Traditional microbiological methods, including routine bacterial cultures, Gram staining, and phenotypic identification, are essential tools for guiding the treatment of bacterial meningitis. However, these methods have limitations, including a low positive rate in clinical diagnosis. CSF cultures are time-intensive, restricted to bacteria that grow on specific media, and may not always align with findings from microscopy. For example, only 25% of cases with bacterial concentrations <10³ CFU/mL yield positive microscopy results, while 60% are detected when concentrations range from 10³ to 10u CFU/mL.²³ A 27-year study also found that CSF culture could miss bacterial meningitis diagnoses in more than 10% of cases.^3,24

CSF culture remains the gold standard, showing 70-85% positivity in patients who have not received prior antibiotic treatment. While antibiotics typically do not alter CSF cell counts, glucose, or protein, they reduce Gram stain sensitivity to 40-60% and culture positivity to below 50%. Administering antibiotics before CSF sampling can significantly hinder diagnosis by reducing microbial load or eliminating pathogens entirely, resulting in sterile CSF samples.^25,26

Sulaiman et al. identified the etiology in only about 32% of cases, with similar findings reported in other studies. This limited detection is likely due to the low sensitivity of CSF cultures for non-bacterial pathogens and the underuse of molecular and serologic testing for viral agents.^15,27,28

This diminished sensitivity due to the aforementioned factors complicate timely diagnosis and optimal treatment. Consequently, clinicians often face a diagnostic dilemma when CSF cultures return negative despite a high suspicion of infection, particularly in patients who have received prior antimicrobial therapy.

The introduction of multiplex PCR-based assays, such as the BioFire FilmArray Meningitis/Encephalitis (ME) Panel, has significantly enhanced the diagnostic landscape for CNS infections by offering rapid, sensitive, and comprehensive pathogen detection. These tools enable early and targeted therapy, which is crucial for life-threatening conditions like meningoencephalitis.^5,22

The FilmArray ME Panel, which is US FDA approved, provides a comprehensive, accurate, and time-efficient solution for pathogen detection.

Despite certain challenges, such as small sample volumes, the FilmArray ME Panel demonstrated robust diagnostic performance by utilizing just 200 µL of CSF, significantly enhancing pathogen detection through multiplex PCR. Its rapid turnaround time and comprehensive pathogen coverage facilitate early therapeutic interventions in critical clinical settings and also in antimicrobial stewardship.^21,29,30

In this study, the BioFire FilmArray ME panel detected Streptococcus pneumoniae in three cases, with a culture-confirmed detection rate of only 33%, highlighting the superior sensitivity of the BioFire panel over traditional culture methods.^30,31 Additionally, culture methods failed to detect Haemophilus influenzae and Escherichia coli K1, further underscoring the limitations of conventional microbiological techniques in identifying pathogens in CSF samples.^32,33

Notably, one patient with E. coli K1 also exhibited concurrent growth of Acinetobacter baumannii in culture, a nosocomial pathogen not included in the BioFire panel’s repertoire. This case emphasizes the need for a comprehensive diagnostic approach, integrating both the BioFire panel and conventional culture methods, particularly for nosocomial pathogens like Acinetobacter and Klebsiella species, which are not part of the panel’s design.³⁴

Additionally, certain studies have highlighted the FilmArray ME Panel’s superior diagnostic yield compared to traditional methods. For example, a study conducted at the Kerala Institute of Medical Sciences found a 23.6% positivity rate with the FA-ME panel, compared to just 3% with standard culture methods.⁵ Other studies similarly reported that enteroviruses were the most commonly detected pathogens, corroborating the findings of this study.^5,13

In line with Infectious Diseases Society of America (IDSA) guidelines, which recommend the use of molecular diagnostics in the evaluation of encephalitis, this study supports the integration of rapid molecular diagnostics into routine clinical practice for optimal management of CNS infections.³

The enhanced performance of PCR-based diagnostics over conventional microbiological testing, including patients who have already received antibiotics, where traditional culture-based methods may not be diagnostic, further solidifies the role of these rapid diagnostics in clinical microbiology.

While CSF culture is considered the gold standard to determine antimicrobial susceptibility, WHO also strongly recommended CSF be assayed using PCR-based molecular tests for relevant pathogens in individuals with suspected acute meningitis. This guideline was supported by an extensive meta-analysis of CSF molecular testing.^5,22,35,36

Finally, the minimal CSF volume requirement (200 µL) and rapid turnaround time (approximately 1 hour) of the FilmArray ME Panel make it a valuable tool in clinical practice, particularly in scenarios requiring prompt diagnosis and intervention.