Clinical significance of a panel tests in evaluating central nervous system infections

Clinical significance of a panel tests in evaluating central nervous system infections | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Clinical significance of a panel tests in evaluating central nervous system infections Fang Jiang, WenJun Yu, Xiaoyang Jiao, Mengya Si, Xuehua Wang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4061701/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Aim The FilmArray ME Panel is an emerging diagnostic method for detecting multiple pathogens in cerebrospinal fluid (CSF). We evaluated the clinical significance of the FilmArray ME Panel in the diagnosis of central nervous system (CNS) infection. Methods CSF specimens of 130 patients with suspected CNS infection were analyzed, along with clinical and laboratory parameters. Results patients shared some clinical symptoms at presentation, including fever, headache, altered mental status, and focal neurologic deficits. In a total of 130 patients, pathogens were detected in 22 cases, which included eight bacterial infections, and fourteen viral infections. The predominant bacteria detected in CSF were Streptococcus pneumonia , while the most common virus was enterovirus. The FilmArray ME panel had a better coincidence rate with PCR for viral detection, but had higher sensitivity compared with conventional bacterial detection. Conclusions the FilmArray ME Panel provides rapid diagnosis that benefits enabling patients to be promptly treated, improving the effectiveness of treatment. Central nervous system infection FilmArray ME panel meningitis encephalitis Introduction Central nervous system (CNS) infections are a significant cause of mortality and morbidity throughout the world[1]. CNS infections, such as meningitis and encephalitis, can result from bacteria, viruses, fungi and parasites. Besides microorganisms, the causes of neuroinflammation include autoimmunity, trauma, degenerative processes, toxins, and malignancy. However, many patients with neuroinflammation have unknown causes[2]. In clinical practice, CNS inflammation with non-infectious causes have similar clinical features to infectious causes, with some overlapping laboratory features based on the cerebrospinal fluid (CSF) or blood measurement[3, 4]. An incomplete understanding of the etiology of CNS infection is the main factor responsible for higher mortality and morbidity in patients with CNS infections[5, 6]. Therefore, insight into microbial - host interactions involving in CNS infections and its relevant neurologic sequelae is instrumental in improving patient treatment and prognosis, reducing mortality, and developing new therapeutic strategies for CNS infection[1]. Many pathogens cause CNS infections. Unfortunately, the underlying pathogenes is not found in as many as 40% - 60% of patients[7]. Examination of CSF is of vital importance for the diagnosis of CNS infection. Routine CSF examinations include biochemical tests (LDH, protein, glucose, and chloride), cytologic tests, including white blood cell (WBC) and differential count, and CSF bacterial culture. None of the above methods can precisely and sensitively detect pathogens. Bacterial and viral meningitis account for the majority of CNS infections, and their detection in CSF includes bacterialculture, antigen detection, and chemical, and cellular analyses[8]. Culture methods provide a definitive diagnosis for bacterial infection, which requires 2 to 5 days and may be falsely negative if the bacteria are fastidious or the patient was treated with antibiotics, or the specimens were improperly processed[9]. The evaluation of patients with probable viral CNS infection is complicated for lack of unified diagnostic criteria, the number of possibilities of virus that cause such infections, and the limited number of diagnostic tools[10]. Polymerase chain reaction (PCR) is a fast and specific method to detect pathogens, but single probe selection is not suitable for the detection of various unknown pathogens. The California Encephalitis Project was a multitudinous study of suspected encephalitis cases (n =1570), over seven years, which was predicated on the pathogeny of encephalitis cases. However, 63% of cases had unexplained etiology in the study despite extensive attempts to identify potential causes[11]. Failure to obtain a timely diagnosis delays choosing an appropriate therapy. The mortality rate of untreated bacterial meningitis approaches 100% and, even with timely treatment, mortality and morbidity still occurs[12]. Nowadays, bacterial meningitis is one of the top 10 reasons for universal infection-related mortality. Present strategies for therapy of CNS infection are compromised by the uncertainty of microbial-host interactions[13]. Etiological specificity tests can improve the therapeutic effect and the prognosis. Compared to the conventional tests, detection focusing on microorganisms undoubtedly has a great advantage. PCR provides high sensitivity and specificity, and can reliably diagnose pathogens, especially for fastidious bacteria[14, 15]. Compared with the culture and serological methods, PCR method requires a shorter time, in addition, the results of PCR are not affected by patient treatment with antibiotics. Currently, PCR is extensively used for detecting microorganisms in some tertiary hospitals. However, the disadvantage of conventional PCR techniques is also significant, since it only detects one pathogen at a time and needs to catch in batches. The time- and labor-intensiveness of PCR limits its widespread use in the diagnosis of CNS infection. In recent years, several advanced molecular diagnostic techniques show promise for rapid diagnosis, such as the GeneXpert MTB/RIF assay and loop-mediated amplification of microorganisms. However, these techniques are impractical because of the relatively high cost and the requirement for experienced professionals. The FilmArray ME Panel is a multiplexed nucleic acid test for the simultaneous qualitative detection and identification of a considerable number of pathogens in the CSF, and has better effectiveness compared with culture and other methods[9]. The whole process of detection only takes about an hour. Compared to traditional PCR, the FilmArray ME Panel provides fast results. Therefore, the method seems to have great potential for application. As the FilmArray ME is an novel method, it has yet to find wide use in clinical specimen detection, and its clinical significance remains to be evaluated. In this study, we recruited 130 patients with suspected meningitis, their pathogens were measured by the FilmArray ME Panel, as well as the conventional CSF tests. Materials and methods Patients Patients were recruited according to the following criteria: patients with fever, headache, seizure or depressed consciousness (at least one presenting symptom). Signs of cervical stiffness, alteration of consciousness, cranial nerve palsy, or plegia/paresis upon physical examination. The CSF specimen met at least one of the following criteria: 1: white blood cells (WBCs) ≥ 5 cells/high power field ( 50 mg/dL, glucose < 60 mg/dL or CSF plasma glucose ratio < 0.4. Patient demographics, laboratory results, clinical characteristics, imaging, therapy, and prognoses were recorded. We acquired clinical data from the patient charts that met the conditions. Biochemical and cytologic testing of CSF. The cytologic tests included WBC count and differential count. Biochemistry results included serum creatinine, LDH, serum or CSF glucose, protein, and chloride. Bacterial culture for blood or CSF Bacterial cultures for both blood and CSF were performed on every specimen enrolled. Testing used standard clinical laboratory procedures. FilmArray ME Panel testing. The FilmArray ME Panel can simultaneously detect 14 pathogens in CSF specimens. Approximately 200 µl of the sample was subjected to FilmArray® ME Panel testing according to the