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  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">87</journal-id>
      <journal-id journal-id-type="index">urn:lsid:arphahub.com:pub:A116C711-4C18-5A38-8F1E-5E97753A8A64</journal-id>
      <journal-title-group>
        <journal-title xml:lang="en">Folia Medica</journal-title>
        <abbrev-journal-title xml:lang="en">FM</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0204-8043</issn>
      <issn pub-type="epub">1314-2143</issn>
      <publisher>
        <publisher-name>Plovdiv Medical University</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="doi">10.3897/folmed.64.e65456</article-id>
      <article-id pub-id-type="publisher-id">65456</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>A comparative study between children and adults with bacterial neuroinfections</article-title>
      </title-group>
      <contrib-group content-type="authors">
        <contrib contrib-type="author" corresp="yes">
          <name name-style="western">
            <surname>Argirova</surname>
            <given-names>Petya K.</given-names>
          </name>
          <email xlink:type="simple">petia_med6@abv.bg</email>
          <xref ref-type="aff" rid="A1">1</xref>
          <xref ref-type="aff" rid="A2">2</xref>
        </contrib>
        <contrib contrib-type="author" corresp="no">
          <name name-style="western">
            <surname>Kalchev</surname>
            <given-names>Yordan I.</given-names>
          </name>
          <uri content-type="orcid">https://orcid.org/0000-0001-8062-6799</uri>
          <xref ref-type="aff" rid="A1">1</xref>
          <xref ref-type="aff" rid="A2">2</xref>
        </contrib>
        <contrib contrib-type="author" corresp="no">
          <name name-style="western">
            <surname>Boev</surname>
            <given-names>Ivan P.</given-names>
          </name>
          <xref ref-type="aff" rid="A1">1</xref>
          <xref ref-type="aff" rid="A2">2</xref>
        </contrib>
        <contrib contrib-type="author" corresp="no">
          <name name-style="western">
            <surname>Vatev</surname>
            <given-names>Nikolay T.</given-names>
          </name>
          <xref ref-type="aff" rid="A1">1</xref>
        </contrib>
        <contrib contrib-type="author" corresp="no">
          <name name-style="western">
            <surname>Murdjeva</surname>
            <given-names>Marianna A.</given-names>
          </name>
          <xref ref-type="aff" rid="A1">1</xref>
          <xref ref-type="aff" rid="A2">2</xref>
        </contrib>
        <contrib contrib-type="author" corresp="no">
          <name name-style="western">
            <surname>Vartigova</surname>
            <given-names>Mariyana S.</given-names>
          </name>
          <xref ref-type="aff" rid="A1">1</xref>
          <xref ref-type="aff" rid="A2">2</xref>
        </contrib>
      </contrib-group>
      <aff id="A1">
        <label>1</label>
        <addr-line content-type="verbatim">Department of Infectious Diseases and Parasitology, Faculty of Medicine, Medical University of Plovdiv, Plovdiv, Bulgaria</addr-line>
        <institution>Medical University of Plovdiv</institution>
        <addr-line content-type="city">Plovdiv</addr-line>
        <country>Bulgaria</country>
      </aff>
      <aff id="A2">
        <label>2</label>
        <addr-line content-type="verbatim">Clinic of Infectious Diseases, St George University Hospital, Plovdiv, Bulgaria</addr-line>
        <institution>St George University Hospital</institution>
        <addr-line content-type="city">Plovdiv</addr-line>
        <country>Bulgaria</country>
      </aff>
      <aff id="A3">
        <label>3</label>
        <addr-line content-type="verbatim">Department of Microbiology and Immunology, Faculty of Pharmacy, Medical University of Plovdiv, Plovdiv, Bulgaria</addr-line>
        <institution>Medical University of Plovdiv</institution>
        <addr-line content-type="city">Plovdiv</addr-line>
        <country>Bulgaria</country>
      </aff>
      <aff id="A4">
        <label>4</label>
        <addr-line content-type="verbatim">Laboratory of Microbiology, St George University Hospital, Plovdiv, Bulgaria</addr-line>
        <institution>St George University Hospital</institution>
        <addr-line content-type="city">Plovdiv</addr-line>
        <country>Bulgaria</country>
      </aff>
      <aff id="A5">
        <label>5</label>
        <addr-line content-type="verbatim">Research Institute, Medical University of Plovdiv, Plovdiv, Bulgaria</addr-line>
        <institution>Medical University of Plovdiv</institution>
        <addr-line content-type="city">Plovdiv</addr-line>
        <country>Bulgaria</country>
      </aff>
      <aff id="A6">
        <label>6</label>
        <addr-line content-type="verbatim">Department of Epidemiology and Disaster Medicine, Faculty of Public Health, Medical University of Plovdiv, Plovdiv, Bulgaria</addr-line>
        <institution>St George University Hospital</institution>
        <addr-line content-type="city">Plovdiv</addr-line>
        <country>Bulgaria</country>
      </aff>
      <author-notes>
        <fn fn-type="corresp">
          <p>Corresponding author: Petya K. Argirova, Department of Infectious Diseases and Parasitology, Faculty of Medicine, Medical University of Plovdiv, 15A Vassil Aprilov Blvd., 4002 Plovdiv, Bulgaria; Email: <email xlink:type="simple">Petya.Argirova@phd.mu-plovdiv.bg</email>; Tel.: +359 895 708 405</p>
        </fn>
      </author-notes>
      <pub-date pub-type="collection">
        <year>2022</year>
      </pub-date>
      <pub-date pub-type="epub">
        <day>30</day>
        <month>06</month>
        <year>2022</year>
      </pub-date>
      <volume>64</volume>
      <issue>3</issue>
      <fpage>408</fpage>
      <lpage>414</lpage>
      <uri content-type="arpha" xlink:href="http://openbiodiv.net/FE6327C6-0A2B-5CFF-826B-31FBA1FBEAD2">FE6327C6-0A2B-5CFF-826B-31FBA1FBEAD2</uri>
      <history>
        <date date-type="received">
          <day>06</day>
          <month>03</month>
          <year>2021</year>
        </date>
        <date date-type="accepted">
          <day>18</day>
          <month>05</month>
          <year>2021</year>
        </date>
      </history>
      <permissions>
        <copyright-statement>Petya K. Argirova, Yordan I. Kalchev, Ivan P. Boev, Nikolay T. Vatev, Marianna A. Murdjeva, Mariyana S. Vartigova</copyright-statement>
        <license license-type="creative-commons-attribution" xlink:href="http://creativecommons.org/licenses/by/4.0/" xlink:type="simple">
          <license-p>This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p>
        </license>
      </permissions>
      <abstract>
        <p>
          <bold>Abstract</bold>
        </p>
        <p><bold>Introduction</bold>: Bacterial <tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Neisseria"/><tp:taxon-name-part taxon-name-part-type="species" reg="meningitis">meningitis</tp:taxon-name-part></tp:taxon-name> is an acute purulent infection of the meninges. There are significant differences in the etiological spectrum, clinical course and outcome of bacterial <tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Neisseria"/><tp:taxon-name-part taxon-name-part-type="species" reg="meningitis">meningitis</tp:taxon-name-part></tp:taxon-name> in the age groups, and their recognition is important for early diagnosis and adequate therapy.</p>
        <p><bold>Aim</bold>: The study aims to determine the differences in the etiology and clinical presentation of bacterial <tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Neisseria"/><tp:taxon-name-part taxon-name-part-type="species" reg="meningitis">meningitis</tp:taxon-name-part></tp:taxon-name> between children and adults.</p>
