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 <!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.0 20120330//EN" "http://jats.nlm.nih.gov/publishing/1.0/JATS-journalpublishing1.dtd"> <article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" article-type="case-report" dtd-version="1.0" xml:lang="en">
  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">JFD</journal-id>
      <journal-title-group>
        <journal-title>Journal of Fungal Diversity</journal-title>
      </journal-title-group>
      <issn pub-type="epub">2766-869X</issn>
      <publisher>
        <publisher-name>Open Access Pub</publisher-name>
        <publisher-loc>United States</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="doi">10.14302/issn.2766-869X.jfd-18-2276</article-id>
      <article-id pub-id-type="publisher-id">JFD-18-2276</article-id>
      <article-categories>
        <subj-group>
          <subject>case-report</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title><italic>Saccharomyces </italic><italic>Kluyveri</italic> Fungemia in a Patient with Human Immunodeficiency Virus Infection</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>E.</surname>
            <given-names>Elleuch</given-names>
          </name>
          <xref ref-type="aff" rid="idm1842461148">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>M.</surname>
            <given-names>Hammami</given-names>
          </name>
          <xref ref-type="aff" rid="idm1842461148">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>C.</surname>
            <given-names>Marrekchi</given-names>
          </name>
          <xref ref-type="aff" rid="idm1842461148">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Fatma</surname>
            <given-names>Cheikhrouhou</given-names>
          </name>
          <xref ref-type="aff" rid="idm1842460140">2</xref>
          <xref ref-type="aff" rid="idm1842488236">*</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>H.</surname>
            <given-names>Trabelsi</given-names>
          </name>
          <xref ref-type="aff" rid="idm1842460140">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>M.</surname>
            <given-names>Maâlej</given-names>
          </name>
          <xref ref-type="aff" rid="idm1842461148">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>B.</surname>
            <given-names>Hammami</given-names>
          </name>
          <xref ref-type="aff" rid="idm1842461148">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>I.</surname>
            <given-names>Maaloul</given-names>
          </name>
          <xref ref-type="aff" rid="idm1842461148">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>A.</surname>
            <given-names>Ayedi</given-names>
          </name>
          <xref ref-type="aff" rid="idm1842460140">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>D.</surname>
            <given-names>Lahiani</given-names>
          </name>
          <xref ref-type="aff" rid="idm1842461148">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>M.</surname>
            <given-names>Ben Jemaa</given-names>
          </name>
          <xref ref-type="aff" rid="idm1842461148">1</xref>
        </contrib>
      </contrib-group>
      <aff id="idm1842461148">
        <label>1</label>
        <addr-line>Infectious diseases Department- HediChaker hospital 3029 Sfax- Tunisia.</addr-line>
      </aff>
      <aff id="idm1842460140">
        <label>2</label>
        <addr-line>Mycology and parasitology Laboratory- Habib Bourguiba hospital 3029 Sfax -Tunisia.</addr-line>
      </aff>
      <aff id="idm1842488236">
        <label>*</label>
        <addr-line>Corresponding Author</addr-line>
      </aff>
      <contrib-group>
        <contrib contrib-type="editor">
          <name>
            <surname>Samantha</surname>
            <given-names>Chandranath Karunarathna</given-names>
          </name>
          <xref ref-type="aff" rid="idm1842213524">1</xref>
        </contrib>
      </contrib-group>
      <aff id="idm1842213524">
        <label>1</label>
        <addr-line>Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China</addr-line>
      </aff>
      <author-notes>
        <corresp>
    
    Fatma Cheikhrouhou, <addr-line>Mycology and parasitology Laboratory- Habib Bourguiba hospital 3029 Sfax -Tunisia.</addr-line><email>fatima_cheikhrouhou@yahoo.fr</email></corresp>