manufacturer’s instructions. The 14 pathogens detected in CSF were: Hemophilus influenza, Neisseria meningitides, Escherichia coli K1, Listeria monocytogenes , Streptococcus pneumonia , Streptococcus agalactiae , enterovirus (EV),cytomegalovirus (CMV), herpes simplex virus type 1/2 (HSV-1/2), human herpesvirus type 6 (HHV-6), varicella zoster virus (VZV), human parechovirus (HPeV), and Cryptococcus neoformans/gattii . Results Between November 2017 to October 2018, 130 patients were enrolled in this study. Clinical and demographic data were presented in Table 1 . The mean age of patients was 28 years. There were 82 male and 48 female patients, giving a male/female ratio of 1.74:1. The most common symptom was fever, which was found in 95% of patients. Headache was the second most common symptom, with 71% of patients having this problem. For other symptoms, 37% of patients had vomiting, 39% of patients were apathetic, 25% of patients had nausea and neck rigidity, 22% of patients had twitches, and 16% of patients had a disorder of consciousness. Signs of meningeal irritation presented in 11.5% of patients, and 80% of patients had fever and apathetic symptoms in the bacterial infection group. The patients with viral and fungal infections also shared the similar symptoms. There was a prominent overlap in clinical features, including fever, headache, focal neurologic deficits, and altered mental status. Twenty-one cases of patients had systemic disease, 18 patients had epilepsy, 7 patients had high blood pressure, 5 patients had heart disease, and 4 patients had diabetes. The onsite analysis showed that all samples had at least five leukocytes /µL in the CSF, indicating an inflammatory reaction within the CNS. During their hospital stay, thirty-one patients received antibiotic treatment (cephalosporins, astaxanthin, and sulbactam), and thirty-seven patients received antiviral drugs (oseltamivir and ribavirin), and 17 patients received combination antibiotic and antiviral treatment. Table 1 Patients’ general characteristics Cases Total 130 Age 0–27 65 ≥ 28 65 Gender Male 82 Female 48 Pathogen infection Virus 14 Bacterial (or fungi) 8 Unidentified 108 Treatment Antibiotic 31 Antiviral 37 Antiviral + Antibiotic 17 Meningitis type ( based on the clinic ) Suppurative meningitis 9 Viral meningitis 60 Autoimmune encephalitis 2 Tuberculous meningitis 13 Systemic diseases Diabetes 4 High blood pressure 7 Heart disease 5 Epilepsy 18 Clinical symptom Headache 71 Nausea 25 Vomiting 37 Fever 95 Apathetic 39 Sleepiness 7 Disorder of consciousness 16 twitch 22 Neck stiffness 25 Meningeal irritation 15 Table 2 Patient characteristics by type of pathogen detected using the CSF or serum testing parameter Value for pathogenic: Bacterial Viruses Fungus S.pneumonia n = 4 E.coli K1 , n = 1 Enterovirus , n = 8 HHV-6 , n = 2 VZV , n = 1 HSV1 , n = 1 HSV2 , n = 1 CMV , n = 1 Cryptococcus neoformans,n = 3 CSF GLU 1.42 4.52 3.34 3.32 3.82 4.09 2.27 3.60 2.7 CL 120.78 116.90 118.82 118.65 125.50 107.20 116.80 113.00 113.83 Protein 1370.28 270 330.10 135.73 531.00 373.00 1207.00 850 489.40 LDH 708 34.00 28.00 40.00 - - - 24.00 29.00 ADA 16.50 - 2.63 7.00 3.00 7.00 11.00 3.00 2.33 IgG 26.27 1.50 14.40 4.81 - - - 14.60 9.17 IgA 5.21 < 1.11 1.48 < 1.11 - - - 2.63 2.50 IgM 1.65 < 0.69 2.27 < 0.69 - - - < 0.69 < 0.69 WBC 5838.75 1 137.38 240.5 184 86 1236 160 220.67 Serum(LDH)/CSF(LDH) 1.68 8.35 6.61 4.33 - - - 5.92 19.04 Cytologic and biochemical tests The subgroup classified by bacterial, viral, and unidentified groups, and the CSF biochemistry tests were compared among the subgroups. The mean CSF glucose was the lowest in the S. pneumonia group, while the highest glucose was in patients with viral infections. Mean CSF protein was the highest for patients with bacterial infections, followed by patients with fungal infections, while protein levels varied widely in the viral group. CSF LDH level was the highest in the S. pneumonia group. The WBC count in CSF was elevated in the S. pneumonia group, while WBC counts in the viral group were lower than those in the bacterial group. Etiology determined in patients with CNS infection Among the 130 patients, pathogens were detected in 22 patients by the FilmArray ME panel, which included 8 cases of bacterial infection, 14 cases of viral infection. Bacteria detected were Streptococcus pneumoniae (n = 4), Cryptococcus neoformans (n = 3), and E.coli K1 (n = 1). In the 14 cases of viral infection, the most common virus was enterovirus, which was detected in eight samples, followed by 2 cases of human herpesvirus type 6 (HHV-6), and the remaining viruses detected were varicella-zoster virus(1 case), cytomegalovirus (1 case), herpes simplex virus (HSV) (1 case) type 1 (HSV-1) (1 case), and 2 cases of HSV-2. Comparison the bacterial cultures and FilmArray ME panel. Eight patients were found to have bacterial infection by the FilmArray ME Panel, among them, 4 cases were confirmed by the CSF bacterial cultures. Besides CSF culture, five patients were positive in the blood culture, thirteen cases of patients were culture positive in sputum, and seven cases of patients were detected bacterial infection in other types of specimens (Table 3 ). The predominant bacterium in CSF was Streptococcus pneumonia (18.2%), followed by Escherichia coli (4.5%). The highest coincidence of the two methods found in Cryptococcus neoformans. Table 3 Comparison of bacterial (or fungi) cultures and FilmArray RP Positive FilmArray Bacterial culture CSF Blood Sputum Others Streptococcus pneumoniae 4 0 1 0 0 Cryptococcus neoformans 3 2 1 0 0 E.coli K1 1 0 0 0 0 Streptococcus agalactiae 0 1 2 0 0 Common bacterium 0 1 0 0 0 Staphylococcus aureus 0 0 1 0 0 Staphylococcus aureus 0 0 0 4 1 Klebsiella pneumoniae 0 0 0 2 0 Acinetobacter baumannii 0 0 0 2 0 ECO-ESBLs 0 0 0 1 0 Haemophilus influenzae 0 0 0 1 0 Moraxella 0 0 0 1 0 Stenotrophomonas maltophilia 0 0 0 1 0 Enterobacter cloacae 0 0 0 1 0 Enterococcus faecium 0 0 0 0 2 Mycoplasma pneumoniae 0 0 0 0 1 Candida tropicalis 0 0 0 0 1 Candida albicans 0 0 0 0 1 Staphylococcus haemolyticus 0 0 0 0 1 Others: Mycoplasma pneumoniae culture, urine culture, lavage fluid, stool culture Discussion Prompt treatment of infectious meningitis and encephalitis are vital to minimize morbidity and mortality[ 9 ]. However, the etiology behind CNS infections is quite complicated, and pathogens are still not found in up to 70% of cases. Therefore, current curative treatment for CNS infections is restricted because of incomplete knowledge of the microbial-host interactions[ 7 , 13 ] In the United States, 80% of CNS infections are induced by bacteria, including Streptococcuspneumonia, Streptococcus agalactiae,Neisseria meningitides, Haemophilus influenzae, Escherichia coli (especially the K1 serotype ), and Listeria monocytogenes [ 9 ]. Streptococcus pneumonia was the main species detected in our patients with bacterial meningitis. Currently, bacterial culture of the CSF is still recognized as the gold standard for the diagnosis of bacterial meningitis[ 16 , 17 ]. However, bacterial culture requires much more time to diagnosis, and the time delay may have fatal ramifications for patients or result in needless application of broad-spectrum antibiotics and delay of effective treatment. In this study, 31 cases of patients were treated empirically, but the therapeutic efficacy varied. CSF pleocytosis is a sensitive marker of inflammation. However, some studies have confirmed that patients with bacterial meningitis may have normal WBC counts. In our study, patients infected with S. pneumonia had much higher WBC counts than patients infected with E.coli K1. WBCs in CSF differed between bacterial infection and viral infection, and the differential WBC count, especially the lymphocyte ratio, as well as the consistency of protein and glucose, are useful in the differential diagnosis of CNS infection. However, the specificity and sensitivity of these tests are low. In this study, only 