Clinical Utilization of the FilmArray Meningitis/Encephalitis (ME) Multiplex Polymerase Chain Reaction (PCR) Assay

Abstract

Objective: To assess the clinical utilization and performance of the FilmArray® Meningitis/Encephalitis (ME) multiplex polymerase chain reaction (PCR) panel in a hospital setting. Background: Rapid diagnosis and treatment of central nervous system (CNS) infections are critical to reduce morbidity and mortality. The ME panel is a Food and Drug Administration (FDA) approved rapid multiplex PCR assay that targets 14 bacteria, viruses, and fungi. Previous studies show an overall agreement of 93–99% between the ME panel and conventional diagnostic testing. However, few studies have evaluated the clinical implementation of the ME assay, which is available for routine use at our institution. Methods: We performed a single center retrospective chart review of inpatients who underwent ME panel testing from August 2016 to May 2017. Clinical, radiologic, and laboratory data were reviewed to determine the clinical significance of results. Indication for lumbar puncture (LP), time to results of the ME panel, and duration of antimicrobial therapy were evaluated. Results: Seven hundred and five inpatients underwent ME testing, of whom 480 (68.1%) had clinical suspicion for CNS infection with 416 (59.0%) receiving empiric antimicrobial treatment for CNS infection. The median time-to-result of the ME panel was 1.5 h (IQR, 1.4–1.7). Overall agreement between the ME panel results and clinico-laboratory assessment was 98.2%. Forty-five patients tested positive by ME, of which 12 (26.6%) were determined likely to be clinically insignificant. Conclusions: Routine availability of the ME panel led to overutilization of diagnostic test ordering, as demonstrated by the fact that over one-third of ME panel tests performed were ordered for patients with little or no suspicion for CNS infection. The median time from LP to ME panel result was 1.5 h (IQR, 1.4–1.7). The ME panel's rapid turn-around time contributed to the overuse of the test. Approximately one-quarter of positive ME results were deemed clinically insignificant, though the impact of these positive results requires additional evaluation. Twenty-four and forty-eight hours after the ME panel resulted, 68 and 25% of patients started on empiric therapy remained on antibiotics, respectively. The median time from diagnosis to discontinuation and/or narrowing of antibiotic coverage was 25.6 h (IQR, 3.6–42.5). Further consideration of the appropriate indications for use of the ME panel in clinical settings is required.

Appropriate Use and Future Directions of Molecular Diagnostic Testing

“…The speed and ease of testing has led to the rapid adoption of this platform in many laboratories before clinical performance and utility could be fully established. For example, many labs chose to adopt due to the fact that send out testing for HSV was expensive and led to delays [43]. The syndromic panel allows them to perform testing in house at perhaps the same cost with the potential benefit of the additional targets.…”

“…However, as mentioned above, the lower analytical sensitivity for HSV raises concern. Some argue that this new ease of testing has possibly led to overuse [42,43]. However, retrospective analyses have the benefit of knowing the final diagnosis while at the time of clinical presentation, it may have been appropriate to order syndromic panel testing [43].…”

“…Some argue that this new ease of testing has possibly led to overuse [42,43]. However, retrospective analyses have the benefit of knowing the final diagnosis while at the time of clinical presentation, it may have been appropriate to order syndromic panel testing [43]. Studies that have looked at pre-and post-panel implementation time-points have found conflicting differences in panel impact in terms of length of stay and time to appropriate antimicrobial narrowing, with some showing significant decreases [44,45] and others showing no difference [46].…”

All-in-One Dual CRISPR-Cas12a (AIOD-CRISPR) Assay: A Case for Rapid, Ultrasensitive and Visual Detection of Novel Coronavirus SARS-CoV-2 and HIV virus

“…Polymerase chain reaction (PCR) method is the most commonly used technology for pathogen nucleic acid detection and has been considered as a "gold standard" for disease diagnostics due to high sensitivity and specificity. 4,5,6 However, it typically relies on expensive equipment and well-trained personnel, all of which is not suitable for point of care diagnostic application. In recent decades, several isothermal amplification methods, such as recombinase polymerase amplification (RPA) 7 , loop-mediated isothermal amplification (LAMP) 8 , have been developed as attractive alternatives to conventional PCR method because of their simplicity, rapidity and low cost.…”

Implementation of the FilmArray ME panel in laboratory routine using a simple sample selection strategy for diagnosis of meningitis and encephalitis

“…were compared to the multicenter evaluation study [6] and three other studies [7,32,33], that reported Film Array performance data on a high quantity of CSF samples tested (n=1,560, n=969, n=705 and n= 253 CSF samples analyzed by Film Array ME, respectively). Figure 3 illustrates positivity rates and pathogen composition in CSF samples analyzed by different studies.…”