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

Abstract

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.

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

“…Our results join those in a growing literature positioning the syndromic assay more as a screening test and not replacing conventional assays and recommending that it never be used as a “standalone” diagnostic option, especially in the presence of severe clinical presentations ( 2 , 6 , 9 ). We agree with the postulate that such a “simple” technique requires experienced users for accurate interpretation and discernment to properly interpret false-negative and false-positive results ( 6 , 11 ). Further studies are warranted concerning feedback on the use and potential adaptation of this algorithm, which we first plan to apply to pediatric patients in our hospital to optimize the utilization of both syndromic and specific assays.…”

“…In our study, we mainly observed false-negative results in cases of the pathogen not being included in the panel of sought targets, highlighting the remaining position of bacterial culture as a gold standard. In cases of positive diagnosis, bacterial culture is obviously still necessary for antimicrobial susceptibility testing ( 11 ). The main issue for bacterial targets is still the low but significant rate of false-positive FilmArray results.…”

Cerebrospinal fluid analysis in emergency patients with suspected infection of the central nervous system

“…We suggest that a preselection for CSF cell count and clinical presentation needs to be taken into consideration before the is used. Studies with such a pre-selection (e.g., positive gram stain, detection of leukocytes and/ or bacteria, urgent clinical suspicion) show relatively high detection rates of pathogens in comparison to other studies [20]. Use of the array in patients with no suspicion for a CNS infection or in samples with normal CSF cell count could be avoided [21,22].…”

Meningitis

“…Therefore, the FilmArray ME Panel should not be used as the only microbiological test and must be complemented by other techniques. 6 Metagenomic Next-Generation Sequencing for Diagnosis of Meningitis Metagenomic next-generation sequencing is an unbiased, hypothesis-free method of assessing for any microbial genetic material in the CSF. 7 Using this technique, a 2019 study of 204 pediatric and adult patients with meningitis or encephalitis identified 13 infections not discovered through other testing modalities; 7 of these 13 diagnoses guided change in treatment.…”

“…Finally, even when diagnostic testing is accurate, antimicrobial susceptibility testing requires concurrent use of standard culture techniques. Therefore, the FilmArray ME Panel should not be used as the only microbiological test and must be complemented by other techniques 6 …”