4 cases of suspected patients had bacteria detected by culture, whereas in 8 cases bacteria could be detected by The FilmArray ME, a detection rate twice that of bacterial culture. Four percents of patients had a positive blood culture, 10% patients were sputum-positive who were negative in both the FilmArray ME Panel and culture methods. Whether the patient's meningeal irritation is part of a systemic infection remains to be determined. Previous large-scale study on bacterial meningitis in pediatric patients showed that only 7% of cases had positive blood cultures[ 18 ]. Viruses are the primary cause of aseptic meningitis. The main causes of viral meningitis are enteroviruses[ 19 – 21 ], which have been related to outbreaks of CNS infections worldwide[ 22 ]. However, the etiology of viral encephalitis varies from one region to another. HSV is the main pathogen of viral encephalitis in many countries, such as England, the USA,France, and Spain[ 21 , 23 , 24 ]. Enterovirus is the major pathogen inducing viral encephalitis in China[ 19 ]. In our study, more than half of viral meningitis infected by enterovirus, and those patients presented multifarious clinical syndromes, including aseptic meningitis, and acute flaccid paralysis/myelitis. In a state of unknown etiology, epidemiology and clinical symptoms may provide some diagnostic clues. In clinic, one of the challenges in the diagnosis of CNS disease is the coincide in the clinical presentation of a considerable variety of diseases[ 25 ]. Rapidly distinguishing CNS infections from other brain and spinal cord disorders is critical for adequate treatment, which ultimately determines the patient's prognosis. The FilmArray ME Panel can detect a broad range of pathogens in CSF, representing a significant paradigm shift of performance from culture to molecular reference methods. In this study, enterovirus-positive specimens were re-examined by PCR, and the coincidence rate was 100%, whereas for bacterial detection, the FilmArray ME Panel had twice the detection rate of bacterial culture. The high incidence of prior antibiotic treatment before intervention may have reduced the detection rate of pathogenic bacteria[ 26 ]. Our results show that the FilmArray ME Panel has significant advantages compared to bacterial culture. In a previous study, about 60% of patients obtained a definite diagnosis[ 4 ] and mandated empiric antimicrobial therapy. Frequent use of broad-spectrum antibiotics will result in multidrug resistance[ 27 , 28 ]. Empiric therapy for patients with bacterial meningitis is prevalent in areas with penicillin-resistant and third-generation cephalosporin-resistant S. pneumonia[ 13 ]. Rapid tests for both bacterial and viral pathogens will be considerably useful for young infants, and may potentially provide more targeted therapy. Because of its large number of advantages, including close-to-patient, rapid detection of a broad range of infectious agents associated with CNS infections[ 9 ], the FilmArray ME Panel has a wide range of prospective applications in clinical practice. Declarations Funding There was no funding for my paper. Conflicts of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Ethics approval The study protocol was approved by the Ethics Committee of Shantou University Medical College(B-2021-037). Availability of data All the data has been listed in the tables of the article, so there is no need to upload it separately. Code availability : There is not available for my paper. Consent for publication Written informed consent for publication was obtained from all participants. I hope this paper will be considerated by your journal. This article was not submitted to other magazines. Authors' contributions Fang Jiang:ConceptualizationIdeas; Methodology and Data Curation Wenjun Yu: Writing Original Draft MengYa Si :Formal analysis and Investigation XiaoYang Jiao::Writing - Review and Editing the paper XueHua Wang::Writing - Review and Editing the paper References Shah, S., et al., The Promise of Molecular Imaging: Focus on Central Nervous System Infections. J Infect Dis, 2023. 228 (Suppl 4): p. S311-S321. Graus, F., et al., A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol, 2016. 15 (4): p. 391-404. Shives, K.D., K.L. Tyler, and J.D. Beckham, Molecular mechanisms of neuroinflammation and injury during acute viral encephalitis. J Neuroimmunol, 2017. 308 : p. 102-111. Brown, B., et al., Defining diagnostic approaches and outcomes in patients with inflammatory CSF: A retrospective cohort study. Clin Neurol Neurosurg, 2018. 172 : p. 105-111. Weisfelt, M., et al., A risk score for unfavorable outcome in adults with bacterial meningitis. Ann Neurol, 2008. 63 (1): p. 90-7. Kim, K.S., Mechanisms of microbial traversal of the blood-brain barrier. Nat Rev Microbiol, 2008. 6 (8): p. 625-34. Tack, D.M., et al., Trends in encephalitis-associated deaths in the United States, 1999-2008. Neuroepidemiology, 2014. 43 (1): p. 1-8. Gomes, H.R., Cerebrospinal fluid analysis: current diagnostic methods in central nervous system infectious diseases. Arq Neuropsiquiatr, 2022. 80 (5 Suppl 1): p. 290-295. Hanson, K.E., 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 (9): p. 2222-4. Mantke, R., [Complexity of DRG routine data also makes the interpretation of thyroid surgery difficult]. Chirurg, 2017. 88 (6): p. 532-533. Glaser, C.A., et al., Beyond viruses: clinical profiles and etiologies associated with encephalitis. Clin Infect Dis, 2006. 43 (12): p. 1565-77. Kim, K.S., Investigating Bacterial Penetration of the Blood-Brain Barrier for the Pathogenesis, Prevention, and Therapy of Bacterial Meningitis. ACS Infect Dis, 2020. 6 (1): p. 34-42. Kim, K.S., Treatment strategies for central nervous system infections. Expert Opin Pharmacother, 2009. 10 (8): p. 1307-17. Gao, Z.X., et al., Advances in laboratory diagnostic methods for cerebrospinal fluid testing for neurosyphilis. Front Public Health, 2022. 10 : p. 1030480. Ruuskanen, O., et al., Viral pneumonia. Lancet, 2011. 377 (9773): p. 1264-75. Nigrovic, L.E., et al., Effect of antibiotic pretreatment on cerebrospinal fluid profiles of children with bacterial meningitis. Pediatrics, 2008. 122 (4): p. 726-30. !!! INVALID CITATION !!! {}. Nigrovic, L.E., et al., Clinical prediction rule for identifying children with cerebrospinal fluid pleocytosis at very low risk of bacterial meningitis. JAMA, 2007. 297 (1): p. 52-60. Ai, J., et al., Etiology and prognosis of acute viral encephalitis and meningitis in Chinese children: a multicentre prospective study. BMC Infect Dis, 2017. 17 (1): p. 494. de Ory, F., et al., Viral infections of the central nervous system in Spain: a prospective study. J Med Virol, 2013. 85 (3): p. 554-62. Desmond, R.A., et al., Enteroviral meningitis: natural history and outcome of pleconaril therapy. Antimicrob Agents Chemother, 2006. 50 (7): p. 2409-14. Sall, O., et al., Etiology of Central Nervous System Infections in a Rural Area of Nepal Using Molecular Approaches. Am J Trop Med Hyg, 2019. 101 (1): p. 253-259. Jarrin, I., et al., Etiologies and Management of Aseptic Meningitis in Patients Admitted to an Internal Medicine Department. Medicine (Baltimore), 2016. 95 (2): p. e2372. Tan le, V., et al., Viral aetiology of central nervous system infections in adults admitted to a tertiary referral hospital in southern Vietnam over 12 years. PLoS Negl Trop Dis, 2014. 8 (8): p. e3127. Fortuna, D., et al., Potential role of CSF cytokine profiles in discriminating infectious from non-infectious CNS disorders. PLoS One, 2018. 13 (10): p. e0205501. Bronska, E., et al., Dynamics of PCR-based diagnosis in patients with invasive meningococcal disease. Clin Microbiol Infect, 2006. 12 (2): p. 137-41. John, C.C., Treatment failure with use of a third-generation cephalosporin for penicillin-resistant pneumococcal meningitis: case report and review. Clin Infect Dis, 1994. 18 (2): p. 188-93. Zhang, S., et al., Advances in Potential Cerebrospinal Fluid Biomarkers for Autoimmune Encephalitis: A Review. Front Neurol, 2022. 