A review of a 13-month period of FilmArray Meningitis/Encephalitis panel implementation as a first-line diagnosis tool at a university hospital


Autoři: Agathe Boudet aff001;  Alix Pantel aff001;  Marie-Josée Carles aff002;  Hélène Boclé aff003;  Sylvie Charachon aff002;  Cécilia Enault aff002;  Robin Stéphan aff001;  Lucile Cadot aff004;  Jean-Philippe Lavigne aff001;  Hélène Marchandin aff005
Působiště autorů: U1047, INSERM, Montpellier University, Department of Microbiology, Nîmes University Hospital, Nîmes, France aff001;  Department of Microbiology, Nîmes University Hospital, Nîmes, France aff002;  U1047, INSERM, Montpellier University, Department of Infectious Diseases, Nîmes University Hospital, Nîmes, France aff003;  Laboratory of Medical Biology, Alès General Hospital, Alès, France aff004;  HydroSciences Montpellier, CNRS, IRD, Montpellier University, Department of Microbiology, Nimes University Hospital, Nîmes, France aff005
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0223887

Souhrn

Early diagnosis and treatment of meningitis and encephalitis is essential for reducing both their morbidity and mortality. The FilmArray® Meningitis/Encephalitis (FA-M/E) panel is a recently available molecular tool allowing the simultaneous detection of 14 pathogens in about one hour. We evaluated its routine use over a 13-month period at Nîmes University Hospital, France. Cerebrospinal fluid (CSF) specimens were prospectively analyzed, independently of cell count; results were retrospectively analyzed and positive results compared to clinical and microbiological data. Among the 708 patients included (734 CSF samples), 89 (12.6%) had a positive FA-M/E panel, 71 (80%) for a viral pathogen and 18 (20%) for a bacterial pathogen. Enterovirus and HHV-6 were the main detected pathogens. Mean time-to-results was 1h46mn. Four non-clinically relevant results were detected (3 HHV-6 and 1 Haemophilus influenzae) on the basis of inconsistent clinical and/or biological data, and/or after visualization of melting curves. No CSF pleocytosis was observed in 11% of the patients with a positive FA-M/E panel. For the 18 patients with a positive FA-M/E panel for a bacterial pathogen, five (28%) had CSF samples showing a positive Gram stain allowing an early diagnosis of bacterial infection and 67% had CSF displaying a positive culture. Altogether the panel detected 5 cases of bacterial M/E (29%) not diagnosed by culture. Despite undeniable advantages, mainly ease of use, quick result availability, and an extremely low rate of invalid results, measures should be implemented to limit false-positive results due to contamination and a careful interpretation based on the overall data for each patient is required.

Klíčová slova:

Bacterial pathogens – Cerebrospinal fluid – Melting – Pediatric infections – Pediatrics – Physicians – Pneumococcus – Haemophilus influenzae


Zdroje

1. Dodge PR, Swartz MN. Bacterial meningitis—a review of selected aspects. II. Special neurologic problems, postmeningitic complications and clinicopathological correlations. N Engl J Med. 1965;272:954–960. doi: 10.1056/NEJM196505062721806

2. van de Beek D, de Gans J, Tunkel AR, Wijdicks EF. Community-acquired bacterial meningitis in adults. N Engl J Med. 2006;354:44–53. doi: 10.1056/NEJMra052116 16394301

3. Aronin SI, Peduzzi P, Quagliarello VJ. Community-acquired bacterial meningitis: risk stratification for adverse clinical outcome and effect of antibiotic timing. Ann Intern Med. 1998;129:862–869. doi: 10.7326/0003-4819-129-11_part_1-199812010-00004 9867727

4. Brouwer MC, Tunkel AR, van de Beek D. Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis. Clin Microbiol Rev. 2010;23:467–492. doi: 10.1128/CMR.00070-09 20610819

5. Martin NG, Iro MA, Sadarangani M, Goldacre R, Pollard AJ, Goldacre MJ. Hospital admissions for viral meningitis in children in England over five decades: a population-based observational study. Lancet Infect Dis. 2016;16:1279–1287. doi: 10.1016/S1473-3099(16)30201-8 27527749

6. Société Française de Microbiologie [French Society for Microbiology]. Diagnostic microbiologique des infections du système nerveux central [Microbiological diagnostic of central nervous system infections]. Référentiel en microbiologie médicale (REMIC): Société Française de Microbiologie Ed; 2015, pp. 155–164.

