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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.68.e161534</article-id>
      <article-id pub-id-type="publisher-id">161534</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Research Article</subject>
        </subj-group>
        <subj-group subj-group-type="scientific_subject">
          <subject>Dental medicine</subject>
          <subject>Microbiology</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Species composition and antibiotic susceptibility of microorganisms present in the maxillary sinus and other biotopes during the sinus lift procedure</article-title>
      </title-group>
      <contrib-group content-type="authors">
        <contrib contrib-type="author" corresp="yes">
          <name name-style="western">
            <surname>Mochalov</surname>
            <given-names>Iurii</given-names>
          </name>
          <email xlink:type="simple">u.mochalov@gmail.com</email>
          <uri content-type="orcid">https://orcid.org/0000-0002-5654-1725</uri>
          <xref ref-type="aff" rid="A1">1</xref>
        </contrib>
        <contrib contrib-type="author" corresp="no">
          <name name-style="western">
            <surname>Kryvtsova</surname>
            <given-names>Marina</given-names>
          </name>
          <uri content-type="orcid">https://orcid.org/0000-0001-8454-2509</uri>
          <xref ref-type="aff" rid="A1">1</xref>
        </contrib>
        <contrib contrib-type="author" corresp="no">
          <name name-style="western">
            <surname>Tsuperiak</surname>
            <given-names>Serhii</given-names>
          </name>
          <uri content-type="orcid">https://orcid.org/0000-0002-6897-5037</uri>
          <xref ref-type="aff" rid="A1">1</xref>
        </contrib>
        <contrib contrib-type="author" corresp="no">
          <name name-style="western">
            <surname>Mykhailychenko</surname>
            <given-names>Bogdan</given-names>
          </name>
          <uri content-type="orcid">https://orcid.org/0009-0007-0001-1921</uri>
          <xref ref-type="aff" rid="A2">2</xref>
        </contrib>
        <contrib contrib-type="author" corresp="no">
          <name name-style="western">
            <surname>Guzo</surname>
            <given-names>Nutsu</given-names>
          </name>
          <uri content-type="orcid">https://orcid.org/0009-0005-1409-6028</uri>
          <xref ref-type="aff" rid="A1">1</xref>
        </contrib>
        <contrib contrib-type="author" corresp="no">
          <name name-style="western">
            <surname>Kizim</surname>
            <given-names>Alla</given-names>
          </name>
          <uri content-type="orcid">https://orcid.org/0009-0003-6037-2607</uri>
          <xref ref-type="aff" rid="A3">3</xref>
        </contrib>
      </contrib-group>
      <aff id="A1">
        <label>1</label>
        <addr-line content-type="verbatim">Uzhhorod National University, Uzhhorod, Ukraine</addr-line>
        <institution>Uzhhorod National University</institution>
        <addr-line content-type="city">Uzhhorod</addr-line>
        <country>Ukraine</country>
      </aff>
      <aff id="A2">
        <label>2</label>
        <addr-line content-type="verbatim">Shupyk National Healthcare University of Ukraine, Kyiv, Ukraine</addr-line>
        <institution>Shupyk National Healthcare University of Ukraine</institution>
        <addr-line content-type="city">Kyiv</addr-line>
        <country>Ukraine</country>
      </aff>
      <aff id="A3">
        <label>3</label>
        <addr-line content-type="verbatim">Taras Shevchenko National University, Kyiv, Ukraine</addr-line>
        <institution>Taras Shevchenko National University</institution>
        <addr-line content-type="city">Kyiv</addr-line>
        <country>Ukraine</country>
      </aff>
      <author-notes>
        <fn fn-type="corresp">
          <p><bold>Corresponding author</bold>: Iurii Mochalov, Uzhhorod National University, Uzhhorod, Ukraine; Email: <email xlink:type="simple">u.mochalov@gmail.com</email></p>
        </fn>
      </author-notes>
      <pub-date pub-type="collection">
        <year>2026</year>
      </pub-date>
      <pub-date pub-type="epub">
        <day>26</day>
        <month>02</month>
        <year>2026</year>
      </pub-date>
      <volume>68</volume>
      <issue>1</issue>
      <elocation-id>e161534</elocation-id>
      <uri content-type="arpha" xlink:href="http://openbiodiv.net/A11E4716-BFEA-5B0B-B384-DD0306F4BA12">A11E4716-BFEA-5B0B-B384-DD0306F4BA12</uri>
      <history>
        <date date-type="received">
          <day>08</day>
          <month>06</month>
          <year>2025</year>
        </date>
        <date date-type="accepted">
          <day>11</day>
          <month>09</month>
          <year>2025</year>
        </date>
      </history>
      <permissions>
        <copyright-statement>Iurii Mochalov, Marina Kryvtsova, Serhii Tsuperiak, Bogdan Mykhailychenko, Nutsu Guzo, Alla Kizim</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>
        <label>Abstract</label>
        <p><bold>Introduction</bold>: Lateral sinus lift is a common procedure in the field of dentistry, employed for the purpose of preparing the maxilla for subsequent dental implantation. This procedure is associated with a significant risk of intra- and postoperative complications, largely attributable to the presence of pathogenic microorganisms within the oral cavity and maxillary sinus.</p>
        <p><bold>Aim</bold>: The aim of the present study was to determine the species composition of the microorganisms (pathogenic and opportunistic) in four biotopes in the maxillofacial region (Schneiderian membrane, pharynx, nasal passage, and oral mucosa) during a planned sinus lift and detect their sensitivity to antibiotics.</p>
        <p><bold>Materials and methods</bold>: Biological material (swabs) was examined bacteriologically by cultivating it on standard and differential diagnostic nutritional media; antibiotic sensitivity of the isolated strains was assessed using the disk diffusion method.</p>