13 : p. 746653. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4061701","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":288862432,"identity":"b9951385-7fe6-460a-8f38-5284e9d983e6","order_by":0,"name":"Fang Jiang","email":"","orcid":"","institution":"First Affiliated Hospital of Shantou University Medical College","correspondingAuthor":false,"prefix":"","firstName":"Fang","middleName":"","lastName":"Jiang","suffix":""},{"id":288862433,"identity":"081573a4-3e54-401b-a52d-36c2cb7185d4","order_by":1,"name":"WenJun Yu","email":"","orcid":"","institution":"Second Affiliated Hospital of Shantou University Medical College","correspondingAuthor":false,"prefix":"","firstName":"WenJun","middleName":"","lastName":"Yu","suffix":""},{"id":288862434,"identity":"12bc659c-142f-4a6f-910a-b5fb75bd16f2","order_by":2,"name":"Xiaoyang Jiao","email":"","orcid":"","institution":"Shantou University Medical College","correspondingAuthor":false,"prefix":"","firstName":"Xiaoyang","middleName":"","lastName":"Jiao","suffix":""},{"id":288862435,"identity":"7a40143a-72f5-4fde-9f12-7ff81218329f","order_by":3,"name":"Mengya Si","email":"","orcid":"","institution":"First Affiliated Hospital of Shantou University Medical College","correspondingAuthor":false,"prefix":"","firstName":"Mengya","middleName":"","lastName":"Si","suffix":""},{"id":288862436,"identity":"7ffab120-c7c2-42a3-9413-206e99bde08c","order_by":4,"name":"Xuehua Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABCUlEQVRIie3PMUvDQBTA8XccXJdE14hg/QivBAIF0a/yjkK7pF0EyVqEN0nndNGvkMn5SsAuqVkDLgFHO6S4ZKuBglvSjoL3g+PB4/2HA7CsPwjNYVLzREm4v1K9R3NyIrGKpH/mvNHJibqIM6mfvfC6O1lv0i+Xb2a4NnDpspowhAB19NqaBNlsPFzy+B4zAt9lZ8qwMeIp+2hPTBjgjlOdGIKRy96UxYKk4I4k3waoea+TvITUZZwo6WBncleEfrljo5OCxDzOiJQ6kgyLbSDi95FeFqWEKjIDdhStuv6Ceeh/Ow+3epFTryY0/f7L56qso/akobzDPK9+V6brviGrIweWZVn/3Q9oF2FBz0PBlAAAAABJRU5ErkJggg==","orcid":"","institution":"First Affiliated Hospital of Shantou University Medical College","correspondingAuthor":true,"prefix":"","firstName":"Xuehua","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2024-03-10 04:30:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4061701/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4061701/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":57700327,"identity":"7a97ac5f-2504-4d2a-bb11-d787acec1374","added_by":"auto","created_at":"2024-06-04 13:44:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":642868,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4061701/v1/af7ed3d1-5bd3-4faa-b5ed-c8da92349b65.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical significance of a panel tests in evaluating central nervous system infections","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCentral nervous system (CNS) infections are a significant cause of mortality and morbidity throughout the world[1]. CNS infections, such as meningitis and encephalitis, can result from bacteria, viruses, fungi and parasites. Besides microorganisms, the causes of neuroinflammation include autoimmunity, trauma, degenerative processes, toxins, and malignancy. However, many patients with neuroinflammation have unknown causes[2]. In clinical practice, CNS inflammation with non-infectious causes have similar\u0026nbsp;clinical features to infectious causes, with some overlapping laboratory features based on the cerebrospinal fluid (CSF) or blood measurement[3, 4]. \u0026nbsp;\u0026nbsp;An incomplete understanding of the etiology of CNS infection is the main factor responsible for higher mortality and morbidity in patients with CNS infections[5, 6].\u0026nbsp;Therefore, insight into\u0026nbsp;microbial - host interactions involving in CNS infections and its relevant neurologic sequelae is instrumental in improving patient treatment and prognosis, reducing mortality, and developing new therapeutic strategies for CNS infection[1].\u003c/p\u003e\n\u003cp\u003eMany pathogens cause CNS infections. Unfortunately, the underlying pathogenes is not found in as many as 40% - 60% of patients[7]. Examination of CSF is of vital\u0026nbsp;importance for the diagnosis of CNS infection. Routine CSF examinations include biochemical tests (LDH, protein, glucose, and chloride), cytologic tests, including white blood cell (WBC) and differential count, and CSF bacterial culture. None of the above methods can precisely and sensitively detect pathogens. Bacterial and viral meningitis account for the majority of CNS infections, and their detection in CSF includes bacterialculture, antigen detection, and chemical, and cellular analyses[8]. Culture methods provide a definitive diagnosis for bacterial infection, which requires 2 to 5 days and may be falsely negative if the bacteria are fastidious or the patient was treated with antibiotics, or the specimens were improperly processed[9]. The evaluation of patients with probable viral CNS infection is complicated for lack of unified diagnostic criteria, the number of possibilities of virus that cause such infections, and the limited number of diagnostic tools[10]. Polymerase chain reaction (PCR) is a fast and specific method to detect pathogens, but single probe selection is not suitable for the detection of various unknown pathogens. The California Encephalitis Project was a multitudinous study of suspected encephalitis cases (n =1570), over seven years, which was predicated on the pathogeny of encephalitis cases. However, 63% of cases had unexplained etiology in the study despite extensive attempts to identify potential causes[11]. Failure to obtain a timely diagnosis delays choosing an appropriate therapy. The mortality rate of untreated bacterial meningitis approaches 100% and, even with timely treatment, mortality and morbidity still occurs[12].\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Nowadays, bacterial meningitis is one of the top 10 reasons for universal infection-related mortality. Present strategies for therapy of CNS infection are compromised by the uncertainty of microbial-host interactions[13]. Etiological specificity tests can improve the therapeutic effect and the prognosis. Compared to the conventional tests, detection focusing on microorganisms undoubtedly has a great advantage. PCR provides high sensitivity and specificity, and can reliably diagnose pathogens, especially for fastidious bacteria[14, 15]. \u0026nbsp;Compared with the culture and serological methods, PCR method requires a shorter time, in addition, the results of PCR are not affected by patient treatment with antibiotics. Currently, PCR is extensively used for detecting microorganisms in some tertiary hospitals. However, the disadvantage of conventional PCR techniques is also significant, since it only detects one pathogen at a time and needs to catch in batches. The time- and labor-intensiveness of PCR limits its widespread use in the diagnosis of CNS infection. In recent years, several advanced molecular diagnostic techniques show promise for rapid diagnosis, such as the GeneXpert MTB/RIF assay and loop-mediated amplification of microorganisms. However, these techniques are impractical because of the relatively high cost and the requirement for experienced professionals.\u003c/p\u003e\n\u003cp\u003eThe FilmArray ME Panel is a multiplexed nucleic acid test for the simultaneous qualitative detection and identification of a considerable number of pathogens in the CSF, and has better effectiveness compared with culture and other methods[9]. The whole process of detection only takes about an hour. Compared to traditional PCR, the FilmArray ME Panel provides fast results. Therefore, the method seems to have great potential for application. As the FilmArray ME is an novel method, it has yet to find wide use in clinical specimen detection, and its clinical significance remains to be evaluated. In this study, we recruited 130 patients with suspected meningitis, their pathogens were measured by the FilmArray ME Panel, as well as the conventional CSF tests.