        <p><bold>Materials and methods</bold>: The study included 90 patients (25 children and 65 adults) with bacterial neuroinfection admitted to St George University Hospital, Plovdiv between January 1, 2016 and September 31, 2019. We applied epidemiological and clinical analysis, microbiological and statistical methods.</p>
        <p><bold>Results</bold>: In adults, the most common etiological agent was <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Streptococcus">Streptococcus</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="pneumoniae">pneumoniae</tp:taxon-name-part></tp:taxon-name></italic> (20%), followed by <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Staphylococcus">Staphylococcus</tp:taxon-name-part></tp:taxon-name></italic> spp. (18.5%), <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Listeria">Listeria</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="monocytogenes">monocytogenes</tp:taxon-name-part></tp:taxon-name></italic> (12.3%), <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Streptococcus">Streptococcus</tp:taxon-name-part></tp:taxon-name></italic> spp. (3.1%), <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Haemophilus">Haemophilus</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="influenzae">influenzae</tp:taxon-name-part></tp:taxon-name></italic> (3.1%), <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Klebsiella">Klebsiella</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="pneumoniae">pneumoniae</tp:taxon-name-part></tp:taxon-name></italic> (1.5%), and <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Mycobacterium">Mycobacterium</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="tuberculosis">tuberculosis</tp:taxon-name-part></tp:taxon-name></italic> (1.5%). The etiological structure in children was different: <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Neisseria">Neisseria</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="meningitidis">meningitidis</tp:taxon-name-part></tp:taxon-name></italic> (20%), <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Streptococcus">Streptococcus</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="pneumoniae">pneumoniae</tp:taxon-name-part></tp:taxon-name></italic> (16%), <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Klebsiella">Klebsiella</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="pneumoniae">pneumoniae</tp:taxon-name-part></tp:taxon-name></italic> (8%), <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Enterococcus">Enterococcus</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="faecium">faecium</tp:taxon-name-part></tp:taxon-name></italic> (8%), <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Streptococcus">Streptococcus</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="salivarius">salivarius</tp:taxon-name-part></tp:taxon-name></italic> (4%), and <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Mycobacterium">Mycobacterium</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="tuberculosis">tuberculosis</tp:taxon-name-part></tp:taxon-name></italic> (4%). In 40% of the cases, both children and adults, the causative agent was not identified.</p>
        <p><bold>Conclusions</bold>: Regarding the clinical presentation, a statistical significance between the age groups was found with headache and alterations in consciousness, more commonly seen in adults, while vomiting, ear pain was more common in children (<italic>p</italic>&lt;0.05). Concomitant otitis, sinusitis, pneumonia, and sepsis were often observed. The mortality rate was much higher in adults (43%) when compared with children (8%).</p>
      </abstract>
      <kwd-group>
        <label>Keywords</label>
        <kwd>age</kwd>
        <kwd>etiology</kwd>
        <kwd>
          <tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Neisseria"/> <tp:taxon-name-part taxon-name-part-type="species" reg="meningitis">meningitis</tp:taxon-name-part></tp:taxon-name>
        </kwd>
        <kwd>meningoencephalitis</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="Introduction" id="SECID0EAEAC">
      <title>Introduction</title>
      <p>Bacterial <tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Neisseria"/><tp:taxon-name-part taxon-name-part-type="species" reg="meningitis">meningitis</tp:taxon-name-part></tp:taxon-name> is an acute purulent infection of the meninges and subarachnoid space. If the brain parenchyma is also involved in the inflammatory reaction, meningoencephalitis develops.<sup>[<xref ref-type="bibr" rid="B1">1</xref>]</sup> In adults, the majority of bacterial <tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Neisseria"/><tp:taxon-name-part taxon-name-part-type="species" reg="meningitis">meningitis</tp:taxon-name-part></tp:taxon-name> in Europe is caused by <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Streptococcus">S.</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="pneumoniae">pneumoniae</tp:taxon-name-part></tp:taxon-name></italic> (53%), followed by <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Neisseria">N.</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="meningitidis">meningitidis</tp:taxon-name-part></tp:taxon-name></italic> (27%). <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Listeria">L.</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="monocytogenes">monocytogenes</tp:taxon-name-part></tp:taxon-name></italic> (4%) is the third most common cause in adults and is associated with old age and immunosuppression. <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Haemophilus">H.</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="influenzae">influenzae</tp:taxon-name-part></tp:taxon-name></italic> (3%) in adults has been associated with concomitant conditions such as otitis and sinusitis. <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Staphylococcus">Staphylococcus</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="aureus">aureus</tp:taxon-name-part></tp:taxon-name></italic> association with <tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Neisseria"/><tp:taxon-name-part taxon-name-part-type="species" reg="meningitis">meningitis</tp:taxon-name-part></tp:taxon-name> is rare (1-2%).<sup>[<xref ref-type="bibr" rid="B2">2</xref>]</sup> Bacterial <tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Neisseria"/><tp:taxon-name-part taxon-name-part-type="species" reg="meningitis">meningitis</tp:taxon-name-part></tp:taxon-name> in children in Europe is due to <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Neisseria">N.</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="meningitidis">meningitidis</tp:taxon-name-part></tp:taxon-name></italic> (50%), <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Streptococcus">S.</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="pneumoniae">pneumoniae</tp:taxon-name-part></tp:taxon-name></italic> (37%), and <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Haemophilus">H.</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="influenzae">influenzae</tp:taxon-name-part></tp:taxon-name></italic> (5%). In China, the main etiological agent in this age group is <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Streptococcus">S.</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="pneumoniae">pneumoniae</tp:taxon-name-part></tp:taxon-name></italic> (33.2%), followed by <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Escherichia">Escherichia</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="coli">coli</tp:taxon-name-part></tp:taxon-name></italic> (10.9%), <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Enterococcus">Enterococcus</tp:taxon-name-part></tp:taxon-name></italic> spp. (10%), <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Streptococcus">Streptococcus</tp:taxon-name-part></tp:taxon-name> group B</italic> (8.2%), <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Staphylococcus">S.</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="aureus">aureus</tp:taxon-name-part></tp:taxon-name></italic> (4.1%), <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Pseudomonas">Pseudomonas</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="aeruginosa">aeruginosa</tp:taxon-name-part></tp:taxon-name></italic> (4.1%), <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Salmonella">Salmonella</tp:taxon-name-part></tp:taxon-name></italic> spp. (3.6%).<sup>[<xref ref-type="bibr" rid="B3">3</xref>]</sup></p>
