥18 years who had a second C. difficile tEIA test ordered within 96 h after a negative tEIA test, remnant fecal specimens from the first (negative) tEIA test were evaluated using the BioFire FilmArray Gastrointestinal Panel PCR, C. difficile toxigenic culture, and culture on a blood agar plate (BAP) to identify other potential causes of infectious diarrhea. Growth of organisms on the BAP was also used to assess potential disruptions in the gastrointestinal microbiota. Among 84 remnant specimens, toxigenic C. difficile was identified in 9 (11%) by culture or PCR, while potential alternative causes of infectious diarrhea, including norovirus, rotavirus, enteropathogenic Escherichia coli, and Salmonella, were identified in 11 specimens (13%) by PCR. For the majority of patients, no infectious cause of diarrhea was identified, but 84% exhibited disrupted gastrointestinal microbiota, which may contribute to diarrhea. When a hospitalized patient has a negative C. difficile tEIA test but continues to have diarrhea, alternative infectious and noninfectious causes of diarrhea should be considered. If the patient has clinical signs and symptoms suggestive of infection or risk factors for gastrointestinal infection, laboratory testing for other etiologic agents may be appropriate.

Colonization with Gastrointestinal Pathogens Prior to Hematopoietic Cell Transplantation and Associated Clinical Implications

Infectious diarrhea following hematopoietic cell transplantation (HCT) significantly contributes to morbidity and mortality. Most HCT recipients experience diarrhea in the post-transplantation period, and infectious pathogens are frequently detected during diarrheal episodes. However, little is known about how frequently these patients are colonized with gastrointestinal (GI) pathogens before their transplantation and whether colonization predicts future diarrheal illness. We sought to determine how frequently HCT recipients are colonized with GI pathogens before HCT and the degree to which pre-HCT colonization predicts post-transplantation infectious diarrheal illness. We conducted a prospective cohort study of allogeneic and autologous HCT recipients at a single center between December 2016 and January 2019. Stool samples were collected during the week before HCT, and formed samples were evaluated for the presence of 22 diarrheal pathogens using the BioFire FilmArray GI panel. We determined the frequency with which participants were colonized with each pathogen and identified factors associated with colonization. We then determined how frequently pretransplantation colonization led to post-transplantation diarrheal infections due to the colonizing pathogen and whether colonization was associated with increased number of days of post-transplantation diarrhea during the transplant hospitalization. We enrolled 112 asymptomatic patients (allogeneic, 61%; autologous, 39%) who had a formed stool specimen before HCT, of whom 41 (37%) had a GI pathogen detected. The most commonly detected organisms were Clostridioides difficile (n=21; 19%), Yersinia enterocolitica (n = 9; 8%), enteropathogenic Escherichia coli (EPEC) (n=6; 6%), and norovirus (n = 5; 4%). Female sex and previous C. difficile infection were associated with C. difficile colonization, and having non-Hodgkin lymphoma was associated with being colonized with a diarrheal pathogen other than C. difficile. Thirteen of 21 patients (62%) with pretransplantation C. difficile colonization developed a clinical C. difficile infection post-transplantation, and 8 of 10 patients (80%) colonized with EPEC or enteroaggregative E. coli developed post-transplantation infections due to their colonizing pathogen. Pretransplantation C. difficile colonization was also associated with an increased duration of post-transplantation diarrhea (P=.048). Conversely, none of the 9 patients with pretransplantation Yersinia enterocolitica colonization developed a post-transplantation Y. enterocolitica infection. Patients admitted for HCT are frequently colonized with a diverse range of GI pathogens. Colonization with C. difficile colonization and diarrheagenic E. coli is frequently associated with post-transplantation diarrheal infections caused by these organisms, but the clinical significance of colonization with other GI pathogens is not clear.

Study of Zoonotic Enteric Pathogens of Atelerix algirus in Tenerife, Canary Islands, Spain.

