FilmArray Meningitis/encephalitis Research Articles

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.

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 >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.

The Evaluation of the Diagnostic Performance of the BioFire FilmArray Meningitis/Encephalitis Panel in Children: A Retrospective Multicenter Study

Abstract Objective Acute bacterial meningitis (ABM) declined after implementing conjugate Haemophilus influenzae type B and the pneumococcal vaccines worldwide. However, it still contributes to significant morbidity and mortality. The Biofire FilmArray Meningitis Encephalitis (FAME) panel can rapidly diagnose common bacterial and viral pathogens. Several studies suggested that the use of FAME may accelerate diagnosis and decrease the time to pathogen-specific therapy. However, the clinical utility is still controversial due to scarce data and relatively high costs. Therefore, we aimed to evaluate the diagnostic performance of FAME in children. Methods A retrospective multicenter cross-sectional study was conducted to evaluate FAME in diagnosing ABM in children with a suspected central nervous system infection between January 2017 and May 2021. Results This study consisted of 179 children diagnosed with central nervous system infection who had parallel testing done using FAME and traditional microbiological diagnostic methods. Twenty-two FAME results were positive; 8 (36.3%) were bacterial pathogens and 14 (53.7%) were viral pathogens. The most common viral pathogen was human herpesvirus 6 (n = 6; 27.2%), followed by herpes simplex virus 1 (n = 4; 18.1%), Enterovirus spp. (n = 2; 9%), Parechovirus (n = 2; 9%), and Cytomegalovirus (n = 1; 4.5%). Bacterial pathogens included S. pneumoniae (n = 3; 13.6%), H. influenzae (n = 3; 13.6%), Neisseria meningitidis (n = 1; 4.5%), and Streptococcus agalactiae (n = 1; 4.5%). Bacterial culture confirmed S. pneumoniae infection in only 1 of 8 (12.5%) patients, while 7 of 8 bacterial meningitis were only detected by FAME. Conclusion FAME may also help with diagnosis and pathogen identification in patients who have already had antibiotics before cerebrospinal fluid collection. The use of FAME to detect infections quickly may minimize the improper use of medications, treatment duration, and the cost of hospitalization.

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.

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.

Biofire FilmArray Meningitis/Encephalitis panel for the aetiological diagnosis of central nervous system infections: A systematic review and diagnostic test accuracy meta-analysis.

SummaryBackgroundThe FilmArray Meningitis/Encephalitis(FA/ME) panel brings benefits in clinical practice, but its diagnostic test accuracy (DTA) remains unclear. We aimed to determine the DTA of FA/ME for the aetiological diagnostic in patients with suspected central nervous system(CNS) infection.MethodsWe performed a systematic review with DTA meta-analysis (PROSPERO: CRD42020139285). We searched Embase, Medline (Ovid), and Web of Science from inception until September 1st, 2021. We assessed the study-level risk of bias with the QUADAS-2 tool and applied the GRADE approach to assess the certainty of the synthesised evidence. We included studies that simultaneously measured the reference test (CSF/blood culture for bacteria, and specific polymerase chain reaction for viruses) and the FA/ME in patients with suspected CNS infection. We performed random-effects bivariate meta-analysis models of combined sensitivity and specificity using CSF/blood cultures(reference test 1) and a final diagnosis adjudication based on clinical/laboratory criteria (reference test 2).FindingsWe included 19 studies (11,351 participants). For all bacteria with reference test 1 (16 studies/6183 patients) sensitivity was estimated at 89·5% (95%CI 81·1–94·4), and specificity at 97·4% (95%CI 94–98·9). With reference test 2 (15 studies/5,524 patients), sensitivity was estimated at 92·1%(95%CI 86·8–95·3) and specificity at 99.2(95%CI 98·3–99·6) For herpes simplex virus-2(HSV-2), enteroviruses, and Varicella-Zoster virus (VZV), we obtained sensitivities between 75·5 and 93·8%, and specificities above 99% (reference test 1). Certainty of the evidence was low.InterpretationFA/ME may have acceptable-to-high sensitivities and high specificities for identifying bacteria, especially for S.pneumoniae, and viruses, especially for HSV-2, and enteroviruses. Sensitivities for L.monocytogenes, H.influenzae, E.coli, and HSV-1 were suboptimal.FundingNone.