        <p><bold>Results</bold>: The ambiguous picture of microorganism persistence in the various biotopes of the maxillofacial region was identified. , <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>, and <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Candida">Candida</tp:taxon-name-part></tp:taxon-name></italic> were detected in clinically significant amounts in the maxillary sinuses of healthy patients. Ceftriaxone and cefoperazone/sulbactam were the most effective antibiotics against microorganisms isolated in clinically significant concentrations across all biotopes. Cefuroxime was effective against 75% of all bacteria tested. Gatifloxacin was effective, with no cases of resistance reported. The fungi in the maxillary sinus mucoperiosteum were sensitive to fluconazole, ketoconazole, and clotrimazole, but only moderately sensitive to itraconazole and nystatin.</p>
        <p><bold>Conclusion</bold>: The findings suggest that patients undergoing sinus lift surgery may have fewer options for prophylactic antibacterial therapy. Bacteriological studies on oral and nasal mucosa do not predict the presence of pathogenic microorganisms in the maxillary sinus.</p>
      </abstract>
      <kwd-group>
        <label>Keywords</label>
        <kwd>antimicrobial resistance</kwd>
        <kwd>maxillary sinus</kwd>
        <kwd>microbiome</kwd>
        <kwd>oral cavity</kwd>
        <kwd>sinus lift</kwd>
      </kwd-group>
    </article-meta>
    <notes>
      <sec sec-type="Citation" id="sec1">
        <title>Citation</title>
        <p>Mochalov I, Kryvtsova M, Tsuperiak S, Mykhailychenko B, Guzo N, Kizim A. Species composition and antibiotic susceptibility of microorganisms present in the maxillary sinus and other biotopes during the sinus lift procedure. Folia Med (Plovdiv) 2026;68(1):е161534. <ext-link ext-link-type="doi" xlink:href="10.3897/folmed.68.e161534">doi: 10.3897/folmed.68.e161534</ext-link>.</p>
      </sec>
    </notes>
  </front>
  <body>
    <sec sec-type="Introduction" id="sec2">
      <title>Introduction</title>
      <p>The replacement of dentition defects with implant-supported prosthetic structures is a widely adopted practice considered the “golden standard” of functional rehabilitation for dental patients. However, in clinical practice, dental surgeons often face the problem of bone deficiency and the lack of the necessary volume of bone tissue to install dental implants in the desired prosthetic position. This problem is prevalent in the lateral zones of the upper jaw and is the main limiting factor in the application of modern methods of replacing dentition defects.<sup>[<xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B2">2</xref>]</sup> The proximity of the maxillary sinus limits the possibility of installing an implant of the required length in the optimal prosthetic position. Also, it increases the risk of complications arising during surgery among patients with an edentulous upper jaw. It is well known that in patients with a pneumatic upper jaw structure, the maxillary sinus fills the alveolar process and causes “counter resorption”; when the teeth are missing, the alveolar bone may be lost simultaneously from the oral cavity and the maxillary sinus.<sup>[<xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B4">4</xref>]</sup></p>
      <p>Restoring the required volume and quality of alveolar bone on the maxilla is a challenging clinical task that can be approached in a variety of ways. According to numerous studies, the most common method in the aforementioned clinical situations is lateral sinus floor augmentation (open sinus lift). Tatum proposed this technique in 1974, and Boyne and James (1980), as well as other authors, improved it later. The lateral sinus floor augmentation procedure entails cutting the lateral wall of the maxillary sinus and carefully elevating the sinus’s internal mucoperiosteal membrane. During this procedure, a new space is formed that must be filled with bone-substituting material (graft), sometimes simultaneously with the installation of dental implants.<sup>[<xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B6">6</xref>]</sup></p>
      <p>Experience of using lateral sinus floor augmentation in clinical practice allows us to consider it a procedure characterized by high efficiency and the predictability of its results. Even though lateral sinus floor augmentation is regarded as a reasonably safe and predictable procedure, the literature data indicate the high possibility of developing intra- and postoperative complications associated with this operation. Among the most threatening complications, the authors highlight the development of acute and chronic maxillary sinusitis. It is often associated with infection and complete loss of bone grafts or bone substitute material. The authors determine the frequency of acute maxillary sinusitis at 10–26%. The frequency of graft loss, according to other researchers, is lower (3–10%). Since some infectious complications in the case of timely diagnosis and the use of the correct treatment tactics may be effectively eliminated, their negative consequences are minimized. The chronic inflammatory process in the maxillary sinus was noted in 1.3–5% of cases. However, the number of scientific publications devoted to the study of this complication in lateral sinus floor augmentation is limited, and their results are often contradictory.<sup>[<xref ref-type="bibr" rid="B7">7</xref>-<xref ref-type="bibr" rid="B9">9</xref>]</sup></p>
      <p>Some researchers argue that the maxillary sinuses are often a sterile anatomical region. According to some authors, a healthy maxillary sinus is not sterile. The maxillary sinuses of clinically healthy adult patients are slightly polluted with transitory bacteria as the presence of small numbers of inflammatory cells within the maxillary sinus mucosa is a typical state of the airway defense system. Under normal conditions, saprophytic and opportunistic bacteria predominate in the nasal cavity, with microbial interactions occurring in 69.9% of instances. As a result, the nasal cavity microbiota should be deemed “transient” and have no etiological importance. In normal homeostasis, the maxillary sinuses have a varied bacterial colonization (several bacteria, both in the forms of biofilm and planktonic forms)<sup>[<xref ref-type="bibr" rid="B8">8</xref>,<xref ref-type="bibr" rid="B10">10</xref>]</sup></p>
