Abstract
ObjectivesIn central nervous system infections, early and correct management is of utmost importance. Rapid syndromic panel testing can potentially provide valuable guidance. The FilmArray meningitis/encephalitis (ME) panel detects 14 pathogens through multiplex PCR. Our study objectives were to assess its performance compared with established diagnostic procedures, especially real-time quantitative PCR for detection of viruses, and to determine the diagnostic and clinical significance of discrepant results. MethodsAll cerebrospinal fluid samples sent for viral diagnostics to our microbiological laboratory over 34 months were analysed with the ME panel and in-house real-time PCR for herpes simplex virus type 1 (HSV-1), HSV-2, varicella zoster virus and enteroviruses. Other pathogens detected by the panel were confirmed by routine diagnostic procedures. Discrepant results were analysed through interpretation of biological and clinical data, and performance data were calculated for individual pathogens. ResultsAltogether, 315 pathogens were detected by the ME panel in 4199 cerebrospinal fluid samples (7.5%) and an additional 21 viral targets were identified using real-time PCR. Thirty-four ME panel detections were not confirmed, totalling 55 discrepant results. After discrepancy analysis, 20 false-positive and 21 false-negative ME panel results remained. Performance varied between pathogens. Sensitivity for HSV-1 was calculated at 82.4% (59.0%–93.8%) with three false-negative results. Also noteworthy were 13 false-negative enterovirus and eight false-positive Streptococcus pneumoniae results. ConclusionsOur analysis shows good performance for the ME panel in diagnosing central nervous system infection. The risk of false-negative HSV-1 results, however, warrants additional testing when encephalitis is suspected. Uncertainties in interpretation of enterovirus and S. pneumoniae results represent other limitations.
Highlights
Diagnosis and identification of aetiology in central nervous system (CNS) infections such as meningitis and encephalitis are challenges for the clinician
The meningitis/ encephalitis (ME) panel is tailored to target pathogens commonly associated with community-acquired CNS infection, rather than for the testing of specimens collected from indwelling CNS medical devices or in postoperative/nosocomial CNS infections
The FilmArray ME panel was introduced in our laboratory in April 2017, and cerebrospinal fluid (CSF) samples were consecutively tested using this panel as well as previously established in-house real-time PCR methods for herpes simplex virus 1 (HSV-1), herpes simplex virus 2 (HSV-2), varicella zoster virus (VZV) and enterovirus [7e9]
Summary
Diagnosis and identification of aetiology in central nervous system (CNS) infections such as meningitis and encephalitis are challenges for the clinician. Symptoms often overlap between syndromes, and early treatment is of utmost importance. Broad antimicrobial therapy is frequently initiated empirically. Traditional diagnostic methods such as bacterial cultures and PCR-based assays using cerebrospinal fluid (CSF) samples often have a turnaround time of 24 hours or more, and the availability of methods varies greatly between laboratories. J. Lindstro€m et al / Clinical Microbiology and Infection xxx (xxxx) xxx (CMV), enterovirus (EV), varicella zoster virus (VZV), herpes simplex virus 1 (HSV-1), herpes simplex virus 2 (HSV-2), human herpesvirus 6 (HHV-6), human parechovirus (HPeV) and Cryptococcus neoformans/Cryptococcus gattii. The ME panel is tailored to target pathogens commonly associated with community-acquired CNS infection, rather than for the testing of specimens collected from indwelling CNS medical devices or in postoperative/nosocomial CNS infections
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