      <p>Bacterial <tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Neisseria"/><tp:taxon-name-part taxon-name-part-type="species" reg="meningitis">meningitis</tp:taxon-name-part></tp:taxon-name> in children usually begins with fever (93%). Headache is registered in 75% of children over 5 years; vomiting in 61%; rash - 60%; neck stiffness - 61%. Seizures occur in 33% of children, alteration in consciousness in 34.5%, and focal neurological deficit in 13.5%.<sup>[<xref ref-type="bibr" rid="B4">4</xref>]</sup> The most common symptoms associated with the disease in adults are headache, fever, neck stiffness, and changes in consciousness. Data from European studies (1996–2010) show that in adults fever occurs on average in 90% of cases; headache in 77%; vomiting - 60%; rash - 33%; seizures - 22.5%; neck stiffness - 75%, impaired consciousness - 57% (coma - 13%), and focal deficits in 23%.<sup>[<xref ref-type="bibr" rid="B5">5</xref>,6]</sup> Concomitant diseases occur in 48% of adults, with otitis or sinusitis (25%) and pneumonia (12%) being among the most common.<sup>[<xref ref-type="bibr" rid="B7">7</xref>,8]</sup></p>
      <p>There are significant differences in the etiological spectrum, clinical presentation and outcome of bacterial <tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Neisseria"/><tp:taxon-name-part taxon-name-part-type="species" reg="meningitis">meningitis</tp:taxon-name-part></tp:taxon-name> in the age groups, and their recognition is important for early diagnosis and adequate therapy.</p>
    </sec>
    <sec sec-type="Aim" id="SECID0ECMAC">
      <title>Aim</title>
      <p>The aim of the study was to establish the differences in the etiology and clinical course of bacterial neuroinfections between children and adults.</p>
    </sec>
    <sec sec-type="materials|methods" id="SECID0EHMAC">
      <title>Materials and methods</title>
      <p>The study included 90 patients with bacterial neuroinfection admitted to St George University Hospital in Plovdiv from January 1, 2016 to September 31, 2019. There were 25 children (up to 17 years of age) and 65 adults (range 18–87 years). The diagnosis was based on the clinical presentation, cerebrospinal fluid (CSF) examination, and microbiological testing.</p>
      <p>Only patients with typical CSF abnormalities consistent with bacterial <tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Neisseria"/><tp:taxon-name-part taxon-name-part-type="species" reg="meningitis">meningitis</tp:taxon-name-part></tp:taxon-name> were included in the study (cell count &gt;100×10<sup>6</sup>/l, protein &gt;1 g/l, CSF/serum glucose ratio ≤0.4) and/or identified etiology by the CSF microbiological analysis.</p>
      <p>We used in the study:</p>
      <p>1. Epidemiological data about age and sex;</p>
      <p>2. Clinical analysis;</p>
      <p>3. Microbiological testing included CSF Gram stain and culture. Multiplex PCR for viral and bacterial agents was performed in 28 of the patients with bacterial neuroinfection. It is based on the detection of specific target genes of the most common causative agents by Biofire FilmArray Multiplex PCR (bioMerieux, France). The panel simultaneously identifies the following bacterial pathogens: <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Streptococcus">S.</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="pneumoniae">pneumoniae</tp:taxon-name-part></tp:taxon-name></italic>, <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Streptococcus">Streptococcus</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="agalactiae">agalactiae</tp:taxon-name-part></tp:taxon-name></italic>, <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Neisseria">N.</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="meningitis">meningitis</tp:taxon-name-part></tp:taxon-name></italic>, <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Listeria">L.</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="monocytogenes">monocytogenes</tp:taxon-name-part></tp:taxon-name></italic>, <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Haemophilus">H.</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="influenzae">influenzae</tp:taxon-name-part></tp:taxon-name></italic>, <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Escherichia">Escherichia</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="coli">coli</tp:taxon-name-part></tp:taxon-name></italic> K1.</p>
      <p>4. Statistical analysis: descriptive methods; parametric and non-parametric methods: Fisher’s exact test and <italic>χ</italic><sup>2</sup>; Kolmogorov-Smirnov test. The significance level of the null hypothesis is <italic>p</italic>&lt;0.05. Statistical data analysis was performed using the software product SPSS v.17 (IBM, USA).</p>
    </sec>
    <sec sec-type="Results" id="SECID0EHPAC">
      <title>Results</title>
      <sec sec-type="Distribution of patients according to age, gender, and etiology" id="SECID0ELPAC">
        <title>Distribution of patients according to age, gender, and etiology</title>
        <p>Over the observation period, we found 25 children (27.8%) and 65 adults (72.2%) with bacterial <tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Neisseria"/><tp:taxon-name-part taxon-name-part-type="species" reg="meningitis">meningitis</tp:taxon-name-part></tp:taxon-name>/meningoencephalitis. Children were divided into the following age groups: &lt;1 year (n=7); 1 to 4 years (n=10); 5 to 9 years (n=5), and 10 to 17 years (n=3).</p>
        <p>The gender distribution showed that among adults males were 39 (60%) and females - 26 (40%). In the group of children, 16 were males (64%) and 9 females (36%).</p>
        <p>In adults <bold>(Fig. <xref ref-type="fig" rid="F1">1</xref>)</bold> the most common etiological cause was <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Streptococcus">S.</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="pneumoniae">pneumoniae</tp:taxon-name-part></tp:taxon-name></italic> (n=13), followed by <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Staphylococcus">Staphylococcus</tp:taxon-name-part></tp:taxon-name></italic> spp. (n=12), mainly <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Staphylococcus">S.</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="aureus">aureus</tp:taxon-name-part></tp:taxon-name></italic> and two <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Staphylococcus">Staphylococcus</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="coagulase">coagulase</tp:taxon-name-part></tp:taxon-name></italic>-<italic>negative</italic> (CоNS), <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Listeria">L.</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="monocytogenes">monocytogenes</tp:taxon-name-part></tp:taxon-name></italic> (n=8). Less frequent agents were <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Streptococcus">Streptococcus</tp:taxon-name-part></tp:taxon-name></italic> spp. (n=2), <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Haemophilus">H.</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="influenzae">influenzae</tp:taxon-name-part></tp:taxon-name></italic> (n=2), <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Klebsiella">K.</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="pneumoniae">pneumoniae</tp:taxon-name-part></tp:taxon-name></italic> (n=1), and <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Mycobacterium">Mycobacterium</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="tuberculosis">tuberculosis</tp:taxon-name-part></tp:taxon-name></italic> (n=1).</p>
