Meningitis/encephalitis Panel Research Articles

Utilization of a Meningitis/Encephalitis PCR panel at the University Hospital Basel - a retrospective study to develop a diagnostic decision rule.

The Biofire® FilmArray® Meningitis/Encephalitis (ME) PCR panel covers 14 viral, bacterial, and fungal pathogens and has been implemented in many institutions worldwide. Post-marketing studies indicate a reduced sensitivity and overutilization underscoring the need for a more targeted usage. The aim of our study is to describe the utilization of the ME panel and to develop a diagnostic-stewardship based decision rule. Adult patients, who underwent CSF analysis with the ME panel between August 2016 and June 2021 at the University Hospital Basel, were included. Demographic, clinical, microbiological, and laboratory data were extracted from the electronic health record. Factors associated with a positive ME panel result were identified, and a decision rule was developed to potentially optimize the diagnostic yield and reduce the number of unnecessary tests. 1,236 adult patients received at least one panel in the observed period, of whom 106 panels tested positive (8.6%). The most frequently observed pathogens were Varicella Zoster Virus (VZV, 27%), Streptococcus pneumoniae (19%), Enterovirus (16%), Herpes simplex Virus 1/2 (16%), and Human Herpesvirus 6 (HHV-6, 13%). Fever, vomiting, headache, and photophobia were more frequently present in test positive patients as were significantly higher CSF leukocytes and protein concentrations. When simulating a decision rule based on CSF leukocytes and protein concentration, only 35% of all patients would have qualified for a ME panel tests, thereby increasing the positivity rate to 22.7%. 10 of 106 positive ME panels would have been missed, only involving HHV-6 and VZV (6 and 4 cases, respectively). As these subjects were either severely immunocompromised or had clinical features of shingles we propose extending the testing algorithm by including those criteria. The ME panel positivity rate at our institution was similar as previously published. Our results highlight the need for diagnostic-stewardship interventions when utilizing this assay by implementing a stepwise approach based on a limited number of clinical and laboratory features. This decision rule may improve the pretest probability of a positive test result, increase the quality of test utilization, and reduce costs.

2713. Risk factors and clinical presentation of Herpes Simplex Virus Encephalitis in cancer patients

Abstract Background Herpes Simplex Virus Encephalitis (HSVE) can have lifelong sequelae. Presentation can be nonspecific in cancer patients. Cerebrospinal fluid testing may be falsely negative early in illness [1]. New immune-based or targeted radiation (RT) modalities may change risk, incidence of HSVE in cancer patients. Methods Retrospective study at Memorial Sloan Kettering Cancer Center (MSK). Review of records of patients with CSF meningitis/encephalitis (ME) PCR panels from 8/1/2016 to 7/31/2022. All unique patients who received brain RT at MSK during those dates were used to calculate incidence rates. Results 2749 patients had 5497 CSF analyses with ME panel. Of these, 12 tests from 10 patients showed HSV-1 or -2; 1 patient had relapsing HSVE and 3 positive HSV2 tests each done at least 6 months apart. Table 1 shows 10 patients with HSVE. 8 had solid tumors, 6 with receipt of chemo- or immunotherapy within 30 days. All solid tumor patients with HSVE had brain RT; 6 received steroids. 1 patient with relapsing HSVE was on immune checkpoint inhibitor (ICI). 4/8 patients with MRIs (Table 2) lacked typical findings; 4/8 patients with EEGs had focal temporal seizure activity. CSF pleocytosis was absent in 4/10 cases. 5 patients had residual deficits. 4 died due to progression of disease. Incidence of HSVE with brain radiation was 2.6/10,000 patient-years. Conclusion General population incidence of HSVE ranges from 1-4 per million population per year [2]. Those receiving cancer treatment and brain RT have elevated HSVE risk. We found the risk after brain RT is much higher: 2.6/10,000 person-years. Only 1 of 10 patients in our series made a full recovery. Other key findings include: Limitations: Disclosures Mini Kamboj, MD , ASCO: speaker fee|Medscape: speaker fee|MJH life sciences: speaker fee|Regeneron: Advisor/Consultant|Web md: speaker fee

Evaluation of the QIAstat-Dx Meningitis/Encephalitis Panel, a multiplex PCR platform for the detection of community-acquired meningoencephalitis.

