Meningitis/encephalitis Panel Research Articles

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".

#22: Clinical Significance of Human Herpes Virus 6 Positivity in Children

Abstract Background Human Herpes Virus 6 (HHV6) is a common childhood disease that is typically mild, however, cases where it is the causative agent of meningitis/encephalitis (ME) have been reported. The treatment for HHV6 ME consists of ganciclovir, which is associated with bone marrow suppression and renal insufficiency. While the clinical significance of the presence of HHV6 in cerebrospinal fluid (CSF) in adults has been studied, there is a paucity of research on the clinical significance of HHV6 in the CSF of children with ME. We want to determine if there is clinical significance to HHV6 positivity in the CSF of children. Methods 20 patients were included whose CSF tested positive for HHV6 on the CSF ME panel from Jan 1, 2017 to May 20, 2020. We obtained a sample of 80 patients whose CSF tested negative for every pathogen on the same CSF ME panel from the same period. Logistic regression was used based on age, sex, race/ethnicity, admission to neonatal intensive care unit (NICU)/pediatric intensive care unit (PICU), clinical presentation, and presence of abnormalities on neuroimaging to determine the propensity score matching (PSM) for each patient. (Table I) The HHV6 positive patients were matched with patients who tested negative for every pathogen on the panel at a 1:1 ratio and within a caliper size of 0.25. The odds ratio (OR) of neurological sequelae at discharge was determined by performing a logistic regression based on HHV6 status in both the group with PSM and without PSM. The length of stay between the HHV6 positive group and the control group were compared with and without PSM using Mann-Whitney U test with p&amp;lt;0.05 considered significant Results The OR for HHV6 positivity and experiencing neurological sequelae is 1.35 with a 95% confidence interval (CI) 0.133,13.721 (p=0.799) when compared to the control group without PSM. The OR for HHV6 positivity and experiencing neurological sequelae is 1 with a 95% CI 0.063, 15.988 (p=0.549) when compared to the control group with PSM. Table I shows the neurological sequelae between the HHV6 positive group, control group without PSM and the control group with PSM. It shows the Mann-Whitney U test comparing HHV6 status to the median length of hospital stay in both unmatched- and matched cohorts. We failed to reject the null hypothesis that there was a difference in the median length of hospital stay between HHV6 positive patients and all negative patients with and without PSM. Conclusion There is no clinical significance of HHV6 detection on the CSF ME panel in children as well as no statistical significance between the median length of hospital stay among HHV6 positive patients and all negative patients. Further, 10% of the HHV6 positive patients were inappropriately started on ganciclovir. Development of a consensus statement is in place regarding releasing the result of a positive HHV6 from the ME panel only among immunocompromised children to prevent inappropriate antiviral therapy.

Clinical Significance of Positive Results of the BioFire Cerebrospinal Fluid FilmArray Meningitis/Encephalitis Panel at a Tertiary Medical Center in the United States.

The FilmArray Meningitis/Encephalitis (ME) panel is the first US Food and Drug Administration-cleared multiplex polymerase chain reaction panel for the detection of central nervous system infections. While the assay's performance characteristics have been described, the real-world significance of positive results has not been fully characterized. To evaluate the clinical significance of positive ME panel results in a tertiary care medical center in New York, New York. Four physicians independently performed retrospective clinical assessments of all positive ME panel results at Columbia University Irving Medical Center, including the Children's Hospital of New York, during an 18-month period. Each reviewer determined the likelihood of central nervous system infection for all cases and whether cases fit Brighton diagnostic criteria for meningitis, encephalitis, or meningoencephalitis. Among 119 cases, there was 75% positive agreement (95% CI, 54%-89%) between ME panel results and clinical consensus, which varied among panel targets. The ME panel showed good agreement with expert clinical consensus for patients presenting with acute meningitis/encephalitis. Factors contributing to clinically insignificant ME positive results included low pretest probability, traumatic lumbar puncture, specimen contamination, and detection of incidental viral targets such as human herpesvirus 6. Notably, the ME panel detected more than twice the number of cases of bacterial meningitis detected by culture alone, particularly among patients receiving empiric antimicrobial therapy before lumbar puncture. Appropriate test use and contextual interpretation of results are critical to leveraging the advantages of the platform while avoiding potential pitfalls.

