Diagnostic challenges of central nervous system infection: extensive multiplex panels versus stepwise guided approach

Abstract

Background: Cerebrospinal fluid (CSF) testing is a key component for the diagnosis of central nervous system (CNS) infections. Current meningitis and encephalitis management guidelines agree on the need for CSF molecular testing in combination with other direct and indirect biological testing, both in CSF and blood. Multiplex molecular tests have been developed to reduce turnaround times and facilitate the diagnostic approach. Objectives: We aim to discuss the role of multiplex molecular panels in the management of CNS infections. Sources: The MEDLINE database and the grey literature have been searched for relevant articles. Content: New molecular multiplex panels are being developed to simultaneously detect a large array of neuropathogens in CSF. Although one of these assays has been US Food and Drug Administrationapproved, extensive analytical and clinical validation is still missing, and suboptimal performance related issues have been raised. Its use has been associated with decreased costs, reduced length of hospital stay and reduced antiviral therapy administration in retrospective, industry-sponsored studies. The pros and cons of this multiplex syndromic approach are discussed in this narrative review. Implications: Molecular multiplex CNS infection diagnosis panels have been developed and present several attractive features, including ease of use and low turnaround time. However, suboptimal analytical performances render these tests difficult to use without additional confirmatory tests. Such panels are not comprehensive nor adapted to all situations, depending on the epidemiological or clinical context. Overall, available data in the literature currently do not support the use of a multiplex PCR panel in clinical routine as a 'stand-alone' molecular assay. Except in restricted laboratory capacity settings where such easy-to-use multiplex panels offer the diagnostic means that would otherwise not be available, the stepwise testing approach remains a more rational option. Serological testing both in blood and CSF should not be neglected, but it represents essential complementary tools regarding some neuropathogens.

Detection of bacteria via multiplex PCR in respiratory samples of critically ill COVID-19 patients with suspected HAP/VAP in the ICU

“…Tracheal aspirates and bronchoalveolar lavages (BAL) were analyzed in 83% and 17% of the patients, respectively. The PP was performed on average 7.5 days [ 3 – 10 , 17 , 18 ] after ICU admission. Most patients (73%) received an antibiotic at the time when the PP was performed (Table 1 ).…”

“…While multiplex polymerase chain reaction (PCR) based panels from cerebrospinal fluid on top of standard diagnostic procedures for suspected meningitis/encephalitis have been shown to have excellent diagnostic accuracy in two meta-analyses [ 17 , 18 ], data for respiratory tract infections are conflicting, with some studies indicating a decrease in length of stay and antibiotic prescriptions [ 19 , 20 ], while others failed to demonstrate any impact [ 21 – 23 ].…”

Differential Performance of the FilmArray Meningitis/Encephalitis Assay To Detect Bacterial and Viral Pathogens in Both Pediatric and Adult Populations

“…A timely diagnosis is obviously required in this ME setting. However, the true performance of such syndromic assays is still under evaluation, and disparate results have been reported ( 2 ). In our multisite university hospital in eastern Paris, France, ME syndromic testing has been gradually implemented since 2017 for adult and pediatric patients with neurological symptoms presenting to an emergency unit.…”

Unexpectedly High False-Positive Rates for Haemophilus influenzae Using a Meningoencephalitis Syndromic PCR Panel in Two Tertiary Centers

“…These molecular rapid diagnostic tests are increasingly used in routine diagnostic laboratories for the diagnosis of CNS infections, including meningitis and meningoencephalitis, with the advantages of being easy to use and having short turn-around times. Nevertheless, these syndromic panels lack extensive analytical and clinical validation and concerns have been raised regarding their suboptimal performances (Vetter et al, 2020). Several cases of false-positive results for some targeted pathogens, more specifically for Haemophilus influenzae, have been reported with the BioFire FilmArray ® Meningitis/Encephalitis (ME) Panel (bioMeŕieux, Lyon, France) (Naccache et al, 2018;Boudet et al, 2019).…”