Atelerix algirus is an invasive species in the Canary Islands (Spain). There are few studies about the zoonotic pathogens this species could be hosting; therefore, this study was focused on analyzing causative agents of diarrhea in humans in feces from hedgehogs. A total of 45 fecal samples obtained in Tenerife (Canary Islands) were analyzed in this study using Biofire FilmArray gastrointestinal panel with an integrated Biofire FilmArray system. Forty-two (93.33%) of the samples presented at least one of the pathogens detected by the panel. The prevalence of four bacteria stands out as for enteropathogenic Escherichia coli (71.11%), Salmonella (66.67%), Clostridioides difficile (33.33%), and Campylobacter sp. (22.22%), all of which were widely distributed along Tenerife. Besides, other pathogens were found, Cryptosporidium sp. and enterotoxigenic E. coli lt/st in 6.66% of the animals, Shigella/enteroinvasive E. coli in 4.44%, and Norovirus GI/GII, Plesiomonas shigelloides, and Vibrio sp. in 2.22%. Of the hedgehogs, 26.66% were hosting just one pathogen, and the others showed coinfection: 24.44% hosted two, 31.11% hosted three, and 11.11% hosted four or more. The close contact with hedgehogs may imply the transmission of not only one causative agent of diarrhea but also multiple agents, since coinfection is highly prevalent. The lack of management measurements for this animal in the Canary Islands, the common habit of adopting hedgehogs from wildlife without veterinary control, and the fact that most of the hedgehogs studied belonged to highly populated areas imply a high risk of transmission of pathogens to humans.

Performance of a new molecular assay for the detection of gastrointestinal pathogens.

Introduction Conventional diagnostic laboratory algorithms for determining the cause of infectious gastroenteritis include culture, biochemical identification and immunoassays. In addition, multiplex PCR-based testing has advanced into the gastroenterology diagnostic arena in recent years.Aim The purpose of this study was to evaluate the performance of a new molecular test (Diagnostics Solutions Laboratory GI-MAP) for the detection of bacterial and parasitic pathogens in stool samples spiked with known organisms.Methodology Faeces from a healthy human subject were pooled into a standard matrix and screened for the absence of bacteria, parasites and Helicobacter pylori antigen. Once confirmed negative single faecal aliquots from the matrix were spiked with solely one pathogen-type from a panel of 14 bacterial pathogens or one of 2 parasitic pathogens at a density of 5×106 organisms ml−1. Sixteen spiked samples in appropriate transport media were sent to two testing labs, specifically a reference site using the PCR-based BioFire FilmArray Gastrointestinal Panel, and a second lab using the GI-MAP assay. Seven negative control samples comprised solely of stool matrix were also submitted.Results Significant variability was found when the GI-MAP assay was used to test normal stool matrix with and without known bacteria and parasites at densities well within the expected limits of detection. The GI-MAP assay displayed a sensitivity of 80 % and a specificity of only 26 % due to many false positive results. This assay also reported quantitative numbers for pathogens. The BioFire FilmArray Gastrointestinal Panel achieved a sensitivity and specificity of 100 %.Conclusion The highly variable results for the GI-MAP assay were unexpected due to the precise pre-spike analysis and the overall maturation of nucleic acid amplification methods within the industry. Problematic to this assay is the poor level of specificity displayed by this assay reporting the presence of several pathogens, which could cause clinicians to treat with antibacterial and/or antiparasitic agents in the absence of any true pathogens.

Use of BioFire FilmArray gastrointestinal PCR panel associated with reductions in antibiotic use, time to optimal antibiotics, and length of stay

BackgroundRapid and accurate diagnostic tools are needed for appropriate management of infectious diarrhea.MethodsWe evaluated the impact of the introduction of rapid multiplex PCR testing using the FilmArray gastrointestinal (GI) panel (BioFire Diagnostics, LLC, Salt Lake City, UT) at our institution, and compared the results to those of standard stool cultures.ResultsThe most common pathogens detected by the FilmArray GI panel were Clostridium difficile (55.0%), Campylobacter species (20.9%), Salmonella species (12.4%), and Shigella/EIEC species (12.4%). Rates of reproducibility in stool culture for these pathogens ranged from 56.3 to 77.8%. Co-detection of two or more organisms was common (24.2%), most commonly involving EPEC, EAEC, ETEC, and STEC. The time from arrival in the Emergency Department to discharge or admission to the hospital was unchanged after the introduction of FilmArray GI panel, but length of hospital stay was shorter (3 vs. 7.5 days, p = 0.0002) for the FilmArray group. The time to empiric antibiotics did not differ significantly, but optimal antibiotics were started earlier after introduction of the FilmArray GI panel (hospital day 1 vs. 2, p < 0.0001). More patients were discharged without antibiotics after introduction of the FilmArray GI panel (14.0% vs. 4.5%; p < 0.001).ConclusionOur results demonstrate that the FilmArray GI panel is an important tool for improving both patient care and antibiotic stewardship, despite the tendency for positive results with multiple pathogens.