      <p>Performing any surgical interventions in the oral cavity is accompanied by the risk of contamination of the surgical wound with pathogenic microorganisms. That microorganisms may be identified even in healthy patients in clinically significant concentrations. And the lateral sinus floor augmentation procedure (which is also performed intraorally) is not an exception. That is why this is a rational basis for prescribing prophylactic antibacterial therapy. In modern clinical practice, the problem of identifying pathogens in disease is a component of the ongoing process of updating medical and diagnostic protocols and standards. Especially for the treatment of infectious and inflammatory diseases of the maxillofacial region. In those cases, various methods of identifying pathogenic microorganisms may be used.<sup>[<xref ref-type="bibr" rid="B11">11</xref>,<xref ref-type="bibr" rid="B12">12</xref>]</sup> Usually, when using the cultural identification method in the oral cavity, the pathogen may be identified in 85.50% of patients. In general, associations of microorganisms were determined in 96.00% of cases, and monoculture in 4.00%. At the same time, maximum information may be obtained when using molecular genetic identification methods, especially for anaerobes. Because, in standard cultivation, the families <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Streptococcus">Streptococcus</tp:taxon-name-part></tp:taxon-name></italic>, <italic>Staphylococcus</italic>, and <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Prevotella">Prevotella</tp:taxon-name-part></tp:taxon-name></italic> spp. (aerobic and facultative anaerobic bacteria) are mainly isolated.<sup>[<xref ref-type="bibr" rid="B13">13</xref>,<xref ref-type="bibr" rid="B14">14</xref>]</sup></p>
      <p>Antibacterial resistance in microorganisms is a unique problem in modern medicine. Antibacterial resistance can be either natural or acquired. The first type of resistance is defined as the absence of target microorganisms for an antimicrobial drug’s action or its unavailability. Acquired resistance is caused by the effect of antimicrobial drugs on microorganisms, particularly at low concentrations. In recent decades, there has been a greater emphasis on understanding bacterial survival mechanisms. Antibiotic resistance among infectious and inflammatory disease pathogens is widespread, posing a serious threat to most countries’ healthcare systems. And the wide usage of antibiotics in the dental practice may enhance the abovementioned problem. Today, it is known that clinical strains of streptococci are the most frequently identified bacteria with resistance to antibiotics, especially to penicillin and clindamycin.<sup>[<xref ref-type="bibr" rid="B15">15</xref>]</sup></p>
      <p>The vast majority of clinical recommendations for antibacterial prophylaxis involve the use of semisynthetic penicillins (amoxicillin or clavulanate). However, due to the spread of beta-lactam antibiotic resistance among oral microbiome participants, the true efficacy of this class of agents may be questioned.<sup>[<xref ref-type="bibr" rid="B16">16</xref>,<xref ref-type="bibr" rid="B17">17</xref>]</sup> Recommendations for the initiation of antibiotic therapy before planned surgery, including shortened regimens for cephalosporins (within 1 day), seem more rational. However, the “right” antimicrobial agent for prophylactic therapy is an unresolved issue that must be addressed in almost every clinical case.<sup>[<xref ref-type="bibr" rid="B18">18</xref>,<xref ref-type="bibr" rid="B19">19</xref>]</sup></p>
    </sec>
    <sec sec-type="Aim" id="sec3">
      <title>Aim</title>
      <p>To determine the species composition of the microorganisms (pathogenic and opportunistic) of the four biotopes in the maxillofacial region (Schneiderian membrane, pharynx, nasal passage, and oral mucosa) during a planned sinus lift, and detect their sensitivity to antibiotics.</p>
    </sec>
    <sec sec-type="materials|methods" id="sec4">
      <title>Materials and methods</title>
      <sec sec-type="Study design" id="sec5">
        <title>Study design</title>
        <p>This cross-sectional study included 15 participants (8 females and 7 males) aged 38 to 45 who were patients of the Serhiy Tsuperiak Dental Implant Center, a private dental clinic in Uzhhorod, Ukraine. All patients were diagnosed with partial maxillary edentulism and a lack of bone volume for dental implants. Treatment plans included the performing of lateral sinus lift surgery with one-stage dental implantation or delayed dental implantation.</p>
      </sec>
      <sec sec-type="Inclusion and exclusion criteria" id="sec6">
        <title>Inclusion and exclusion criteria</title>
        <sec sec-type="Inclusion criteria" id="sec7">
          <title>
            <italic>Inclusion criteria</italic>
          </title>
          <p>The study group included patients from a private dental medical center. For all patients, the open sinus lift was performed as a stage of preparing the maxilla for dental implantation and subsequent dental prosthetics. All patients were somatically healthy at the time of operation. The existing general chronic somatic diseases were in stable remission and were not contraindications to surgical intervention. Patients did not have any acute or chronic inflammation in the upper airways or sore throat during the month before surgery. Patients from the study group did not take any systemic or local antibiotics during the month prior to surgery.</p>
        </sec>
        <sec sec-type="Exclusion criteria" id="sec8">
          <title>
            <italic>Exclusion criteria</italic>
          </title>
          <list list-type="order">
            <list-item>
              <p>The study group did not include patients who took antibiotics and antimicrobial agents generally and locally within a month before the material was collected.
</p>
            </list-item>
            <list-item>
              <p>Patients who had a history of surgical interventions on the maxillary sinuses.
</p>
            </list-item>
            <list-item>
              <p>Patients with existing allergic and chronic inflammatory diseases of the upper respiratory tract, oral and nasal cavity.
</p>
            </list-item>
            <list-item>
              <p>Patients who periodically or constantly take corticosteroids (local and general).