Rapid identification of the causative pathogens of central nervous system infections is essential for providing appropriate management and improving patient outcomes. The performance of QIAstat-Dx Meningitis/Encephalitis (ME) Panel-a multiplex PCR testing platform-in detecting pathogens implicated in meningitis and/or encephalitis was evaluated using BioFire FilmArray ME Panel as a comparator method. This multicenter study analyzed 585 retrospective residual cerebrospinal fluid specimens and 367 contrived specimens. The QIAstat-Dx ME Panel showed positive percent agreement (PPA) values of 100% for Neisseria meningitidis, Streptococcus agalactiae, Escherichia coli K1, Listeria monocytogenes, and Cryptococcus gattii/neoformans on clinical samples compared to the BioFire FilmArray ME Panel. The PPA values observed for Haemophilus influenzae and Streptococcus pneumoniae were 80% and 88.24%, respectively. Negative percent agreement (NPA) values were >99.0% for each of the six bacterial targets and one fungal target tested with clinical samples. One viral target, herpes simplex virus 1, exhibited a PPA value of 100.0%, while the remaining viral targets-human parechovirus, herpes simplex virus 2, human herpes virus 6, and varicella zoster virus-were >90.0%, with the exception of enterovirus, which had a PPA value of 77.8%. The QIAstat-Dx ME Panel detected five true-positive and four true-negative cases compared to BioFire FilmArray ME Panel. The NPA values for all viral pathogens were >99.0%. Overall, the QIAstat-Dx ME Panel showed comparable performance to the BioFire FilmArray ME Panel as a rapid diagnostic tool for community-acquired meningitis and encephalitis.

Comparison of two assays to diagnose herpes simplex virus in patients with central nervous system infections.

Multiplex PCR panels are frequently used for detecting the diagnosis of central nervous system infection, but have demonstrated lower sensitivity for herpes simplex virus (HSV) compared to targeted PCRs. Providers in our institution frequently order both multiplex (BioFire Meningitis/Encephalitis Panel (MEP)) and targeted HSV PCR (Diasorin Simplexa HSV-1/2 Direct), allowing comparison of assay performance in practice and a unique clinical characterization of patients with concordant positive or discordant results. We retrospectively analyzed all HSV testing performed using the two assays simultaneously in a large multi-center institution between 12/10/2018 and 6/6/2022. We described and compared laboratory, diagnostic and therapeutic data between patients with positive results on both assays with patients with discordant results. 1,387 patients were tested with both assays, of which 25 were positive on at least one assay. Eleven (44%) had discordant results; 9 were targeted-PCR-positive/MEP-negative and 2 were targeted-PCR-negative/MEP-positive. Compared with patients with concordant positive results, discordant targeted PCR-positive/MEP-negative patients had a higher PCR cycle threshold value (i.e., >35) and milder illness characterized by lower CSF WBC counts (4vs 152; p=0.032), fewer MRI abnormalities (37.5% vs. 87.5%; p=0.039), HSV meningoencephalitis as primary discharge diagnosis (33% vs. 100%; p<0.0001) and were more often treated with oral medication or none at all. Patients with discordant targeted PCR-positive/MEP-negative results represent a population with milder clinical disease. These findings will help clinicians and laboratorians determine when both targeted HSV and multiplex assays should be performed simultaneously and identify patients for whom a multiplex PCR may suffice, despite lower assay sensitivity.