        <fig id="F1" position="float" orientation="portrait">
          <object-id content-type="arpha">D94D5312-1B6F-5F98-8B07-CE710AAA670D</object-id>
          <label>Figure 1.</label>
          <caption>
            <p>Etiology of bacterial neuroinfections in adults (n=65).</p>
          </caption>
          <graphic xlink:href="foliamedica-64-3-e65456-g001.jpg" position="float" orientation="portrait" xlink:type="simple" id="oo_708297.jpg">
            <uri content-type="original_file">https://binary.pensoft.net/fig/708297</uri>
          </graphic>
        </fig>
        <p>The most common etiological cause in children <bold>(Fig. <xref ref-type="fig" rid="F2">2</xref>)</bold> was <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Neisseria">N.</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="meningitidis">meningitidis</tp:taxon-name-part></tp:taxon-name></italic> (n=5), and <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Streptococcus">S.</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="pneumoniae">pneumoniae</tp:taxon-name-part></tp:taxon-name></italic> came second (n=4). They were followed by <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Klebsiella">K.</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="pneumoniae">pneumoniae</tp:taxon-name-part></tp:taxon-name></italic> (n=2), <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Enterococcus">Enterococcus</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="faecium">faecium</tp:taxon-name-part></tp:taxon-name></italic> (n=2), <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Streptococcus">Streptococcus</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="salivarius">salivarius</tp:taxon-name-part></tp:taxon-name></italic> (n=1), and <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Mycobacterium">Mycobacterium</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="tuberculosis">tuberculosis</tp:taxon-name-part></tp:taxon-name></italic> (n=1). Forty percent of the cases remained unidentified in both age groups.</p>
        <fig id="F2" position="float" orientation="portrait">
          <object-id content-type="arpha">D4F1323A-0172-585E-A02D-44FA4A3B2251</object-id>
          <label>Figure 2.</label>
          <caption>
            <p>Etiology of bacterial neuroinfections in children (n=25).</p>
          </caption>
          <graphic xlink:href="foliamedica-64-3-e65456-g002.jpg" position="float" orientation="portrait" xlink:type="simple" id="oo_708298.jpg">
            <uri content-type="original_file">https://binary.pensoft.net/fig/708298</uri>
          </graphic>
        </fig>
        <p>The etiological distribution in children and adults differed significantly (<italic>χ</italic><sup>2</sup>=23.799; <italic>р</italic>=0.0001) <bold>(Table <xref ref-type="table" rid="T1">1</xref>)</bold>. Meningococcal <tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Neisseria"/><tp:taxon-name-part taxon-name-part-type="species" reg="meningitis">meningitis</tp:taxon-name-part></tp:taxon-name> affects only children, and listerial and staphylococcal <tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Neisseria"/><tp:taxon-name-part taxon-name-part-type="species" reg="meningitis">meningitis</tp:taxon-name-part></tp:taxon-name> - exclusively adults. Adults predominated (76.5%) in the group of pneumococcal <tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Neisseria"/><tp:taxon-name-part taxon-name-part-type="species" reg="meningitis">meningitis</tp:taxon-name-part></tp:taxon-name>. The ratio is similar for the etiologically unidentified cases of <tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Neisseria"/><tp:taxon-name-part taxon-name-part-type="species" reg="meningitis">meningitis</tp:taxon-name-part></tp:taxon-name> (72.2% were adults).</p>
        <table-wrap id="T1" position="float" orientation="portrait">
          <label>Table 1.</label>
          <caption>
            <p>Etiology of bacterial neuroinfections in children and adults</p>
          </caption>
          <table id="TID0ELHAE" rules="all">
            <tbody>
              <tr>
                <td rowspan="1" colspan="1">
                  <bold>Etiology groups (EG)</bold>
                </td>
                <td rowspan="1" colspan="1">
                  <bold>Children n (% of ЕG)</bold>
                </td>
                <td rowspan="1" colspan="1">
                  <bold>Adults n (% of ЕG)</bold>
                </td>
                <td rowspan="1" colspan="1">
                  <bold>Total n (% of ЕG)</bold>
                </td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">
                  <italic>
                    <tp:taxon-name>
                  <tp:taxon-name-part taxon-name-part-type="genus" reg="Streptococcus">S.</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="pneumoniae">pneumoniae</tp:taxon-name-part></tp:taxon-name>
                  </italic>
                </td>
                <td rowspan="1" colspan="1">4 (23.5%)</td>
                <td rowspan="1" colspan="1">13 (76.5%)</td>
                <td rowspan="1" colspan="1">17 (100%)</td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">
                  <italic>
                    <tp:taxon-name>
                  <tp:taxon-name-part taxon-name-part-type="genus" reg="Neisseria">N.</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="meningitidis">meningitidis</tp:taxon-name-part></tp:taxon-name>
                  </italic>
                </td>
                <td rowspan="1" colspan="1">5 (100%)</td>
                <td rowspan="1" colspan="1">0</td>
                <td rowspan="1" colspan="1">5 (100%)</td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">
                  <italic>
                    <tp:taxon-name>
                  <tp:taxon-name-part taxon-name-part-type="genus" reg="Listeria">L.</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="monocytogenes">monocytogenes</tp:taxon-name-part></tp:taxon-name>
                  </italic>
                </td>
                <td rowspan="1" colspan="1">0</td>
                <td rowspan="1" colspan="1">8 (100%)</td>
                <td rowspan="1" colspan="1">8 (100%)</td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1"><italic><tp:taxon-name>
                  <tp:taxon-name-part taxon-name-part-type="genus" reg="Staphylococcus">Staphylococcus</tp:taxon-name-part>
                </tp:taxon-name></italic> spp.</td>
                <td rowspan="1" colspan="1">0</td>
                <td rowspan="1" colspan="1">12 (100%)</td>
                <td rowspan="1" colspan="1">12 (100%)</td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">Other identified †</td>
                <td rowspan="1" colspan="1">6 (50%)</td>
                <td rowspan="1" colspan="1">6 (50%)</td>
                <td rowspan="1" colspan="1">12 (100%)</td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">Unidentified</td>
                <td rowspan="1" colspan="1">10 (27.8%)</td>
                <td rowspan="1" colspan="1">26 (72.2%)</td>
                <td rowspan="1" colspan="1">36 (100%)</td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">Total</td>
                <td rowspan="1" colspan="1">25</td>
                <td rowspan="1" colspan="1">65</td>
                <td rowspan="1" colspan="1">90</td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1"/>
