Point-Counterpoint: Meningitis/Encephalitis Syndromic Testing in the Clinical Laboratory

Abstract

INTRODUCTIONSyndromic panels were first FDA cleared for detection of respiratory pathogens in 2008. Since then, other panels have been approved by the FDA, and most recently, the FilmArray meningitis/encephalitis panel (BioFire, Salt Lake City, UT) has become available. This assay detects 14 targets within 1 h and includes pathogens that typically cause different manifestations of infection, although they infect the same organ system. Several studies have reported both false-positive and false-negative results with this test, and all agree that the cost is significant. As with other panels, health care systems have adopted different strategies for offering this assay. Some have implemented strategies to limit the use of the test to certain patient populations, others have elected not to offer the test, and others have elected not to offer the test and instead request that providers order specific PCRs for the pathogens that best fit the patient's symptoms. In this Point-Counterpoint, Jennifer Dien Bard of the Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, and of the Keck School of Medicine at the University of Southern California explains why laboratories should offer these assays without restriction. Kevin Alby of the University of Pennsylvania explains the concerns about the use of these assays as first-line tests and why some limitations on their use might be appropriate.

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

“…As the most appropriate patient population for testing with the FA-M/E panel is a point that still requires consideration [10,38], we also discussed the strategy for use of the panel in our laboratory. We found that diagnostic yield in patients hospitalized in units other than those selected for systematic FA-M/E testing were rare, suggesting that use of the panel should be restricted to patients with a high suspicion of M/E in these units to limit unnecessary tests.…”

“…Despite certain pitfalls identified, the authors concluded that the FA-M/E panel was a sensitive and specific test to aid in diagnosis of M/E. However, certain aspects regarding the use of the panel are still a matter of debate as illustrated by a recent point/counterpoint, underlining that prospective studies are still required and that the most appropriate patient population for testing with the FA-M/E panel has yet to be defined [10].…”

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

“…One of the major concerns regarding widespread use of the FA-ME panel has revolved around the relevance of HHV-6 detection and its effects on antimicrobial management (24,25). As the majority of primary HHV-6 infections in immunocompetent hosts are self-limiting, and unnecessary exposure to ganciclovir and foscarnet can lead to bone marrow suppression and renal insufficiency (26), routine antiviral therapy is not recommended.…”

Molecular diagnosis of meningitis and meningoencephalitis with an automated real-time multiplex polymerase chain reaction in a tertiary reference complex in Medellín, Colombia

“…Particularly, two studies reported the highest proportion of false positive results to S. pneumoniae ( 17.5 and 80%) 13 , 21 , and in the present study, there were 16 detections of S. pneumoniae , of which six were negative in cultures, and clinical correlations showed that only four of them had a high level of bacterial meningitis suspicion. A positive result should be analyzed carefully and correlated with the medical chart data; repeating the test may be helpful, but a repeated negative result may not necessarily rule out an initial positive result in cases of low pathogen loads 33 , 34 other panels have been approved by the FDA, and most recently, the FilmArray meningitis/encephalitis panel (BioFire, Salt Lake City, UT.…”