Evaluation of the Performance Characteristics of a New POC Multiplex PCR Assay for the Diagnosis of Viral and Bacterial Neuromeningeal Infections

Point-of-care syndromic PCR (POC SPCR) assays are useful tools for the rapid detection of the most common causative agents of community-acquired infections responsible for meningitis and encephalitis infections. We evaluated the performance characteristics of the new QIAstat-Dx® Meningitis/Encephalitis panel (QS) compared to the laboratory reference methods and the POC SPCR Biofire® FilmArray® Meningitis Encephalitis Panel (FA). Viral (Enterovirus, Parechovirus, HSV-1, HSV-2, HHV-6, VZV) and bacterial (E. coli K1, H. influenzae, L. monocytogenes, encapsulated N. meningitidis, M. pneumoniae, S. agalactiae, S. pneumoniae, S. pyogenes) pathogens were suspended at low concentrations and tested with the POC SPCR systems. The reproducibility, analytical specificity, carryover contamination, interferences and clinical samples were evaluated. All samples tested positive with both QS and FA except for those containing the lowest concentrations of Enterovirus-D68-B3, Echovirus-30 and S. agalactiae which were only detected by FA. In terms of analytical specificity, we observed 3 false positive results out of 48 QS tests versus 1 out of 37 FA tests. For the other studied criteria, both QS and FA performed as expected. Our results suggest that the performance characteristics of QS are close to those of FA. A prospective multicenter study would be useful to complete the performances evaluation of QS.

Hunting for mpox (monkeypox) mimickers: Use of the Biofire meningitis/encephalitis panel on lesion swabs to support alternative viral diagnoses

Mpox (formerly monkeypox) is an emerging zoonotic disease of public health concern that presents as a rash mimicking other common viral exanthems. Unlike traditional testing algorithms relying on several assays, the BioFire FilmArray meningitis/encephalitis (ME) panel simultaneously detects common viruses causing rashes; however, Biofire ME is only licensed for testing on cerebral spinal fluid. This study evaluated use of the Biofire ME panel for detection and discrimination of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella zoster virus (VZV), human herpesviruses type 6 (HHV-6), enteroviruses (EVs), and human paraechoviruses (HPeVs) from a dermal or mucocutaneous swabs collected in universal transport media (UTM). Results of the BioFire ME panel were compared against methods used during clinical testing. Ten-fold serial dilutions in UTM of cultured viruses were used to compare analytical sensitivity, and analytical specificity was assessed using panels of microorganisms in UTM. Clinical sensitivity and specificity were assessed using 20 positive specimens each for HHV-1, HHV-2, HHV-6, VZV, EVs, and HPeV, as well as 35 known negative specimens that included 15 mpox-positive specimens. Biofire ME was as sensitive as comparator methods, and correctly discriminated all HSV-1, HSV-2, VZV, HHV-6, EVs, and HPeVs from mpox and mpox-mimickers. Cross-reaction between EV and rhinoviruses A, B, and C were noted in the specificity panel. Swabs in UTM collected for mpox testing are suitable for use on the Biofire ME panel, allowing more streamlined diagnostic testing for viral exanthems in patients under investigation for mpox infection.