                <td rowspan="1" colspan="1"><italic>χ</italic><sup>2</sup>=23.799; <italic>р</italic>=0.0001</td>
                <td rowspan="1" colspan="1"/>
                <td rowspan="1" colspan="1"/>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn>
              <p>† including <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Streptococcus">Streptococcus</tp:taxon-name-part></tp:taxon-name></italic> spp., <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Haemophilus">H.</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="influenzae">influenzae</tp:taxon-name-part></tp:taxon-name></italic>, <italic>K. рneumoniaе</italic>, <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Enterococcus">E.</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="faecium">faecium</tp:taxon-name-part></tp:taxon-name></italic>, <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Mycobacterium">M.</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="tuberculosis">tuberculosis</tp:taxon-name-part></tp:taxon-name></italic></p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
      <sec sec-type="The period before hospitalization" id="SECID0E6GAE">
        <title>The period before hospitalization</title>
        <p>Most of the children were admitted to the hospital within the first 3 days of the onset of the symptom (64%). Adult patients were hospitalized later (usually after 4-5 days), and in 21.5% we noticed hospitalisation to be delayed (&gt;7 days from the onset of complaints). However, no significant difference was found between the age groups <bold>(Table <xref ref-type="table" rid="T2">2</xref>)</bold>. Antibiotics were taken by 10 children (40%) and 28 adults (43.1%) prior to performing an initial lumbar puncture, without significant difference (<italic>p</italic>=0.817).</p>
        <table-wrap id="T2" position="float" orientation="portrait">
          <label>Table 2.</label>
          <caption>
            <p>Duration of the period before hospitalization</p>
          </caption>
          <table id="TID0EROAE" rules="all">
            <tbody>
              <tr>
                <td rowspan="2" colspan="1">
                  <bold>Period before hospitalization</bold>
                </td>
                <td rowspan="1" colspan="2">
                  <bold>Children (n=25)</bold>
                </td>
                <td rowspan="1" colspan="2">
                  <bold>Adults (n=65)</bold>
                </td>
                <td rowspan="1" colspan="2">
                  <bold>Total (n=90)</bold>
                </td>
                <td rowspan="1" colspan="1">
                  <bold><italic>p</italic>-value</bold>
                </td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">
                  <bold>n</bold>
                </td>
                <td rowspan="1" colspan="1">%</td>
                <td rowspan="1" colspan="1">
                  <bold>n</bold>
                </td>
                <td rowspan="1" colspan="1">%</td>
                <td rowspan="1" colspan="1">
                  <bold>n</bold>
                </td>
                <td rowspan="1" colspan="1">%</td>
                <td rowspan="1" colspan="1"/>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">≤3 days</td>
                <td rowspan="1" colspan="1">16</td>
                <td rowspan="1" colspan="1">64%</td>
                <td rowspan="1" colspan="1">28</td>
                <td rowspan="1" colspan="1">43.1%</td>
                <td rowspan="1" colspan="1">44</td>
                <td rowspan="1" colspan="1">48.9%</td>
                <td rowspan="3" colspan="1"><italic>χ</italic><sup>2</sup>=5.009  <italic>p</italic>=0.082</td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">4-7 days</td>
                <td rowspan="1" colspan="1">8</td>
                <td rowspan="1" colspan="1">32%</td>
                <td rowspan="1" colspan="1">23</td>
                <td rowspan="1" colspan="1">35.4%</td>
                <td rowspan="1" colspan="1">31</td>
                <td rowspan="1" colspan="1">34.4%</td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">&gt;7 days</td>
                <td rowspan="1" colspan="1">1</td>
                <td rowspan="1" colspan="1">4%</td>
                <td rowspan="1" colspan="1">14</td>
                <td rowspan="1" colspan="1">21.5%</td>
                <td rowspan="1" colspan="1">15</td>
                <td rowspan="1" colspan="1">16.7%</td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
      </sec>
      <sec sec-type="Clinical features in children and adults" id="SECID0EOHAE">
        <title>Clinical features in children and adults</title>
        <p>Significant differences between the age groups were found for some clinical symptoms <bold>(Table <xref ref-type="table" rid="T3">3</xref>)</bold>. Headache was more frequent in adults, while vomiting was significantly more common in children, as well as otalgia and the presence of angina. Somnolence, sopor, coma, and especially qualitative alterations in consciousness (agitation, bradypsychia, hallucinations) were significantly more common in adults. Only 17.8% of patients had photophobia. The presence of rash (maculopapular, petechial, hemorrhagic), and seizures were more common in children, but without significant difference (<italic>p</italic>&gt;0.05).</p>
        <p>Neck stiffness, Kernig, Brudzinski’s signs, and focal deficits (paresis, hemiparesis, aphasia) were more common in adults, even without a significant difference (<italic>p</italic>&gt;0.05) <bold>(Table <xref ref-type="table" rid="T4">4</xref>)</bold>.</p>
        <table-wrap id="T3" position="float" orientation="portrait">
          <label>Table 3.</label>
          <caption>
            <p>Clinical features in children and adults with bacterial neuroinfections</p>
          </caption>
          <table id="TID0EWUAE" rules="all">
            <tbody>
              <tr>
                <td rowspan="2" colspan="1">
                  <bold>Symptoms</bold>
                </td>
                <td rowspan="1" colspan="2">
                  <bold>Children (n=25)</bold>
                </td>
                <td rowspan="1" colspan="2">
                  <bold>Adults (n=65)</bold>
                </td>
                <td rowspan="1" colspan="2">
                  <bold>Total (n=90)</bold>
                </td>
                <td rowspan="2" colspan="1">
                  <bold><italic>p</italic> (Fisher)</bold>
                </td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">
                  <bold>n</bold>
                </td>
                <td rowspan="1" colspan="1">%</td>
                <td rowspan="1" colspan="1">
                  <bold>n</bold>
                </td>
                <td rowspan="1" colspan="1">%</td>
                <td rowspan="1" colspan="1">
                  <bold>n</bold>
                </td>
                <td rowspan="1" colspan="1">%</td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">Fever &gt;37.5°C</td>
                <td rowspan="1" colspan="1">24</td>
                <td rowspan="1" colspan="1">96%</td>
                <td rowspan="1" colspan="1">63</td>
                <td rowspan="1" colspan="1">96.9%</td>
                <td rowspan="1" colspan="1">87</td>
                <td rowspan="1" colspan="1">96.7%</td>
                <td rowspan="1" colspan="1">1.000</td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">Headache †</td>
                <td rowspan="1" colspan="1">10</td>
                <td rowspan="1" colspan="1">40%</td>
                <td rowspan="1" colspan="1">43</td>
                <td rowspan="1" colspan="1">66.2%</td>
                <td rowspan="1" colspan="1">53</td>
                <td rowspan="1" colspan="1">58.9%</td>
