Skip to main content

Advertisement

SpringerLink
Log in

Point-of-care multiplexed diagnosis of meningitis using the FilmArray® ME panel technology

  • Original Article
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

Infectious meningitis is a medical urgency and rapid detection of the causative pathogen into the cerebrospinal fluid (CSF) is mandatory to guide the management of patients. We compared the performances of the multiplexed PCR FilmArray® ME panel with standard microbiological analyses, for rapid diagnosis of infectious meningitis. All the CSF samples received in our routine laboratory for the diagnosis of infectious meningitis were prospectively analyzed by the FilmArray® ME panel for the detection of fourteen targets in parallel to standard routine real-time PCR assays and bacterial culture. We reviewed clinical and biological records of patients for whom a discrepant result was obtained to achieve a definite diagnosis. Among 1124 CSF samples tested over a 43-week period, 113 (10.1%) and 87 (7.74%) were positive using the FilmArray® ME panel and the standard techniques, respectively. Among 40 CSF samples which yielded discrepant results, 34 were positive only using the FilmArray® ME panel and 6 were positive only using standard techniques. A total of 16/34 (47.1%) FilmArray® ME panel−positive CSF, and 6/6 (100%) of standard technique−positive CSF were interpreted as true positive. We were able to estimate the sensitivity, the specificity, the positive predictive value, and the negative predictive value of the FilmArray® ME panel at 94.2%, 98.2%, 84.3%, and 99.4%, respectively. The FilmArray® ME panel is an efficient tool for the rapid diagnosis of infectious meningitis at the point-of-care. Its higher sensitivity compared with that of standard molecular biology and culture techniques yields an increase of true positive diagnosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Tan CY, Gonfrier G, Ninove L, Zandotti C, Dubot-Pérès A, de Lamballerie X, Charrel RN (2012) Screening and detection of human enterovirus 71 infection by a real-time RT-PCR assay in Marseille, France, 2009-2011. Clin Microbiol Infect 18:E77–E80

    Article  CAS  Google Scholar 

  2. Taha MK (2000) Simultaneous approach for nonculture PCR-based identification and serogroup prediction of Neisseria meningitidis. J Clin Microbiol 38:855–857

    Article  CAS  Google Scholar 

  3. Delacroix R, Morel SN, Hervé L, Bordy T, Dinten JM, Drancourt M, Allier C (2017) Cerebrospinal fluid lens-free microscopy: a new tool for the laboratory diagnosis of meningitis. Sci Rep 7:39893

    Article  CAS  Google Scholar 

  4. Jing-Zi P, Zheng-Xin H, Wei-Jun C, Yong-Qiang J (2018) Detection of bacterial meningitis pathogens by PCR-mass spectrometry in cerebrospinal fluid. Clin Lab 64:1013–1019

    Article  Google Scholar 

  5. Walls T, McSweeney A, Anderson T, Jennings LC (2017) Multiplex-PCR for the detection of viruses in the CSF of infants and young children. J Med Virol 89:559–561

    Article  CAS  Google Scholar 

  6. Shin SY, Kwon KC, Park JW, Kim JM, Shin SY, Koo SH (2012) Evaluation of the Seeplex® meningitis ACE detection kit for the detection of 12 common bacterial and viral pathogens of acute meningitis. Ann Lab Med 32:44–49

    Article  CAS  Google Scholar 

  7. Liesman RM, Strasburg AP, Heitman AK, Theel ES, Patel R, Binnincker MJ (2018) Evaluation of a commercial multiplex molecular panel for diagnosis of infectious meningitis and encephalitis. J Clin Microbiol 56:e01927–17

    Article  Google Scholar 

  8. Arora HS, Asmar BI, Salimnia H, Agarwal P, Chawla S, Abdel-Haq N (2017) Enhanced identification of group B Streptococcus and Escherichia coli in young infants with meningitis using the Biofire FilmArray meningitis/encephalitis panel. Pediatr Infect Dis J 36(7):685–687

    Article  Google Scholar 

  9. Chang D, Okulicz JF, Nielsen LE, White BK (2018) A tertiary care center’s experience with novel molecular meningitis/encephalitis diagnostics and implementation with antimicrobial stewardship. Mil Med 183(1–2):e24–e27

    Article  Google Scholar 

  10. Lumley SF, Pritchard D, Dutta A, Matthews PC, Cann K (2018) Multiplex PCR reveals high prevalence of enterovirus and HHV6 in acellular paediatric cerebrospinal fluid samples. J Inf Secur 77:249–257

