ME Panel Research Articles

Etiology, Clinical Profiles, and Outcomes of Acute Encephalitis Syndrome Cases Admitted to a Tertiary Care Center in Myanmar in 2023.

The diagnosis of encephalitis is a challenging problem due to the heterogeneity of clinical presentations. The objective was to determine the etiology, clinical features, laboratory parameters, radiological findings, and in-hospital outcome of acute encephalitis syndrome (AES) cases in Myanmar. A prospective descriptive study was conducted at the Neuromedical Ward of Yangon General Hospital from March to August 2023. Eighty-one AES cases were enrolled, and cerebrospinal fluid (CSF) samples were collected. A Qiastat ME Panel was used to detect viral, bacterial, and fungal pathogens. Seventeen out of eighty-one (21%) cases were non-encephalitis with alternative definite diagnosis. Among the remaining 64 encephalitis cases, the exact infectious and immune etiologies were identified in 31 of 64 cases (48.4%); 26 of these (83.9%) were due to infectious causes and 5 (16.1%) were immune encephalitis. Among the infectious causes, six Herpes Simplex Virus-1-, one bacteriologically confirmed and seven probable Mycobacterium tuberculosis-, three Haemophilus influenzae-, two Streptococcus pneumoniae-, one Streptococcus pyogenes-, one Varicella-Zoster Virus (Ramsay Hunt Syndrome with meningoencephalitis)-, and two Cryptococcus neoformans-infected patients and rare causes such as Listeria monocytogenes, Burkholdelria cepacia, Sphingomonas paucimobilis, and Aspergillus were identified. One case was a dual infection with Haemophilus influenzae and Cryptococcus neformans. Abnormal protein levels and CSF pleocytosis were significantly higher among bacterial causes (p < 0.05). In total, 6.45% (2/31) of encephalitis patients with identified causes and 12.12% (4/33) of those without an identified organism had poor outcome. Herpes encephalitis and tuberculous meningoencepalitis were the commonest. This study highlighted that molecular testing with a multidisciplinary approach is required to ensure the right treatment on time.

Comparison of bacterial culture with BioFire® FilmArray® multiplex PCR screening of archived cerebrospinal fluid specimens from children with suspected bacterial meningitis in Nigeria

BackgroundDiagnosis of bacterial meningitis remains a challenge in most developing countries due to low yield from bacterial culture, widespread use of non-prescription antibiotics, and weak microbiology laboratories. The objective of this study was to compare the yield from standard bacterial culture with the multiplex nested PCR platform, the BioFire® FilmArray® Meningitis/Encephalitis Panel (BioFire ME Panel), for cases with suspected acute bacterial meningitis.MethodsFollowing Gram stain and bacterial culture on cerebrospinal fluid (CSF) collected from children aged less than 5 years with a clinical suspicion of acute bacterial meningitis (ABM) as defined by the WHO guidelines, residual CSF specimens were frozen and later tested by BioFire ME Panel.ResultsA total of 400 samples were analyzed. Thirty-two [32/400 (8%)] of the specimens were culture positive, consisting of; three Salmonella spp. (2 Typhi and 1 non-typhi), three alpha hemolytic Streptococcus, one Staphylococcus aureus, six Neisseria meningitidis, seven Hemophilus influenzae, 11 Streptococcus pneumoniae and 368 were culture negative. Of the 368 culture-negative specimens, the BioFire ME Panel detected at least one bacterial pathogen in 90 (24.5%) samples, consisting of S. pneumoniae, N. meningitidis and H. influenzae, predominantly. All culture positive specimens for H. influenzae, N. meningitidis and S. pneumoniae also tested positive with the BioFire ME Panel. In addition, 12 specimens had mixed bacterial pathogens identified. For the first time in this setting, we have data on the viral agents associated with meningitis. Single viral agents were detected in 11 (2.8%) samples while co-detections with bacterial agents or other viruses occurred in 23 (5.8%) of the samples.ConclusionsThe BioFire® ME Panel was more sensitive and rapid than culture for detecting bacterial pathogens in CSF. The BioFire® ME Panel also provided for the first time, the diagnosis of viral etiologic agents that are associated with meningoencephalitis in this setting. Institution of PCR diagnostics is recommended as a routine test for suspected cases of ABM to enhance early diagnosis and optimal treatment.