Diagnostic Stewardship for Comprehensive Gastrointestinal Pathogen Panel Tests

Syndromic gastrointestinal (GI) panels are molecular tests that evaluate stool specimens for multiple enteric pathogens simultaneously, including viruses, bacteria, and parasites. The Luminex xTAG GI panel includes 14 microbial targets and the Biofire FilmArray GI panel includes 22. The purpose of this scoping review was to describe clinical use of these two commercially available syndromic GI panels. Compared with conventional testing, syndromic panels increase the number of potential pathogens identified by two- to fivefold. Syndromic panels were associated with non-reproducible results, positive results in the absence of clinical disease, and positive results for pathogens of unclear clinical significance. Syndromic panels were less likely to provide new information when performed > 72 h after hospital admission or when repeated within 4 weeks of a previous test. Process measures or clinical outcomes related to testing were infrequently reported. Outcomes-based research is needed to determine the clinical impact of syndromic GI panels. Strategies for diagnostic stewardship that may increase the utility of GI panels include (1) development of clinical criteria for testing, (2) use of multi-step testing algorithms that start with tests for the most common organisms (Clostridium difficile and norovirus), (3) selective reporting of results, (4) reporting results through a mediator such as the infection preventionist or antibiotic stewardship pharmacist, and (5) maintenance of separate pathways for C. difficile testing.

Impact of the BioFire FilmArray gastrointestinal panel on patient care and infection control.

ObjectivesConventional routine PCR testing for gastrointestinal infections is generally based on pathogen related panels specifically requested by clinicians and can be erroneous and time consuming. The BioFire FilmArray gastrointestinal (GI) panel combines 22 pathogens into a single cartridge-based test on a random-access system, thereby reducing the turnaround time to less than 2 hours. We described the clinical impact of implementing the BioFire FilmArray on patients with gastroenteritis in our hospital.MethodsPatients attending a Dutch tertiary care center (Radboud University Medical Center), from whom stool samples were obtained, were eligible for inclusion. The clinicians selected one or a combination of different routinely performed PCR panels (bacterial panel, viral panel, clostridium testing, and three parasitic panels) based on clinical history and symptoms. All samples were in parallel tested with the FilmArray. We retrospectively collected patient data regarding infection control and patient management to assess the potential impact of implementing the FilmArray.ResultsIn total 182 patients were included. Routine PCR detected one or more pathogens in 52 (28.6%) patients compared to 72 (39.6%) using the FilmArray. Turnaround time (including transport) decreased from median 53 hours for the routine PCR to 16 hours for the FilmArray. Twenty-six patients could have been removed from isolation 29 hours sooner, 3.6 antibiotic days could have been saved and in five patients additional imaging testing (including colonoscopies) could have been prevented.ConclusionThe theoretical implementation of the BioFire FilmArray GI panel in patients with clinical suspicion of gastroenteritis resulted in a significant better patient management.

2358. Understanding the Clinical Implications of Clostridium difficile Detection in the Molecular Age: Colonization vs. Infection in Children Less Than 3 Years of Age

BackgroundInfants have a high rate of asymptomatic Clostridium difficile (CD) colonization (up to 37%) but can rarely develop true CD infection (CDI). However, currently available polymerase chain reaction (PCR) and enzyme immunoassays (EIA) have suboptimal sensitivity/specificity to distinguish CDI from colonization. Recent data from adults showed that lower cycle threshold (Ct) values of a semi-quantitative CD toxin B gene (tcdB) PCR assay in stool correlated with detection of free CD toxin in stool and poor clinical outcomes. We hypothesized that a tcdB PCR assay may be utilized to distinguish CDI from colonization in patients < 3 years old.MethodsSymptomatic patients < 3 years old with CD detected by the BioFire FilmArray Gastrointestinal Panel (FGP) were enrolled 2/2018–3/2019. We performed CD tcdB PCR and toxin A/B/GDH EIA on frozen aliquots of stool in Cary Blair. CDI was defined among those that were tcdB PCR positive as (1) a consistent clinical syndrome (diarrhea + no current laxative use), (2) CD EIA toxin+, (3) symptomatic improvement with CDI-directed treatment, and (4) no alternative etiology of diarrhea identified. Patients who did not meet criteria for CDI were considered colonized. We compared median tcdB PCR Ct values between the CDI and colonized groups using the Mann–Whitney test.ResultsOf 193 FGP CD+ patient samples with charts available for review, 37 (19%) samples were EIA GDH+/toxin+, 121 (63%) were GDH+/toxin− and 35 (18%) were EIA−. 150 (78%) samples had detectable tcdB by PCR. Six (4%) patients met criteria for CDI and 144 (96%) for colonization. Median (interquartile range) tcdB PCR Ct values were 23.8 (22.0–29.5) and 30.5 (26.3–35.8) in patients with CDI and colonization, respectively (P = 0.03).ConclusionUsing a strict clinical and laboratory definition, 4% of evaluable patients < 3 years old met criteria for CDI and had significantly lower tcdB PCR Ct values than colonized patients. A combination of clinical and laboratory criteria, including semi-quantitative tcdB PCR, may help differentiate colonization from CDI in this patient population.Disclosures All authors: No reported disclosures.

