A review of a 13-month period of FilmArray Meningitis/Encephalitis panel implementation as a first-line diagnosis tool at a university hospital

Abstract

Early diagnosis and treatment of meningitis and encephalitis is essential for reducing both their morbidity and mortality. The FilmArray® Meningitis/Encephalitis (FA-M/E) panel is a recently available molecular tool allowing the simultaneous detection of 14 pathogens in about one hour. We evaluated its routine use over a 13-month period at Nîmes University Hospital, France. Cerebrospinal fluid (CSF) specimens were prospectively analyzed, independently of cell count; results were retrospectively analyzed and positive results compared to clinical and microbiological data. Among the 708 patients included (734 CSF samples), 89 (12.6%) had a positive FA-M/E panel, 71 (80%) for a viral pathogen and 18 (20%) for a bacterial pathogen. Enterovirus and HHV-6 were the main detected pathogens. Mean time-to-results was 1h46mn. Four non-clinically relevant results were detected (3 HHV-6 and 1 Haemophilus influenzae) on the basis of inconsistent clinical and/or biological data, and/or after visualization of melting curves. No CSF pleocytosis was observed in 11% of the patients with a positive FA-M/E panel. For the 18 patients with a positive FA-M/E panel for a bacterial pathogen, five (28%) had CSF samples showing a positive Gram stain allowing an early diagnosis of bacterial infection and 67% had CSF displaying a positive culture. Altogether the panel detected 5 cases of bacterial M/E (29%) not diagnosed by culture. Despite undeniable advantages, mainly ease of use, quick result availability, and an extremely low rate of invalid results, measures should be implemented to limit false-positive results due to contamination and a careful interpretation based on the overall data for each patient is required.

Fig 1. Algorithm for performing the FilmArray Meningitis/Encephalitis assay on CSF samples.

All children in the study were put into the “pediatric & neonatology” category.

Fig 2. Chronogram presenting the weekly results of the FilmArray Meningitis/Encephalitis panel during the study period.

Grey: no pathogen detected. Each colored square represents a patient with positive detection (for the few patients with successive positive detections, only the first positive detection has been considered in the figure). The pathogens detected are indicated by a specific color. A bicolor square indicates the unique co-detection of two pathogens during the study. N. meningitidis serogroup (B or C) is indicated in the corresponding area.

Fig 3. Melting curves for HHV-6 detection declared positive by the system.

A & B. Noisy melting curves observed for two analyses of CSF with non-confirmed detection of HHV-6 by an alternative method. The two analyses showed that 2 replicates out of the 3 performed by the system were positive. C. Melting curves observed after analysis of a CSF sample with confirmed detection of HHV-6 by an alternative method. The 3 replicates performed by the system are positive.