                <td rowspan="1" colspan="1">0.032</td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">Vomiting †</td>
                <td rowspan="1" colspan="1">20</td>
                <td rowspan="1" colspan="1">80%</td>
                <td rowspan="1" colspan="1">28</td>
                <td rowspan="1" colspan="1">43.1%</td>
                <td rowspan="1" colspan="1">48</td>
                <td rowspan="1" colspan="1">53.3%</td>
                <td rowspan="1" colspan="1">0.002</td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">Photophobia</td>
                <td rowspan="1" colspan="1">5</td>
                <td rowspan="1" colspan="1">20%</td>
                <td rowspan="1" colspan="1">11</td>
                <td rowspan="1" colspan="1">16.9%</td>
                <td rowspan="1" colspan="1">16</td>
                <td rowspan="1" colspan="1">17.8%</td>
                <td rowspan="1" colspan="1">0.763</td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">Somnolence, sopor, coma †</td>
                <td rowspan="1" colspan="1">11</td>
                <td rowspan="1" colspan="1">44%</td>
                <td rowspan="1" colspan="1">50</td>
                <td rowspan="1" colspan="1">76.9%</td>
                <td rowspan="1" colspan="1">61</td>
                <td rowspan="1" colspan="1">67.8%</td>
                <td rowspan="1" colspan="1">0.005</td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">Agitation, hallucinations †</td>
                <td rowspan="1" colspan="1">0</td>
                <td rowspan="1" colspan="1">0</td>
                <td rowspan="1" colspan="1">38</td>
                <td rowspan="1" colspan="1">58.5%</td>
                <td rowspan="1" colspan="1">38</td>
                <td rowspan="1" colspan="1">42.2%</td>
                <td rowspan="1" colspan="1">0.0001</td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">Seizures</td>
                <td rowspan="1" colspan="1">6</td>
                <td rowspan="1" colspan="1">24%</td>
                <td rowspan="1" colspan="1">12</td>
                <td rowspan="1" colspan="1">18.5%</td>
                <td rowspan="1" colspan="1">18</td>
                <td rowspan="1" colspan="1">20%</td>
                <td rowspan="1" colspan="1">0.566</td>
              </tr>
              <tr>
                <td rowspan="1" colspan="8"/>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">Cough, sore throat</td>
                <td rowspan="1" colspan="1">11</td>
                <td rowspan="1" colspan="1">44%</td>
                <td rowspan="1" colspan="1">15</td>
                <td rowspan="1" colspan="1">23.1%</td>
                <td rowspan="1" colspan="1">26</td>
                <td rowspan="1" colspan="1">28.9%</td>
                <td rowspan="1" colspan="1">0.69</td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">Diarrhea</td>
                <td rowspan="1" colspan="1">2</td>
                <td rowspan="1" colspan="1">8%</td>
                <td rowspan="1" colspan="1">7</td>
                <td rowspan="1" colspan="1">10.8%</td>
                <td rowspan="1" colspan="1">9</td>
                <td rowspan="1" colspan="1">10%</td>
                <td rowspan="1" colspan="1">1.000</td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">Ear pain†</td>
                <td rowspan="1" colspan="1">5</td>
                <td rowspan="1" colspan="1">20%</td>
                <td rowspan="1" colspan="1">3</td>
                <td rowspan="1" colspan="1">4.6%</td>
                <td rowspan="1" colspan="1">8</td>
                <td rowspan="1" colspan="1">8.9%</td>
                <td rowspan="1" colspan="1">0.035</td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">Skin rash</td>
                <td rowspan="1" colspan="1">6</td>
                <td rowspan="1" colspan="1">24%</td>
                <td rowspan="1" colspan="1">10</td>
                <td rowspan="1" colspan="1">15.4%</td>
                <td rowspan="1" colspan="1">10</td>
                <td rowspan="1" colspan="1">16%</td>
                <td rowspan="1" colspan="1">0.365</td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">
              angina †</td>
                <td rowspan="1" colspan="1">15</td>
                <td rowspan="1" colspan="1">60%</td>
                <td rowspan="1" colspan="1">14</td>
                <td rowspan="1" colspan="1">21.5%</td>
                <td rowspan="1" colspan="1">29</td>
                <td rowspan="1" colspan="1">32.2%</td>
                <td rowspan="1" colspan="1"><italic>χ</italic><sup>2</sup>=12.233  <italic>p</italic>=0.002</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn>
              <p>† significant difference at <italic>p</italic>&lt;0.05</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <table-wrap id="T4" position="float" orientation="portrait">
          <label>Table 4.</label>
          <caption>
            <p>Neurological status in children and adults with bacterial neuroinfections</p>
          </caption>
          <table id="TID0EPFAG" rules="all">
            <tbody>
              <tr>
                <td rowspan="2" colspan="1">
                  <bold>Signs</bold>
                </td>
                <td rowspan="1" colspan="2">
                  <bold>Children (n=25)</bold>
                </td>
                <td rowspan="1" colspan="2">
                  <bold>Adults (n=65)</bold>
                </td>
                <td rowspan="1" colspan="2">
                  <bold>Total (n=90)</bold>
                </td>
                <td rowspan="2" colspan="1">
                  <bold><italic>p</italic> (Fisher)</bold>
                </td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">
                  <bold>n</bold>
                </td>
                <td rowspan="1" colspan="1">%</td>
                <td rowspan="1" colspan="1">
                  <bold>n</bold>
                </td>
                <td rowspan="1" colspan="1">%</td>
                <td rowspan="1" colspan="1">
                  <bold>n</bold>
                </td>
                <td rowspan="1" colspan="1">%</td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">Neck stiffness</td>
                <td rowspan="1" colspan="1">21</td>
                <td rowspan="1" colspan="1">84%</td>
                <td rowspan="1" colspan="1">62</td>
                <td rowspan="1" colspan="1">95.4%</td>
                <td rowspan="1" colspan="1">83</td>
                <td rowspan="1" colspan="1">92.2%</td>
                <td rowspan="1" colspan="1">0.090</td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">Kernig</td>
                <td rowspan="1" colspan="1">13</td>
                <td rowspan="1" colspan="1">52%</td>
                <td rowspan="1" colspan="1">41</td>
                <td rowspan="1" colspan="1">63.1%</td>
                <td rowspan="1" colspan="1">54</td>
                <td rowspan="1" colspan="1">60%</td>
                <td rowspan="1" colspan="1">0.349</td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">Upper Brudzinski</td>
                <td rowspan="1" colspan="1">8</td>
                <td rowspan="1" colspan="1">32%</td>
                <td rowspan="1" colspan="1">23</td>
                <td rowspan="1" colspan="1">35.4%</td>
                <td rowspan="1" colspan="1">31</td>
                <td rowspan="1" colspan="1">34.2%</td>
                <td rowspan="1" colspan="1">0.810</td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">Lower Brudzinski</td>
                <td rowspan="1" colspan="1">3</td>
                <td rowspan="1" colspan="1">12%</td>
                <td rowspan="1" colspan="1">15</td>
                <td rowspan="1" colspan="1">23.1%</td>
                <td rowspan="1" colspan="1">18</td>
                <td rowspan="1" colspan="1">20%</td>