Comparison of cerebrospinal fluid results analysis against meningitis pathogens in meningitis patients

Introduction: Meningitis is a major contributor to global mortality and morbidity rates. The rapid diagnosis of its etiology is crucial. Cerebrospinal fluid (CSF) analysis plays a key role in this process. This study aims to compare CSF analysis results with the Biofire Filmarray ME panel to expedite and simplify the diagnosis of meningitis etiology. Method: Using an observational analytical cross-sectional design, the study was conducted over 4 months. CSF samples were collected from multiple hospitals. The CSF analysis involved flow cytometry using Sysmex XN 1000 and Dimension EXL platforms. The Biofire Filmarray ME panel employed multiplex PCR technology. Result: Of the 30 samples, 83.3% exhibited clear appearance, 93.3% lacked clots, and 83.3% were clear in color. Increased cell counts were noted in 56.7% of samples, elevated protein levels in 43.3%, and normal glucose levels in 56.7%. CSF analysis interpretations indicated 70% normal, 3.3% viral infection, and 26.7% bacterial infection. The Biofire Filmarray ME panel results showed 96.7% negatives and 3.3% positive for Cytomegalovirus. Comparing CSF analysis with Biofire Filmarray ME panel results using McNemar's test indicated significant differences. The study highlighted the quality assurance of CSF analysis, challenges of antibiotic use, low prevalence of pathogens detected by the Biofire Filmarray, and the potential for false negatives due to untargeted pathogens. Conclusion: In conclusion, this study provides insights into CSF analysis and its comparison with the Biofire Filmarray ME panel. However, limitations include the Biofire Filmarray's inability to detect all pathogens and absence of certain data during CSF sampling. Further improvements are needed to enhance accuracy in meningitis diagnosis..

Human parechovirus encephalitis in infants: a retrospective single-center study (2017-2022).

PeV can cause encephalitis and sepsis-like syndrome in infants, and it should be considered even with normal CSF parameters. Prospective studies are needed to better understand PeV epidemiology and to monitor outbreaks. • PeV is a frequent cause of encephalitis and clinical sepsis in infants in the first 90 days. • Normal CSF parameters in PeV encephalitis and diagnostic importance of MEP to avoid unnecessary prolonged antibiotics and hospitalization.. • Centers for Disease Control and Prevention (CDC) issued a Health Advisory alert in Summer 2022 of uptick PeV encephalitis cases in the USA likely secondary of COVID-19 mitigation measures relaxation, but no comparison with previous years.. • Knowledge of radiological MRI brain characteristics in PeV encephalitis can be a clue diagnosis. • Knowledge of the biennial seasonality pattern in PeV infection. • PeV was the second most detected pathogen in BIOFIRE ME panel in both 2018 and 2022 in our cohort sample.

Clinical Usefulness of a Multiplex Molecular Panel for Central Nervous System Infection: An 11-Month Experience at a Tertiary Center in Korea

Purpose: The purpose of our study was to evaluate the usefulness of the BiofireFilmArray Meningitis/Encephalitis (FA ME) panel and identify factors associated with positive FA ME panel results. Methods: We retrospectively analyzed the medical records of 129 patients (45 children, 84 adults) with central nervous system infections and FA ME panel test results. We compared the results of the FA ME panel and the diagnostic yield between pediatric and adult patients with positive and negative FA ME panel results. Positive FA ME panel results were compared with conventional microbiological testing. Results: Forty-three patients (33.3%) had positive results on the FA ME panel. The detected pathogens were enterovirus (n=17, 39.5%), varicella zoster virus (n=10, 23.3%), herpes simplex virus-2 (n=2, 16.3%), herpes simplex virus-1 (n=2, 4.7%), human parechoviruses (n=2), Cryptococcus neoformans/gattii (n=2), Streptococcus agalactiae (n=1, 2.3%), Streptococcus pneumoniae (n=1), and Haemophilus influenzae (n=1). The time to detection of the FA ME panel (4.9±6.6 hours) was significantly shorter than that of conventional culture (77.4±48.2 hours) (P=0.005). Fever was more common in the positive FA ME group than in the negative FA ME group (81.4% vs. 41.9%) and in pediatric patients than in the adult patients (93.3% vs. 34.5%) (P&lt;0.001 for both). The detection rate of the FA ME panel was higher in pediatric patients than in adult patients (55.8% vs. 22.6%, P&lt;0.001). Conclusion: The FA ME panel improves the diagnostic rate in patients with suspected central nervous system infections, with potential favorable implications for the quality of management and prognosis.