</p>
            </list-item>
          </list>
        </sec>
      </sec>
      <sec sec-type="Samples collection" id="sec9">
        <title>Samples collection</title>
        <p>Biological material (swabs) for bacteriological examination and further identification of microbiome species were collected from 15 patients during a planned surgical procedure (open (lateral) sinus lift). The material was collected from the following biotopes: the oral mucosa in the area of the operation prior to incisions, the surface of the palatine tonsil, the nasal passage on the side of the intervention, and the surface of the internal mucoperiosteum of the maxillary sinus (Schneiderian membrane) following trepanation of the maxillary sinus wall and opening of the mucoperiosteum surface. The total number of samples was sixty.</p>
      </sec>
      <sec sec-type="Microbiological studies" id="sec10">
        <title>Microbiological studies</title>
        <sec sec-type="Cultivation and identification of microorganisms" id="sec11">
          <title>
            <italic>Cultivation and identification of microorganisms</italic>
          </title>
          <p>The samples were immediately placed in a sterile gel transport medium (a tube with sterile AMIES gel and an applicator for biological fluids). The material transported to the laboratory was seeded on Sabouraud Dextrose Agar nutrient media (HiMedia Laboratories, India) for cultivation of microscopic fungi of the genus <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Candida">Candida</tp:taxon-name-part></tp:taxon-name></italic>. We used blood agar for the cultivation of hemolytic microflora, specifically bacteria from the genera <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Streptococcus">Streptococcus</tp:taxon-name-part></tp:taxon-name></italic> and <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Neisseria">Neisseria</tp:taxon-name-part></tp:taxon-name></italic>. <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Enterobacteriaceae">Enterobacteriaceae</tp:taxon-name-part></tp:taxon-name></italic> were cultivated on Endo nutrient media and Ploskirev’s agar (both from HiMedia Laboratories, India). <tp:taxon-name><tp:taxon-name-part taxon-name-part-type="superkingdom" reg="Bacteria">Bacteria</tp:taxon-name-part></tp:taxon-name> of the genus <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Staphylococcus">Staphylococcus</tp:taxon-name-part></tp:taxon-name></italic> were cultivated on Mannitol Salt Agar (Biolife, Italy). <tp:taxon-name><tp:taxon-name-part taxon-name-part-type="superkingdom" reg="Bacteria">Bacteria</tp:taxon-name-part></tp:taxon-name> of the genus <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Enterococcus">Enterococcus</tp:taxon-name-part></tp:taxon-name></italic> were cultivated on Bile Esculin Agar (Biolife, Italy). A pure culture of microorganisms was isolated using Gold’s sectoral culture method. Identification of microorganisms was carried out according to the morphological, tinctorial, cultural, and biochemical properties of bacteria using ENTEROtest, STREPTOtest, and STAPHYLOtest produced by Erba Lachema (Czech Republic).</p>
        </sec>
        <sec sec-type="Testing of bacteria’s sensitivity to antibiotics" id="sec12">
          <title>
            <italic>Testing of bacteria’s sensitivity to antibiotics</italic>
          </title>
          <p>The disk diffusion method was used to determine the antibiotic sensitivity of isolated pathogenic microorganisms. A disc set was used (HiMedia Laboratories, India). Antibiotic susceptibility was determined using the diameter in millimeters of bacterial culture inhibition on nutrient medium and the 2022 EUCAST recommendations.</p>
          <p>All stages of the bacteriological studies were carried out by the bacteriological laboratory of the Department of Clinical, Laboratory, and Morphofunctional Diagnostics of Uzhhorod National University, Ukraine. Certificate of compliance with the requirements for working with pathogens of III-IV pathogenicity groups and compliance with epidemiological regimens in accordance with State Standard 9.9.5.-080-2002 concerning the rules of arrangement and safety of laboratories [sections and departments] of a microbiological profile was issued on 24.12.2024 by the City District Monitoring Group on Biosafety of Uzhhorod, State Institution “Transcarpathian Regional Laboratory Center of the Ministry of Healthcare of Ukraine”). Prof. M. Kryvtsova, DBiolSc (equivalent to PhD), leads the laboratory.</p>
        </sec>
      </sec>
      <sec sec-type="Statistical analysis" id="sec13">
        <title>Statistical analysis</title>
        <p>All data were analyzed using Microsoft Excel 2016’s tabular and descriptive statistics methods. The total number of pathogenic microorganisms (and their associations) found in various biotopes of the maxillofacial area was calculated. In addition, the concentration of identified microorganisms was calculated in colony-forming units (CFU).</p>
      </sec>
    </sec>
    <sec sec-type="Results" id="sec14">
      <title>Results</title>
      <sec sec-type="The species composition in different biotopes" id="sec15">
        <title>The species composition in different biotopes</title>
        <p>The studies we conducted revealed an ambiguous picture of the population of different biotopes in the maxillary sinus, including bacteria and fungi. Thus, pathogenic microorganisms were isolated and identified on the oral mucosa near the future surgical wound in 12 of 15 cases. Members of the <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Streptococcus">Streptococcus</tp:taxon-name-part></tp:taxon-name></italic> genus dominated in the isolated strains. <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> was isolated in 6 out of 15 cases at clinically significant concentrations of 10<sup>5</sup>–10<sup>6</sup> CFU/ml. A small amount of <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="pyogenes">pyogenes</tp:taxon-name-part></tp:taxon-name></italic> were identified in 5 cases (10<sup>3</sup>–10<sup>4</sup> CFU/ml), and <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Candida">Candida</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="albicans">albicans</tp:taxon-name-part></tp:taxon-name></italic> were identified in concentrations of 10<sup>1</sup>–10<sup>2</sup> CFU/ml. Such results are often possible at a dental practice, since streptococci and yeast-like fungi are prominent participants in the oral microbiome.</p>