7. Chang D, Okulicz JF, Nielsen LE, White BK. A tertiary care center’s experience with novel molecular meningitis/encephalitis diagnostics and implementation with antimicrobial stewardship. Mil Med. 2018;183:e24–e27. doi: 10.1093/milmed/usx025 29401338

8. Bårnes GK, Gudina EK, Berhane M, Abdissa A, Tesfaw G, Abebe G, et al. New molecular tools for meningitis diagnostics in Ethiopia—a necessary step towards improving antimicrobial prescription. BMC Infect Dis. 2018;18:684. doi: 10.1186/s12879-018-3589-4

9. Leber AL, Everhart K, Balada-Llasat JM, Cullison J, Daly J, Holt S, et al. Multicenter evaluation of BioFire FilmArray Meningitis/Encephalitis panel for detection of bacteria, viruses, and yeast in cerebrospinal fluid specimens. J Clin Microbiol. 2016;54:2251–2261. doi: 10.1128/JCM.00730-16 27335149

10. Dien Bard J, Alby K. Point-counterpoint: meningitis/encephalitis syndromic testing in the clinical laboratory. J Clin Microbiol. 2018;56. doi: 10.1128/JCM.00018-18 29343540

11. Lumley SF, Pritchard D, Dutta A, Matthews PC, Cann K. Multiplex PCR reveals high prevalence of enterovirus and HHV6 in acellular paediatric cerebrospinal fluid samples. J Infect. 2018;77(3):249–257.

12. Lee SH, Chen SY, Chien JY, Lee TF, Chen JM, Hsueh PR. Usefulness of the FilmArray meningitis/encephalitis (M/E) panel for the diagnosis of infectious meningitis and encephalitis in Taiwan. J Microbiol Immunol Infect. 2019; doi: 10.1016/j.jmii.2019.04.005 31085115

13. Liesman RM, Strasburg AP, Heitman AK, Theel ES, Patel R, Binnicker MJ. Evaluation of a commercial multiplex molecular panel for diagnosis of infectious meningitis and encephalitis. J Clin Microbiol. 2018;26;56. doi: 10.1128/JCM.01927-17 29436421

14. Wootton SH, Aguilera E, Salazar L, Hemmert AC, Hasbun R. Enhancing pathogen identification in patients with meningitis and a negative Gram stain using the BioFire FilmArray(®) Meningitis/Encephalitis panel. Ann Clin Microbiol Antimicrob. 2016;15:26. doi: 10.1186/s12941-016-0137-1

15. Eichinger A, Hagen A, Meyer-Bühn M, Huebner J. Clinical benefits of introducing real-time multiplex PCR for cerebrospinal fluid as routine diagnostic at a tertiary care pediatric center. Infection. 2019;47(1):51–58. doi: 10.1007/s15010-018-1212-7 30187216

16. Blaschke AJ, Holmberg KM, Daly JA, Leber AL, Dien Bard J, Korgenski EK, et al. Retrospective evaluation of infants aged 1 to 60 days with residual cerebrospinal fluid (CSF) tested using the FilmArray Meningitis/Encephalitis (ME) panel. J Clin Microbiol. 2018;56: doi: 10.1128/JCM.00277-18 29669791

17. Arora HS, Asmar BI, Salimnia H, Agarwal P, Chawla S, Abdel-Haq N. 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. 2017;36:685–687. doi: 10.1097/INF.0000000000001551 28114152

18. Graf EH, Farquharson MV, Cárdenas AM. Comparative evaluation of the FilmArray meningitis/encephalitis molecular panel in a pediatric population. Diagn Microbiol Infect Dis. 2017;87:92–94. doi: 10.1016/j.diagmicrobio.2016.09.022 27771208

19. Messacar K, Breazeale G, Robinson CC, Dominguez SR. Potential clinical impact of the film array meningitis encephalitis panel in children with suspected central nervous system infections. Diagn Microbiol Infect Dis. 2016;86:118–120. doi: 10.1016/j.diagmicrobio.2016.05.020 27342782

20. Rhein J, Bahr NC, Hemmert AC, Cloud JL, Bellamkonda S, Oswald C, et al. Diagnostic performance of a multiplex PCR assay for meningitis in an HIV-infected population in Uganda. Diagn Microbiol Infect Dis. 2016;84:268–273. doi: 10.1016/j.diagmicrobio.2015.11.017 26711635

21. Richards RJ, Simon MS, Phillips CD, Lief L, Jenkins SG, Satlin MS. Rapid detection of Listeria monocytogenes rhombencephalitis in an immunocompetent patient by multiplexed PCR. BMJ Case Rep. 2018;8:2018. doi: 10.1136/bcr-2018-225575 30413440

22. Kenneth S, Bangdiwala AS, Kwizera R, Kandole TK, Tugume L, Kiggundu R, et al. Symptomatic cryptococcal antigenemia presenting as early cryptococcal meningitis with negative CSF analysis. Clin Infect Dis. Forthcoming 2018. doi: 10.1093/cid/ciy817

23. Green DA, Pereira M, Miko B, Radmard S, Whittier S, Thakur K. Clinical significance of Human Herpesvirus 6 positivity on the FilmArray Meningitis/Encephalitis panel. Clin Infect Dis. 2018;67:1125–1128. doi: 10.1093/cid/ciy288 29635334

24. Launes C, Casas-Alba D, Fortuny C, Valero-Rello A, Cabrerizo M, Muñoz-Almagro C. Utility of FilmArray Meningitis/Encephalitis panel during outbreak of brainstem encephalitis caused by enterovirus in Catalonia in 2016. J Clin Microbiol. 2016;55:336–338. doi: 10.1128/JCM.01931-16 27795349

