Bridging the diagnostic gap: the role of culture methods in the era of syndromic panels for central nervous system infections

Introduction Syndromic molecular panels have improved the rapid etiological diagnosis of central nervous system (CNS) infections by enabling the simultaneous detection of multiple pathogens directly from cerebrospinal fluid (CSF). Their speed and standardization support early clinical decision−making, particularly in emergency and referral settings. However, the closed architecture of these panels limits pathogen coverage and does not allow antimicrobial susceptibility testing, potentially resulting in incomplete diagnostic assessment. A retrospective real−world evaluation of the BioFire ® FilmArray ® Meningitis/Encephalitis Panel (FA) was conducted over three years at a national reference center, comparing its performance with conventional culture. Methods A total of 2,586 CSF samples with paired molecular and culture results were included. Diagnostic concordance, sensitivity, specificity, and predictive values were calculated using standard statistical methods. Analyses were conducted both on the complete dataset and after restriction to bacterial targets included in the syndromic panel. Results Overall, there was moderate agreement between syndromic testing and culture (Cohen’s kappa = 0.61), with the FilmArray panel showing a specificity of 97.5% and a sensitivity of 64.1%. Restricting the analysis to the bacterial targets included in the panel substantially improved the agreement (κ = 0.74), increasing the sensitivity to 93.5% and giving the test a negative predictive value of 99.7%. Importantly, conventional culture identified clinically relevant pathogens not included in the syndromic panel, including Staphylococcus aureus , Streptococcus pyogenes , and rare environmental organisms, highlighting its essential complementary role. Discussion Although syndromic molecular panels represent a valuable diagnostic tool for CNS infections, they cannot be used as standalone assays. Optimal diagnostic accuracy requires systematic integration of syndromic testing with conventional culture to ensure comprehensive pathogen detection and appropriate antimicrobial management. These findings support the need for next−generation multiplex platforms with expanded target coverage informed by real−world epidemiology.