Efficacy of FilmArray® ME panel for the rapid diagnosis of meningitis and encephalitis

Microbial tests are essential for appropriate management for acute meningitis and encephalitis, but it often takes several days to identify the results of culture tests or PCR. BioFire FilmArray® meningitis/encephalitis panel (ME panel) is a rapid multiplex PCR assay that targets 14 bacteria, viruses, and yeast in 1 hour. In this single-center retrospective study, we reviewed adult patients who underwent ME panel test in parallel with conventional microbial tests from January to August 2021. Eighteen of 70 patients (26%) tested positive by ME panel, of which 8 patients (11%) were helpful in altering treatment strategy. Fifty-two patients (74%) could stop empirical treatment such as acyclovir or antibiotics due to negative results on ME panel. All results of ME panel were same as traditional assays. Use of ME panel can contribute to early diagnosis and treatment.

Assessment of the Impact of a Meningitis/Encephalitis Panel on Hospital Length of Stay: A Systematic Review and Meta-Analysis.

Meningitis and encephalitis are central nervous system infections with considerable morbidity and mortality. The BioFire® FilmArray® Meningitis/Encephalitis Panel (multiplex ME panel) can identify pathogens rapidly potentially aiding in targeted therapy and curtail antimicrobial exposure. This systematic review and meta-analysis synthesized the literature on the association between the multiplex ME panel and length of hospital stay (LOS), length of acyclovir therapy, and days with antibiotics. MEDLINE and EMBASE were searched. Only studies presenting novel data were retained. Random-effects meta-analyses were performed to assess the impact of the multiplex ME panel on outcomes. Of 169 retrieved publications, 13 met the criteria for inclusion. Patients tested with the multiplex ME panel had a reduction in the average LOS (mean difference [MD] [95% CI]: −1.20 days [−1.96, −0.44], n = 11 studies). Use of the multiplex ME panel was also associated with a reduction in the length of acyclovir therapy (MD [95% CI]: −1.14 days [−1.78, −0.50], n = 7 studies) and a nonsignificant reduction in the average number of days with antibiotics (MD [95% CI]: −1.01 days [−2.39, 0.37], n = 6 studies). The rapidity of pathogen identification contributes to an overall reduced LOS, reductions in the duration of empiric antiviral utilization, and a nonsignificant reduction in antibiotic therapy.

Impact of Implementing the Cerebrospinal Fluid FilmArray Meningitis/Encephalitis Panel on Duration of Intravenous Acyclovir Treatment

BackgroundHerpes simplex virus–1 is the most common cause of sporadic encephalitis worldwide and requires prompt antiviral treatment. Traditionally, herpes simplex virus–1 (HSV-1) cerebrospinal fluid (CSF) testing is conducted using standalone polymerase chain reaction (PCR). The BioFire CSF FilmArray Meningitis/Encephalitis Panel (BioFire ME Panel) was introduced in 2015 at our institution, providing an alternative method of HSV-1 CSF testing. This study assesses the impact of the BioFire ME Panel on duration of intravenous acyclovir treatment.MethodsA retrospective review of electronic medical records between 2010 and 2019 was performed. Information on intravenous acyclovir treatment and HSV-1 CSF testing was collected and analyzed. Our descriptive analysis included Mann-Whitney tests, 2 proportion Z-tests, and logistic regression.ResultsOur CSF HSV-1-negative cohort included 524 BioFire patients (125 pediatric, 399 adult) and 287 standalone PCR patients (115 pediatric, 172 adult). Across both pediatric and adult groups, patients who were tested for HSV-1 with the BioFire ME Panel had shorter average (SD) durations of intravenous acyclovir treatment (pediatric: 2.00 [5.71] days; adult: 3.26 [6.59] days) compared with patients tested with standalone PCR (pediatric: 4.83 [8.62] days; adult: 4.93 [8.46] days; P < .001). Time from lumbar puncture collection to HSV-1 results was additionally faster on average for the BioFire ME Panel than the standalone PCR (P < .001).ConclusionsThe implementation of the BioFire ME Panel shortened CSF HSV-1 PCR result time and intravenous acyclovir duration. The shortened treatment and testing times from the BioFire ME Panel implementation may reduce hospital treatment costs and unnecessary use of antiviral treatments.

