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Cerebrospinal Fluid Findings Are Poor Predictors of Appropriate FilmArray Meningitis/Encephalitis Panel Utilization
Mimi R Precit1, Rebecca Yee1, Utsav Pandey1
1Department of Pathology and Laboratory Medicine, Children's Hospital of Los Angeles, Los Angeles, California, USA.
Abstract:
Molecular testing of cerebrospinal fluid (CSF) using the BioFire FilmArray meningitis/encephalitis (FA-M/E) panel permits rapid, simultaneous pathogen detection. Due to the broad spectrum of targeted organisms, FA-M/E testing may be restricted to patients with abnormal CSF findings. We sought to determine if restriction is appropriate in our previously healthy and/or immunocompromised pediatric patients. FA-M/E was ordered on 1,025 CSF samples from 948 patients; 121 (11.8%) specimens were FA-M/E positive. Of these, 89 (73.6%) were virus positive, and 30 (24.8%) were bacterium positive. The most common targets detected were enterovirus (n = 38), human herpesvirus 6 (HHV-6) (n = 30), and Streptococcus pneumoniae (n = 14). Pleocytosis with white blood cell (WBC) levels of ≥5 cells/mm3 and ≥10 cells/mm3 were found in 33.1% and 24.3% of all specimens, respectively. Using WBC levels of ≥5 cells/mm3, 63.4% (59/93) of positive specimens exhibited pleocytosis, compared to 29.5% (233/789) of negative specimens. Among positive specimens, 54.4% (37/68) of viral and 87% (20/23) of bacterial cases had pleocytosis. The use of a pleocytosis cutoff of ≥10 cells/mm3 would have missed an additional enterovirus, one cytomegalovirus (CMV), and two HHV-6 diagnoses. CSF glucose and protein levels were normal for 83/116 (75.2%) and 51/116 (44%) positive specimens. Abnormal glucose in combination with WBC levels of ≥10 cells/mm3 showed high specificity (94.5%) and was a better predictor of FA-M/E positivity than abnormal protein. Sensitivity and positive predictive values were <90% for all biomarkers. CSF pleocytosis and abnormal glucose/protein were poor predictors of FA-M/E. Restricting FA-M/E orders based on pleocytosis or other abnormal parameters would have resulted in missed diagnostic opportunities, particularly for the detection of viruses in both previously healthy and immunocompromised patients.
Insights
Restricting molecular testing for meningitis/encephalitis (FA-M/E) based on cerebrospinal fluid (CSF) abnormalities like pleocytosis may lead to missed diagnoses, especially for viral infections in pediatric patients. This study highlights the importance of broad testing for accurate pathogen detection.
Area of Science:
- Clinical Microbiology
- Molecular Diagnostics
- Pediatric Infectious Diseases
Background:
- The BioFire FilmArray meningitis/encephalitis (FA-M/E) panel offers rapid, simultaneous detection of multiple pathogens in cerebrospinal fluid (CSF).
- Broad-spectrum molecular panels like FA-M/E are sometimes restricted to patients with abnormal CSF findings to optimize resource use.
- The clinical utility of restricting FA-M/E testing based on CSF parameters in pediatric patients, including those who are immunocompromised, requires evaluation.
Purpose of the Study:
- To assess the appropriateness of restricting BioFire FilmArray meningitis/encephalitis (FA-M/E) panel testing based on cerebrospinal fluid (CSF) findings in pediatric patients.
- To determine if CSF pleocytosis or other CSF biomarkers can reliably predict positive FA-M/E results.
- To evaluate the impact of restricting FA-M/E testing on diagnostic yield, particularly for viral pathogens.
Main Methods:
- Retrospective analysis of 1,025 CSF samples from 948 pediatric patients tested with the FA-M/E panel.
- Correlation of FA-M/E positivity with CSF white blood cell (WBC) counts (pleocytosis), glucose, and protein levels.
- Evaluation of sensitivity, specificity, and predictive values of CSF biomarkers for predicting FA-M/E positivity.
Main Results:
- 11.8% of CSF samples were FA-M/E positive, with viruses (73.6%) being more common than bacteria (24.8%).
- Pleocytosis (WBC ≥5 cells/mm³) was present in 63.4% of positive specimens, but restricting testing based on this cutoff would miss diagnoses.
- CSF glucose and protein levels were often normal in positive cases; abnormal glucose with WBC ≥10 cells/mm³ showed high specificity but limited sensitivity.
Conclusions:
- Restricting FA-M/E testing based on CSF pleocytosis or other abnormal parameters would lead to missed diagnostic opportunities, particularly for viral meningitis/encephalitis.
- CSF biomarkers like pleocytosis, glucose, and protein are poor predictors of FA-M/E positivity, underscoring the value of broad molecular testing.
- The FA-M/E panel should be utilized broadly in pediatric patients, regardless of initial CSF findings, to ensure timely and accurate diagnosis of meningitis and encephalitis.
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