Abstract
Aim: Given the significant mortality and sequelae due to meningitis, rapid diagnosis and initiation of treatment have a major impact on patient outcomes. In many cases of meningitis/meningoencephalitis, empirical treatment should be initiated immediately. This empirical treatment regimen is initiated based on the cumulative antibiotic susceptibility results in the region. The aim of our study was to retrospectively determine the causative agents in cerebrospinal fluid samples of patients who received a presumptive diagnosis of meningitis, using Multiplex Polymerase Chain Reaction (PCR) tests.
Materials and Methods: The study included 206 cerebrospinal fluid samples from different patients with a preliminary diagnosis of meningitis sent from various clinics. The Biospeedy viral nucleic acid isolation kit (Bioeksen, Türkiye) was used for the isolation of genetic material. Genetic materials (DNA/RNA) related to Herpes simplex virus 1-2, Humman herpesvirus 6-7-8, Varicella zoster virus, Enterovirus, Cytomegalovirus, Human Parechoviruses, Haemophilus influenzae, Listeria monocytogenes, Streptococcus pneumoniae, Neisseria meningitidis, Streptococcus agalactiae, Escherichia coli K1, Cryptococcus gattii/neoformans in cerebrospinal fluid samples were investigated using the Meningitis/Encephalitis RT-qPCR MX-17 Panel (RT-qPCR MX-17S Panel, Bio-Speedy®, Bioeksen, Türkiye) multiplex PCR kit.
Results: According to the PCR results, the causative agent was identified in a total of 19 patients. Nine patients were found to have Streptococcus pneumoniae, two had Varicella zoster virus, and two had Enterovirus. Additionally, six patients had separate detections of Haemophilus influenzae, Cytomegalovirus, Herpes simplex virus 1, Human herpesvirus 6, Human herpesvirus 8, and Parechoviruses.
Conclusion: Recently, simple and rapid molecular tests such as PCR have contributed to an increase in the early detection of causative agents. Based on the performance of diagnostic tests, we propose an algorithm for the use of both syndromic and specific tests in patients at risk for meningitis/encephalitis.
Keywords: cerebrospinal fluid, meningitis, multiplex PCR
Copyright and license
Copyright © 1970 The Author(s). This is an open-access article published by Bolu İzzet Baysal Training and Research Hospital under the terms of the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium or format, provided the original work is properly cited.
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References
- Leber AL, Everhart K, Balada-Llasat JM, 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(9): 2251-61. https://doi.org/10.1128/JCM.00730-16
- Brouwer MC, Tunkel AR, van de Beek D. Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis. Clin Microbiol Rev. 2010; 23(3): 467-92. https://doi.org/10.1128/CMR.00070-09
- van de Beek D, Brouwer M, Hasbun R, Koedel U, Whitney CG, Wijdicks E. Community-acquired bacterial meningitis. Nat Rev Dis Primers. 2016; 2: 16074. https://doi.org/10.1038/nrdp.2016.74
- Philip AGS. Neonatal bacterial meningitis. In: Stevenson DK, Benitz WE, Sunshine P, Hintz SR, Druzin ML, editors. Fetal and Neonatal Brain Injury. Cambridge University Press; 2009: 347-60. https://doi.org/10.1017/CBO9780511581281.033
- McGill F, Heyderman RS, Panagiotou S, Tunkel AR, Solomon T. Acute bacterial meningitis in adults. Lancet. 2016; 388(10063): 3036-47. https://doi.org/10.1016/S0140-6736(16)30654-7
- Poplin V, Boulware DR, Bahr NC. Methods for rapid diagnosis of meningitis etiology in adults. Biomark Med. 2020; 14(6): 459-79. https://doi.org/10.2217/bmm-2019-0333
- Kumar A, Debata PK, Ranjan A, Gaind R. The role and reliability of rapid bedside diagnostic test in early diagnosis and treatment of bacterial meningitis. Indian J Pediatr. 2015; 82(4): 311-4. https://doi.org/10.1007/s12098-014-1357-z
- Buch K, Bodilsen J, Knudsen A, et al. Cerebrospinal fluid lactate as a marker to differentiate between community-acquired acute bacterial meningitis and aseptic meningitis/encephalitis in adults: a Danish prospective observational cohort study. Infect Dis (Lond). 2018; 50(7): 514-21. https://doi.org/10.1080/23744235.2018.1441539