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec2\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003ePatients were recruited according to the following criteria: patients with fever, headache, seizure or depressed consciousness (at least one presenting symptom). Signs of cervical stiffness, alteration of consciousness, cranial nerve palsy, or plegia/paresis upon physical examination. The CSF specimen met at least one of the following criteria: 1: white blood cells (WBCs) \u0026ge; 5 cells/high power field (\u0026lt;\u0026thinsp;50% polymorphonuclear leukocytes), protein\u0026thinsp;\u0026gt;\u0026thinsp;50 mg/dL, glucose\u0026thinsp;\u0026lt;\u0026thinsp;60 mg/dL or CSF plasma glucose ratio\u0026thinsp;\u0026lt;\u0026thinsp;0.4. Patient demographics, laboratory results, clinical characteristics, imaging, therapy, and prognoses were recorded. We acquired clinical data from the patient charts that met the conditions.\u003c/p\u003e \u003cp\u003e \u003cb\u003eBiochemical and cytologic testing of CSF.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe cytologic tests included WBC count and differential count. Biochemistry results included serum creatinine, LDH, serum or CSF glucose, protein, and chloride.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eBacterial culture for blood or CSF\u003c/h2\u003e \u003cp\u003eBacterial cultures for both blood and CSF were performed on every specimen enrolled. Testing used standard clinical laboratory procedures.\u003c/p\u003e \u003cp\u003e \u003cb\u003eFilmArray ME Panel testing.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe FilmArray ME Panel can simultaneously detect 14 pathogens in CSF specimens. Approximately 200 \u0026micro;l of the sample was subjected to FilmArray\u0026reg; ME Panel testing according to the manufacturer\u0026rsquo;s instructions. The 14 pathogens detected in CSF were: \u003cem\u003eHemophilus influenza, Neisseria meningitides, Escherichia coli K1, Listeria monocytogenes\u003c/em\u003e, \u003cem\u003eStreptococcus pneumonia\u003c/em\u003e, \u003cem\u003eStreptococcus agalactiae\u003c/em\u003e, enterovirus (EV),cytomegalovirus (CMV), herpes simplex virus type 1/2 (HSV-1/2), human herpesvirus type 6 (HHV-6), varicella zoster virus (VZV), human parechovirus (HPeV), and \u003cem\u003eCryptococcus neoformans/gattii\u003c/em\u003e.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eBetween November 2017 to October 2018, 130 patients were enrolled in this study. Clinical and demographic data were presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The mean age of patients was 28 years. There were 82 male and 48 female patients, giving a male/female ratio of 1.74:1. The most common symptom was fever, which was found in 95% of patients. Headache was the second most common symptom, with 71% of patients having this problem. For other symptoms, 37% of patients had vomiting, 39% of patients were apathetic, 25% of patients had nausea and neck rigidity, 22% of patients had twitches, and 16% of patients had a disorder of consciousness. Signs of meningeal irritation presented in 11.5% of patients, and 80% of patients had fever and apathetic symptoms in the bacterial infection group. The patients with viral and fungal infections also shared the similar symptoms. There was a prominent overlap in clinical features, including fever, headache, focal neurologic deficits, and altered mental status. Twenty-one cases of patients had systemic disease, 18 patients had epilepsy, 7 patients had high blood pressure, 5 patients had heart disease, and 4 patients had diabetes. The onsite analysis showed that all samples had at least five leukocytes /\u0026micro;L in the CSF, indicating an inflammatory reaction within the CNS. During their hospital stay, thirty-one patients received antibiotic treatment (cephalosporins, astaxanthin, and sulbactam), and thirty-seven patients received antiviral drugs (oseltamivir and ribavirin), and 17 patients received combination antibiotic and antiviral treatment.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatients\u0026rsquo; general characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCases\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTotal\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e130\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u0026ndash;27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e65\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e65\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGender\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e82\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePathogen infection\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVirus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBacterial (or fungi)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnidentified\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e108\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTreatment\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntibiotic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntiviral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntiviral\u0026thinsp;+\u0026thinsp;Antibiotic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMeningitis type (\u003c/b\u003e\u003cem\u003ebased on the clinic\u003c/em\u003e\u003cb\u003e)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSuppurative meningitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eViral meningitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAutoimmune encephalitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTuberculous meningitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSystemic diseases\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh blood pressure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeart disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEpilepsy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eClinical symptom\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeadache\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e71\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNausea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVomiting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e95\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eApathetic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSleepiness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisorder of consciousness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003etwitch\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeck stiffness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMeningeal irritation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient characteristics by type of pathogen detected using the CSF or serum testing\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eparameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"9\" nameend=\"c10\" namest=\"c2\"\u003e \u003cp\u003eValue for pathogenic:\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eBacterial\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"6\" nameend=\"c9\" namest=\"c4\"\u003e \u003cp\u003eViruses\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eFungus\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eS.pneumonia\u003c/em\u003en\u0026thinsp;=\u0026thinsp;4\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eE.coli K1\u003c/em\u003e,\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eEnterovirus\u003c/em\u003e,\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;8\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eHHV-6\u003c/em\u003e,\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003eVZV\u003c/em\u003e,\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eHSV1\u003c/em\u003e,\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003eHSV2\u003c/em\u003e,\u003c/p\u003e \u003cp\u003e\u003cem\u003en\u0026thinsp;=\u0026thinsp;1\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cem\u003eCMV\u003c/em\u003e,\u003c/p\u003e \u003cp\u003e\u003cem\u003en\u0026thinsp;=\u0026thinsp;1\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cem\u003eCryptococcus neoformans,n\u0026thinsp;=\u0026thinsp;3\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCSF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eGLU\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e2.