                <td rowspan="1" colspan="1">0.378</td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">Focal deficits</td>
                <td rowspan="1" colspan="1">2</td>
                <td rowspan="1" colspan="1">8%</td>
                <td rowspan="1" colspan="1">7</td>
                <td rowspan="1" colspan="1">10.8%</td>
                <td rowspan="1" colspan="1">9</td>
                <td rowspan="1" colspan="1">10%</td>
                <td rowspan="1" colspan="1">1.000</td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">Cranial nerve palsy</td>
                <td rowspan="1" colspan="1">2</td>
                <td rowspan="1" colspan="1">8%</td>
                <td rowspan="1" colspan="1">5</td>
                <td rowspan="1" colspan="1">7.7%</td>
                <td rowspan="1" colspan="1">7</td>
                <td rowspan="1" colspan="1">7.8%</td>
                <td rowspan="1" colspan="1">1.000</td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">Babinski’s signs (+)</td>
                <td rowspan="1" colspan="1">9</td>
                <td rowspan="1" colspan="1">36%</td>
                <td rowspan="1" colspan="1">24</td>
                <td rowspan="1" colspan="1">36.9%</td>
                <td rowspan="1" colspan="1">33</td>
                <td rowspan="1" colspan="1">36.7%</td>
                <td rowspan="1" colspan="1">1.000</td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
      </sec>
      <sec sec-type="Comparative assessment based on comorbidities and outcome" id="SECID0ELIAE">
        <title>Comparative assessment based on comorbidities and outcome</title>
        <p>We found otitis media, mastoiditis, otomastoiditis, and sinusitis, pneumonia, and sepsis in patients with bacterial <tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Neisseria"/><tp:taxon-name-part taxon-name-part-type="species" reg="meningitis">meningitis</tp:taxon-name-part></tp:taxon-name>/meningoencephalitis. Sepsis was more common in adults, even without significant differences between children and adults <bold>(Table <xref ref-type="table" rid="T5">5</xref>)</bold>.</p>
        <p>The mortality rate was much higher in adults (43%) than in children (8%). Neurological sequelae (motor deficits and cognitive defects) in survivors were also more common in adults (13.8%) <bold>(Table <xref ref-type="table" rid="T6">6</xref>)</bold>.</p>
        <table-wrap id="T5" position="float" orientation="portrait">
          <label>Table 5.</label>
          <caption>
            <p>Comorbidities in patients with bacterial neuroinfections</p>
          </caption>
          <table id="TID0E6PAG" rules="all">
            <tbody>
              <tr>
                <td rowspan="2" colspan="1">
                  <bold>Comorbidities</bold>
                </td>
                <td rowspan="1" colspan="2">
                  <bold>Children (n=25)</bold>
                </td>
                <td rowspan="1" colspan="2">
                  <bold>Adults (n=65)</bold>
                </td>
                <td rowspan="1" colspan="2">
                  <bold>Total (n=90)</bold>
                </td>
                <td rowspan="2" colspan="1">
                  <bold><italic>p</italic>-value</bold>
                </td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">
                  <bold>n</bold>
                </td>
                <td rowspan="1" colspan="1">%</td>
                <td rowspan="1" colspan="1">
                  <bold>n</bold>
                </td>
                <td rowspan="1" colspan="1">%</td>
                <td rowspan="1" colspan="1">
                  <bold>n</bold>
                </td>
                <td rowspan="1" colspan="1">%</td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">Otogenic †</td>
                <td rowspan="1" colspan="1">7</td>
                <td rowspan="1" colspan="1">28%</td>
                <td rowspan="1" colspan="1">18</td>
                <td rowspan="1" colspan="1">27.7%</td>
                <td rowspan="1" colspan="1">25</td>
                <td rowspan="1" colspan="1">27.8%</td>
                <td rowspan="1" colspan="1">1.000</td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">Pneumonia</td>
                <td rowspan="1" colspan="1">3</td>
                <td rowspan="1" colspan="1">12%</td>
                <td rowspan="1" colspan="1">12</td>
                <td rowspan="1" colspan="1">18.5%</td>
                <td rowspan="1" colspan="1">15</td>
                <td rowspan="1" colspan="1">16.7%</td>
                <td rowspan="1" colspan="1">0.545</td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">Sepsis</td>
                <td rowspan="1" colspan="1">1</td>
                <td rowspan="1" colspan="1">4%</td>
                <td rowspan="1" colspan="1">10</td>
                <td rowspan="1" colspan="1">15.4%</td>
                <td rowspan="1" colspan="1">11</td>
                <td rowspan="1" colspan="1">12.2%</td>
                <td rowspan="1" colspan="1">0.279</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn>
              <p>† otogenic diseases in children - otitis (1), mastoiditis (1), otomastoiditis (3), sinusitis (3); in adults - otitis (4), mastoiditis (4), sinusitis (13)</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <table-wrap id="T6" position="float" orientation="portrait">
          <label>Table 6.</label>
          <caption>
            <p>Outcome in patients with bacterial neuroinfections</p>
          </caption>
          <table id="TID0ELWAG" rules="all">
            <tbody>
              <tr>
                <td rowspan="2" colspan="1">
                  <bold>Outcome</bold>
                </td>
                <td rowspan="1" colspan="2">
                  <bold>Children (n=25)</bold>
                </td>
                <td rowspan="1" colspan="2">
                  <bold>Adults (n=65)</bold>
                </td>
                <td rowspan="1" colspan="2">
                  <bold>Total (n=90)</bold>
                </td>
                <td rowspan="1" colspan="1">
                  <bold><italic>p</italic>-value</bold>
                </td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">
                  <bold>n</bold>
                </td>
                <td rowspan="1" colspan="1">%</td>
                <td rowspan="1" colspan="1">
                  <bold>n</bold>
                </td>
                <td rowspan="1" colspan="1">%</td>
                <td rowspan="1" colspan="1">
                  <bold>n</bold>
                </td>
                <td rowspan="1" colspan="1">%</td>
                <td rowspan="1" colspan="1"/>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">Recovery</td>
                <td rowspan="1" colspan="1">21</td>
                <td rowspan="1" colspan="1">84%</td>
                <td rowspan="1" colspan="1">28</td>
                <td rowspan="1" colspan="1">43.1%</td>
                <td rowspan="1" colspan="1">49</td>
                <td rowspan="1" colspan="1">54.4%</td>
                <td rowspan="3" colspan="1"><italic>χ</italic><sup>2</sup>=12.72 <italic>p</italic>=0.002</td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">Neurological sequelae †</td>
                <td rowspan="1" colspan="1">2</td>
                <td rowspan="1" colspan="1">8%</td>
                <td rowspan="1" colspan="1">9</td>
                <td rowspan="1" colspan="1">13.8%</td>
                <td rowspan="1" colspan="1">11</td>
                <td rowspan="1" colspan="1">12.2%</td>
              </tr>
              <tr>
                <td rowspan="1" colspan="1">Death</td>
                <td rowspan="1" colspan="1">2</td>
                <td rowspan="1" colspan="1">8%</td>
                <td rowspan="1" colspan="1">28</td>