        <p>The study of biological material from the nasal passage (nostril) on the side of the surgical intervention showed a predominance of cases of isolation of bacteria of the <italic>Staphylococci</italic> family (9 cases out of 15, <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>: 10<sup>1</sup>–10<sup>3</sup> CFU/ml, <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="epidermidis">epidermidis</tp:taxon-name-part></tp:taxon-name></italic>: 10<sup>1</sup>–10<sup>2</sup> CFU/ml) and 3 cases of isolation of streptococci (<italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Streptococcus">Streptococcus</tp:taxon-name-part></tp:taxon-name><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Streptococcus"/><tp:taxon-name-part taxon-name-part-type="species">viridans</tp:taxon-name-part></tp:taxon-name>)</italic>, which were the only bacteria we found in clinically significant concentrations (10<sup>5</sup>–10<sup>6</sup> CFU/ml). Similar studies performed with material from the palatine tonsils showed the presence of both staphylococci and streptococci in the specified biotope. Pathogenic microorganisms were identified in 9 cases out of 15 — 5 cases with <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="pyogenes">pyogenes</tp:taxon-name-part></tp:taxon-name></italic> in clinically insignificant concentrations (10<sup>3</sup>–10<sup>4</sup> CFU/ml) and 3 cases with <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> in the amount of 10<sup>5</sup>–10<sup>7</sup> CFU/ml. Furthermore, there was one case of simultaneous isolation of <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> in a minimal amount (3 CFU/ml) 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> in a clinically significant concentration (10<sup>5</sup> CFU/ml).</p>
        <p>The most interesting were the results of the bacteriological study of the inner membrane of the maxillary sinus (Schneiderian membrane). In this biotope, pathogenic microorganisms were isolated in all cases. Among them, there were 3 cases of simultaneous identification of <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 <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="epidermidis">epidermidis</tp:taxon-name-part></tp:taxon-name></italic> in clinically insignificant concentrations (6–9 CFU/ml). All other cases (12 out of 15) were represented by pathogenic microflora in clinically significant concentrations (10<sup>5</sup>–10<sup>6</sup> CFU/ml) – <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> (one case), <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Candida">C.</tp:taxon-name-part> <tp:taxon-name-part taxon-name-part-type="species" reg="albicans">albicans</tp:taxon-name-part></tp:taxon-name></italic> (5 cases), and 6 cases of <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>.</p>
        <p>The frequency of detection of pathogenic microorganisms, their composition, and concentrations did not allow us to identify correlations between different biotopes of the maxillofacial area.</p>
      </sec>
      <sec sec-type="Antibacterial sensitivity of identified microorganisms" id="sec16">
        <title>Antibacterial sensitivity of identified microorganisms</title>
        <p>The sensitivity of the isolated pathogenic microorganisms to antibiotics was then determined using the disk diffusion method. The results revealed the presence of antibacterial resistance in many isolates <bold>(Fig. <xref ref-type="fig" rid="F1">1</xref>)</bold>. All isolated strains were completely methicillin resistant. The vast majority of them were resistant to macrolides, including azithromycin and clarithromycin. The most resistant bacteria to cephalosporins were cephalexin, cefazolin, and ceftazidime. There was also a high level of resistance to amoxicillin/clavulanate and carbapenems. Among the fluoroquinolones, most of the cases of resistance were determined for moxifloxacin. Ceftriaxone and cefoperazone/sulbactam were the most effective antibacterial agents tested (no resistant isolates were found). A slightly lower level of effectiveness can be predicted when cefuroxime, cefpodoxime, and cefepime are used. In the group of fluoroquinolones, levofloxacin and gatifloxacin were the most effective. Ciprofloxacin, ofloxacin, and norfloxacin were found to be agents of average effectiveness.</p>
        <fig id="F1">
          <object-id content-type="arpha">B1021484-E5B8-58F5-9096-63C5F375E2AA</object-id>
          <label>Figure 1.</label>
          <caption>
            <p>Sensitivity of isolated strains of pathogenic microorganisms to antibacterial agents (disk diffusion method, EUCAST recommendations) (%).</p>
          </caption>
          <graphic xlink:href="foliamedica-68-1-e161534-g001.jpg" id="oo_1553965.jpg">
            <uri content-type="original_file">https://binary.pensoft.net/fig/1553965</uri>
          </graphic>
        </fig>
      </sec>
      <sec sec-type="Antibacterial sensitivity of microorganisms presented in clinically significant concentrations" id="sec17">
        <title>Antibacterial sensitivity of microorganisms presented in clinically significant concentrations</title>
        <p>In addition, we analyzed the antibiotic sensitivity of microorganisms isolated from the patients’ biotopes in clinically significant concentrations. Such representatives of bacteria were entirely resistant to cephalexin, methicillin, and azithromycin. The isolated microorganisms were mainly resistant to cefazolin, amoxicillin/clavulanate, and clarithromycin. The bacterial cultures in half of the cases were carbapenem (imipenem and meropenem) resistant <bold>(Fig. <xref ref-type="fig" rid="F2">2</xref>)</bold>. Cefuroxime, ceftazidime, cefpodoxime, and the great majority of the fluoroquinolones used (ofloxacin, norfloxacin, ciprofloxacin, and moxifloxacin) were found to be resistant in 25% of the cases. In all cases, the indicated group of microorganisms was moderately sensitive to cefepime and levofloxacin. Ceftriaxone and cefoperazone/sulbactam were the most effective against such isolates. Cultures were mostly sensitive to cefuroxime, but the risk of resistance was 25%. Gatifloxacin was effective enough, in which the frequency of cases of sensitivity and moderate sensitivity was distributed equally, without resistance. Such results indicate a tendency to narrow the options for choosing antibacterial agents for a prophylactic course when performing sinus-lift surgery. <tp:taxon-name><tp:taxon-name-part taxon-name-part-type="kingdom" reg="Fungi">Fungi</tp:taxon-name-part></tp:taxon-name> found in one clinical case on the mucoperiosteum of the maxillary sinus were sensitive to fluconazole, ketoconazole, and clotrimazole and moderately sensitive to itraconazole and nystatin <bold>(Table 1)</bold>.</p>