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eCL\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e120.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e116.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e118.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e118.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e125.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e107.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e116.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e113.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e113.83\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eProtein\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1370.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e270\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e330.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e135.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e531.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e373.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1207.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e850\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e489.40\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eLDH\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e708\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e28.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e40.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e24.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e29.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eADA\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e11.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e2.33\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eIgG\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e14.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e14.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e9.17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eIgA\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;1.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;1.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e2.50\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eIgM\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.69\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eWBC\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5838.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e137.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e240.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e184\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1236\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e160\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e220.67\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum(LDH)/CSF(LDH)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e5.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e19.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eCytologic and biochemical tests\u003c/h2\u003e \u003cp\u003eThe subgroup classified by bacterial, viral, and unidentified groups, and the CSF biochemistry tests were compared among the subgroups. The mean CSF glucose was the lowest in the \u003cem\u003eS. pneumonia\u003c/em\u003e group, while the highest glucose was in patients with viral infections. Mean CSF protein was the highest for patients with bacterial infections, followed by patients with fungal infections, while protein levels varied widely in the viral group. CSF LDH level was the highest in the \u003cem\u003eS. pneumonia\u003c/em\u003e group. The WBC count in CSF was elevated in the \u003cem\u003eS. pneumonia\u003c/em\u003e group, while WBC counts in the viral group were lower than those in the bacterial group.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eEtiology determined in patients with CNS infection\u003c/h2\u003e \u003cp\u003eAmong the 130 patients, pathogens were detected in 22 patients by the FilmArray ME panel, which included 8 cases of bacterial infection, 14 cases of viral infection. Bacteria detected were \u003cem\u003eStreptococcus pneumoniae\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;4), \u003cem\u003eCryptococcus neoformans\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;3), and \u003cem\u003eE.coli K1\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;1). In the 14 cases of viral infection, the most common virus was enterovirus, which was detected in eight samples, followed by 2 cases of human herpesvirus type 6 (HHV-6), and the remaining viruses detected were varicella-zoster virus(1 case), cytomegalovirus (1 case), herpes simplex virus (HSV) (1 case) type 1 (HSV-1) (1 case), and 2 cases of HSV-2.\u003c/p\u003e \u003cp\u003e \u003cb\u003eComparison the bacterial cultures and FilmArray ME panel.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eEight patients were found to have bacterial infection by the FilmArray ME Panel, among them, 4 cases were confirmed by the CSF bacterial cultures. Besides CSF culture, five patients were positive in the blood culture, thirteen cases of patients were culture positive in sputum, and seven cases of patients were detected bacterial infection in other types of specimens (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The predominant bacterium in CSF was \u003cem\u003eStreptococcus pneumonia\u003c/em\u003e (18.2%), followed by \u003cem\u003eEscherichia coli\u003c/em\u003e (4.5%). The highest coincidence of the two methods found in Cryptococcus neoformans.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of bacterial (or fungi) cultures and FilmArray RP\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eFilmArray\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c6\" namest=\"c3\"\u003e \u003cp\u003eBacterial culture\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCSF\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBlood\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSputum\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eStreptococcus pneumoniae\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eCryptococcus neoformans\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eE.coli K1\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eStreptococcus agalactiae\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eCommon bacterium\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eStaphylococcus aureus\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eStaphylococcus aureus\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eAcinetobacter baumannii\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eECO-ESBLs\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eHaemophilus influenzae\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eMoraxella\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eStenotrophomonas maltophilia\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eEnterobacter cloacae\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eEnterococcus faecium\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eMycoplasma pneumoniae\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eCandida tropicalis\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eCandida albicans\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eStaphylococcus haemolyticus\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eOthers: Mycoplasma pneumoniae culture, urine culture, lavage fluid, stool culture\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003ePrompt treatment of infectious meningitis and encephalitis are vital to minimize morbidity and mortality[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. However, the