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Central nervous system infections

Unexpectedly high false positive Haemophilus influenzae rates using a meningoencephalitis syndromic PCR panel in two tertiary centres

May 18 • P0247

MC. Zanella1/2/3, V. Hinic4, A. Cherkaoui1, D. Goldenberger4, R. Renzi1, A. Egli4/5, J. Schrenzel1/2

1) Geneva University Hospitals, Bacteriology Laboratory, Division of Laboratory Medicine, Geneva, Switzerland
2) University of Geneva Medical School, Geneva, Switzerland
3) Geneva University Hospitals, Division of Infectious Diseases, Department of Medical specialities, Geneva, Switzerland
4) University Hospital Basel, Clinical Bacteriology and Mycology, Basel, Switzerland
5) University of Basel, Applied Microbiology Research, Department of Biomedicine, Basel, Switzerland

Background: PCR panel assays are increasingly used in routine diagnostic laboratories for meningitis and (meningo-) encephalitis diagnosis. Since the implementation of the BIOFIRE® Meningitis/Encephalitis (ME) Panel, several cases of false-positive (FP) results for Haemophilus influenzae have been reported.

Materials/methods: Retrospective case review conducted at Geneva and Basel University Hospitals on all H. influenzae positive results determined by BIOFIRE® ME Panel on cerebrospinal fluid (CSF) samples sequentially analyzed from June 2016 to October 2019. The panel was performed in strict accordance with the manufacturer’s instructions. Clinical and laboratory data were collected. Cases were defined as a true positive (TP) when confirmed by a positive H. influenzae specific qPCR on the same sample and/or CSF cultures, in addition to clinical manifestations and CSF analysis. Other cases were considered as a FP. Both laboratories are accredited (ISO/IEC17025) and participate in external quality control.

Results: A total of 3082 BIOFIRE® ME Panel corresponding to 2895 patients (2252 adult; 643 paediatric) were performed: results for H. influenzae were negative in 99.4% (3064/3082) (95% CI 99.1–99.6%) and positive in 0.6% (18/3082) (95% CI 0.4–0.9%) CSF samples. CSF white blood cell count was determined in 13 samples (median 7M/L [range 1-4031M/L]). Culture and specific qPCR were performed on 17/18 and 3/18 CSF samples, respectively. Among 17 samples sent for culture, 10 concerned patients not treated with antibiotics prior to lumbar puncture and one only was H. influenza – positive. Clinical manifestations and CSF analysis were barely compatible with H. influenzae ME and/or an alternative diagnosis was made in 72.2% (13/18) cases. A total of 2 TP (one case, positive blood and CSF cultures; one case, positive blood culture), and 16 FP (three culture and qPCR negative; 14 culture-negative without qPCR performed) cases were retained. Nine patients received specific antibiotics for ME.

Conclusions: False-positive results for H. influenzae with the BIOFIRE® ME Panel were surprisingly frequent. ME panel results should always be interpreted together with clinical presentation and CSF analysis. Special caution should be paid to H. influenza – positive results and a H. influenzae specific qPCR should be considered to mitigate the consequences of FP results.


ME Panel

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