Clinical Performance of FilmArray Meningitis/Encephalitis Multiplex Polymerase Chain Reaction Panel in Central Nervous System Infections.

IntroductionEarly identification of etiology is very important for initiating appropriate therapy promptly in patients with meningoencephalitis (ME). BioFire FilmArray® meningitis/encephalitis (FA-ME) panel is a fully automated multiplex polymerase chain reaction (PCR) that detects 14 pathogens simultaneously in an hour. There is a dearth of studies highlighting its usefulness in ME syndrome in Indian patients.Materials and methodsWe performed a retrospective analysis of patients, admitted to the Kerala Institute of Medical Sciences Hospital, Thiruvananthapuram, Kerala, South India, with meningitis/encephalitis syndrome who underwent the multiplex PCR test on cerebrospinal fluid (CSF) over a period of 2 years from 2016 to 2018. Patients presenting with clinical diagnosis of acute meningitis, encephalitis, or ME who underwent CSF FA-ME panel were studied. The performance of the FA-ME panel was compared to CSF bacterial culture.ResultsTwo-hundred and fifty-nine patients between December 2016 and December 2018 underwent the FA-ME test in CSF. FA-ME test detected pathogens in 61 (23.6%) out of 259 patients with ME syndrome. Among the pathogens detected by FA-ME panel, enterovirus was the commonest accounting for 29 cases (47.5%), followed by varicella in 11 patients (18%) and pneumococci in 9 (14.8%). CSF bacterial culture yield was low, positive only in 8 (3%) out of 259 cases, and matched with FA-ME panel in only one sample that grew Streptococcus pneumoniae. Bacterial culture yielded seven pathogens in those whose FA-ME panels were negative.ConclusionFA-ME panel improves diagnostic yield as compared to bacterial culture (26.3 vs 3%). FA-ME test helps in the early initiation of targeted antibiotic therapy and greater antibiotic de-escalation.How to cite this articleChandran S, Arjun R, Sasidharan A, Niyas VKM, Chandran S. Clinical Performance of FilmArray Meningitis/Encephalitis Multiplex Polymerase Chain Reaction Panel in Central Nervous System Infections. Indian J Crit Care Med 2022;26(1):67–70.

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

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

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

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

Evaluation of the Utilization of FilmArray Meningitis/Encephalitis in Children With Suspected Central Nervous System Infection: A Retrospective Case Series.

The etiology of central nervous system infections is often difficult to establish. FilmArray meningitis/encephalitis (ME) panel is a multiplex polymerase chain reaction for rapid identification of 14 pathogens. The aim of this study was to evaluate potential real-life contributions of the use of this method in the pediatric population. We herein report the results obtained with FilmArray ME in a retrospective case series of 367 children with suspected central nervous system infection. We identified viral and bacterial agents by FilmArray, and we evaluated the potential diagnostic contributions of the use of the panel taking into account the cytological, biochemical, and microbiological results of the cerebrospinal fluid (CSF) analysis. The FilmArray ME panel detected a viral infection in 186 cases (50.7%) and a bacterial infection in 12 cases (3.3%). Fifty-three cases (28.4%) of viral infection had at least 1 CSF finding that could be mistaken for bacterial meningitis. Enterovirus was identified in 2 cases with normal CSF findings. Among 12 bacterial infection cases, only 6 (50%) had a positive result with conventional microbiology analysis (Gram stain and culture). The CSF findings suggestive of bacterial meningitis were found in all 6 cases in which FilmArray was the only method to identify bacterial etiological agent. FilmArray ME panel identified an etiological agent in cases in which conventional CSF analysis failed, providing potential clinical contributions to the management of such cases.

