Diagnostic test accuracy of the BioFire® FilmArray® meningitis/encephalitis panel: a systematic review and meta-analysis.

BACKGROUND: The FilmArray® meningitis/encephalitis (ME) panel is a multiplex PCR assay which can detect the most commonly identified pathogens in central nervous system infections. It significantly decreases the time to diagnosis of ME and data has yielded several positive outcomes. However, in part, reports of both false positive and false negative detections have resulted in concerns about adoption.

OBJECTIVES: The aim was to evaluate the ME panel in a diagnostic test accuracy review.

DATA SOURCES: The PubMed and EMBASE databases were systematically searched through May 2019.

STUDY ELIGIBILITY CRITERIA: Eligible studies were those providing sensitivity and specificity data for the ME panel compared with a reference standard. Studies providing details on false positive and false negative results of the panel as well as further investigation (adjudication) of the discordant results between the panel and comparator assays were included and assessed separately.

PARTICIPANTS: Patients with suspected ME for whom a panel was ordered were included.

METHODS: The ME panel was compared to reference standard methods for diagnosing community-acquired ME. We performed a meta-analysis and calculated the summary sensitivity and specificity of the ME panel. Moreover, we evaluated the false positive and false negative results of the panel.

RESULTS: Thirteen studies (3764 patients) were included in the review and 8 of them (3059 patients) were pooled in a meta-analysis. The summary estimates of sensitivity and specificity with 95% confidence intervals (CI) was 90% (95% CI 86-93%) and 97% (95% CI 94-99%), respectively. When we looked specifically at studies that assessed further the false positive and false negative results, false positive detections were 11.4% and 4% before and after adjudication, respectively. The highest proportion of false positive was observed for Streptococcus pneumoniae followed by Streptococcus agalactiae. False negative isolates were 2.2% and 1.5% before and after adjudication, respectively. Herpes simplex virus 1 and 2, enterovirus and Cryptococcus neoformans/gattii had the highest proportions of false negative determinations. False negative C. neoformans/gattii were mostly patients with positive antigen titres, on treatment or cleared disease.

CONCLUSIONS: The currently available literature suggests that the ME panel has high diagnostic accuracy. However, the decision for implementation should be individualized based on the needs of the patient population, the capabilities of the laboratory, and the knowledge of the healthcare providers that will utilize the test.