How do we reduce acyclovir overuse? Impact of FilmArray meningitis/encephalitis panel tests for pediatric patients

BackgroundFew Japanese hospitals can perform in-house cerebrospinal fluid (CSF) polymerase chain reaction (PCR) to screen for herpes simplex virus, leading to patients being administered acyclovir (ACV) for several days. The FilmArray Meningitis/Encephalitis Panel (ME Panel) is a multiplex PCR test that can identify 14 major pathogens within 1 h. We aimed to investigate the efficacy of the ME Panel in children admitted with central nervous system infections in Japan. MethodsWe conducted a single-center, quasi-experimental study. The ME panel was introduced in April 2020. We outsourced the CSF samples to a laboratory during the pre-intervention period (April 2016 to March 2020) and performed the ME panel at our hospital during the post-intervention period (April 2020 to December 2021). Duration and dose of ACV and antibiotic use, length of stay (LOS) in the pediatric intensive care unit (PICU), and total LOS after testing were compared using the Mann-Whitney U test. ResultsThe number of cases in the pre- and post-intervention periods was 67 and 22 cases, respectively. The median duration of ACV decreased significantly from 6 days to 0 day (p < 0.001), and the median dose of ACV use decreased significantly from 14 vials to 0 vial (p < 0.001). No significant differences were noted in the total duration and dose of antibiotic use, LOS in PICU, and the total LOS after testing. ConclusionThe introduction of ME panel may contribute to appropriate ACV use; however, there was no significant change in the duration and dose of antibiotic use or LOS.

Differential Performance of the FilmArray Meningitis/Encephalitis Assay To Detect Bacterial and Viral Pathogens in Both Pediatric and Adult Populations.

ABSTRACTMeningitis/encephalitis (ME) syndromic diagnostic assays can be applied for the rapid one-step detection of the most common pathogens in cerebrospinal fluid (CSF). However, the comprehensive performance of multiplex assays is still under evaluation. In our multisite university hospital of eastern Paris, France, ME syndromic testing has been gradually implemented since 2017 for patients with neurological symptoms presenting to an adult or pediatric emergency unit. We analyzed the results from the BioFire FilmArray ME panel versus standard routine bacteriology and virology techniques, together with CSF cytology and clinical data, over a 2.5-year period to compare the diagnostic accuracy of the FilmArray ME panel to that of the reference methods. In total, 1,744 CSF samples from 1,334 pediatric and 336 adult patients were analyzed. False-positive (mostly bacterial) and false-negative (mostly viral) cases were deciphered with the help of clinical data. The performance of the FilmArray ME panel in our study was better for bacterial detection (specificity >99%, sensitivity 100%) than viral detection (specificity >99%, sensitivity 75% for herpes simplex virus 1 [HSV-1] and 89% for enterovirus), our study being one of the largest, to date, concerning enteroviruses. The use of a threshold of 10 leukocytes/mm3 considerably increased the positive agreement between the results of the FilmArray ME panel and the clinical features, especially for bacterial pathogens, for which agreement increased from 58% to 87%, avoiding two-thirds of inappropriate testing. Based on this analysis, we propose an algorithm for the use of both syndromic and specific assays for the optimal management of suspected meningitis/encephalitis in adult and pediatric patients.IMPORTANCE Based on our comparative analysis of performances of the diagnostic assays, we propose an algorithm for the use of both syndromic and specific assays, for an optimal care of the meningitis/encephalitis threat in adult and pediatric patients.

259. Impact of a Multiplex Meningitis and Encephalitis PCR on the Management of CNS Infections in Adults and Children, Houston, Texas

BackgroundThe majority of adults and children with meningitis and encephalitis have unknown etiologies fostering universal admission, prolonged length of stay, empirical antibiotic and antiviral therapies. A qualitative multiplexed nucleic acid-based in vitro diagnostic test (FilmArray) is helping clinicians identify organisms and improve clinical outcomes.MethodsPatients presenting between July 5, 2018, to April 26, 2021, with meningitis or encephalitis, cerebrospinal fluid (CSF) with WBC >5 cells/mm3, and leftover CSF were available for testing. All CSF specimens underwent testing with the Biofire® Film Array Meningitis Encephalitis (FAME) panel. This multiplex PCR tool utilizes 0.2 ml CSF sample to identify the presence of 14 viral, bacterial and fungal pathogens in 1 hour.ResultsOf 5291 CSF specimens screened, 285 (5.3%) met the criteria for meningitis or encephalitis and underwent FAME testing. The majority were adults (240, 84.2%), male (147, 51.5%), White (111, 38.9%), immunocompetent (213, 74.3%) and (212, 74.3%) had meningitis presentation. Median age was 41 years (0 mo-100 yrs) and (283, 99.2%) were admitted to the hospital. Median duration between CSF collection and viral PCR result as 13 hrs for Enterovirus, 31 hrs for HSV, and 57 hrs for VZV. The FAME panel detected a pathogen in 103 patients (36.1%) of whom 76 (73.7%) had a viral etiology. 166 (58.2%) patients were discharged with unknown etiology of whom FAME was positive in 24 (14.4%) [VZV (37.5%), HSV2 (16.6%), Enterovirus (16.6%), Haemophilus influenzae (8.3%), HHV6 (8.3%), Streptococcus pneumoniae (8.3%) and HSV1 (4.1%)]. The addition of the FAME panel to the standard of care evaluation increased the known etiologies from 119 (41.7%) to 197 pathogens (69.1%), (p< 0.05). 52 patients (18.2%) underwent a repeat LP (30, 57.6% done for additional testing). Empirical antibiotic and antiviral therapy were given to 89% and 63% of patients, respectively.ConclusionA rapid multiplex PCR decreases the proportion of unknown etiologies and has the potential to decrease length of stay and the use of empirical antibiotic and antiviral therapies. Testing with the FA ME panel resulted in pathogen detections not previously recognized and for which treatment is recommended.Disclosures Rodrigo Hasbun, MD, MPH, Biofire (Speaker’s Bureau) Rodrigo Hasbun, MD, MPH, Biofire (Individual(s) Involved: Self): Consultant, Research Grant or Support