159: LEFT VENTRICULAR APICAL THROMBUS AFTER COVID-19 INFECTION ASSOCIATED WITH PEDIATRIC STROKE

Introduction: Stroke is rare in the pediatric population but is often associated with significant morbidity and mortality prompting evaluation for a wide range of pathologic processes. Neurologic manifestations of COVID-19 infection include meningoencephalitis, acute demyelinating encephalomyelitis, Guillain barre and stroke. Throughout the literature, patients seen with neurologic disease had severe COVID-19 infection and/or the multi-system inflammatory syndrome (MIS-C). Only a small proportion of patients had neurologic manifestations as the presenting feature with confusion and seizures being most common. Description: We report the case of a 12-year-old male who presented with left sided weakness and confused speech. This occurred following a 3-day illness with reported fever, malaise, and headache with photophobia resolved. On admission he was afebrile with a left facial droop, grade 4 power in the left hemibody and ankle clonus. Labs revealed an elevated WBC (16.4 x 103 cell/mm3) and CRP (7.3mg/dl), a negative respiratory viral panel and COVID-19 PCR test but positive COVID-19 antibody 315 s/co ratio and increased fibrinogen (523mg/dl) and d-dimers (2.69 mcg/ml). CSF had no WBCs and a negative meningitis-encephalitis panel. Computed tomography of the brain was normal but an MRI brain with angiography and venography showed multiple infarcts consistent with embolic strokes. An echocardiogram revealed a mobile mass at the left ventricular apex measuring 2.5 x 1.6 cm suggestive of a large clot in the presence of normal biventricular function, and no wall motion abnormalities. Due to the risk of re-embolization with devastating neuro-cardiac effects, he underwent left ventriculotomy and clot removal with cardiopulmonary bypass and was continued on therapeutic anticoagulation. Alternative etiologies such as thrombophilia, infective endocarditis or an intracardiac tumor were ruled out. Discussion: Intracardiac thrombosis has been reported in adults and children with COVID-19 but often along with pneumonia, dilated cardiomyopathy and myocardial infarction or acute MIS-C and intracardiac devices. Delayed thrombosis in the absence of MIS-C or cardiac dysfunction is not as frequently seen and brings to light the prolonged prothrombotic state post COVID infection.

Analysis of the Clinical Impact of the BioFire FilmArray Meningitis Encephalitis Panel on Antimicrobial Use and Duration of Therapy at an Academic Medical Center.

The purpose of this study was to assess the clinical impact of the BioFire FilmArray Meningitis/Encephalitis (ME) panel on antimicrobial use and clinical outcomes. This retrospective, quasi-experiment evaluated adult and pediatric patients with suspected ME, evidenced by cerebrospinal fluid (CSF) culture. Hospital-acquired meningitis patients and patients who received antimicrobials &gt;48 h prior to lumbar puncture were excluded. The primary endpoint was days of antimicrobial therapy pre- and post-implementation of the ME panel. Secondary endpoints included total length of stay, 30-day readmission, and individual days of antimicrobial therapy. Two hundred and sixty-four total adult and pediatric patients were included. Antimicrobial days of therapy had a median of 3 days (IQR 0-5) in the pre vs. post group with a median of 2 days (2-5) (p = 0.099). Days of therapy for acyclovir were significantly decreased in the post group (median 2 days [IQR 1-3] vs. 3 days [IQR 2.5-4.5], p = 0.0002). There were no significant differences in the secondary endpoints. Overall, implementation of the ME panel impacted the duration of antimicrobials, particularly acyclovir; however, opportunities for further education regarding antimicrobial de-escalation and utilization of the panel were identified. Antimicrobial stewardship program intervention is critical to maximize benefit of this rapid diagnostic test.

Current state and practice variation in the use of Meningitis/Encephalitis (ME) FilmArray panel in children

BackgroundThe Meningitis/Encephalitis FilmArray® Panel (ME panel) was approved by the U.S. Food and Drug Administration in 2015 and provides rapid results when assessing patients with suspected meningitis or encephalitis. These patients are evaluated by various subspecialties including pediatric hospital medicine (PHM), pediatric emergency medicine (PEM), pediatric infectious diseases, and pediatric intensive care unit (PICU) physicians. The objective of this study was to evaluate the current use of the ME panel and describe the provider and subspecialty practice variation.MethodsWe conducted an online cross-sectional survey via the American Academy of Pediatrics Section of Hospital Medicine (AAP-SOHM) ListServe, Brown University PEM ListServe, and PICU Virtual pediatric system (VPS) Listserve.ResultsA total of 335 participants out of an estimated 6998 ListServe subscribers responded to the survey. 68% reported currently using the ME panel at their institutions. Among test users, most reported not having institutional guidelines on test indications (75%) or interpretation (76%). 58% of providers self-reported lack of knowledge of the test’s performance characteristics. Providers from institutions that have established guidelines reported higher knowledge compared to those that did not (51% vs. 38%; p = 0.01). More PHM providers reported awareness of ME panel performance characteristics compared to PEM physicians (48% vs. 27%; p = 0.004); confidence in test interpretation was similar between both groups (72 vs. 69%; p = 0.80).ConclusionDespite the widespread use of the ME panel, few providers report having institutional guidelines on test indications or interpretation. There is an opportunity to provide knowledge and guidance about the ME panel among various pediatric subspecialties.