        <fig id="F2">
          <object-id content-type="arpha">1BE62D87-BB8C-5BDC-9893-62B975D4A526</object-id>
          <label>Figure 2.</label>
          <caption>
            <p>Antibacterial sensitivity of isolated strains of pathogenic microorganisms in clinically significant concentrations (disk diffusion method, EUCAST recommendations) (%).</p>
          </caption>
          <graphic xlink:href="foliamedica-68-1-e161534-g002.jpg" id="oo_1553966.jpg">
            <uri content-type="original_file">https://binary.pensoft.net/fig/1553966</uri>
          </graphic>
        </fig>
      </sec>
      <sec sec-type="Antibacterial sensitivity of microorganisms presented on the oral mucosa" id="sec18">
        <title>Antibacterial sensitivity of microorganisms presented on the oral mucosa</title>
        <p>All of the data gathered during the study was taken into account when calculating the sensitivity characteristics of the pathogenic microflora present in the different biotopes of the maxillofacial region. This included data on the effect of antibacterial agents on the microflora present at clinically insignificant concentrations. The following features of sensitivity to antibacterial agents in microorganisms detected on the oral mucosa were established: complete resistance was observed to first-generation cephalosporins (cefazolin and cephalexin), methicillin, and azithromycin. Amoxicillin/clavulanate and ceftazidime resistance were present in 50% of the isolates we identified. One hundred percent sensitivity of the isolated isolates was noted to a number of cephalosporins (cefuroxime, ceftriaxone, and cefoperazone/sulbactam) and new fluoroquinolones—gatifloxacin and moxifloxacin. Moderate sensitivity in the absence of resistance was determined for cefpodoxime and cefepime, ofloxacin, norfloxacin, and levofloxacin. Normal sensitivity and moderate sensitivity were noted to ciprofloxacin <bold>(Fig. <xref ref-type="fig" rid="F3">3A</xref>)</bold>.</p>
        <fig id="F3">
          <object-id content-type="arpha">E4774819-467D-5918-84F9-62F9B155BB0F</object-id>
          <label>Figure 3</label>
          <caption>
            <p>. Antibacterial sensitivity of isolates of pathogenic microorganisms detected in different biotopes (disk diffusion method, EUCAST recommendations) (%). <bold>A</bold>. Oral mucosa; <bold>B</bold>. Pharynx, tonsilla palatina; <bold>C</bold>. Nasal passage (nostril); <bold>D</bold>. Mucoperiosteum of the maxillary sinus.</p>
          </caption>
          <graphic xlink:href="foliamedica-68-1-e161534-g003.jpg" id="oo_1553967.jpg">
            <uri content-type="original_file">https://binary.pensoft.net/fig/1553967</uri>
          </graphic>
        </fig>
      </sec>
      <sec sec-type="Antibacterial sensitivity of microorganisms present on the palatine tonsil (pharynx)" id="sec19">
        <title>Antibacterial sensitivity of microorganisms present on the palatine tonsil (pharynx)</title>
        <p>Antibiotic sensitivity was then assessed in isolates from the surface of the palatine tonsil mucosa. The isolated bacterial cultures were completely resistant to cephalexin, methicillin, and azithromycin. The overwhelming majority of isolates were resistant to cefazolin, ceftazidime, amoxicillin/clavulanate, clarithromycin, ofloxacin, norfloxacin, and ciprofloxacin. One-third of the cases showed resistance to carbapenems and levofloxacin. Cefuroxime and ceftriaxone were found to have 100% sensitivity among the tonsil microflora isolates. In two-thirds of cases, sensitivity to cefoperazone/sulbactam, imipenem, gatifloxacin, and moxifloxacin was discovered. Cefpodoxime, cefoperazone/sulbactam, gatifloxacin, and moxifloxacin all showed normal or moderate sensitivity (without resistance) <bold>(Fig. <xref ref-type="fig" rid="F3">3B</xref>)</bold>.</p>
      </sec>
      <sec sec-type="Antibacterial sensitivity of microorganisms presented in the nasal passage" id="sec20">
        <title>Antibacterial sensitivity of microorganisms presented in the nasal passage</title>
        <p>Similarly, antibiotic sensitivity was analyzed in isolates of microorganisms that were isolated from the nasal passage of patients on the side of sinus-lift surgery. The findings showed that the microorganisms from this biotope were resistant to cephalexin, methicillin, amoxicillin/clavulanate, and macrolides (azithromycin and clarithromycin) in 100% of cases. The overwhelming majority of isolates were resistant to cefazolin, ceftazidime, and carbapenems (imipenem and meropenem). Resistance to all fluoroquinolones except levofloxacin was found in one-third of the cases. 100% sensitivity was observed to some representatives of the cephalosporins—to cefuroxime, ceftriaxone, and cefoperazone/sulbactam. Bacterial cultures were mainly sensitive to ciprofloxacin and gatifloxacin, but resistance to these agents was found in a third of the cases. Only moderate sensitivity was observed to cefepime. Moderate and marked sensitivity was presented to cefpodoxime and levofloxacin <bold>(Fig. <xref ref-type="fig" rid="F3">3C</xref>)</bold>.</p>
      </sec>
      <sec sec-type="Antibacterial sensitivity of microorganisms present on the maxillary sinus internal membrane" id="sec21">
        <title>Antibacterial sensitivity of microorganisms present on the maxillary sinus internal membrane</title>