        <fn fn-type="conflict" id="idm1841884524">
          <p>The authors have declared that no competing interests exist.</p>
        </fn>
      </author-notes>
      <pub-date pub-type="epub" iso-8601-date="2018-11-27">
        <day>27</day>
        <month>11</month>
        <year>2018</year>
      </pub-date>
      <volume>1</volume>
      <issue>1</issue>
      <fpage>1</fpage>
      <lpage>5</lpage>
      <history>
        <date date-type="received">
          <day>02</day>
          <month>08</month>
          <year>2018</year>
        </date>
        <date date-type="accepted">
          <day>21</day>
          <month>11</month>
          <year>2018</year>
        </date>
        <date date-type="online">
          <day>27</day>
          <month>11</month>
          <year>2018</year>
        </date>
      </history>
      <permissions>
        <copyright-statement>© </copyright-statement>
        <copyright-year>2018</copyright-year>
        <copyright-holder>E. Elleuch, et al.</copyright-holder>
        <license 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p>
        </license>
      </permissions>
      <self-uri xlink:href="http://openaccesspub.org/jfd/article/908">This article is available from http://openaccesspub.org/jfd/article/908</self-uri>
      <abstract>
        <p>We report a case of a young woman with acquired immune deficiency syndrome admitted with fever and abdominal pain. <italic>Saccharomyces </italic><italic>kluyveri</italic> was isolated in blood culture. She was successfully treated with fluconazole. This case demonstrates the pathogenicity of <italic>Saccharomyces </italic><italic>Kluyveri</italic> in immunocompromised host.</p>
      </abstract>
      <kwd-group>
        <kwd>AIDS</kwd>
        <kwd>Amphotericin B</kwd>
        <kwd>emergent pathogen</kwd>
        <kwd>yeast.</kwd>
      </kwd-group>
      <counts>
        <fig-count count="3"/>
        <table-count count="0"/>
        <page-count count="5"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec id="idm1842205308" sec-type="intro">
      <title>Introduction </title>
      <p>Systemic fungal infections are one of the              major causes of morbidity and mortality in              immunocompromised patients. Although <italic>Candida</italic>                and <italic>Aspergillus</italic> species are the common fungal pathogen responsible of infection in these patients,               <italic>Saccharomyces</italic> was reported as an emergent               pathogen <xref ref-type="bibr" rid="ridm1842512252">1</xref>. It is frequently referred as brewers or baker’s yeast. Invasive <italic>Saccharomyces </italic>infections are relatively rare. It mainly presents as septicemia that resist in broad-spectrum antibiotics. Despite appropriate antifungal therapy, the disease has been associated with unfavorable outcome and a high mortality rate. We report a case of <italic>Saccharomyces (S) </italic><italic>Kluyveri</italic> fungemia in patient with human immunodeficiency virus syndrome.</p>
    </sec>
    <sec id="idm1842204660" sec-type="cases">
      <title>Case Report</title>
      <p> A 32-year-old woman with acquired immune deficiency syndrome presented with a one week history of fever and abdominal pain. His medical history was significant for hepatitis C cirrhosis and Kaposi sarcoma. She presented <italic>Salmonella enteritidis</italic> septicemia one month prior to admission treated with cefotaxime during 15 days.</p>
      <p>Seven days before admission, she presented with severe abdominal pain, asthenia and fever.</p>
      <p>Physical examination revealed a high temperature as 39°C, pulse rate 94/min; blood pressure was 80/40 mm Hg and diffuses abdominal tenderness. Pertinent laboratory findings included pancytopenia,            CD4 count as 14 cells/mm<sup>3</sup> and HIV viral load 3, 87.10<sup>5</sup>copy/ml.</p>
      <p>Abdominal ultrasonography demonstrated hepatosplenomegaly. Trans thoracic echocardiography and chest X ray were normal.</p>
      <p>Parasitological examination of stools and coproculture were negative.</p>