Assessment of the FilmArray ME panel in 4199 consecutively tested cerebrospinal fluid samples

ObjectivesIn central nervous system infections, early and correct management is of utmost importance. Rapid syndromic panel testing can potentially provide valuable guidance. The FilmArray meningitis/encephalitis (ME) panel detects 14 pathogens through multiplex PCR. Our study objectives were to assess its performance compared with established diagnostic procedures, especially real-time quantitative PCR for detection of viruses, and to determine the diagnostic and clinical significance of discrepant results. MethodsAll cerebrospinal fluid samples sent for viral diagnostics to our microbiological laboratory over 34 months were analysed with the ME panel and in-house real-time PCR for herpes simplex virus type 1 (HSV-1), HSV-2, varicella zoster virus and enteroviruses. Other pathogens detected by the panel were confirmed by routine diagnostic procedures. Discrepant results were analysed through interpretation of biological and clinical data, and performance data were calculated for individual pathogens. ResultsAltogether, 315 pathogens were detected by the ME panel in 4199 cerebrospinal fluid samples (7.5%) and an additional 21 viral targets were identified using real-time PCR. Thirty-four ME panel detections were not confirmed, totalling 55 discrepant results. After discrepancy analysis, 20 false-positive and 21 false-negative ME panel results remained. Performance varied between pathogens. Sensitivity for HSV-1 was calculated at 82.4% (59.0%–93.8%) with three false-negative results. Also noteworthy were 13 false-negative enterovirus and eight false-positive Streptococcus pneumoniae results. ConclusionsOur analysis shows good performance for the ME panel in diagnosing central nervous system infection. The risk of false-negative HSV-1 results, however, warrants additional testing when encephalitis is suspected. Uncertainties in interpretation of enterovirus and S. pneumoniae results represent other limitations.

Impact of a Rapid Diagnostic Meningitis/Encephalitis Panel on Antimicrobial Use and Clinical Outcomes in Children.

Rapid molecular diagnostic assays are increasingly used to guide effective antimicrobial therapy. Data on their effectiveness to decrease antimicrobial use in children have been limited and varied. We aimed to assess the impact of the implementation of the FilmArray Meningitis Encephalitis Panel (MEP) on antimicrobial use and outcomes in children. In an observational retrospective study performed at Atlantic Health System (NJ), we sought to evaluate the duration of intravenous antibiotic treatment (days of therapy (DoT)) for patients <21 years of age hospitalized and evaluated for presumptive meningitis or encephalitis before and after the introduction of the MEP. A secondary analysis was performed to determine if recovery of a respiratory pathogen influenced DoT. The median duration of antibiotic therapy prior to the implementation of the MEP was 5 DoT (interquartile range (IQR): 3–6) versus 3 DoT (IQR: 1–5) (p < 0.001) when MEP was performed. The impact was greatest on intravenous third-generation cephalosporin and ampicillin use. We found a reduction in the number of inpatient days associated with the MEP. In the regression analysis, a positive respiratory pathogen panel (RPP) was not a significant predictor of DoT (p = 0.08). Furthermore, we found no significant difference between DoT among patients with negative and positive RPP (p = 0.12). Our study supports the implementation of rapid diagnostics to decrease the utilization of antibiotic therapy among pediatric patients admitted with concerns related to meningitis or encephalitis.

Preventing contamination of PCR-based multiplex assays including the use of a dedicated biosafety cabinet.

We retrospectively investigated cases of false-positive diagnoses using the BIOFIRE® FilmArray® meningitis/encephalitis (ME) panel to measure the impact of using a dedicated biosafety cabinet combined with preventive measures to reduce the prevalence of false-positive diagnoses due to pre-analytical in-laboratory contamination. False-positive results were identified by reviewing clinical data, biological parameters and cytology results of cerebrospinal fluid (CSF) samples showing discrepant results between the FilmArray ME panel and routine PCR assays. A total of 327 CSF were analysed over 16weeks in point-of-care (POC) A and B, over two 8-week periods, periods 1 and 2. The analysis yielded 30 (9·17%) detection of at least one pathogen including 21/30 (70%) viruses and 9/30 (30%) bacteria. During period 1, POC-A and POC-B manipulated CSF under a non-dedicated hood featuring laminar flow, whereas during period 2, CSFs were manipulated under a dedicated biosafety cabinet without any airflow in POC-A. During period 1, false positives were detected in 3/114 CSF (2·63%) in POC-A and 1/36 (2·77%) in POC-B (P=0·97); during period 2, false positives were detected in 0/139 CSF (0%) in POC-A and 1/38 (2·63%) in POC-B (P=0·23). All false positives were bacterial. The use of a dedicated cabinet without ventilation along with preventive measures during period 2 in POC-A significantly reduced the number of false-positive results (P=0·05). Preventive measures described in this study can mitigate false positives when using PCR-based multiplex assays such as the BIOFIRE FilmArray ME Panel for the diagnosis of meningitis and other infectious diseases.