Impact of CSF Meningitis and Encephalitis Panel on Resource Use for Febrile Well-Appearing Infants.

To determine whether the BioFire FilmArray Meningitis/Encephalitis (ME) panel is associated with decreased resource use for febrile infants. The ME panel has a rapid turnaround time (1-2 hours) and may shorten length of stay (LOS) and antimicrobial use for febrile well-appearing infants. Retrospective cohort study of febrile well-appearing infants ≤60 days with cerebrospinal fluid culture sent in the emergency department from July 2017 to April 2019. We examined the frequency of ME panel use and its relationship with hospital LOS and initiation and duration of antibiotics and acyclovir. We used nonparametric tests to compare median durations. The ME panel was performed for 85 (36%) of 237 infants. There was no difference in median hospital LOS for infants with versus without ME panel testing (42 hours, interquartile range [IQR] 36-52 vs 40 hours, IQR: 35-47, P = .09). More than 97% of infants with and without ME panel testing were initiated on antibiotics. Patients with ME panel were more likely to receive acyclovir (33% vs 18%; odds ratio: 2.2, 95%: confidence interval 1.2-4.0). There was no difference in median acyclovir duration with or without ME panel testing (1 hour, IQR: 1-7 vs 4.2 hours, IQR: 1-21, P = .10). When adjusting for potential covariates, these findings persisted. ME panel use was not associated with differences in hospital LOS, antibiotic initiation, or acyclovir duration in febrile well-appearing infants. ME panel testing was associated with acyclovir initiation.

Use of the FilmArray® Meningitis/Encephalitis panel to detect pathogenic microorganisms in cerebrospinal fluid specimens: a single-center retrospective study.

ObjectiveMeningitis and encephalitis are neurological emergencies requiring rapid diagnosis and treatment. The performance of the FilmArray® Meningitis/Encephalitis (ME) panel, a multiplex polymerase chain reaction test, and conventional methods for diagnosing meningitis and encephalitis was compared.MethodsThis retrospective study assessed 20 patients diagnosed with meningitis or encephalitis according to clinical symptoms and laboratory examination findings between January 2018 and December 2019. The results of the FilmArray® ME panel were compared with those of conventional methods.ResultsPathogens were identified in 11 (55%) patients using the FilmArray® ME panel and in nine (45%) patients using conventional methods. The test identified herpes simplex virus type 1 in two patients, herpes simplex virus type 2 in one, varicella-zoster virus in four, Streptococcus pneumoniae in three, and Cryptococcus neoformans in one. Furthermore, additional pathogens were detected (n = 1, S. pneumoniae and n = 1, varicella-zoster virus). The median times to pathogen identification were 2 hours using the FilmArray® ME panel and 96 hours with conventional methods.ConclusionsThe sensitivity of the FilmArray® ME panel for rapidly detecting the most common pathogens was similar to that of conventional methods. Hence, this method could decrease the time to definitive diagnosis and treatment initiation.