    Google Scholar 

  11. Naccache SN, Lustestica M, Fahit M, Mestas J, Dien Bard J (2018) One year in the life of a rapid syndromic panel for meningitis/encephalitis: a pediatric tertiary care facility’s experience. J Clin Microbiol 56:e01940–17

    Article  Google Scholar 

  12. Lewis PO, Lanier CG, Patel PD, Krolikowski WD, Krolikowski MA (2019) False negative diagnostic errors with polymerase chain reaction for the detection of cryptococcal meningoencephalitis. Med Mycol myz064

  13. Rhein J, Bahr NC, Hemmert AC, Cloud JL, Bellamkonda S, Oswald C, Lo E, Nabeta H, Kiggundu R, Akampurira A, Musubire A, Williams DA, Meya DB, Boulware DR (2016) Diagnostic performance of a multiplex PCR assay for meningitis in an HIV-infected population in Uganda. Diagn Microbiol Infect Dis 84(3):268–273

    Article  CAS  Google Scholar 

  14. Lee SH, Chen SY, Chien JY, Lee TF, Chen JM, Hsueh PR (2019) Usefulness of the FilmArray meningitis/encephalitis (M/E) panel for the diagnosis of infectious meningitis and encephalitis in Taiwan. J Microbiol Immunol Infect 52(5):760–768

    Article  Google Scholar 

  15. Leber AL, Everhart K, Balada-Llasat JM, Cullison J, Daly J, Holt S, Lephart P, Salimnia H, Schreckenberger PC, DesJarlais S, Reed SL, Chapin KC, LeBlanc L, Johnson JK, Soliven NL, Carroll KC, Miller JA, Dien Bard J, Mestas J, Bankowski M, Enomoto T, Hemmert AC, Bourzac KM (2016) Multicenter evaluation of BioFire FilmArray meningitis/encephalitis panel for detection of bacteria, viruses, and yeast in cerebrospinal fluid specimens. J Clin Microbiol 54:2251–2261

    Article  CAS  Google Scholar 

  16. Drancourt M, Michel-Lepage A, Boyer S, Raoult D (2016) The point-of-care laboratory in clinical microbiology. Clin Microbiol Rev 29:429–447

    Article  Google Scholar 

  17. Tapparel C, Cordey S, Van Belle S, Turin L, Lee WM, Regamey N, Meylan P, Mühlemann K, Gobbini F, Kaiser L (2009) New molecular detection tools adapted to emerging rhinoviruses and enteroviruses. J Clin Microbiol 47:1742–1749

    Article  CAS  Google Scholar 

  18. Bennett S, Harvala H, Witteveldt J, McWilliam Leitch EC, McLeish N, Templeton K, Gunson R, Carman WF, Simmonds P (2011) Rapid simultaneous detection of enterovirus and parechovirus RNAs in clinical samples by one-step real-time reverse transcription-PCR assay. J Clin Microbiol 49:2620–2624

    Article  CAS  Google Scholar 

  19. Corless CE, Guiver M, Borrow R, Edwards-Jones V, Fox AJ, Kaczmarski EB (2001) Simultaneous detection of Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae in suspected cases of meningitis and septicemia using real-time PCR. J Clin Microbiol 39(4):1553–1558

    Article  CAS  Google Scholar 

  20. Cohen-Bacrie S, Ninove L, Nougairède A, Charrel R, Richet H, Minodier P, Badiaga S, Noël G, La Scola B, de Lamballerie X, Drancourt M, Raoult D (2011) Revolutionizing clinical microbiology laboratory organization in hospitals with in situ point-of-care. PLoS One 7:e22403

    Article  Google Scholar 

  21. Carvalho Mda G, Tondella ML, McCaustland K, Weidlich L, McGee L, Mayer LW, Steigerwalt A, Whaley M, Facklam RR, Fields B, Carlone G, Ades EW, Dagan R, Sampson JS (2007) Evaluation and improvement of real-time PCR assays targeting lytA, ply, and psaA genes for detection of pneumococcal DNA. J Clin Microbiol 45(8):2460–2466

    Article  Google Scholar 

  22. Million M, Angelakis E, Maraninchi M, Henry M, Giorgi R, Valero R, Vialettes B, Raoult D (2013) Correlation between body mass index and gut concentrations of Lactobacillus reuteri, Bifidobacterium animalis, Methanobrevibacter smithii and Escherichia coli. Int J Obes 37:1460–1466