        <p>Later, we examined the sensitivity of bacterial isolates from the Schneiderian membrane taken from patients having sinus-lift surgery. These cultures showed complete resistance to azithromycin, methicillin, meropenem, cephalexin, and cefazolin. The majority of bacteria exhibited resistance to ciprofloxacin, imipenem, clarithromycin, and amoxicillin/clavulanate. The bacteria were resistant to moxifloxacin, cefuroxime, and ceftazidime in one-third of the cases. Only cefpodoxime, cefepime, and half of the fluoroquinolones (ofloxacin, norfloxacin, and levofloxacin) caused moderate bacterial sensitivity. Cultures showed a moderate sensitivity to ceftazidime. In this biotope, ceftriaxone and cefoperazone/sulbactam worked best. The high sensitivity of gatifloxacin in the absence of resistance suggests that it could be very effective in the studied biotope <bold>(Fig. <xref ref-type="fig" rid="F3">3D</xref>)</bold>.</p>
      </sec>
    </sec>
    <sec sec-type="Discussion" id="sec22">
      <title>Discussion</title>
      <p>Analysis of the literature on the study of various biotopes of the maxillary sinus and Schneiderian membrane during a planned sinus-lift procedure, in particular, shows rather ambiguous and discordant results. Thus, in the study of Carreño Carreño et al.<sup>[<xref ref-type="bibr" rid="B20">20</xref>]</sup>, the published results showed that the maxillary sinus was non-sterile in only 18.10% of patients. The authors reported that the <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Streptococcus">Streptococcus</tp:taxon-name-part></tp:taxon-name></italic> family was prevailing (45.00%), with dominance of <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="viridans">viridans</tp:taxon-name-part></tp:taxon-name></italic> (61.1%). Also prevailing were the <italic>Staphylococci</italic> (25.00%) and <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>. In addition, <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> and <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="oxytoca">oxytoca</tp:taxon-name-part></tp:taxon-name></italic> were isolated. In 33% of cases, the culture of microorganisms could not be identified. The isolated microorganisms were resistant to macrolides and had higher sensitivity to penicillins, cephalosporins, and fluoroquinolones. Ampicillin, amoxicillin/clavulanate, and ciprofloxacin were proposed as the most effective antibiotics.<sup>[<xref ref-type="bibr" rid="B20">20</xref>]</sup></p>
      <p>Salgado-Peralvo et al.<sup>[<xref ref-type="bibr" rid="B21">21</xref>]</sup> reported higher efficacy of preoperative antibacterial therapy in cases of the sinus lift and dental implantation. The positive effect of local administration of metronidazole solution during surgery was described. Sinus irrigation and wetting of osteoplastic material with metronidazole was believed to improve the integration of bone substitute material and promote the formation of more complete native bone tissue. Penicillins (including amoxicillin/clavulanate) were most often chosen. Ciprofloxacin was prescribed only in cases of allergic reactions to penicillins. Clindamycin and cefazolin were also recommended for preventive antibacterial therapy.<sup>[<xref ref-type="bibr" rid="B21">21</xref>]</sup></p>
      <p>There are a few reports that demonstrate that administration of azithromycin also helps to reduce the intensity of inflammatory reactions. This effect, however, may be achieved not only by the substance’s antibacterial effect, but also by its anti-inflammatory side effect: azithromycin reduces production of granulocyte colony-stimulating factor, interleukin-6, and interleukin-8, macrophage inflammatory protein 1, and interferon-induced 10 kDa protein in the early stages of the inflammatory process. Azithromycin also reduces the mobilization of granulocyte precursors, as well as immune and inflammatory cell activity during the healing process. In general, similar effects to immunomodulation were observed in all members of the macrolide group, necessitating further investigation. Therefore, azithromycin and clarithromycin were included in the recommended regimens of prophylactic antibacterial therapy when performing dental implantation and sinus-lift procedures.<sup>[<xref ref-type="bibr" rid="B22">22</xref>]</sup></p>
      <p>The results of Peleg et al.<sup>[<xref ref-type="bibr" rid="B23">23</xref>]</sup> indicated that in somatically healthy patients during the sinus-lift surgery, the inner sinus membrane was non-sterile (72%). The authors identified the aerobes in 58% of cases and anaerobes in 56%. In 50% of cases, polymicrobial flora was detected.<sup>[<xref ref-type="bibr" rid="B23">23</xref>]</sup> On et al.<sup>[<xref ref-type="bibr" rid="B24">24</xref>]</sup> reported that the frequency of infectious and inflammatory complications after sinus-lift surgery was 21%. Mainly, the processes had a bacterial origin, and rare cases of <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Aspergillus">Aspergillus</tp:taxon-name-part></tp:taxon-name></italic> fungi and methicillin-resistant <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> identification were described.<sup>[<xref ref-type="bibr" rid="B24">24</xref>]</sup></p>
      <p>It is also worth considering the recommendations of one of the founders of the open sinus-lift technique: according to the recommendations of Testori et al., prophylactic antibacterial therapy also included two options – amoxicillin/clavulanate (before and after surgery), and for patients with an existing allergy to penicillins the clarithromycin with metronidazole were recommended. In cases of complications, the first group of patients was recommended to receive amoxicillin/clavulanate with metronidazole, and the second group—to replace antibiotics with levofloxacin.<sup>[<xref ref-type="bibr" rid="B25">25</xref>]</sup></p>
    </sec>
    <sec sec-type="Conclusions" id="sec23">
      <title>Conclusions</title>