2148. Performance of the BioFire FilmArray Gastrointestinal Panel in a Clinical Setting of Infectious Diarrhea

BackgroundInfectious diarrhea remains as one of the leading causes of morbidity and mortality worldwide among all age groups. Conventional methods for diagnosis are time consuming and expensive. The BioFire FilmArray gastrointestinal panel (FA-GIP) tests for 22 enteric pathogens, provides results in a few hours and improves healthcare costs. The impact on antibiotic stewardship is unknown.MethodsWe conducted a retrospective cohort, multi-center study to evaluate FA-GIP clinical performance in hospitalized patients with acute diarrhea. Patients from 3 hospitals from the Christus Muguerza health group were included between January 2017 and August 2018. The FA-GIP was ordered by the treating physician and was not influenced by the study. Duration of antibiotic therapy, length of hospital stay, and therapy modification were assessed. The comparison group consisted of patients with acute diarrhea in which no FA-GIP was ordered.ResultsData from 130 patients with FA-GIP and 107 patients with conventional methods were collected. Pathogens were detected by FA-GIP in 72.3% of the cases. The median of duration of antibiotic therapy in FA-GIP group was 5 days (IQR 0–8) vs. 3 days (IQR 0–6) in conventional methods group, (P < 0.05). The mean length of stay was 3.3(SD ± 2.4) in FA-GIP group vs. 1.9 (SD ± 1.0) in the control group (P < 0.05). Patients in FA-GIP group had more days with diarrhea, lower hemoglobin levels, and higher creatinine levels at admission (Table 1). The most frequent pathogens detected were enteropathogenic Escherichia coli in 24.4%, norovirus in 19.1%, Clostridium difficile in 17.0% and Campylobacter jejuni in 15.9% (Table 2). Therapy modification after FA-GIP results was made in 51.1% of the patients with a detected pathogen, and in 42.8% of patients with no pathogen detected in FA-GIP the antibiotic was stopped.ConclusionPatients in the FA-GIP group had a more complex clinical scenario upon admission, they also had a longer duration of antibiotic therapies and longer length of stay. Although antibiotic therapy was positively influenced by the FA-GIP result, and no pathogen detection leads to withdrawal of unnecessary antibiotics. Disclosures All authors: No reported disclosures.

Exploring the Less Common Pathogens of Infectious Diarrhea

ABSTRACT Objective: Gastrointestinal (GI) panels have allowed for faster and accurate detection, treatment, and control of pathogens. Because of the large number of potential pathogens included in the panel the clinical significance and manifestations of some organisms, such as Enteroaggregative Escherichia coli (EAEC) and Enteropathogenic E. coli (EPEC), remains undetermined. Methodology: We performed a single-institution retrospective chart review for 222 patients with a stool sample tested on BioFire FilmArray Gastrointestinal Panel (GI Panel) between June 1, 2016 and March 9, 2017. Results: Of the 222 patients, four had EAEC and 17 and EPEC. Patients who tested positive for EAEC and EPEC were younger (26.3 years and 33.9 years, respectively) than patients that did not test positive for a GI pathogen (47.7 years). In cases where multiple organisms were detected, EPEC was present 56.3% of the time. Analysis of symptoms showed that EPEC patients had a high prevalence of abdominal pain (p=0.0425) and vomiting (p=0.0045), but not diarrhea, when compared to the presence of these symptoms in patients with no targets detected. With only four patients positive for EAEC in this study, the results of symptoms in EAEC patients were inconclusive. Cases involving EPEC and EAEC were treated similarly to other cases of diarrhea with no significant difference in the number of imaging studies and medication changes. Conclusions: While further studies are required to determine the specific clinical significance of EAEC or EPEC, it is evident that patients positive for EPEC often experience abdominal pain and diarrhea, suggesting EPEC may be more pathogenic than previously thought. J Microbiol Infect Dis 2019; 9(1):1-9.