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.

Human herpesvirus 6 and central nervous system disease in oncology patients: A retrospective case series and literature review.

Human herpesvirus 6 (HHV-6) can reactivate with immunosuppression and cause central nervous system (CNS) dysfunction. Much of the literature describes cases after hematopoietic stem cell transplantation (HSCT), ranging from encephalitis to a post-transplant acute limbic encephalitis syndrome (PALE). Outside of HSCT, studies of HHV-6 encephalitis are limited to case reports. This study was designed to review HHV-6 CNS infection, and evaluate all patients admitted to MD Anderson Cancer Center between March 2016 and December 2018 with detectable HHV-6 DNA in the cerebrospinal fluid (CSF). Patients with HHV-6 DNA detected in the CSF using the Viracor or Biofire® Meningitis Encephalitis Panel platforms and no other identified etiology were identified and demographic features, known risk factors, imaging findings, CSF analysis, treatments and patient outcomes were extracted from medical records. 725 patients underwent HHV-6 testing during the study timeframe, with 19 cases (2.6 %) of HHV-6 mediated CNS disease identified. Most patients, 13/19 (68 %), had undergone HSCT with median time to presentation of 31 days after transplant. Survival at 240 days after transplant was 62 %. CSF had lymphocyte predominance and nearly all patients had peripheral lymphopenia. Other at risk populations identified included patients who received chimeric antigen receptor (CAR) T-cell therapy and biologic immunotherapy. Notable discordance among testing platforms was found in 5/9 (55 %) instances. In addition to HSCT patients, HHV-6 reactivation leading to CNS disease also occurs in settings such as following adoptive T cell therapy or biologic immunotherapy. Significant diagnostic discordance exists between testing platforms.

Molecular Epidemiology of Enterovirus in Children with Central Nervous System Infections.

Limited recent molecular epidemiology data are available for pediatric Central Nervous System (CNS) infections in Europe. The aim of this study was to investigate the molecular epidemiology of enterovirus (EV) involved in CNS infections in children. Cerebrospinal fluid (CSF) from children (0–16 years) with suspected meningitis–encephalitis (ME) who were hospitalized in the largest pediatric hospital of Greece from October 2017 to September 2020 was initially tested for 14 common pathogens using the multiplex PCR FilmArray® ME Panel (FA-ME). CSF samples positive for EV, as well as pharyngeal swabs and stools of the same children, were further genotyped employing Sanger sequencing. Of the 330 children tested with FA-ME, 75 (22.7%) were positive for EV and 50 different CSF samples were available for genotyping. The median age of children with EV CNS infection was 2 months (IQR: 1–60) and 44/75 (58.7%) of them were male. There was a seasonal distribution of EV CNS infections, with most cases detected between June and September (38/75, 50.7%). EV genotyping was successfully processed in 84/104 samples: CSF (n = 45/50), pharyngeal swabs (n = 15/29) and stools (n = 24/25). Predominant EV genotypes were CV-B5 (16/45, 35.6%), E30 (10/45, 22.2%), E16 (6/45, 13.3%) and E11 (5/45, 11.1%). However, significant phylogenetic differences from previous described isolates were detected. No unusual neurologic manifestations were observed, and all children recovered without obvious acute sequelae. Specific EV circulating genotypes are causing a significant number of pediatric CNS infections. Phylogenetic analysis of these predominant genotypes found genetic differences from already described EV isolates.