                <td rowspan="1" colspan="1">43.1%</td>
                <td rowspan="1" colspan="1">30</td>
                <td rowspan="1" colspan="1">33.3%</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn>
              <p>† motor deficits – facial nerve palsy (2), quadriparesis (2), hemiparesis (4), paraparesis (3); cognitive defects – cognitive slowness (3), neuropsychologic sequelae (2), and epilepsy (1)</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
    </sec>
    <sec sec-type="Discussion" id="SECID0EKJAE">
      <title>Discussion</title>
      <p><italic><tp:taxon-name>
            <tp:taxon-name-part taxon-name-part-type="genus" reg="Streptococcus">Streptococcus</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="pneumoniae">pneumoniae</tp:taxon-name-part></tp:taxon-name></italic> remains the most common etiologic agent of purulent <tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Neisseria"/><tp:taxon-name-part taxon-name-part-type="species" reg="meningitis">meningitis</tp:taxon-name-part></tp:taxon-name> in adults, although there has been a reduction in the incidence after the introduction of the pneumococcal vaccines. Unexpectedly high frequency was found for <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Staphylococcus">Staphylococcus</tp:taxon-name-part></tp:taxon-name></italic> spp. (18.5%), which according to other studies is quite a rare cause of neuroinfections.<sup>[<xref ref-type="bibr" rid="B9 B10 B11">9–11</xref>]</sup> This is probably due to a large number of patients with sepsis, in which staphylococcal <tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Neisseria"/><tp:taxon-name-part taxon-name-part-type="species" reg="meningitis">meningitis</tp:taxon-name-part></tp:taxon-name> followed. <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Listeria">Listeria</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="monocytogenes">monocytogenes</tp:taxon-name-part></tp:taxon-name></italic>, which is the third leading cause of bacterial neuroinfections in our patients and according to numerous European studies, will be increasingly important in the near future, because of the growing number of people with concomitant oncological and autoimmune diseases and immunosuppression.</p>
      <p>Similar to European data<sup>[<xref ref-type="bibr" rid="B2">2</xref>,12]</sup>, the main causative agents of bacterial <tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Neisseria"/><tp:taxon-name-part taxon-name-part-type="species" reg="meningitis">meningitis</tp:taxon-name-part></tp:taxon-name> in children are <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Neisseria">Neisseria</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="meningitidis">meningitidis</tp:taxon-name-part></tp:taxon-name></italic> and <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Streptococcus">Streptococcus</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="pneumoniae">pneumoniae</tp:taxon-name-part></tp:taxon-name></italic>, but no case of <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Haemophilus">Haemophilus</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="influenzae">influenzae</tp:taxon-name-part></tp:taxon-name></italic> was observed, in contrast to studies in Poland and Turkey, reporting an incidence of 18%.<sup>[<xref ref-type="bibr" rid="B13">13</xref>,14]</sup> There is still a high incidence of <tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Neisseria"/><tp:taxon-name-part taxon-name-part-type="species" reg="meningitis">meningitis</tp:taxon-name-part></tp:taxon-name> due to <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Haemophilus">Haemophilus</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="influenzae">influenzae</tp:taxon-name-part></tp:taxon-name></italic> in countries with incomplete immunization programs such as Iran and Pakistan (12.4%).<sup>[<xref ref-type="bibr" rid="B15">15</xref>,16]</sup></p>
      <p>In our study, there is a high proportion of etiologically unidentified neuroinfections (40%). May be due to the fact that a significant proportion of patients were initiated on antibiotic therapy before undergoing a lumbar puncture, that makes it difficult to identify the cause by CSF culture</p>
      <p>The distribution of patients by gender showed a male prevalence regardless of age. According to other authors, men and women suffer equally often, with insignificant differences.<sup>[<xref ref-type="bibr" rid="B5">5</xref>,17]</sup></p>
      <p>The analysis of the clinical presentation showed that fever was the most common symptom (96.7%). While vomiting was more prevalent in children (80% vs. 43.1% in adults), the headache was more common in adults (66.2% vs. 40%). Similar data on the main clinical symptoms have been reported by a number of researchers in Europe.‌<sup>[<xref ref-type="bibr" rid="B8">8</xref>,13,18,19]</sup> Photophobia had an unexpectedly low frequency (17.8%). Our patients had a skin rash in 24% of children and 15.4% of adults. Many authors reported a significantly higher frequency of rash in both children (39-51%) and adults groups (20-26%).<sup>[17,20-22]</sup></p>
      <p>In the observed patients neck stiffness, Kernig and Brudzinski’s signs are more widespread in adults. Seizures are more common in children (24%) than in adults (18.5%). These findings correlate with the data of many European authors.<sup>[6,23-25]</sup></p>
      <p>The frequency of cranial nerve palsy in the studied patients (7.8%) was several times lower compared to the data of Van de Beek et al. (28%).<sup>[<xref ref-type="bibr" rid="B8">8</xref>]</sup> The incidence of focal neurological deficit (10%) is also lower when compared to other European studies, reporting 15–34%.<sup>[<xref ref-type="bibr" rid="B17">17</xref>,20,26]</sup></p>
      <p>Comorbidities were more common in adults (53.8%) than in children (36%). Weisfelt et al. reported 32.5% for otitis or sinusitis, 15.2% pneumonia, and 13% sepsis, similar to our results.<sup>[<xref ref-type="bibr" rid="B6">6</xref>,7]</sup> The disease prognosis was more favourable for children. The mortality rate was much higher in adults, which is in accordance with the literature.<sup>[<xref ref-type="bibr" rid="B7">7</xref>,16,17]</sup></p>
    </sec>
    <sec sec-type="Conclusions" id="SECID0ERPAE">
      <title>Conclusions</title>
      <p>The most common etiological agents of bacterial agents are <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Streptococcus">Streptococcus</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="pneumoniae">pneumoniae</tp:taxon-name-part></tp:taxon-name></italic> in adults, and <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Neisseria">Neisseria</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="meningitidis">meningitidis</tp:taxon-name-part></tp:taxon-name></italic> and <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Streptococcus">Streptococcus</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="pneumoniae">pneumoniae</tp:taxon-name-part></tp:taxon-name></italic> in children. Headache and disturbances in consciousness are more common in adults, while vomiting and ear pain are more typical in children. Because of the high mortality and sequelae in patients with bacterial neuroinfections, rapid clinical recognition and laboratory diagnosis are needed in order to begin adequate treatment as soon as possible.</p>
    </sec>
  </body>
  <back>
    <ack>
      <title>Acknowledgments</title>
      <p>This study was funded by a research project of Medical University of Plovdiv, Grant No. 09/2017.</p>
      <p>
        <bold>Competing Interests</bold>
      </p>
      <p>The authors have declared that no competing interests exist.</p>
    </ack>
    <ref-list>
      <title>References</title>
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