Comparison of a commercial real-time PCR panel to routine laboratory methods for the diagnosis of meningitis-encephalitis

Meningitis-encephalitis can range from a mild, self limiting illness to a life threatening disease. Rapid microbial diagnosis allows for early targeted management. This study aimed to compare the BioFire FilmArray Meningitis/Encephalitis multiplex PCR panel (ME panel) to traditional testing algorithms for accuracy and turnaround time in the diagnosis of meningitis-encephalitis. From April to November 2018, cerebrospinal fluid (CSF) samples meeting existing laboratory testing criteria for suspected community acquired meningitis-encephalitis were tested on the ME panel and by routine laboratory methods. The methods were compared for accuracy of diagnosis and turnaround time. Where an organism was not identified, the study investigators came to a consensus on whether an infective aetiology was likely based on CSF parameters, clinical features, management and final discharge diagnosis. A total of 147 CSF samples met criteria for testing. Results were concordant in 143 (97%) of cases, including 27 samples where the same organism was identified by both methods. Of the four discordant samples, three organisms identified by the ME panel alone were considered clinically insignificant. One sample, which was culture and antigen positive for Cryptococcus neoformans, was not detected on the ME panel. The ME panel and routine methods identified an organism in 55% and 58% of clinically compatible cases of infection, respectively. The median turnaround time for the ME panel was 2.9 hours, compared to 21.1 hours for routine testing. The ME panel showed high concordance with traditional testing, simplified laboratory workflow, and significantly reduced turnaround time. The failure of the ME panel to detect Cryptococcus spp. is concerning. When cryptococcal meningitis is suspected, we would recommend using culture and cryptococcal antigen testing as the investigations of choice. Despite the availability of molecular assays targeting the common causes of CNS infection, the diagnostic yield remains suboptimal.

Evaluation of FilmArray ME panel for the rapid diagnosis of meningitis-encephalitis in emergency departments.

To assess the impact of a rapid diagnostic system based on nucleic acid amplification techniques (FilmArray ME) on the diagnosis and treatment of patients with meningitis or encephalitis admitted to our emergency department. Between November 2016, and June 2019 we studied 79 samples of cerebrospinal fluid from patients admitted to our emergency department with suspected diagnoses of meningitis or encephalitis. FilmArray ME panel was used routinely in addition to conventional laboratory methods for the identification of microorganisms in cerebrospinal fluid samples (CSF). A total of 46 (58%) patients had clinical and CSF results suggestive of meningitis or encephalitis, and 24 (30%) had a confirmed microbiological diagnosis. Patients' mean age was 41years (range 2months to 90years) and 56% were male. Four patients had been partially treated with antibiotics. FilmArray ME identified 23 cases (1 fungal, 11 bacterial, and 11 viral). Gram staining showed microorganisms in 5 cases (1 fungal, 4 bacterial), and conventional microbiology cultures identified 8 cases (1 fungal and 7 bacterial). The time difference (95% confidence interval) between FilmArray ME and cerebrospinal fluid culture results was 3.2days (95% CI 2.7-3.7; P < 0.001). FilmArray ME results induced modifications in antimicrobial treatment in 27 (59%) patients. The FilmArray ME panel provided a fast and reliable result in a large proportion of patients, even in those patients with culture-negative bacterial meningitis. Use of FilmArray ME can contribute to antimicrobial stewardship.