      <p>A study of the species composition of microorganisms in the maxillary sinus and other biotopes of the maxillofacial area in patients who underwent a planned sinus-lift surgery showed that they differ significantly both in species and in sensitivity to antibacterial agents. In the maxillary sinus, in the absence of clinical signs of inflammation, pathogenic microorganisms were present in clinically significant concentrations, mainly <italic>Streptococci</italic>, <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>, and fungi of the <italic><tp:taxon-name><tp:taxon-name-part taxon-name-part-type="genus" reg="Candida">Candida</tp:taxon-name-part></tp:taxon-name></italic> genus. The frequency of detection of pathogenic microorganisms, their species composition, and concentrations did not allow us to identify relationships between different biotopes of the maxillofacial area. Considering the differences in the species composition of different biotopes of the maxillary sinus, as well as the impossibility of complete isolation of the surgical field when performing sinus-lift surgery, there is a high risk of sinus contamination with microflora that persists in the oral cavity and nasal passages during surgery and in the early postoperative period. Therefore, when planning a prophylactic course of antibacterial therapy in the postoperative period, it is advisable to also take into account the sensitivity to antibacterial agents in representatives of all biotopes. Ceftriaxone and cefoperazone/sulbactam were the most effective in terms of their effect on isolates isolated in clinically significant concentrations. The cultures were mainly sensitive to cefuroxime – 75% of the isolates. Gatifloxacin appeared to be quite effective, with an equal distribution of susceptibility and intermediate susceptibility cases, with no resistance. These findings point to a narrowing of the antibacterial agents available for prophylactic use during sinus-lift surgery. The identified fungi on the mucoperiosteum of the maxillary sinus were sensitive to fluconazole, ketoconazole, and clotrimazole, moderately sensitive to itraconazole and nystatin.</p>
    </sec>
    <sec sec-type="Ethical statement" id="sec24">
      <title>Ethical statement</title>
      <p>Study procedures were approved by the Bioethics Committee of the State University Uzhhorod National University (Ukraine) (No. 14/1, 17 November 2023). The study adhered to ethical principles as outlined by the Declaration of Helsinki. All participants provided informed consent after a thorough explanation of the study objectives and procedures. All patients provided prior voluntary consent for the collection of biological material for research during the operation.</p>
      <p>Performing the study, the results of which are presented in the form of an article, is not related to violation of the ethics of scientific research and relations regulated by the following regulatory legal acts:</p>
      <list list-type="order">
        <list-item>
          <p>1. Declaration of Helsinki, adopted by the General Assembly of the World Medical Association (1964-2016),
</p>
        </list-item>
        <list-item>
          <p>2. Council of Europe Convention on Human Rights and Biomedicine (1997)
</p>
        </list-item>
        <list-item>
          <p>3. European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes (1986),
</p>
        </list-item>
        <list-item>
          <p>4. WHO Policy Documents,
</p>
        </list-item>
        <list-item>
          <p>5. Documents of the International Council of Medical Societies,
</p>
        </list-item>
        <list-item>
          <p>6. International Code of Medical Ethics (1983)
</p>
        </list-item>
        <list-item>
          <p>7. Relevant laws of Ukraine.
</p>
        </list-item>
      </list>
    </sec>
    <sec sec-type="Limitations of the study" id="sec25">
      <title>Limitations of the study</title>
      <p>This study was performed on a small group of patients (n=15). And that fact may affect the significance of the obtained results. Also, the selection of patients (only persons who planned to install dental implants on the maxilla) may cause a systemic misunderstanding of the real situation of microbiome composition in different maxillofacial biotopes among patients in dental practice. The methods used for sample transportation, microorganism cultivation, and identification allowed the detection of aerobic and facultative anaerobic microorganisms. The potential application of methods specialized for anaerobes may show other results and may change the final clinical recommendation, which is possible to derive from the obtained results. Also, the application of PCR identification of microorganisms might change the final understanding of the situation. The chosen list of antibiotics is wide enough but also adapted to the local situation and experience of infection control in Ukraine.</p>
    </sec>
    <sec sec-type="Ethical approval" id="sec26">
      <title>Ethical approval</title>
      <p>This study received ethical approval from the Bioethics Committee of the State University Uzhhorod National University (Ukraine) (approval No. 14/1) on November 17, 2023. The study adhered to ethical principles as outlined by the Declaration of Helsinki.</p>
    </sec>
    <sec sec-type="Ethical statements" id="sec27">
      <title>Ethical statements</title>
      <p>The authors declared that no clinical trials were used in the present study.</p>
      <p>The authors declared that no experiments on humans or human tissues were performed for the present study.</p>
      <p>The authors declared that all participants provided informed consent after a thorough explanation of the study objectives and procedures. All patients provided prior voluntary consent for the collection of biological material for research during the operation</p>
      <p>The authors declared that no experiments on animals were performed for the present study.</p>
      <p>The authors declared that no commercially available immortalized human and animal cell lines were used in the present study.</p>
    </sec>
    <sec sec-type="Conflict of interest" id="sec28">
      <title>Conflict of interest</title>
      <p>The authors have declared that no competing interests exist.</p>
    </sec>
    <sec sec-type="Funding" id="sec29">
      <title>Funding</title>
      <p>No funding was reported.</p>
    </sec>
    <sec sec-type="Use of AI" id="sec30">
      <title>Use of AI</title>
      <p>No use of AI was reported.</p>
    </sec>
    <sec sec-type="Author contributions" id="sec31">
      <title>Author contributions</title>
      <p>All authors have contributed equally.</p>
    </sec>
    <sec sec-type="Data availability" id="sec32">
      <title>Data availability</title>
      <p>All data used are referenced or included in the article.</p>
    </sec>
  </body>
  <back>
    <ack>
      <title>Acknowledgements</title>
      <p>The authors have no support to report.</p>
    </ack>
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