Improving the diagnosis of central nervous system infections: experience with the off-label use of FA-BCID2

KEYWORDS meningitis, molecular syndromic panel, multiplex PCR assays M ultiplex PCR panels for central nervous system (CNS) infections are widely used but have well-recognized limitations: the FilmArray Meningitis/Encephalitis (FA-ME) panel (bioMérieux, Marcy l'Étoile, France) is strong for "ruling in" yet limited for "ruling out, " and negative results do not exclude infection (1-3).We report our experience with the off-label use of the FilmArray Blood Culture Identification 2 (FA-BCID2) panel (bioMérieux) on cerebrospinal fluid (CSF), focusing on bacterial pathogens relevant to hospital-acquired (HA) CNS infections and lateonset neonatal meningitis (e.g., Klebsiella pneumoniae, Enterobacter cloacae complex, Acinetobacter baumannii complex, and coagulase-negative staphylococci) in contrast to FA-ME, which primarily targets community-acquired (CA) bacteria (4).Previous small studies on FA-BCID/BCID2 in CSF have reported promising performance (5-7).This study was performed at a large tertiary-care university hospital with neurosur gical services and analyzed two periods, that is, before and after implementation of FA-BCID2.We included all culture-positive bacterial meningitis cases for which at least one FilmArray assay (FA-ME or FA-BCID2) was performed: 79 cases in the pre-implemen tation period and 34 in the post-implementation period.These cases represented 11.2 (79/703) and 9.5% (34/358) of all CSF samples for which a FilmArray assay was performed for suspected meningitis in the respective periods.In the post-implementation period, infectious disease specialists requested molecular testing for suspected meningitis by phone and indicated whether the case was adult CA or HA or neonatal early-ver sus late-onset using standard clinical and epidemiological criteria consistent with the corresponding published definitions (8, 9).Based on this classification, CSF samples were tested with FA-ME for CA/viral differential diagnoses and with FA-BCID2 for suspected HA infections.FA-BCID2 was used off-label directly on CSF (no enrichment) after internal verification using contrived/spiked CSF and known-positive samples.In the pre-implementation period (May 2018-April 2023), FA-ME was the only molecular assay used; there were 79 culture-confirmed bacterial meningitis cases (HA 41, CA 28, neonatal 10), and FA-ME detected the pathogen in 31/79 (39.2%).The 48 FA-ME-negative results represented missed opportunities for early targeted antimicro bial therapy.In the post-implementation period (May 2023-June 2025), a combined algorithm with FA-ME and FA-BCID2 was adopted; culture-positive cases were 34 (HA 16, CA 13, late-onset neonatal 5), with an overall molecular detection of 31/34 (91.2%).Excluding the 13 CA cases (all correctly detected by FA-ME), 14/16 (87.5%)HA and 4/5 (80.0%) neonatal late-onset cases were correctly detected by FA-BCID2.Notably, two neurosurgical patients-one with K. pneumoniae, the other with Cutibacterium acnes meningitis-tested negative with FA-BCID2 and were confirmed only by 16S rRNA PCR/ sequencing, while Citrobacter koseri meningitis in a neonate was missed as an off-panel pathogen.The corresponding pathogen distributions and detection rates by period and category are shown in Fig. 1.