50. Evaluation of Discordant Results Between Filmarray Meningitis/encephalitis Panel and Conventional Testing in Pediatric Patients: A Multi-site Retrospective Cohort Study

BackgroundFilmArray Meningitis/Encephalitis Panel (ME panel) has a 11% false positive and 2.2% false negative rate compared to conventional testing. We aim to describe characteristics, treatment decisions and outcomes in pediatric patients with discordant results between ME panel and conventional testing.MethodsWe conducted a multisite (n=4) retrospective review of patients < 18 years with positive cerebrospinal fluid (CSF) results by ME panel or conventional testing (CSF culture, Herpes Simplex Virus [HSV] and enterovirus [EV] PCR) from time of local ME panel implementation to February 2019. We excluded CSF obtained for non-infectious reasons. Demographic and clinical data were extracted from electronic medical records. Comparison between concordant and discordant results were made using Mann-Whitney test for continuous and Fisher’s exact test for categorical variables.ResultsA total of 355 patients had at least 1 positive result. Baseline characteristics and pathogens are shown in Table 1 and 2. Of the 53 bacterial pathogens identifiable by ME panel, 31 (58%) had discordant results – 29 positive by ME panel only and 2 by culture only (both E.coli). Patients with bacterial pathogens identified by ME panel only had lower CSF WBC and protein but higher CSF glucose (Table 3). Five patients with bacteria identified on ME panel only were not treated as meningitis given lack of pleocytosis, no antibiotic pretreatment and negative repeat cultures. Of these, 4 recovered without complications but one had hypoxic encephalopathy.Two patients had HSV noted in ME panel but individual PCR negative. The first was a 13-day-old with typical skin lesions and positive surface swab. The other was a 6-day old only with CSF pleocytosis. Both had abnormal neuroimaging and were treated as true cases. Of 24 who had both EV PCR and ME panel, 7 were positive by ME panel only and 3 by PCR only.Table 1: Baseline Characteristics of the Study Population Table 2: Pathogens identified via CSF Culture, ME panel or Conventional PCR Table 3: Characteristics of Discordant Results for Bacterial Pathogens Tested in ME panel ConclusionMore than half of bacterial pathogens identified by ME panel did not have a corresponding positive CSF culture. No difference was noted by antibiotic pretreatment. Treatment decisions based on positive ME panel should be made in the appropriate clinical context. Likewise, a negative ME panel does not rule out infection especially when atypical organisms are suspected.Disclosures Krow Ampofo, MBChB, Merck (Grant/Research Support)

Implementation of the FilmArray ME panel in laboratory routine using a simple sample selection strategy for diagnosis of meningitis and encephalitis

BackgroundInfectious meningitis is a serious disease and patient outcome relies on fast and reliable diagnostics. A syndromic panel testing approach like the FilmArray ME can accelerate diagnosis and therefore decrease the time to pathogen specific therapy. Yet, its clinical utility is controversial, mainly because of a remaining uncertainty in correct interpretation of results, limited data on its performance on clinical specimens and its relatively high costs. The aim of this study was to analyze clinical performance of the assay in a real life setting at a tertiary university hospital using a pragmatic and simple sample selection strategy to reduce the overall cost burden.MethodsOver a period of 18 months we received 4623 CSF samples (2338 hospitalizations, 1601 individuals). FilmArray ME analysis was restricted to CSF-samples with a high pretest probability of infectious meningitis, e.g. positive Gram-stain, samples in which leukocytes and/or bacteria were evident or urgent suspicion of infection was communicated by clinicians. N = 171 samples matched to our risk criteria and were subjected to FilmArray ME analysis. Those samples were also analyzed by reference methods: culture only (n = 45), PCR only (n = 20) or both methods (n = 106).Results56/171 (32.75%) were FilmArray ME positive. Bacterial pathogens were detected in 30/56 (53.57%), viral pathogens were detected in 27/56 (48.21%) and yeast DNA was detected in 1/56 (1.79%) of positive samples. Double detection occurred in 2/56 samples. In 52/56 (92.86%) FilmArray ME positive samples, results could be confirmed by the reference assays (sensitivity = 96.30%, specificity =96.58%).ConclusionThe FilmArray ME assay is a fast and reliable diagnostic tool for the management of infectious meningitis and can easily be implemented in routine diagnostic workflows. However, correlation of test results and underlying clinical symptoms requires experienced users and the awareness of potentially false negative or false positive results. Moreover, considering the need for antimicrobial susceptibility testing, the use of molecular tests as a stand-alone diagnostic cannot be recommended.