      <p>Blood and urine specimens were collected for bacterial culture and subsequently found to be negative. Fungal Sabouraud culture of blood was positive for <italic>S. </italic><italic>kluyveri</italic>. <xref ref-type="fig" rid="idm1842741012">Figure 1</xref>, <xref ref-type="fig" rid="idm1842732316">Figure 2</xref> and <xref ref-type="fig" rid="idm1842733612">Figure 3</xref> show the macroscopic and microscopic aspects of <italic>Saccharomyces </italic><italic>kluyveri</italic>. The strain was susceptible to all antifungal treatment.  <italic>Aspergillus and leishmaniasis</italic> serology were both negative. The patient was treated with fluconazole (400 mg/day). Ten days later, she became afebrile.  She received 1 month of antifungal treatment. She developed on day 17 an abdominal pain and fever. Sabouraud blood cultures performed were sterile. Bacterial blood cultures were positive to <italic>Salmonella enteritidis.</italic> A CT scan confirmed appendiularperitinotis. She underwent a surgical treatment. After her operation, the general condition of the patient worsened progressively and she persisted febrile for 12 days. She developed a respiratory distress and she died.</p>
      <fig id="idm1842741012">
        <label>Figure 1.</label>
        <caption>
          <title> Macroscopic aspect of Saccharomyces kluyveri isolated from blood culture.</title>
        </caption>
        <graphic xlink:href="images/image1.jpg" mime-subtype="jpg"/>
      </fig>
      <fig id="idm1842732316">
        <label>Figure 2.</label>
        <caption>
          <title> Macroscopic aspect of Saccharomyces kluyveri isolated from blood culture.</title>
        </caption>
        <graphic xlink:href="images/image2.jpg" mime-subtype="jpg"/>
      </fig>
      <fig id="idm1842733612">
        <label>Figure 3.</label>
        <caption>
          <title> Macroscopic aspect of Saccharomyces kluyveri isolated from blood culture.</title>
        </caption>
        <graphic xlink:href="images/image3.jpeg" mime-subtype="jpeg"/>
      </fig>
    </sec>
    <sec id="idm1842187820" sec-type="discussion">
      <title>Discussion</title>
      <p><italic>Saccharomyces </italic><italic>kluyveri</italic>, also named <italic>Lachancea</italic><italic>kluyveri</italic>, is budding yeast related to <italic>Saccharomyces cerevisiae</italic><xref ref-type="bibr" rid="ridm1842574884">2</xref>. It is widespread in the environment and can be found on drosophila species, fruit, plants and in soil <xref ref-type="bibr" rid="ridm1842512252">1</xref>. It is a common colonizer of human respiratory, gastrointestinal and urinary tracts and considered as a benign organism <xref ref-type="bibr" rid="ridm1842512252">1</xref>. Thus, infection must be considered and patient should be treated for an invasive fungal infection when the organism is isolated from a normally sterile body site <xref ref-type="bibr" rid="ridm1842574884">2</xref><italic>. Saccharomyces cerevisiae, S. </italic><italic>carlsbergensis</italic>and <italic>S. </italic><italic>boulardii</italic> have been associated with serious human infection. The role of <italic>S. </italic><italic>kluyverii</italic> as human pathogen is unknown <xref ref-type="bibr" rid="ridm1842615348">3</xref>. To our knowledge, this is the second reported case of <italic>S. </italic><italic>kluyveri</italic>fungemia in the literature. The first case was reported in 1998.        A-47-year-old man infected with human immune deficiency virus was hospitalized for fever, asthenia, defective memory and shortness of breath. He was diagnosed with disseminated <italic>S. </italic><italic>kluyveri</italic><italic> i</italic>nfection. The yeast was isolated from blood cultures and CSF. The autopsy revealed the presence of the microorganism in different organs: liver, spleen, pancreas, lungs, kidneys and brain <xref ref-type="bibr" rid="ridm1842615348">3</xref>.  </p>
      <p>Systemic infections in immunocompromised patients are uncommon as compared to invasive aspergillosis and candidiasis. The incidence of <italic>Saccharomyces</italic> fungemia is unknown; it varied from 0.1% to 3.6% of all episodes of fungemia <xref ref-type="bibr" rid="ridm1842574884">2</xref><xref ref-type="bibr" rid="ridm1842363812">4</xref>. Hospital-acquired transmission has been              demonstrated <xref ref-type="bibr" rid="ridm1842574884">2</xref><xref ref-type="bibr" rid="ridm1842363812">4</xref><xref ref-type="bibr" rid="ridm1842368204">5</xref><xref ref-type="bibr" rid="ridm1842345140">6</xref>.</p>