25. Naccache SN, Lustestica M, Fahit M, Mestas J, Dien Bard J. One year in the life of a rapid syndromic panel for meningitis/encephalitis: a pediatric tertiary care facility’s experience. J Clin Microbiol. 2018;56: doi: 10.1128/JCM.01940-17 29540454

26. Radmard S, Reid S, Ciryam P, Boubour A, Ho N, Zucker J, et al. Clinical utilization of the FilmArray Meningitis/Encephalitis (ME) multiplex Polymerase Chain Reaction (PCR) assay. Front Neurol. 2019;10:281. doi: 10.3389/fneur.2019.00281 30972012

27. Tarai B, Das P. FilmArray® meningitis/encephalitis (ME) panel, a rapid molecular platform for diagnosis of CNS infections in a tertiary care hospital in North India: one-and-half-year review. Neurol Sci. 2019;40:81–88.

28. Marchandin H, Ventura V, Alonso JM, Van de Perre P. Mixed bacterial meningitis due to Streptococcus pneumoniae and Neisseria meningitidis in an 18-month-old child. J Clin Microbiol. 2005;43:1477–1479. doi: 10.1128/JCM.43.3.1477-1479.2005 15750140

29. Sorek N, Ashkenazi S, Livni G, Ben-Zvi H. Neisseria meningitidis and cytomegalovirus simultaneous detection in the filmarray meningitis/encephalitis panel and its clinical relevance. IDCases. 2019;17:e00516. doi: 10.1016/j.idcr.2019.e00516 31193598

30. Lee CK, Chiu L, Yan G, Chew KL, Yan B, Jureen R, et al. False negative results caused by erroneous automated result interpretation algorithm on the FilmArray 2.0 instrument. Clin Chem Lab Med. 2018;56:e43–e45. doi: 10.1515/cclm-2017-0518 28763299

31. González-Donapetry P, García-Rodríguez J, Cendejas-Bueno E. A case of a FilmArray® ME false negative in meningococcal meningitis. J Infect. 2019; doi: 10.1016/j.jinf.2019.05.002

32. Piccirilli G, Chiereghin A, Gabrielli L, Giannella M, Squarzoni D, Turello G, et al. Infectious meningitis/encephalitis: evaluation of a rapid and fully automated multiplex PCR in the microbiological diagnostic workup. New Microbiol. 2018;41:118–125. 29620789

33. Slenker AK, Royer TL, Villalobos T. Human Herpes Virus 6 positivity on theFilmArray Meningitis/Encephalitis needs clinical interpretation. Clin. Infect.Dis. Forthcoming 2019. doi: 10.1093/cid/ciz058

34. Bhaskaran A, Racsa L, Gander R, Southern P, Cavuoti D, Alatoom A. Interpretation of positive molecular tests of common viruses in the cerebrospinal fluid. Diagn Microbiol Infect Dis. 2013;77:236–240. doi: 10.1016/j.diagmicrobio.2013.07.017 24035384

35. Weerkamp N, van de Beek D, de Gans J, Koehler PJ. Herpes reactivation in patients with bacterial meningitis. J Infect. 2008;57: 493–494. doi: 10.1016/j.jinf.2008.10.001 19027168

36. Ericsdotter AC, Brink M, Studahl M, Bengnér M. Reactivation of herpes simplex type 1 in pneumococcal meningitis. J Clin Virol. 2015;66:100–102. doi: 10.1016/j.jcv.2015.03.014 25866347

37. Gomez CA, Pinsky BA, Liu A, Banaei N. Delayed diagnosis of tuberculous meningitis misdiagnosed as Herpes Simplex Virus-1 encephalitis with the FilmArray syndromic polymerase chain reaction panel. Open Forum Infect Dis. 2016;4:ofw245.

38. Hanson KE. The first fully automated molecular diagnostic panel for meningitis and encephalitis: how well does it perform, and when should it be used? J Clin Microbiol. 2016;54:2222–2224. doi: 10.1128/JCM.01255-16 27413189

39. Duff S, Hasbun R, Ginocchio CC, Balada-Llasat JM, Zimmer L, Bozzette SA. Economic analysis of rapid multiplex polymerase chain reaction testing for meningitis/encephalitis in pediatric patients. Future Microbiol. 2018;13:617–629. doi: 10.2217/fmb-2017-0238 29316801

40. Soucek DK, Dumkow LE, VanLangen KM, Jameson AP. Cost justification of the BioFire FilmArray Meningitis/Encephalitis panel versus standard of care for diagnosing meningitis in a community hospital. J Pharm Pract. 2019;32(1):36–40. doi: 10.1177/0897190017737697 29092659

41. Hasbun R, Balada-Llasat JM, Duff S. Letter to the Editor reply: economic model of the FilmArray Meningitis Encephalitis panel in children. Future Microbiol. 2018;13:1555–1556. doi: 10.2217/fmb-2018-0232 30426786


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2019 Číslo 10