    Article  CAS  Google Scholar 

  23. Ninove L, Nougairede A, Gazin C, Thirion L, Delogu I, Zandotti C, Charrel RN, De Lamballerie X (2011) RNA and DNA bacteriophages as molecular diagnosis controls in clinical virology: a comprehensive study of more than 45,000 routine PCR tests. PLoS One 6:e16142

    Article  CAS  Google Scholar 

  24. Kim EJ, Bauer C, Grevelding CG, Quack T (2013) Improved PCR/nested PCR approaches with increased sensitivity and specificity for the detection of pathogens in hard ticks. Ticks Tick Borne Dis 4:409–416

    Article  Google Scholar 

  25. Hahn G, Jores R, Mocarski ES (1998) Cytomegalovirus remains latent in a common precursor of dendritic and myeloid cells. Proc Natl Acad Sci U S A 95:3937–3942

    Article  CAS  Google Scholar 

  26. Kondo K, Kondo T, Okuno T, Takahashi M, Yamanishi K (1991) Latent human herpesvirus 6 infection of human monocytes/macrophages. J Gen Virol 72:1401–1408

    Article  CAS  Google Scholar 

  27. Green DA, Pereira M, Miko B, Radmard S, Whittier S, Thakur K (2018) Clinical significance of human herpesvirus 6 positivity on the FilmArray meningitis/encephalitis panel. Clin Infect Dis 67:1125–1112

    Article  Google Scholar 

  28. Al-Soud WA, Rådström P (2001) Purification and characterization of PCR-inhibitory components in blood cells. J Clin Microbiol 39(2):485–493

    Article  CAS  Google Scholar 

  29. Gomez CA, Pinsky BA, Liu A, Banaei N (2016) Delayed diagnosis of tuberculous meningitis misdiagnosed as herpes simplex virus-1 encephalitis with the FilmArray syndromic polymerase chain reaction panel. Open Forum Infect Dis 4:245

    Article  Google Scholar 

Download references

Acknowledgments

The authors acknowledge the expert help of Mrs. Olga CUSACK in the preparation of the manuscript.

Funding

The authors did not receive any external funding for this study. This work was supported by the French Government under the “Investissements d’avenir” (Investments for the Future) program managed by the Agence Nationale de la Recherche (ANR, fr: National Agency for Research) (reference: Méditerranée Infection 10-IAHU-03). This work was supported by Région Provence Alpes Côte d’Azur and European funding FEDER PRIMMI.

Author information

Authors and Affiliations

  1. Laboratoire de Microbiologie, IHU Méditerranée Infection, Marseille, France

    Jean-Jacques Vincent, Christine Zandotti, Sophie Baron, Christian Kandil, Pierre-Yves Levy, Michel Drancourt, Didier Raoult & Laetitia Ninove

  2. Aix-Marseille Univ, IRD, MEPHI, IHU Méditerranée Infection, 19-21 bd Jean Moulin, 13385, Marseille CEDEX 05, France

    Sophie Baron, Michel Drancourt & Didier Raoult

  3. POCRAME, Aubagne, France

    Pierre-Yves Levy

  4. Aix-Marseille Univ, UVE (Unité des Virus Emergents) IRD 190, Inserm 1207, IHU Méditerranée Infection, Marseille, France

    Laetitia Ninove

Authors
  1. Jean-Jacques Vincent
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christine Zandotti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sophie Baron
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christian Kandil
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Pierre-Yves Levy
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Michel Drancourt
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Didier Raoult
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Laetitia Ninove
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michel Drancourt.

Ethics declarations

Conflict of interest

MD, PYL, and DR are co-founders and stockholders of POCRAME, Marseille, France, the start-up cited in this study.

Ethical approval

This study has been approved by the Ethical Committee of the IHU Méditerranée Infection (decision no. 2016–024).

Informed consent

Not necessary. Diagnosis done on medical prescription.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(XLSX 18 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vincent, JJ., Zandotti, C., Baron, S. et al. Point-of-care multiplexed diagnosis of meningitis using the FilmArray® ME panel technology. Eur J Clin Microbiol Infect Dis 39, 1573–1580 (2020). https://doi.org/10.1007/s10096-020-03859-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-020-03859-y

Keywords

Search

Navigation