AN UNUSUAL PRESENTATION OF CNS CANDIDIASIS

AN UNUSUAL PRESENTATION OF CNS CANDIDIASIS

Assessing the impact of a positive Biofire® FilmArray® Meningitis/Encephalitis Panel result on clinical management and outcomes

A rapid and accurate diagnosis of meningitis/encephalitis (ME) is required for early and effective intervention or adjustment of empirical treatment. This study retrospectively analyzed 485 records of patients hospitalized at the Padeh Poriya Medical Center during 2016−2020, due to a suspicion of ME. Pathogen distribution in cerebrospinal fluid samples, as determined using the BioFire® FilmArray ME Panel (MEP), is presented, as well as comparison of demographic and clinical characteristics, clinical management and outcomes of MEP+ (105) vs MEP− (380) patients. Pathogen distribution correlated with that reported in the literature, with Enterovirus (62%) being the most common causative agent. MEP+ patients were significantly younger than MEP− patients. Antibiotics use prior to lumbar puncture was significantly higher among MEP+ patients. MEP+ was associated with more frequent antibiotic change, compared to MEP−. While MEP+ contributed to early treatment adjustment or cessation, it did not necessarily impact the length of stay or patient outcomes.

A Diagnostic Stewardship Intervention that Optimizes CNS Infection Management

The introduction of molecular testing has led to more rapid diagnosis and optimization of treatment in the field of infectious diseases. In this volume of The Journal, Messacar et al used a diagnostic stewardship approach to address the role of the FilmArray® Meningitis Encephalitis Panel (MEP), a multiplex CSF PCR, in children with suspected central nervous system infection. After the implementation of pre-test criteria and real-time assistance from an infectious diseases specialist, they found that the use of MEP significantly reduced the time to optimal antimicrobial therapy (28 vs.

Clinical and Financial Impact of a Diagnostic Stewardship Program for Children with Suspected Central Nervous System Infection

To investigate the optimal implementation and clinical and financial impacts of the FilmArray Meningitis Encephalitis Panel (MEP) multiplex polymerase chain reaction testing of cerebrospinal fluid (CSF) in children with suspected central nervous system infection. A pre-post quasiexperimental cohort study to investigate the impact of implementing MEP using a rapid CSF diagnostic stewardship program was conducted at Children's Hospital Colorado (CHCO). MEP was implemented with electronic medical record indication selection to guide testing to children meeting approved use criteria: infants <2months, immunocompromised, encephalitis, and ≥5 white blood cells/μL of CSF. Positive results were communicated with antimicrobial stewardship real-time decision support. All cases with CSF obtained by lumbar puncture sent to the CHCO microbiology laboratory meeting any of the 4 aforementioned criteria were included with preimplementation controls (2015-2016) compared with postimplementation cases (2017-2018). Primary outcome was time-to-optimal antimicrobials compared using log-rank test with Kaplan-Meier analysis. Time-to-optimal antimicrobials decreased from 28hours among 1124 preimplementation controls to 18hours (P<.0001) among 1127 postimplementation cases (72% with MEP testing conducted). Postimplementation, time-to-positive CSF results was faster (4.8 vs 9.6hours, P<.0001), intravenous antimicrobial duration was shorter (24 vs 36hours, P=.004), with infectious neurologic diagnoses more frequently identified (15% vs 10%, P=.03). There were no differences in time-to-effective antimicrobials, hospital admissions, antimicrobial starts, or length of stay. Costs of microbiologic testing increased, but total hospital costs were unchanged. Implementation of MEP with a rapid central nervous system diagnostic stewardship program improved antimicrobial use with faster results shortening empiric therapy. Routine MEP testing for high-yield indications enables antimicrobial optimization with unchanged overall costs.

Evaluation of Discordant Results Between FilmArray Meningitis/Encephalitis Panel and Conventional Testing in Pediatric Patients: A Multisite Retrospective Cohort Study.