      <p>Risk factors are nearly the same of systemic candidiasis. They mainly include deep and prolonged neutropenia, immune cell deficiency, broad- spectrum antibiotics, cytotoxic chemotherapy, parenteral nutrition, hemodialysis and catherization <xref ref-type="bibr" rid="ridm1842512252">1</xref><xref ref-type="bibr" rid="ridm1842574884">2</xref><xref ref-type="bibr" rid="ridm1842368204">5</xref>. The use of probiotic is an important risk factor for  fungemia which may be especially dangerous in patients at high risk for infection <xref ref-type="bibr" rid="ridm1842512252">1</xref><xref ref-type="bibr" rid="ridm1842363812">4</xref><xref ref-type="bibr" rid="ridm1842345140">6</xref>. It was responsible for 40.2% of invasive <italic>Saccharomyces</italic> infections reported in the literature <xref ref-type="bibr" rid="ridm1842512252">1</xref>. In our case, the acquired immune cell deficiency (HIV) was noted associated with the use of broad- spectrum antibiotics. She did not receive any dietary supplementation or probiotic preparations. The portal of entry is mainly supposed to be digestive <xref ref-type="bibr" rid="ridm1842512252">1</xref>. In our patient, no clear portal of entry has been defined. </p>
      <p>The main clinical presentation is similar to other invasive fungal infections as a fever unresponsive to antibiotics<italic>.</italic>Non specific symptoms are usually noted and can roam the diagnosis and delay support.            <italic>Saccharomyces </italic>spp. can cause a wide variety of clinical syndrome, such as genitor-urinary tract infection,     gastro-intestinal infection (peritonitis, eosophagitis and liver abscess), respiratory infection, endocarditis and septic shock <xref ref-type="bibr" rid="ridm1842363812">4</xref><xref ref-type="bibr" rid="ridm1842349532">7</xref><xref ref-type="bibr" rid="ridm1842341876">8</xref>. </p>
      <p>The diagnosis is based on positive blood cultures and also the mycological and pathological examinations of organ biopsies guided by clinical symptoms.</p>
      <p>The identification of the fungus in cultures is simple and is based on its unique morphology, growth and biochemical aspects. <xref ref-type="bibr" rid="ridm1842349532">7</xref></p>
      <p>ESCMID and ECMM suggested treatment guidelines for S. yeast based on his sensitivity profile studied in vitro and in reference to the data of the few cases reported in the literature. <xref ref-type="bibr" rid="ridm1842312660">10</xref></p>
      <p><italic>Saccharomyces</italic> sensitivity profile is similar to <italic>C. glabrata</italic>. It has a high MICs to fluconazole and low MICs to Amphoterecin B and Flucytosine. S. is claimed susceptible to Amphoterecin B and Flucytosine and has a reduced susceptibility to fluconazole.  Echinocandins are active on <italic>Saccharomyces</italic>. Despite the fact that data are scarce, both posaconazole and voriconazole have been reported to have good activity in vitro against this fungus <xref ref-type="bibr" rid="ridm1842363812">4</xref>.</p>
      <p>Amphoterecin B is the antifungal of choice in the treatment of these infections. <xref ref-type="bibr" rid="ridm1842363812">4</xref><xref ref-type="bibr" rid="ridm1842336764">9</xref><xref ref-type="bibr" rid="ridm1842312660">10</xref><xref ref-type="bibr" rid="ridm1842308124">11</xref></p>
      <p>Besides, no therapeutic failure has been clearly attributable to resistance, even in strains with reduced susceptibility to fluconazole,  it has been proposed as an alternative to Amphoterecin B.<xref ref-type="bibr" rid="ridm1842363812">4</xref><xref ref-type="bibr" rid="ridm1842336764">9</xref></p>
      <p>In our case, our patient was successively treated with fluconazole during one month.</p>
      <p>Despite this spectrum of susceptibility, a favorable outcome was observed in 63% of cases, which is a slightly higher percentage than that reported for cases of invasive candidiasis <xref ref-type="bibr" rid="ridm1842363812">4</xref>.</p>
      <p>In conclusion, <italic>Saccharomyces</italic> organisms are increasingly reported as agents of invasive infection, especially in immunocompromised or critically ill patients. </p>
    </sec>
  </body>
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