Diagnostic Accuracy of the FilmArray™ Meningitis/Encephalitis Panel in Adult Patients with Suspected Bacterial Meningitis in a Tertiary Care Hospital in the Philippines

Objective. Bacterial meningitis is associated with significant morbidity and mortality if not diagnosed and treated early. Isolation of the causative agent from cerebrospinal fluid culture is the gold standard for the diagnosis of this condition; however, it takes several days for results to be available. The FilmArray™ Meningitis/Encephalitis (ME) panel is a nucleic acid-based test that allows simultaneous detection of 14 bacterial, viral, and fungal pathogens in the cerebrospinal fluid with a rapid turnaround time. Our aim was to evaluate the diagnostic performance of the ME panel in detecting bacterial pathogens in the cerebrospinal fluid of adult patients with suspected bacterial meningitis in a tertiary hospital in the Philippines. Methods. We performed a retrospective review of hospital records of adult patients with suspected bacterial meningitis who were admitted at our institution and underwent diagnostic testing with the FilmArray™ ME panel from January 1, 2018 to July 31, 2019. Overall percent agreement, sensitivity, and specificity for individual bacterial pathogens included in the panel were determined. Results. A total of 88 cerebrospinal fluid samples were included in the analysis of diagnostic accuracy. The ME panel demonstrated 93.2% overall agreement, 50% sensitivity for E. coli, and 99–100% specificity in comparison with CSF culture in detecting bacterial pathogens that are included in the ME panel. Conclusion. The results show that the FilmArray™ ME panel has high diagnostic accuracy and can be utilized in the rapid diagnosis and targeted treatment of patients with suspected bacterial meningitis.

341. Clinical and Laboratory Data in Patients with Viral and Bacterial Meningitis in Conjunction with FilmArray Meningitis/Encephalitis Panel Use: A Multi-Site Retrospective Cohort Study

BackgroundThe ability to quickly recognize and diagnose meningitis is a critical component in its management. The use of the FilmArray Meningitis/Encephalitis (ME) panel has made pathogen identification easier and faster. Although literature exists regarding clinical and laboratory data in patients with bacterial meningitis, less is known about the characteristics of viral meningitis caused by viruses detected by the ME panel This study aims to compare differences in clinical and laboratory characteristics between viral and bacterial meningitis identified by the ME panel.MethodsWe conducted a multisite retrospective review of pediatric patients with cerebral spinal fluid (CSF) positive for viral or bacterial organisms from January 2015 - February 2019. Demographic, clinical, and lab characteristics were extracted from medical records. Frequencies and percentages are used to explain descriptive data. Fisher’s exact test was used for categorical data. The Mann-Whitney test was used for continuous data.ResultsFour hundred thirty-eight patients were included in the analysis with baseline characteristics found in Table 1. Among these, 345 and 93 patients tested positive for viral and bacterial organisms respectively. Viral organisms identified are presented in Figure 1. Patients with bacterial organisms were more likely to have a history of prematurity, a prior neurosurgical procedure, neurological symptoms at presentation, neurological complications, and death within 30 days of admission. The median serum white blood cell (WBC) count, C-reactive protein (CRP), procalcitonin, CSF WBC count, CSF neutrophil percentage, and CSF protein were significantly higher in patients with bacterial organisms compared to viral organisms (Table 2).Table 1: Baseline Characteristics of the Study Population Figure 1: Viral organisms identified. Table 2: Comparison of Laboratory Data by CSF Pathogen Group ConclusionPatients positive for bacterial meningitis were more likely to have higher markers of infection compared to patients with viral organisms. Patients with bacterial organisms were also more likely to have death within 30 days of admission and neurological symptoms and subsequent complications, although the small number of patients limits these conclusions. These findings may help clinicians utilize clinical and laboratory data in conjunction with a ME panel result.Disclosures All Authors: No reported disclosures

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.

Point-of-Care Approaches for Meningitis Diagnosis in a Low-Resource Setting (Southwestern Uganda): Observational Cohort Study Protocol of the "PI-POC" Trial.

