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

Background: The 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. Methods: We 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). Findings: We 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. Interpretation: FA/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. Funding: None.