The FilmArray Meningitis/Encephalitis panel (MEP) has an 11% false-positive and 2.2% false-negative rate compared with conventional testing. We describe clinical characteristics, treatment decisions, and outcomes in children with discordant results between MEP and conventional testing. We conducted a multisite review of patients ≤ 18 years with suspected central nervous system infection and positive results by MEP or conventional testing (cerebrospinal fluid [CSF] culture, herpes simplex virus [HSV] polymerase chain reaction (PCR), and enterovirus [EV] PCR). Descriptive results are provided for patients with discordant results. Comparison between group 1 (MEP and CSF culture positive) and group 2 (MEP positive, CSF culture negative, or showing a different pathogen) was made by Mann-Whitney test for continuous and Fisher's test for categorical variables. A total of 355 patients had at least one pathogen identified. More than half of patients with bacterial pathogens identified that are included in the MEP had discordant results (30/52; 58%). There were 28 samples with bacterial pathogen identified on MEP only, 1 with different bacterial pathogens on MEP and culture, and 1 with Escherichia coli identified on CSF culture only. Patients in group 1 were more likely to have CSF pleocytosis, elevated CSF protein, and decreased CSF glucose than group 2 (P < .05). Two patients were HSV positive by MEP while HSV negative by PCR. Ten patients had discordant results between MEP and EV PCR. Discordant results between MEP and conventional testing are common. Treatment decisions based on a positive MEP should be made in the appropriate clinical context.

77. Opportunity for Improved Use of a Commercially Available Meningitis/Encephalitis Panel in Pediatric Patients

Abstract Background The BioFire® FilmArray Meningitis/Encephalitis (ME) panel delivers timely CSF analysis when meningitis or encephalitis is suspected and has the potential for earlier optimization of patient care. It is unclear if the M/E panel provides incremental benefit over standard microbiologic methods such as culture and cell counts, especially in the absence of significant pleocytosis. We evaluated the clinical utility of the ME panel with respect to CSF white blood cell count per high power field (WBC/hpf) and patient age. Methods We identified paired CSF ME panels and CSF cultures collected throughout a large healthcare system from 2016–May 2021 in children &amp;lt; 18 years of age. CSF results from the same calendar day were included in the dataset. We reviewed standalone HSV and Enterovirus (EV) CSF studies to determine frequency of duplicative testing. Results were stratified by CSF WBC/hpf and patient age (&amp;lt; 14 days, 14–60 days, &amp;gt; 60 days and &amp;lt; 5 years, and &amp;gt; 5 years). Results 1045 paired cultures and ME panels were identified. Of those, 921 (88%) ME panels were negative, but 5 of those cultures grew bacteria. Of 124 (12%) positive ME panel results, 66% were viral: 46 (37%) EV, 22 (18%) HHV-6 and 6 (5%) parechovirus. In 498 cases, ME panels were sent when CSF had &amp;lt; 10 WBC/hpf, resulting in only 2 (0.4%) PCRs positive for bacteria, one which was gram stain positive and the other was considered a false positive (Table 1). In addition to a ME panel, standalone PCRs for enterovirus and HSV were sent in 134 (13%) and 213 (20%) of cases, respectively, with &amp;lt; 2% discordance. Pathogen distribution by ME panel did not vary with age (Table 2). Meningitis and encephalitis panel, standalone PCR and culture results overall and by age group. Conclusion In our cohort, the ME panels were overwhelmingly negative. Only 12% of ME panels were positive, mostly with self-limited viral pathogens (e.g., EV, parechovirus). Performance was worse when samples had &amp;lt; 10 WBC/hpf. Duplicative testing was common and had no benefit. Performance was similar across age groups. More targeted use of the ME panel could improve the utility and efficacy of this test. Disclosures Anne Bonkowsky, MD/PhD, BioFire Diagnostics (Consultant, Grant/Research Support, Other Financial or Material Support, I have intellectual property through the University of Utah in BioFire Diagnostics and the FilmArray and receive royalties through the University of Utah.)Merck (Advisor or Review Panel member)

1019. Clinical Impact of a Rapid Cerebrospinal Fluid Diagnostic Stewardship Program for Suspected Central Nervous System Infections in Children