Burden of Pediatric Central Nervous System Infection and Cost-Benefit Simulation of Multiplex Polymerase Chain Reaction in Japan.

To investigate the clinical use of multiplex polymerase chain reaction (mPCR) in Japan, epidemiological and clinical data for central nervous infections are needed. Here, we report on the epidemiology and economic burden of central nervous system infections and a simulation of the cost-benefit analysis of the Filmarray® Meningitis/Encephalitis (FAME) test for possible clinical use in Japan. We performed FAME tests on samples from 27 patients with pleocytosis aged between 0 and 20 years seen in six community hospitals in Nara and Osaka prefectures. All clinical management procedures were performed without knowledge of the mPCR test results. We analyzed the clinical data and calculated the required reduction in average length of stay for the FAME test to be cost-beneficial. Among the 27 cases, the FAME test revealed causal pathogens in 13 cases (48.1%). The average medical and social costs per case were ¥299,118 ($2,719.2) and ¥171,768 ($1,561.5), respectively. The minimal needed reduction in average length of stay for the FAME test to be cost-beneficial was 0.32- 0.86 days per meningitis case. The result can be informative for evaluating the cost-effectiveness of the clinical use of the FAME test in Japan.

Impact of cerebrospinal fluid syndromic testing in the management of children with suspected central nervous system infection.

The aim of the study was to evaluate the impact of the use of BioFire® FilmArray® meningitis/encephalitis(FA-ME) panel which enables rapid automated CSF testing for 14 common viral, bacterial, and yeast pathogens that cause CNS infections, in the management of children with suspected CNS infection. A prospective cohort study was performed on children admitted to a tertiary pediatric hospital, over a period of 1year, with possible CNS infection and CSF pleocytosis (> 15cells/mm3). Children were randomized 1:1, either to use FA-ME or separate molecular CSF microbiological tests according to usual pediatric practice in the hospital. Length of hospital stay, duration of antimicrobials, and total cost of hospitalization were compared between groups. A total of 142 children were included in the study (71 cases). A pathogen was detected in 37/71(52.1%) children with the use of FA-ME and in 16/71(22.5%) in the control group (P value < 0.001). In aseptic meningitis cases a virus was detected in 27/61(44.2%) and in 11/66(16.7%) controls (P value < 0.001). Median (IQR) length of stay in cases and controls with aseptic meningitis was 5(4-8) and 8(6-10)days, respectively (P value < 0. 001). The median (IQR) duration of antimicrobials in cases and controls was 4(2-5.7) and 7(5-10)days, respectively (P value < 0.001). The hospitalization cost was calculated in cases and controls 1042€ (932-1372) and 1522€ (1302-1742), respectively (P value < 0.001). The use of FA-ME was able to reduce significantly the use of antimicrobials, the hospitalization days, and the total cost comparing to the control group in children with suspected CNS infection.

Impact of FilmArray meningitis encephalitis panel on HSV testing and empiric acyclovir use in children beyond the neonatal period

Following implementation of the FilmArray meningitis and encephalitis panel, which enables rapid syndromic cerebrospinal fluid testing, HSV testing doubled in children >60 days with suspected central nervous system infection at Children’s Hospital Colorado. Acyclovir initiation was unchanged, but duration decreased. Diagnostic and antimicrobial stewardship is needed for MEP optimization.

Cerebrospinal Fluid Findings Are Poor Predictors of Appropriate FilmArray Meningitis/Encephalitis Panel Utilization in Pediatric Patients.