Diagnostic determination of Norovirus infection as one of the major causes of infectious diarrhea in HIV patients using a multiplex polymerase chain reaction assay.

Although infectious diarrhea is one of the most common complications in human immunodeficiency virus (HIV)-infected patients, robust diagnostic methods for determining potential pathogens are still limited in the clinic. Norovirus, a type of calicivirus, has been shown to be the most common cause of gastroenteritis. Here, we used multiplex polymerase chain reaction as a diagnostic tool to verify Norovirus as the diarrhea-related pathogen in HIV-infected patients with unknown etiological information. Stool specimens obtained from 81 HIV-infected patients with diarrhea were analyzed by BioFire FilmArray Gastrointestinal (GI) panel. Among 26 HIV-infected patients with unknown etiological information, we detected Norovirus in 14 stool specimens of these patients with 100% sensitivity and specificity as confirmed by reverse transcription polymerase chain reaction (RT-PCR), and one specimen showed both Norovirus and enterotoxigenic Escherichia coli infection. Among the remaining 55 patients with verified Clostridium difficile infection, nine patients also detected positive for Norovirus infection. In conclusion, using FilmArray GI panel and RT-PCR, we determined that Norovirus infection as one of the main pathogens responsible for diarrhea in HIV patients.

Shiga-like Toxin Producing E. coli Identified in Patients with Multiple Myeloma (MM) Hospitalized Due to Acute Onset Diarrhea; First Report on the Clinical Use of the Biofire Film Array Gastrointestinal Panel

Introduction:Infections are a major cause of morbidity and mortality in patients with multiple myeloma (MM) and of these, one of the most frequent is gastroenteritis. This can be explained by immunoparesis, a known manifestation of MM and immunosuppression due to multiple lines of treatment.Other causes of diarrhea such as drugs or gastro-intestinal infiltration by plasma cells should also be excluded.Immunoglobulin A(IgA) is a major immunoglobulin on mucosal surface and defends the bowel from pathogens invasion. Data exists in literature about the protective role of IgA against Shiga toxin.Early isolation of pathogen and correct therapeutic intervention are important and can be lifesaving for MM myeloma patients.Until recently, diagnostic clinical laboratories utilized different methodologies to detect bacterial, parasitic, and viral causes of gastroenteritis. These tests have a number of disadvantages, including poor sensitivity, potentially long turnaround times, and complicated workflows. In addition, there are limited or almost no testing methods routinely available for most strains of Escherichia coli causing diarrhea.The Film Array GI Panel, is a relatively new method introduced recently, which provides comprehensive, simultaneous detection of 22 different enteric pathogens on stool specimens with a turnaround time as short as 1 hour . Because of its high cost it is not used routinely in all patients presenting to the emergency room with acute diarrhea.Here we summarize our real-life experience, using the BioFire PCR-Arrayfor 4 patients with relapsed /refractory MM who were admitted to our medical center with an acute presentation of gastroenteritisMethods:The Infectious Diseases Unit at our medical centre decided to introduce a strategic approach of the use of BioFire PCR-Array for the examination of stool samples, in immunocompromised patients who present to the emergency room with acute diarrhea.The panel used includes the following 22 pathogens: Campylobacter spp., Clostridium difficile(toxin A/B), Plesiomonas shigelloides, Salmonella spp., Vibriospp., Vibrio cholerae, Yersinia enterocolitica, enteroaggregative E. coli, enteropathogenic E. coli, enterotoxigenic E. coli, Shiga-like toxin-producing E. coli (stx1 and stx2) (including specific detection of E. coli O157), Shigella spp./enteroinvasive E. coli, Cryptosporidium spp., Cyclospora cayetanensis, Entamoeba histolytica, Giardia lamblia, adenovirus F 40/41, astrovirus, norovirus GI/GII, rotavirus A, and sapovirus.The assay is sent on the first day of patient admission, and results are reported to the Infectious Diseases Unit within one hour.Here we summarize the results obtained in four patients with MM treated at the Hemato-Oncology Unit in Bnai Zion Medical Centre , Haifa , who were hospitalized in 2018 due to acute diarrhea and had positive PCR-Biofire results;Results:All patients examined had relapsed/refractory MM and had received 2-5 treatment lines for MM.Two of the four patients had neutropenia on admission, two had low IgG level, three had low IgM level and all four had low IgA levels. Of the four patients with MM and acute diarrhea, evaluated by BioFire Film Array, one had two episodes of acute diarrhea on different occasions and was evaluated twice.Five pathogens were detected by BioFire FilmArray, STEC (Shiga-like toxin producing E. coli) was the most common bacteria encountered and was detected 3 times: EPEC (Enteropathogenic E. coli) and ETEC (Entertoxogenic E. coli) were detected one time each.Careful review of the literature did not identify any previous case report of patients with multiple myeloma who had Shiga-like toxin producing E. coli.All patients received antibiotics-Azithromycin and improved.Conclusion: In our experience using the PCR- Biofire assay we show that this approach is feasible and can be used safely to tailor therapy in immunocompromised patients. In all cases, E.Coli was found, most frequently STEC (Shiga-like toxin producing E. coli). Using this approach enable us to identify new pathogens causing diarrhea in immunocompromised patients, extremely quickly. These preliminary results reveal the need for more clinical experience using the Biofire FilmArray as a diagnostic test for patients with MM and other haematological malignancies, who present acutely with severe diarrhea. DisclosuresTadmor:NOVARTIS: Consultancy; ABBVIE: Consultancy; JNJ: Consultancy; PFIEZER: Consultancy; ROCHE: Research Funding. Polliack:ABBVIE: Consultancy; ROCHE: Research Funding.