Comparison of antibiotic and acyclovir usage before and after the implementation of an on-site FilmArray meningitis/encephalitis panel in an academic tertiary pediatric hospital: a retrospective observational study

BackgroundPrompt initiation of empiric therapy is common practice in case of suspected meningitis or encephalitis. However, in children the most common pathogens are viruses that usually do not require and are not covered by the applied anti-infective treatment. Novel multiplex PCR (mPCR) panels provide rapid on-site diagnostic testing for a variety of pathogens. This study compared empiric antibiotic and acyclovir usage before and after the introduction of an on-site FilmArray Meningitis/Encephalitis Panel (FA ME Panel).MethodsWe retrospectively compared data for empiric antibiotic and acyclovir usage between pediatric patients with suspected central nervous system (CNS) infection receiving mPCR testing and a matched historical control group. Patients were matched by age and suspected CNS infection. We included all patients for whom empiric antibiotics and/or acyclovir were prescribed.ResultsEach study group consisted of 46 patients with 29 (63.0%) infants and 17 (37.0%) older children. A viral pathogen was diagnosed in 5/46 (10.9%) patients in the control group (all enteroviruses) and in 14/46 (30.4%) patients in the mPCR group (enterovirus n = 9; human herpesvirus 6 (HHV-6) n = 5), (p = 0.038)). Length of Therapy (LoT) and Days of Therapy (DoT) for antibiotics were significantly lower for infants (4.0 vs. 3.0, p = 0.038 and 8.0 vs. 6.0, p = 0.015, respectively). Acyclovir therapy was significantly shorter for both, infants and older children (3.0 vs. 1.0 day, p < 0.001 for both age groups).ConclusionThe findings of our study suggest that the introduction of a FA ME Panel into clinical routine procedures is associated with a significantly reduced LoT and DoT of empiric anti-infective treatment in children with suspected meningoencephalitis. The largest effect was observed in infants.

Fatal E. coli K1 meningitis and ventriculitis in an adult

Escherichia coli K1 is known as highly virulent pathogen, commonly causing neonatal meningitis. It is an extremely uncommon aetiological agent as a community acquired meningitis in adults, which has 25% mortality and neurological complications in over 50% of patients. Many routine clinical microbiology laboratories lack facilities for molecular diagnosis and or serotyping to identify this organism. Our current CSF diagnostic platform includes a 14 target multiplex PCR assay including the PCR target for E. coli K1 capsular antigen. This resulted in us picking up rare, possibly previously underdiagnosed cases of E. coli K1 meningitis. An elderly female, found in a collapsed state at home with fever, vomiting, urine and faecal incontinence was brought to our emergency department. Urgent CT scan demonstrated ventriculitis with extensive pus formation. CSF analysis has demonstrated neutrophil leucocytosis, elevated protein, very low glucose and moderate Gram-negative bacilli, which were identified soon after as E. coli K1 by Biofire film array ME panel. All other cultures of the patient were unremarkable except urine culture which grew extremely susceptible E. coli K1 strain. Despite being treated with meropenem, ceftriaxone, aggressive neurosurgical treatment and intensive care, the patient passed away on day 9 of illness.

Multicenter Evaluation of the Implementation Status of Laboratory Tests in Korea and the Potential Usefulness of a Multiplex PCR Assay in Patients with Suspected Central Nervous System Infections.

The rapid diagnosis and treatment of central nervous system (CNS) infections are critical to minimizing morbidity and mortality. We evaluated the implementation status of laboratory tests in patients with suspected CNS infection, and the potential usefulness of a multiplex PCR assay for rapid and simultaneous detection in cerebrospinal fluid (CSF) of 14 targets capable of causing CNS infections. The study was conducted at 5 hospitals located in Daegu and Gyeongju over a period of 6 months. A total of 140 patients with suspected CNS infection were included. CSF samples were tested for 6 bacteria, 7 viruses, and 1 yeast using multiplex PCR (FilmArray Meningitis/Encephalitis Panel, BioFire Diagnostics/Biomerieux, Salt Lake City, UT, USA) and conventional diagnostic testing including chemistry tests, cell count, bacterial culture, antigen detection assay, and pathogen-specific PCR. The five conventional tests most commonly performed were the chemistry and cell count (100%), bacterial culture (94.3%), enterovirus PCR (52.9%), and herpes simplex virus PCR (25.7%). Among the 140 CSF samples, 27 (19.3%) and 42 (30.0%) tested positive by conventional and the FilmArray ME panel testing, respectively. The detection rate of pathogens for CNS infections increased using only one FilmArray test compared to all of the conventional methods actually performed in patients with suspected CNS infection.

