Cerebrospinal Fluid Findings Are Poor Predictors of Appropriate FilmArray Meningitis/Encephalitis Panel Utilization in Pediatric Patients

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.

Pathogen or Bystander: Clinical Significance of Detecting Human Herpesvirus 6 in Pediatric Cerebrospinal Fluid

“…Abnormal CSF parameters values for glucose, protein, and pleocytosis are often used as an indicator of CNS infection, but the utility of these parameters in pediatric setting has been dubious (12,35,36). In our study, we found that in majority of the cases of HHV-6 infection of the CNS occurred in the presence of normal CSF parameters.…”

Evaluation of the Utilization of FilmArray Meningitis/Encephalitis in Children With Suspected Central Nervous System Infection

“…A prior study already showed that restricting FilmArray ME panel orders based on pleocytosis or other CSF abnormalities can result in missed diagnosis opportunities. 16 In that study, nearly 20% of patients with no pleocytosis and normal CSF glucose and protein had positive result with FilmArray ME panel. The identification of an etiological agent brings relevant information to the physician, the patient, and the family and can contribute to avoid further unnecessary diagnostic tests and clarifying the cause of the symptoms.…”

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

“…While it is true that there are cases of viral CNS infection with normal CSF, such as early stages of herpetic encephalitis, 35 , 36 , 37 and enterovirus meningitis in neonates, 38 , 39 these are rare and occur in precise clinical settings. 40 Considering the limitations of FA/ME for some microorganisms and its relatively high cost, defining diagnostic algorithms approaches to define the group of patients who can benefit the most from this test is an urgent need.…”