BackgroundA timely differential diagnostic is essential to identify the etiology of central nervous system (CNS) infections in children, in order to facilitate targeted treatment, manage patients, and improve clinical outcome.ObjectiveThe Pediatric Infection-Point-of-Care (PI-POC) trial is investigating novel methods to improve and strengthen the differential diagnostics of suspected childhood CNS infections in low-income health systems such as those in Southwestern Uganda. This will be achieved by evaluating (1) a novel DNA-based diagnostic assay for CNS infections, (2) a commercially available multiplex PCR-based meningitis/encephalitis (ME) panel for clinical use in a facility-limited laboratory setting, (3) proteomics profiling of blood from children with severe CNS infection as compared to outpatient controls with fever yet not severely ill, and (4) Myxovirus resistance protein A (MxA) as a biomarker in blood for viral CNS infection. Further changes in the etiology of childhood CNS infections after the introduction of the pneumococcal conjugate vaccine against Streptococcus pneumoniae will be investigated. In addition, the carriage and invasive rate of Neisseria meningitidis will be recorded and serotyped, and the expression of its major virulence factor (polysaccharide capsule) will be investigated.MethodsThe PI-POC trial is a prospective observational study of children including newborns up to 12 years of age with clinical features of CNS infection, and age-/sex-matched outpatient controls with fever yet not severely ill. Participants are recruited at 2 Pediatric clinics in Mbarara, Uganda. Cerebrospinal fluid (for cases only), blood, and nasopharyngeal (NP) swabs (for both cases and controls) sampled at both clinics are analyzed at the Epicentre Research Laboratory through gold-standard methods for CNS infection diagnosis (microscopy, biochemistry, and culture) and a commercially available ME panel for multiplex PCR analyses of the cerebrospinal fluid. An additional blood sample from cases is collected on day 3 after admission. After initial clinical analyses in Mbarara, samples will be transported to Stockholm, Sweden for (1) validation analyses of a novel nucleic acid–based POC test, (2) biomarker research, and (3) serotyping and molecular characterization of S. pneumoniae and N. meningitidis.ResultsA pilot study was performed from January to April 2019. The PI-POC trial enrollment of patients begun in April 2019 and will continue until September 2020, to include up to 300 cases and controls. Preliminary results from the PI-POC study are expected by the end of 2020.ConclusionsThe findings from the PI-POC study can potentially facilitate rapid etiological diagnosis of CNS infections in low-resource settings and allow for novel methods for determination of the severity of CNS infection in such environment.Trial RegistrationClinicalTrials.gov NCT03900091; https://clinicaltrials.gov/ct2/show/NCT03900091International Registered Report Identifier (IRRID)DERR1-10.2196/21430

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.

Impact of clinical guidance and rapid molecular pathogen detection on evaluation and outcomes of febrile or hypothermic infants.

To quantify the impact of clinical guidance and rapid respiratory and meningitis/encephalitis multiplex polymerase chain reaction (mPCR) testing on the management of infants. Before-and-after intervention study. Tertiary-care children's hospital. Infants ≤90 days old presenting with fever or hypothermia to the emergency department (ED). The study spanned 3 periods: period 1, January 1, 2011, through December 31, 2014; period 2, January 1, 2015, through April 30, 2018; and period 3, May 1, 2018, through June 15, 2019. During period 1, no standardized clinical guideline had been established and no rapid pathogen testing was available. During period 2, a clinical guideline was implemented, but no rapid testing was available. During period 3, a guideline was in effect, plus mPCR testing using the BioFire FilmArray respiratory panel 2 (RP 2) and the meningitis encephalitis panel (MEP). Outcomes included antimicrobial and ancillary test utilization, length of stay (LOS), admission rate, 30-day mortality. Outcomes were compared across periods using Kruskal-Wallis and Pearson tests and interrupted time series analysis. Overall 5,317 patients were included: 2,514 in period 1, 2,082 in period 2, and 721 in period 3. Over the entire study period, we detected reductions in the use of chest radiographs, lumbar punctures, LOS, and median antibiotic duration. After adjusting for temporal trends, we observed that the introduction of the guideline was associated with reductions in ancillary tests and lumbar punctures. Use of mPCR testing with the febrile infant clinical guideline was associated with additional reductions in ancillary testing for all patients and a higher proportion of infants 29-60 days old being managed without antibiotics. Use of mPCR testing plus a guideline for young infant evaluation in the emergency department was associated with less antimicrobial and ancillary test utilization compared to the use of a guideline alone.