etiology behind CNS infections is quite complicated, and pathogens are still not found in up to 70% of cases. Therefore, current curative treatment for CNS infections is restricted because of incomplete knowledge of the microbial-host interactions[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] In the United States, 80% of CNS infections are induced by bacteria, including \u003cem\u003eStreptococcuspneumonia, Streptococcus agalactiae,Neisseria meningitides, Haemophilus influenzae, Escherichia coli\u003c/em\u003e (especially \u003cem\u003ethe K1 serotype\u003c/em\u003e), \u003cem\u003eand Listeria monocytogenes\u003c/em\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. \u003cem\u003eStreptococcus pneumonia\u003c/em\u003e was the main species detected in our patients with bacterial meningitis. Currently, bacterial culture of the CSF is still recognized as the gold standard for the diagnosis of bacterial meningitis[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. However, bacterial culture requires much more time to diagnosis, and the time delay may have fatal ramifications for patients or result in needless application of broad-spectrum antibiotics and delay of effective treatment. In this study, 31 cases of patients were treated empirically, but the therapeutic efficacy varied. CSF pleocytosis is a sensitive marker of inflammation. However, some studies have confirmed that patients with bacterial meningitis may have normal WBC counts. In our study, patients infected with \u003cem\u003eS. pneumonia\u003c/em\u003e had much higher WBC counts than patients infected with \u003cem\u003eE.coli K1.\u003c/em\u003e WBCs in CSF differed between bacterial infection and viral infection, and the differential WBC count, especially the lymphocyte ratio, as well as the consistency of protein and glucose, are useful in the differential diagnosis of CNS infection. However, the specificity and sensitivity of these tests are low. In this study, only 4 cases of suspected patients had bacteria detected by culture, whereas in 8 cases bacteria could be detected by The FilmArray ME, a detection rate twice that of bacterial culture. Four percents of patients had a positive blood culture, 10% patients were sputum-positive who were negative in both the FilmArray ME Panel and culture methods. Whether the patient's meningeal irritation is part of a systemic infection remains to be determined. Previous large-scale study on bacterial meningitis in pediatric patients showed that only 7% of cases had positive blood cultures[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eViruses are the primary cause of aseptic meningitis. The main causes of viral meningitis are enteroviruses[\u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], which have been related to outbreaks of CNS infections worldwide[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. However, the etiology of viral encephalitis varies from one region to another. HSV is the main pathogen of viral encephalitis in many countries, such as England, the USA,France, and Spain[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Enterovirus is the major pathogen inducing viral encephalitis in China[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. In our study, more than half of viral meningitis infected by enterovirus, and those patients presented multifarious clinical syndromes, including aseptic meningitis, and acute flaccid paralysis/myelitis. In a state of unknown etiology, epidemiology and clinical symptoms may provide some diagnostic clues.\u003c/p\u003e \u003cp\u003eIn clinic, one of the challenges in the diagnosis of CNS disease is the coincide in the clinical presentation of a considerable variety of diseases[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Rapidly distinguishing CNS infections from other brain and spinal cord disorders is critical for adequate treatment, which ultimately determines the patient's prognosis. The FilmArray ME Panel can detect a broad range of pathogens in CSF, representing a significant paradigm shift of performance from culture to molecular reference methods. In this study, enterovirus-positive specimens were re-examined by PCR, and the coincidence rate was 100%, whereas for bacterial detection, the FilmArray ME Panel had twice the detection rate of bacterial culture. The high incidence of prior antibiotic treatment before intervention may have reduced the detection rate of pathogenic bacteria[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Our results show that the FilmArray ME Panel has significant advantages compared to bacterial culture. In a previous study, about 60% of patients obtained a definite diagnosis[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] and mandated empiric antimicrobial therapy. Frequent use of broad-spectrum antibiotics will result in multidrug resistance[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Empiric therapy for patients with bacterial meningitis is prevalent in areas with penicillin-resistant and third-generation cephalosporin-resistant S. pneumonia[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Rapid tests for both bacterial and viral pathogens will be considerably useful for young infants, and may potentially provide more targeted therapy. Because of its large number of advantages, including close-to-patient, rapid detection of a broad range of infectious agents associated with CNS infections[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], the FilmArray ME Panel has a wide range of prospective applications in clinical practice.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere was no funding for my paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;Ethics approval\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol was approved by the Ethics Committee of Shantou University Medical College(B-2021-037).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eAvailability of data\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the data has been listed in the tables of the article, so there is no need to upload it separately.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCode availability :\u0026nbsp;\u003c/strong\u003eThere is not available for my paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for publication was obtained from all participants. I hope this paper will be considerated by your journal. This article was not submitted to other magazines.\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFang Jiang:ConceptualizationIdeas;\u0026nbsp;Methodology and Data Curation\u003c/p\u003e\n\u003cp\u003eWenjun Yu: Writing Original Draft\u003c/p\u003e\n\u003cp\u003eMengYa Si :Formal analysis and Investigation\u003c/p\u003e\n\u003cp\u003eXiaoYang Jiao::Writing - Review and\u0026nbsp;Editing the paper\u003c/p\u003e\n\u003cp\u003eXueHua Wang::Writing - Review and Editing the paper\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eShah, S., et al., \u003cem\u003eThe Promise of Molecular Imaging: Focus on Central Nervous System Infections.\u003c/em\u003e J Infect Dis, 2023. \u003cstrong\u003e228\u003c/strong\u003e(Suppl 4): p. S311-S321.\u003c/li\u003e\n\u003cli\u003eGraus, F., et al., \u003cem\u003eA clinical approach to diagnosis of autoimmune encephalitis.\u003c/em\u003e Lancet Neurol, 2016. \u003cstrong\u003e15\u003c/strong\u003e(4): p. 391-404.\u003c/li\u003e\n\u003cli\u003eShives, K.D., K.L. Tyler, and J.D. Beckham, \u003cem\u003eMolecular mechanisms of neuroinflammation and injury during acute viral encephalitis.\u003c/em\u003e J Neuroimmunol, 2017. \u003cstrong\u003e308\u003c/strong\u003e: p. 102-111.\u003c/li\u003e\n\u003cli\u003eBrown, B., et al., \u003cem\u003eDefining diagnostic approaches and outcomes in patients with inflammatory CSF: A retrospective cohort study.\u003c/em\u003e Clin Neurol Neurosurg, 2018. \u003cstrong\u003e172\u003c/strong\u003e: p. 105-111.\u003c/li\u003e\n\u003cli\u003eWeisfelt, M., et al., \u003cem\u003eA risk score for unfavorable outcome in adults with bacterial meningitis.