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Evaluation of a Commercial Multiplex Molecular Panel for Diagnosis of Infectious Meningitis and Encephalitis.

ABSTRACT: Rapid and accurate laboratory tests are important for the timely diagnosis and treatment of central nervous system infections. The FilmArray meningitis/encephalitis (ME) panel (BioFire Diagnostics, Salt Lake City, UT) is an FDA-cleared, multiplex molecular panel that allows the detection of 14 pathogens (bacterial [n = 6], viral [n = 7], and fungal [n = 1] pathogens) from cerebrospinal fluid (CSF). In this study, we evaluated the performance characteristics of the FilmArray ME panel using clinical, residual CSF samples (n = 291) that tested positive by a routine method(s) (e.g., bacterial culture, individual real-time PCR assay) for a pathogen represented on the ME panel. Of note, a subset (n = 76) of the CSF specimens was collected during the prevaccine era and had been characterized as positive for a bacterial pathogen. The FilmArray ME panel demonstrated an overall percent positive agreement (PPA) of 97.5% (78/80) for bacterial pathogens, 90.1% (145/161) for viruses, and 52% (26/50) for Cryptococcusneoformans/C. gattii Despite the low overall agreement (52%) between the ME panel and antigen testing for detection of C. neoformans/C. gattii, the percent positive agreement of the FilmArray assay for C. neoformans/C. gattii was 92.3% (12/13) when the results were compared directly to the results of routine fungal smear or culture. The FilmArray ME panel offers a rapid (?60-min), syndrome-based approach for the detection of select meningitis and encephalitis pathogens.

SUBMITTER: Liesman RM

PROVIDER: S-EPMC5869843 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Evaluation of a Commercial Multiplex Molecular Panel for Diagnosis of Infectious Meningitis and Encephalitis.

Liesman Rachael M RM Strasburg Angela P AP Heitman Angela K AK Theel Elitza S ES Patel Robin R Binnicker Matthew J MJ

Journal of clinical microbiology 20180326 4

Rapid and accurate laboratory tests are important for the timely diagnosis and treatment of central nervous system infections. The FilmArray meningitis/encephalitis (ME) panel (BioFire Diagnostics, Salt Lake City, UT) is an FDA-cleared, multiplex molecular panel that allows the detection of 14 pathogens (bacterial [n = 6], viral [n = 7], and fungal [n = 1] pathogens) from cerebrospinal fluid (CSF). In this study, we evaluated the performance characteristics of the FilmArray ...[more]

PMID: 29436421

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

Project description:Background: The differential diagnosis of autoimmune and infectious encephalitis is notoriously difficult. For this study, we compare the presenting clinical symptoms and paraclinical test results of autoimmune and infectious encephalitis patients. A clinical algorithm for the diagnosis of autoimmune encephalitis has recently been published. We test these Graus criteria on our cohort for diagnostic sensitivity and specificity within the first week of presentation. Methods: We included all patients seen at our department within a 10-year-period who were diagnosed with encephalitis. The discharge diagnoses served as the reference standard for testing the clinical algorithm for two conditions: use of all the clinical information available on a patient during the first week of hospital admission assuming undefined autoantibody status and microbiological test results (C1) vs. consideration of all the information available on a patient, including the results of serological and microbiological testing (C2). Results: Eighty-four patients (33 autoimmune, 51 infectious encephalitis) were included in the study. Fifty-one (17 autoimmune, 34 infectious) had a definite clinical diagnosis. The two groups differed significantly for the presence of headache, fever, epileptic seizures, and CSF cell-count at presentation. Application of the clinical algorithm resulted in a low sensitivity (58%) and very low specificity (8%) for the diagnosis of possible autoimmune encephalitis. The latter increased considerably in the subgroups of probable and definite autoimmune encephalitis. Whereas the sensitivity of the individual diagnostic categories was clearly time-dependent, the specificity rested foremost on the knowledge of the results of microbiological testing. Anti-CASPR2- and -LGI1-associated autoimmune encephalitis and tick-borne virus encephalitis presented particular diagnostic pitfalls. Conclusions: We define clinical symptoms and paraclinical test results which prove valuable for the differentiation between infectious and autoimmune encephalitis. Sensitivity and specificity of the clinical algorithm clearly depended on the amount of time passed after hospital admission and knowledge of microbiological test results. Accepting this limitation for the acute setting, the algorithm remains a valuable diagnostic aid for antibody-negative autoimmune encephalitis or in resource-poor settings. The initiation of immune therapy however should not be delayed if an autoimmune etiology is considered likely, even if the diagnostic criteria of the algorithm are not (yet) fulfilled.

Project description:Abstract Background Metagenomic next-generation sequencing (mNGS) of CSF can identify nearly all pathogens in a single test. We previously validated a CSF mNGS assay in a licensed clinical laboratory. To date, the utility of mNGS for infectious disease diagnosis has been described in case reports and small case series, but not in a large-scale clinical trial. Methods The PDAID (“Precision Diagnosis of Acute Infectious Diseases”) study was a 1-year nationwide prospective study across 8 tertiary care hospitals to evaluate the performance and utility of a clinical metagenomic sequencing assay for diagnosis of meningitis, encephalitis, or myelitis from cerebrospinal fluid (CSF) (ClinicalTrials.gov number NCT02910037). We recruited acutely ill hospitalized inpatients lacking a diagnosis at the time of enrollment. CSF samples were processed and analyzed by mNGS testing within 1 week of receipt in the clinical microbiology laboratory, with sequencing results reported in the patient medical record and used to make contemporaneous treatment decisions. Weekly clinical microbial sequencing boards were convened to discuss mNGS results with treating physicians, and clinical impact evaluated by surveys, chart review, and direct clinician feedback. Results A total of 204 patients were enrolled. Patients were severely ill (ICU 48%, average length of stay 26 days, overall 30-day mortality 7.4%). Fifty-nine neurologic infections were diagnosed in 57 patients (27.9%). mNGS identified 15 (25.4%) infections that were missed by all conventional microbiological tests, including emerging and/or uncommon pathogens such as St. Louis encephalitis virus, hepatitis E virus acquired by lung transplant, and Nocardia farcinica. Twelve of the 15 mNGS-only diagnoses (80%) had clinical impact, with 9 of 15 (60%) guiding appropriate treatment. For diagnosis of infections by direct detection CSF testing, mNGS had 79.1% sensitivity and 98.8% specificity, versus 65.1% sensitivity and 99.4% specificity by conventional testing. Conclusion A significant proportion of neurologic infections are missed despite extensive diagnostic testing performed in tertiary care hospitals. Clinical metagenomic CSF testing was found to be useful in increasing the number of diagnosed neurologic infections and providing actionable information for physicians. Disclosures All authors: No reported disclosures.

Dataset Information

Evaluation of a Commercial Multiplex Molecular Panel for Diagnosis of Infectious Meningitis and Encephalitis.

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Evaluation of a Commercial Multiplex Molecular Panel for Diagnosis of Infectious Meningitis and Encephalitis.

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