- van de Beek D, Brouwer MC, Koedel U, Wall EC. Community-acquired bacterial meningitis. Lancet. 2021; 398(10306): 1171-83. https://doi.org/10.1016/S0140-6736(21)00883-7
- Dien Bard J, Alby K. Point-counterpoint: meningitis/encephalitis syndromic testing in the clinical laboratory. J Clin Microbiol. 2018; 56(4): e00018-18. https://doi.org/10.1128/JCM.00018-18
- Evans M, Merkel KG, Harder J, Rose DT. Impact of the implementation of a rapid meningitis/encephalitis multiplex polymerase chain reaction panel on IV acyclovir duration: multicenter, retrospective cohort of adult and pediatric patients. Diagn Microbiol Infect Dis. 2020; 96(2): 114935. https://doi.org/10.1016/j.diagmicrobio.2019.114935
- Gültepe B, Bayram Y, Güdücüoğlu H, Çıkman A, Berktaş M. Investigation of bacterial and viral meningitis agents with different PCR methods at a university hospital. Abant Medical Journal. 2015; 4(2), 125-9. https://doi.org/10.5505/abantmedj.2015.64325
- Albuquerque RC, Moreno ACR, Dos Santos SR, Ragazzi SLB, Martinez MB. Multiplex-PCR for diagnosis of bacterial meningitis. Braz J Microbiol. 2019; 50(2): 435-43. https://doi.org/10.1007/s42770-019-00055-9
- Soylar M, Altuğlu İ, Sertöz R, Aydın D, Akkoyun F, Zeytinoğlu A. Viral agents in patients with central nervous infections admitted to Ege University Hospital. Ege Journal of Medicine. 2014; 53(2): 65-70. https://doi.org/10.19161/etd.344054
- Wall EC, Chan JM, Gil E, Heyderman RS. Acute bacterial meningitis. Curr Opin Neurol. 2021; 34(3): 386-95. https://doi.org/10.1097/WCO.0000000000000934
- Aksamit AJ, Berkowitz AL. Meningitis. Continuum (Minneap Minn). 2021; 27(4): 836-54. https://doi.org/10.1212/CON.0000000000001016
- Gökkılıç B, Çiçek C, Zeytinoğlu A, Kartal E. Evaluation and a bibliometric analysis of viral factors in central nervous system infections detected in the last ten years in Turkey. Turk Mikrobiyol Cemiy Derg. 2021; 51(1): 70-85. https://doi.org/10.5222/TMCD.2021.74508
- Akkaya O, Güvenç Hİ, Güzelant A, et al. Investigation of the causative agents of meningitis by real-time PCR method. Türk Mikrobiyol Cem Derg. 2017; 47(3): 131-7. https://doi.org/10.5222/TMCD.2017.131
- Absinta M, Ha SK, Nair G, et al. Human and nonhuman primate meninges harbor lymphatic vessels that can be visualized noninvasively by MRI. Elife. 2017; 6: e29738. https://doi.org/10.7554/eLife.29738
- Péan de Ponfilly G, Chauvin A, Salmona M, et al. Impact of a 24/7 multiplex-PCR on the management of patients with confirmed viral meningitis. J Infect. 2021; 83(6): 650-5. https://doi.org/10.1016/j.jinf.2021.08.050
- Schnuriger A, Vimont S, Godmer A, et al. Differential performance of the FilmArray meningitis/encephalitis assay to detect bacterial and viral pathogens in both pediatric and adult populations. Microbiol Spectr. 2022; 10(2): e0277421. https://doi.org/10.1128/spectrum.02774-21
- Lindström J, Elfving K, Lindh M, Westin J, Studahl M. Assessment of the FilmArray ME panel in 4199 consecutively tested cerebrospinal fluid samples. Clin Microbiol Infect. 2022; 28(1): 79-84. https://doi.org/10.1016/j.cmi.2021.05.017
- Çaycı YT, Daştan M, Vural DG, et al. Investigation of the causes of cerebrospinal fluid samples of patients with suspected meningitis with the meningitis panel. Journal of Biotechnology and Strategic Health Research. 2021; 5(2): 98-104. https://doi.org/10.34084/bshr.929470
- Akkaya O, Guvenc HI, Yuksekkaya S, et al. Real-time PCR detection of the most common bacteria and viruses causing meningitis. Clin Lab. 2017; 63(4): 827-32. https://doi.org/10.7754/Clin.Lab.2016.160912
- 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; 56(4): e01927-17. https://doi.org/10.1128/JCM.01927-17
- Sundelin T, Bialas J, de Diego J, et al. Evaluation of the QIAstat-Dx meningitis/encephalitis panel, a multiplex PCR platform for the detection of community-acquired meningoencephalitis. J Clin Microbiol. 2023; 61(10): e0042623. https://doi.org/10.1128/jcm.00426-23