Utilization, Yield, and Accuracy of the FilmArray Meningitis/Encephalitis Panel with Diagnostic Stewardship and Testing Algorithm.

The impact of diagnostic stewardship and testing algorithms on the utilization and performance of the FilmArray meningitis/encephalitis (ME) panel has received limited investigation. We performed a retrospective single-center cohort study assessing all individuals with suspected ME between February 2017 and April 2019 for whom the ME panel was ordered. Testing was restricted to patients with cerebrospinal fluid (CSF) pleocytosis. Positive ME panel results were confirmed before reporting through correlation with direct staining (Gram and calcofluor white) and CSF cryptococcal antigen or by repeat ME panel testing. Outcomes included the ME panel test utilization rate, negative predictive value of nonpleocytic CSF samples, test yield and false-positivity rate, and time to appropriate deescalation of acyclovir. Restricting testing to pleocytic CSF samples reduced ME panel utilization by 42.7% (263 versus 459 tests performed) and increased the test yield by 61.8% (18.6% versus 11.5% positivity rate; P < 0.01) with the application of criteria. The negative predictive values of a normal CSF white blood cell (WBC) count for ME panel targets were 100% (195/195) for nonviral targets and 98.0% (192/196) overall. All pathogens detected in nonpleocytic CSF samples were herpesviruses. The application of a selective testing algorithm based on repeat testing of nonviral targets avoided 75% (3/4) of false-positive results without generating false-negative results. The introduction of the ME panel reduced the duration of acyclovir treatment from an average of 66 h (standard deviation [SD], 43 h) to 46 h (SD, 36 h) (P = 0.03). The implementation of the ME panel with restriction criteria and a selective testing algorithm for nonviral targets optimizes its utilization, yield, and accuracy.

Meningitis with Normal Cerebrospinal Fluid: Lactate and FilmArray Can Save my Life? Case Report

Cytological and biochemical examination from cerebrospinal fluid are key essentials in the diagnosis of bacterial meningitis. In most cases, cerebrospinal fluid (CSF) yields white cell counts > 100 mm3, hyperproteinorachia, and hypoglycorrhachia. However, in some patients, these findings do not appear especially in the elderly, pediatric, and the immunocompromised. A 78-year-old immunocompromised woman was admitted for fever and headache. Despite typical meningeal clinical signs, lumbar puncture showed absence of pleiocytosis, normal glycorrhachia, and normal proteinorachia. The lactate level in CSF was high (3.8 mmol/L). The FilmArray ® Meningitis/Encephalitis (ME) panel was positive for Human Herpesvirus 6 (HHV6). Gram staining was negative. In front of a high probability of bacterial meningitis, a second lumbar puncture was performed and showed normal cell counts and high lactate level (4.4 mmol/L). The FilmArray ® ME panel was positive for HHV6 and Streptococcus pneumoniae. The antimicrobial therapy was conducted for 14 days. She was treated with cefotaxime then amoxicillin. This case indicates the importance of repeating a lumbar puncture even if the examination of CSF is normal, whereas the patient has typical meningeal clinical signs. Lactate levels in CSF with a diagnostic cutoff value of 3.8 mmol/L and the FilmArray ® ME panel could help physicians in this situation in order to decrease a poor outcome.

Impact of a Multiplex Polymerase Chain Reaction Assay on the Clinical Management of Adults Undergoing a Lumbar Puncture for Suspected Community-Onset Central Nervous System Infections.