Molecular testing of cerebrospinal fluid (CSF) using the BioFire FilmArray meningitis/encephalitis (FA-M/E) panel permits rapid, simultaneous pathogen detection. Due to the broad spectrum of targeted organisms, FA-M/E testing may be restricted to patients with abnormal CSF findings. We sought to determine if restriction is appropriate in our previously healthy and/or immunocompromised pediatric patients. FA-M/E was ordered on 1,025 CSF samples from 948 patients; 121 (11.8%) specimens were FA-M/E positive. Of these, 89 (73.6%) were virus positive, and 30 (24.8%) were bacterium positive. The most common targets detected were enterovirus (n = 38), human herpesvirus 6 (HHV-6) (n = 30), and Streptococcus pneumoniae (n = 14). Pleocytosis with white blood cell (WBC) levels of ≥5 cells/mm3 and ≥10 cells/mm3 were found in 33.1% and 24.3% of all specimens, respectively. Using WBC levels of ≥5 cells/mm3, 63.4% (59/93) of positive specimens exhibited pleocytosis, compared to 29.5% (233/789) of negative specimens. Among positive specimens, 54.4% (37/68) of viral and 87% (20/23) of bacterial cases had pleocytosis. The use of a pleocytosis cutoff of ≥10 cells/mm3 would have missed an additional enterovirus, one cytomegalovirus (CMV), and two HHV-6 diagnoses. CSF glucose and protein levels were normal for 83/116 (75.2%) and 51/116 (44%) positive specimens. Abnormal glucose in combination with WBC levels of ≥10 cells/mm3 showed high specificity (94.5%) and was a better predictor of FA-M/E positivity than abnormal protein. Sensitivity and positive predictive values were <90% for all biomarkers. CSF pleocytosis and abnormal glucose/protein were poor predictors of FA-M/E. Restricting FA-M/E orders based on pleocytosis or other abnormal parameters would have resulted in missed diagnostic opportunities, particularly for the detection of viruses in both previously healthy and immunocompromised patients.

Impact of the Film Array Meningitis/Encephalitis panel in adults with meningitis and encephalitis in Colombia.

The Biofire® Film Array Meningitis Encephalitis (FAME) panel can rapidly diagnose common aetiologies but its impact in Colombia is unknown. A retrospective study of adults with CNS infections in one tertiary hospital in Colombia. The cohort was divided into two time periods: before and after the implementation of the Biofire® FAME panel in May 2016. A total of 98 patients were enrolled, 52 and 46 were enrolled in the Standard of Care (SOC) group and in the FAME group, respectively. The most common comorbidity was human immunodeficiency virus infection (47.4%). The median time to a change in therapy was significantly shorter in the FAME group than in the SOC group (3 vs. 137.3 h, P < 0.001). This difference was driven by the timing to appropriate therapy (2.1 vs. 195 h, P < 0.001) by identifying viral aetiologies. Overall outcomes and length of stay were no different between both groups (P > 0.2). The FAME panel detected six aetiologies that had negative cultures but missed identifying one patient with Cryptococcus neoformans. The introduction of the Biofire FAME panel in Colombia has facilitated the identification of viral pathogens and has significantly reduced the time to the adjustment of empirical antimicrobial therapy.

Reduction of response time for the assessment of invasive bacterial disease in bacteriology by using h24 molecular tests at low operational impact

In February 2017, the Lombardy Region (Italy) provided some indications for the surveillance of invasive bacterial diseases, including the need to perform molecular tests together with culture and other diagnostic tests. Starting from September 2017, the Microbiology and Virology Unit of ASST Lecco has acquired the FilmArray system (BioMérieux, Marcy-l’Étoile, France) which includes the Meningitis/Encephalitis (ME) panel, able to identify 14 common pathogens responsible for community acquired meningitis or encephalitis including virus, bacteria and yeast with molecular technology directly from cerebrospinal fluid (CFS). In 2018, the organizational model implemented has provided to use of the FilmArray system by the TSLB dedicated to microbiology during routine hours (8.00-16.30) and by the TSLB of Clinical Pathology on active guard from 16.30 to 8.00 with validation of the analysis by the Manager available. The new organization, which involved the use of the FilmArray ME h 24 panel by the TSLB who works belonging to Clinical Pathology and Microbiology and Virology, has allowed a considerable reduction of response times in case of suspected meningitis.