\u003c/em\u003e Ann Neurol, 2008. \u003cstrong\u003e63\u003c/strong\u003e(1): p. 90-7.\u003c/li\u003e\n\u003cli\u003eKim, K.S., \u003cem\u003eMechanisms of microbial traversal of the blood-brain barrier.\u003c/em\u003e Nat Rev Microbiol, 2008. \u003cstrong\u003e6\u003c/strong\u003e(8): p. 625-34.\u003c/li\u003e\n\u003cli\u003eTack, D.M., et al., \u003cem\u003eTrends in encephalitis-associated deaths in the United States, 1999-2008.\u003c/em\u003e Neuroepidemiology, 2014. \u003cstrong\u003e43\u003c/strong\u003e(1): p. 1-8.\u003c/li\u003e\n\u003cli\u003eGomes, H.R., \u003cem\u003eCerebrospinal fluid analysis: current diagnostic methods in central nervous system infectious diseases.\u003c/em\u003e Arq Neuropsiquiatr, 2022. \u003cstrong\u003e80\u003c/strong\u003e(5 Suppl 1): p. 290-295.\u003c/li\u003e\n\u003cli\u003eHanson, K.E., \u003cem\u003eThe First Fully Automated Molecular Diagnostic Panel for Meningitis and Encephalitis: How Well Does It Perform, and When Should It Be Used?\u003c/em\u003e J Clin Microbiol, 2016. \u003cstrong\u003e54\u003c/strong\u003e(9): p. 2222-4.\u003c/li\u003e\n\u003cli\u003eMantke, R., \u003cem\u003e[Complexity of DRG routine data also makes the interpretation of thyroid surgery difficult].\u003c/em\u003e Chirurg, 2017. \u003cstrong\u003e88\u003c/strong\u003e(6): p. 532-533.\u003c/li\u003e\n\u003cli\u003eGlaser, C.A., et al., \u003cem\u003eBeyond viruses: clinical profiles and etiologies associated with encephalitis.\u003c/em\u003e Clin Infect Dis, 2006. \u003cstrong\u003e43\u003c/strong\u003e(12): p. 1565-77.\u003c/li\u003e\n\u003cli\u003eKim, K.S., \u003cem\u003eInvestigating Bacterial Penetration of the Blood-Brain Barrier for the Pathogenesis, Prevention, and Therapy of Bacterial Meningitis.\u003c/em\u003e ACS Infect Dis, 2020. \u003cstrong\u003e6\u003c/strong\u003e(1): p. 34-42.\u003c/li\u003e\n\u003cli\u003eKim, K.S., \u003cem\u003eTreatment strategies for central nervous system infections.\u003c/em\u003e Expert Opin Pharmacother, 2009. \u003cstrong\u003e10\u003c/strong\u003e(8): p. 1307-17.\u003c/li\u003e\n\u003cli\u003eGao, Z.X., et al., \u003cem\u003eAdvances in laboratory diagnostic methods for cerebrospinal fluid testing for neurosyphilis.\u003c/em\u003e Front Public Health, 2022. \u003cstrong\u003e10\u003c/strong\u003e: p. 1030480.\u003c/li\u003e\n\u003cli\u003eRuuskanen, O., et al., \u003cem\u003eViral pneumonia.\u003c/em\u003e Lancet, 2011. \u003cstrong\u003e377\u003c/strong\u003e(9773): p. 1264-75.\u003c/li\u003e\n\u003cli\u003eNigrovic, L.E., et al., \u003cem\u003eEffect of antibiotic pretreatment on cerebrospinal fluid profiles of children with bacterial meningitis.\u003c/em\u003e Pediatrics, 2008. \u003cstrong\u003e122\u003c/strong\u003e(4): p. 726-30.\u003c/li\u003e\n\u003cli\u003e!!! INVALID CITATION !!! {}.\u003c/li\u003e\n\u003cli\u003eNigrovic, L.E., et al., \u003cem\u003eClinical prediction rule for identifying children with cerebrospinal fluid pleocytosis at very low risk of bacterial meningitis.\u003c/em\u003e JAMA, 2007. \u003cstrong\u003e297\u003c/strong\u003e(1): p. 52-60.\u003c/li\u003e\n\u003cli\u003eAi, J., et al., \u003cem\u003eEtiology and prognosis of acute viral encephalitis and meningitis in Chinese children: a multicentre prospective study.\u003c/em\u003e BMC Infect Dis, 2017. \u003cstrong\u003e17\u003c/strong\u003e(1): p. 494.\u003c/li\u003e\n\u003cli\u003ede Ory, F., et al., \u003cem\u003eViral infections of the central nervous system in Spain: a prospective study.\u003c/em\u003e J Med Virol, 2013. \u003cstrong\u003e85\u003c/strong\u003e(3): p. 554-62.\u003c/li\u003e\n\u003cli\u003eDesmond, R.A., et al., \u003cem\u003eEnteroviral meningitis: natural history and outcome of pleconaril therapy.\u003c/em\u003e Antimicrob Agents Chemother, 2006. \u003cstrong\u003e50\u003c/strong\u003e(7): p. 2409-14.\u003c/li\u003e\n\u003cli\u003eSall, O., et al., \u003cem\u003eEtiology of Central Nervous System Infections in a Rural Area of Nepal Using Molecular Approaches.\u003c/em\u003e Am J Trop Med Hyg, 2019. \u003cstrong\u003e101\u003c/strong\u003e(1): p. 253-259.\u003c/li\u003e\n\u003cli\u003eJarrin, I., et al., \u003cem\u003eEtiologies and Management of Aseptic Meningitis in Patients Admitted to an Internal Medicine Department.\u003c/em\u003e Medicine (Baltimore), 2016. \u003cstrong\u003e95\u003c/strong\u003e(2): p. e2372.\u003c/li\u003e\n\u003cli\u003eTan le, V., et al., \u003cem\u003eViral aetiology of central nervous system infections in adults admitted to a tertiary referral hospital in southern Vietnam over 12 years.\u003c/em\u003e PLoS Negl Trop Dis, 2014. \u003cstrong\u003e8\u003c/strong\u003e(8): p. e3127.\u003c/li\u003e\n\u003cli\u003eFortuna, D., et al., \u003cem\u003ePotential role of CSF cytokine profiles in discriminating infectious from non-infectious CNS disorders.\u003c/em\u003e PLoS One, 2018. \u003cstrong\u003e13\u003c/strong\u003e(10): p. e0205501.\u003c/li\u003e\n\u003cli\u003eBronska, E., et al., \u003cem\u003eDynamics of PCR-based diagnosis in patients with invasive meningococcal disease.\u003c/em\u003e Clin Microbiol Infect, 2006. \u003cstrong\u003e12\u003c/strong\u003e(2): p. 137-41.\u003c/li\u003e\n\u003cli\u003eJohn, C.C., \u003cem\u003eTreatment failure with use of a third-generation cephalosporin for penicillin-resistant pneumococcal meningitis: case report and review.\u003c/em\u003e Clin Infect Dis, 1994. \u003cstrong\u003e18\u003c/strong\u003e(2): p. 188-93.\u003c/li\u003e\n\u003cli\u003eZhang, S., et al., \u003cem\u003eAdvances in Potential Cerebrospinal Fluid Biomarkers for Autoimmune Encephalitis: A Review.\u003c/em\u003e Front Neurol, 2022. \u003cstrong\u003e13\u003c/strong\u003e: p. 746653.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Central nervous system infection, FilmArray ME panel, meningitis, encephalitis","lastPublishedDoi":"10.21203/rs.3.rs-4061701/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4061701/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eAim\u003c/h2\u003e \u003cp\u003eThe FilmArray ME Panel is an emerging diagnostic method for detecting multiple pathogens in cerebrospinal fluid (CSF). We evaluated the clinical significance of the FilmArray ME Panel in the diagnosis of central nervous system (CNS) infection.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eCSF specimens of 130 patients with suspected CNS infection were analyzed, along with clinical and laboratory parameters.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003epatients shared some clinical symptoms at presentation, including fever, headache, altered mental status, and focal neurologic deficits. In a total of 130 patients, pathogens were detected in 22 cases, which included eight bacterial infections, and fourteen viral infections. The predominant bacteria detected in CSF were \u003cem\u003eStreptococcus pneumonia\u003c/em\u003e, while the most common virus was enterovirus. The FilmArray ME panel had a better coincidence rate with PCR for viral detection, but had higher sensitivity compared with conventional bacterial detection.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003ethe FilmArray ME Panel provides rapid diagnosis that benefits enabling patients to be promptly treated, improving the effectiveness of treatment.\u003c/p\u003e","manuscriptTitle":"Clinical significance of a panel tests in evaluating central nervous system infections","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-10 04:38:05","doi":"10.21203/rs.3.rs-4061701/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3c760efc-429a-43c2-9988-7d538d91c720","owner":[],"postedDate":"April 10th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-06-04T13:36:25+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-10 04:38:05","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4061701","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4061701","identity":"rs-4061701","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}