Patients admitted from the community with a suspected central nervous system (CNS) infection require prompt diagnostic evaluation and correct antimicrobial treatment. A retrospective, multicenter, pre/post intervention study was performed to evaluate the impact that the BioFire® FilmArray® meningitis/encephalitis (ME) panel run in-house had on the clinical management of adult patients admitted from the community with a lumbar puncture (LP) performed for a suspected CNS infection. The primary outcome was the effect that this intervention had on herpes simplex virus (HSV) polymerase chain reaction (PCR) turnaround time (TAT). Secondary outcomes included the effect that this intervention had on antiviral days of therapy (DOT), total antimicrobial DOT, and hospital length of stay (LOS). A total of 81 and 79 patients were included in the pre-intervention and post-intervention cohorts, respectively. The median HSV PCR TAT was significantly longer in the pre-intervention group (85 vs. 4.1 h, p < 0.001). Total antiviral DOT was significantly greater in the pre-intervention group (3 vs. 1, p < 0.001), as was total antimicrobial DOT (7 vs. 5, p < 0.001). Pre-intervention hospital LOS was also significantly longer (6.6 vs. 4.4 days, p = 0.02). Implementing the ME panel in-house for adults undergoing an LP for a suspected community-onset CNS infection significantly reduced the HSV PCR TAT, antiviral DOT, total antimicrobial DOT, and hospital LOS.

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.

Assessment of the FilmArray® multiplex PCR system and associated meningitis/encephalitis panel in the diagnostic service of a tertiary hospital

SummaryRapid and accurate diagnosis of meningitis/encephalitis (M/E) is essential for successful patient outcomes. The FilmArray® meningitis/encephalitis Panel (MEP) is a multiplexed PCR test for simultaneous, rapid detection of pathogens directly from cerebrospinal fluid (CSF) samples. 94 prospectively collected CSF specimens from patients with clinical suspicion of infective M/E underwent testing for 14 pathogens simultaneously, including Escherichia coli, Haemophilus influenzae, Neisseria meningitidis, and Varicella zoster. MEP demonstrated 95% agreement with current PCR methods, resulting in 16 diagnosed cases of M/E. Typically, the FilmArray® MEP results were delivered within approximately one hour, contrasting with current practices taking up to 5.6 days. Given the significant morbidity and mortality associated with delayed diagnosis of central nervous system infections, the FilmArray® MEP is a useful addition to the diagnostic capabilities of a clinical microbiology department.

Evaluation of the Biofire FilmArray meningitis/encephalitis assay for the detection of Cryptococcus neoformans/gattii

ObjectivesCryptococcal meningitis (CM) remains an important cause of morbidity and mortality among immunocompromised patients. Laboratory diagnostics for CM includes antigen detection, staining and culture. Data on the performance of the Biofire® FilmArray® meningitis/encephalitis (ME) panel for detecting Cryptococcus neoformans/gattii is limited, with several reports describing false negativity for this target. MethodsA retrospective analysis of 1384 physician-ordered ME panel tests ordered between January 2017 to October 2018 was performed. ME panel results were compared to cerebrospinal fluid (CSF) cryptococcal antigen (CrAg) and CSF culture testing and clinical significance of cryptococcal detection was determined. ResultsThere were 34 patients positive for cryptococcal detection by either ME panel, CSF CrAg or CSF culture in 2.7% of CSF specimens tested (38/1384). Of the 34 patients positive for cryptococcal detection, 85.3% were human immunodeficiency virus positive (29/34). The ME panel detected 32/38 (84.2%) cryptococcal-positive specimens, culture detected 28/38 (73.7%) and CSF CrAg was positive in 37/38 specimens (97.4%). The ME panel had a sensitivity and specificity of 96.4% (95% CI 81.7–99.9%) and 99.6% (95% CI 99.2–99.9%) compared with culture, and 83.8% (95% CI 68.0–93.8%) and 99.9% (95% CI 99.6–100.0%) compared to CSF CrAg testing, respectively. CrAg titres were lower among ME panel-negative, culture-negative specimens compared with ME panel-positive, culture-negative specimens (reciprocal median end-point titres of 128 ± 60 vs. 1920 ± 1730, p 0.04). All five CrAg-positive, ME panel- and culture-negative specimens were obtained from previously treated CM patients. DiscussionThe ME panel had high correlation with CSF culture and a somewhat lower correlation with CSF CrAg testing. The potential utility of using negative ME panel test results to predict culture sterility among patients undergoing treatment for CM warrants further study.