2169. An Algorithm-Based Approach Reduces Overuse of Meningitis/Encephalitis Multiplex PCR Panel

BackgroundSyndromic molecular panels enable rapid diagnosis and optimized management of infections with significant morbidity and mortality, but may be overused without clear guidelines. A recent report indicated there was little clinical suspicion of infection in up to 1/3 of cases for which a FILMARRAY® Meningitis/Encephalitis Panel (ME Panel, bioMérieux) was ordered. We recently implemented the ME Panel in our multicenter health system. We assessed ME Panel use for the 6-month period following test implementation.MethodsA testing algorithm was developed, vetted with our system-wide Infectious Diseases (ID) and Neuro-ID Services, and used as the basis for the education of the Emergency Medicine, Internal Medicine, Hospitalist, Pediatric, and Critical Care Medicine Services. Algorithm elements were embedded in the electronic medical record (EMR). Lab records and EMRs were reviewed for all patients tested by ME Panel or cerebrospinal (CSF) culture. Lab results, baseline demographic and underlying medical history, and results of singleplex viral PCR CSF tests and the multiplex NY State Encephalitis PCR Panel (NYS Panel, Wadsworth Laboratory, Albany, NY) were recorded. ME Panel results were compared with other findings.Results115 ME Panels were performed, with 5 (4%) positives [1 N.meningitidis, 1 H.influenzae, 1 cytomegalovirus (CMV), 1 Herpes simplex virus type 1 (HSV1), and 1 varicella zoster virus (VZV)]. Other findings were consistent with true infection for the N. meningitis, HSV and VZV; the CMV was likely reactivation. Significance of the H. influenzae was unclear. There were 830 CSF cultures, with 38 (4%) positive; 5 of the 38 were ME Panel targets. 29 NYS Panels were sent [1 positive each for Human Herpesvirus 6 (HHV6) and Epstein Barr Virus (EBV)]. Finally, 7 singleplex PCRs were positive [5 HSV, 1 CMV and 1 HHV6], including one negative by ME Panel.ConclusionWe did not find ME Panel overuse; rather, we found several cases for which the ME Panel could have given a more rapid diagnosis. We did identify areas for improvement in test ordering, such as minimizing duplicate testing (e.g., singleplex PCR) A multi-disciplinary approach engaging stakeholders in the lab, ID and Neuro-ID can assist appropriate test utilization and diagnostic stewardship.Disclosures All authors: No reported disclosures.

1404. The FilmArray Meningitis/Encephalitis (FA ME) May Be of Higher Yield in the Immunocompromised Patient Population

BackgroundThe FilmArray® Meningitis/Encephalitis (FA ME) panel is a PCR-based assay that rapidly detects 14 pathogens directly from CSF specimens. After the introduction of this assay at our institution, there was a steady increase in requests for use; however, the positivity rate remained stable. We sought to understand the characteristics of the patients most likely to have a positive FA ME panel, with particular interest in the immune status of each patient.MethodsA retrospective chart review was conducted on 124 patients with suspected infectious meningitis/encephalitis at a large academic tertiary referral center who received FA ME testing between October 2016 and November 2018. Patients were considered immunocompromised if they had received chemotherapy, were solid-organ transplant recipients, or were diagnosed with HIV, autoimmune diseases on immunosuppressants, uncontrolled diabetes, cirrhosis, or hematologic malignancy. Clinical CNS infection was determined using chart review based on culture, serologic, or molecular data.Results60 (48%) patients were immunocompromised and 64 (52%) patients were immunocompetent. Clinical CNS infection occurred in ~25% of immunocompetent (17, 26%) and immunocompromised (17, 28%) patients. However, only 6 immunocompetent patients were found to have a positive FA ME; this accounts for only 35% of the total number of positive FA ME assays during this study period (P = 0.08). Notably, 4 out of 6 patients with cryptococcal meningitis had false-negative results on the FA ME.ConclusionIn spite of the relatively small sample size, there was a trend toward significance in the accurate yield of the FA ME panel in the immunocompromised population compared with the immunocompetent. Our immunocompromised patients appear to be more likely to have an infection which is tested for on the panel. The rates of confirmed CNS infections in both populations were very similar, indicating that immunocompromised patients may benefit more from use of this assay. In our study, immunocompetent patients were more likely to have West Nile infection, for example, which is not on the panel. Additionally, had cryptococcal meningitis been accurately diagnosed by the FA ME, an even greater number of immunocompromised patients would have had a positive FA ME. Disclosures All authors: No reported disclosures.