1091. Algorithmic Release of Clostridium difficile PCR Results From a Multiplex Gastrointestinal (GI) Panel in Children &amp;lt;3 Years Old

BackgroundInfants have a high rate of asymptomatic Clostridium difficile (CD) colonization, up to 37%. Given this, our laboratory does not release CD+ results from the BioFire FilmArray Gastrointestinal Panel (FGP) in patients <3 years, unless requested by a physician. We sought to validate this model by comparing results from FGP to semi-quantitative CD PCRs for toxin B and glutamate dehydrogenase (GDH), enzyme immunoassay (EIA) for toxin A/B/GDH, and physician requests for CD results.MethodsRetrospective analysis of children <3 years with GI illness and FGP CD+ results between September 2016 and April 2018. CD PCRs for toxin B and GDH, CD EIA for toxin A/B/GDH were performed on convenience samples of frozen aliquots in Cary Blair. Physician request for release of CD results was used as a surrogate of possible role of CD on GI illness.ResultsOf 5,990 FGP, 2,267 (38%) were in children <3 years: 619 (27%) were CD+. Of these 619, 602 (97%) were not reported per algorithm. 62% (386/619) of CD+ samples had copathogens detected; enteropathogenic Escherichia coli and norovirus most frequently. For CD PCRs and EIA performed in subset of 49 CD+, mean cycle threshold values (Cts) for toxin B were evaluated (Table 1). Of 48 samples with detectable CD by toxin B PCR, 14 (29%) had both GDH and toxin B detected, 24 (51%) had only GDH detected, and 9 (19%) had neither GDH nor toxin B detected.ConclusionOnly 3% of FGP CD results in children <3 years were released per physician request, suggesting limited clinical significance. A copathogen was detected in 62% of CD+ samples that may explain illness. Among evaluable samples, only 28.6% of CD+ had both GDH and toxin detected by EIA, possibly indicating low specificity of CD PCR. Ongoing testing and prospective studies are warranted to determine the validity of our algorithm and if semi-quantitative PCR or EIA can be useful to identify when CD detection by FGP in children <3 years is clinically significant.Table 1: CD Toxin B PCR Ct Values Compared with FGP Result Release, Co-Pathogen Detection, and EIA ResultsMedian CtMedian Ct P-valueFGP-CD+ result released (n = 1)20.64FGP-CD+ result not released (n = 47)28.77NSFGP-CD+ only(n = 24)26.83Co-pathogen(n = 24)29.34NSEIA toxin+(n = 14)23.23EIA toxin−(n = 34)31.110.0005Disclosures A. Leber, Nationwide Children’s Hospital: Research Contractor, Research support.