Evaluation of Discordant Results Between FilmArray Meningitis/Encephalitis Panel and Conventional Testing in Pediatric Patients: A Multisite Retrospective Cohort Study

Abstract

Background The FilmArray Meningitis/Encephalitis panel (MEP) has an 11% false-positive and 2.2% false-negative rate compared with conventional testing. We describe clinical characteristics, treatment decisions, and outcomes in children with discordant results between MEP and conventional testing. Methods We conducted a multisite review of patients ≤ 18 years with suspected central nervous system infection and positive results by MEP or conventional testing (cerebrospinal fluid [CSF] culture, herpes simplex virus [HSV] polymerase chain reaction (PCR), and enterovirus [EV] PCR). Descriptive results are provided for patients with discordant results. Comparison between group 1 (MEP and CSF culture positive) and group 2 (MEP positive, CSF culture negative, or showing a different pathogen) was made by Mann-Whitney test for continuous and Fisher’s test for categorical variables. Results A total of 355 patients had at least one pathogen identified. More than half of patients with bacterial pathogens identified that are included in the MEP had discordant results (30/52; 58%). There were 28 samples with bacterial pathogen identified on MEP only, 1 with different bacterial pathogens on MEP and culture, and 1 with Escherichia coli identified on CSF culture only. Patients in group 1 were more likely to have CSF pleocytosis, elevated CSF protein, and decreased CSF glucose than group 2 (P < .05). Two patients were HSV positive by MEP while HSV negative by PCR. Ten patients had discordant results between MEP and EV PCR. Conclusions Discordant results between MEP and conventional testing are common. Treatment decisions based on a positive MEP should be made in the appropriate clinical context.

Challenges in the Diagnosis of Viral Encephalitis in Children: The Case of Two Siblings

“…Investigation for other infectious causes, such as EBV, CMV, ADV, influenza, HHV-6,7, VZV, measles, Mycoplasma spp., and others, may be performed, depending on the local epidemiology and clinical presentation [ 2 ]. However, even with extensive testing, the etiology of encephalitis often remains elusive [ 2 , 3 , 4 , 5 ].…”

“…However, the etiology of encephalitis is often not found despite extensive evaluation [ 2 , 3 ]. On the other hand, recent advances in diagnostics in infectious diseases, such as the availability of polymerase chain reaction (PCR) analysis for a great variety of microorganisms in the cerebrospinal fluid (CSF), may often lead to ambiguous results that require careful interpretation [ 4 ]. In this article, we describe the challenges that we confronted in identifying the etiologic agent of encephalitis in two siblings.…”

Clinical progress note: Multiplex panels for identifying infection in children

“…The limit of detection for herpes simplex virus (HSV) on PCR panels is higher than that of individual HSV PCR panels, allowing for the potential of false negative results in up to 17% of samples, especially very early in the infection or with reactivation, where the infectious burden may be lower than in primary infection 9 . While overall specificity for MEP testing is high, multiple case studies have noted false–positive or contaminant results with Streptococcus pneumoniae and Streptococcus agalactiae being the most frequently reported , which may lead to overtreatment 8,10 . There are also reports of false negative Cryptococcus neoformans / Cryptococcus gattii results in patients receiving antifungal therapy.…”