BackgroundDespite widespread use, the optimal implementation and clinical impact of FilmArray Meningitis Encephalitis Panel (MEP; Table 1) multiplex PCR testing of cerebrospinal fluid (CSF) in children with suspected (CNS) infections is unknown.Table 1: FilmArray Meningitis Encephalitis Panel Test Characteristics MethodsA pre-post quasi-experimental cohort study to investigate the impact of implementing MEP using a rapid CSF diagnostic stewardship program was conducted at Children’s Hospital Colorado (CHCO). MEP was implemented with EMR indication selection to guide testing to children meeting approved use criteria: i. infants < 2mo, ii. immunocompromised, iii. encephalitis, iv. > 5 WBCs in CSF. Positive results were communicated with antimicrobial stewardship real-time decision support (Fig 1). All cases with CSF obtained by lumbar puncture (LP) sent to the CHCO microbiology laboratory meeting any of the 4 criteria above were included with pre-implementation controls (2015-2016) compared to post-implementation cases (2017-2018). Primary outcome was time-to-optimal antimicrobials (time from LP to 1st dose of antimicrobials targeted to identified pathogen, or cessation when no treatable pathogen identified).Figure 1: Rapid Cerebrospinal Fluid Diagnostic Stewardship Program Intervention Design ResultsPost-implementation (n=1127) and pre-implementation (n=1124) group characteristics are in Table 2. Following implementation, MEP was sent in 72% of cases, largely replacing pathogen-specific singleplex CSF testing (Table 3). Time-to-optimal antimicrobials decreased by 10 hours (p< 0.0001; Fig 2). There were no differences in time-to-effective antimicrobials, hospital admissions, antimicrobial starts or length of stay. Time-to-positive CSF results was faster (4.8 vs. 9.6 hrs, p< 0.0001), IV antimicrobial duration was shorter (24 vs 36 hrs, p=0.004) with infectious neurologic diagnoses more frequently identified (15% vs. 10%, p=0.03). Overall, 3% had bacterial and 9% viral CNS infection identified. Enterovirus (n=128) was most common, then HSV (n=28) and parechovirus (n=17) with similar detection rates between groups ConclusionImplementation of MEP with a rapid CNS diagnostic stewardship program improved antimicrobial use with faster results shortening empiric therapy. Routine MEP testing in high-yield cases rapidly detects common viral causes and rules out bacterial targets to enable antimicrobial optimizationDisclosures Samuel R. Dominguez, MD, PhD, BioFire Diagnostics (Consultant, Research Grant or Support)DiaSorin Molecular (Consultant)Pfizer (Grant/Research Support) Samuel R. Dominguez, MD, PhD, BioFire (Individual(s) Involved: Self): Consultant, Research Grant or Support; DiaSorin Molecular (Individual(s) Involved: Self): Consultant; Pfizer (Individual(s) Involved: Self): Grant/Research Support

Evaluation of cerebrospinal fluid white blood cell count criteria for use of the BioFire® FilmArray® Meningitis/Encephalitis Panel in immunocompromised and nonimmunocompromised patients

We implemented the BioFire® FilmArray® Meningitis/Encephalitis Panel (MEP) with guidance for use based on patient age, cerebrospinal fluid (CSF) white blood cell (WBC) count and immune system status. MEPs results over 2 years (1/1/2017 to 12/31/18) were reviewed and clinical significance of positive MEP results in patients with CSF WBC ≤ 10 evaluated. Overall, 12% (51/453) of MEPs were positive with 4/184 (2%) positive in nonimmunocompromised (non-IC) with ≤ 10 CSF WBCs. Among positive results in non-IC patient with ≤10 CSF WBCs, none were judged clinically significant. Four of 6 results in immunocompromised patients with ≤10 CSF WBCs were clinically significant. Redundant testing was common and guideline adherence could have safely decreased MEPs use 41% saving >$56,000. Guideline adherence was poor and MEP use can be safely avoided in non-IC adults with <10 CSF WBC, but clinically significant results did occur in IC patients with low CSF WBC. Clinical decision support could reduce unneeded testing and result in significant cost savings.

AKI In Suspected Meningitis/Encephalitis May Be "Avoidable Kidney Injury".

AKI In Suspected Meningitis/Encephalitis May Be "Avoidable Kidney Injury".