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  <journal-meta>
   <journal-id journal-id-type="nlm-ta">Ulutas Med J</journal-id>
   <journal-title-group>
    <journal-title>The Ulutas Medical Journal</journal-title>
    <abbrev-journal-title>Ulutas Med J</abbrev-journal-title>
   </journal-title-group>
   <issn pub-type="ppub">2149-0430</issn>
   <issn pub-type="epub">2149-388X</issn>
   <publisher>
    <publisher-name>Hayriye Zehra Ulutaş</publisher-name>
   </publisher>
  </journal-meta>
  <article-meta>
   <article-id pub-id-type="doi">10.5455/umj.20181126062738</article-id>
   <article-id pub-id-type="publisher-id">284199</article-id>
   <article-categories>
    <subj-group subj-group-type="heading">
     <subject>Case Report</subject>
    </subj-group>
    <subj-group subj-group-type="subject">
     <subject>Emergency Medicine</subject>
    </subj-group>
   </article-categories>
   <title-group>
    <article-title>Traumatic Wound Infection with Graphium</article-title>
   </title-group>
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      <surname>Lin</surname>
      <given-names>Wei-Ting</given-names>
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     <label>1</label>
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      <institution-id institution-id-type="ror">https://ror.org/02y2htg06</institution-id>
      <institution>Chi Mei Medical Center, Liouying</institution>
     </institution-wrap>
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      <institution-id institution-id-type="ror">https://ror.org/02y2htg06</institution-id>
      <institution>Chi Mei Medical Center</institution>
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   <pub-date publication-format="electronic" date-type="pub" iso-8601-date="2018-03-29">
    <day>29</day>
    <month>03</month>
    <year>2018</year>
   </pub-date>
   <pub-date publication-format="print" date-type="collection">
    <year>2018</year>
   </pub-date>
   <volume>4</volume>
   <issue>1</issue>
   <fpage>44</fpage>
   <lpage>46</lpage>
   <history>
    <date date-type="received" iso-8601-date="2017-11-26">
     <day>26</day>
     <month>11</month>
     <year>2017</year>
    </date>
    <date date-type="rev-recd" iso-8601-date="2017-12-20">
     <day>20</day>
     <month>12</month>
     <year>2017</year>
    </date>
    <date date-type="accepted" iso-8601-date="2017-12-28">
     <day>28</day>
     <month>12</month>
     <year>2017</year>
    </date>
   </history>
   <permissions>
    <copyright-statement>© 2018 The Author(s)</copyright-statement>
    <copyright-year>2018</copyright-year>
    <license>
     <ali:license_ref>https://creativecommons.org/licenses/by-nc/4.0/</ali:license_ref>
     <license-p>This is an open access article distributed under the CC BY-NC 4.0 licence.</license-p>
    </license>
   </permissions>
   <self-uri xlink:href="https://www.ulutasmedicaljournal.com/?mno=284199"/>
   <self-uri content-type="pdf" xlink:href="https://www.ulutasmedicaljournal.com/pdf/284199.pdf"/>
   <abstract>
    <p>Graphium species are filamentous fungi and belong to the family of Ascomycota. They have been recovered from soil, plant debris, woody substrates, manure, and polluted water, and most of them are plant pathogens. In contrast, human infections caused by Graphium spp are extremely rare. Herein, we reported the first published case of Graphium traumatic wound infection in an immunocompetent patient. Surgery was performed and amphotericin was added into the antimicrobial regimen for better coverage of the fungus. The postoperative course was smooth, and the patient was discharged uneventfully.</p>
   </abstract>
   <kwd-group kwd-group-type="author">
    <kwd>Wound infection</kwd>
    <kwd>Graphium</kwd>
   </kwd-group>
   <funding-group>
    <funding-statement>Funding information was not reported in the published version of this article.</funding-statement>
   </funding-group>
  </article-meta>
 </front>
 <body>
  <sec id="sec-1">
   <title>Introduction</title>
   <p id="b-1">Graphium species are filamentous fungi and belong to the family of Ascomycota. They have been recovered from soil, plant debris, woody substrates, manure, and polluted water, and most of them are plant pathogens (    <xref ref-type="bibr" rid="ref1">1</xref>
). In contrast, human infections caused by Graphium spp are extremely rare (    <xref ref-type="bibr" rid="ref2">2</xref>
–    <xref ref-type="bibr" rid="ref4">4</xref>
). Thus, the clinical significance of this pathogen remains unclear due to limited knowledge. Herein, we report the first published case of Graphium traumatic wound infection in an immunocompetent patient.</p>
  </sec>
  <sec id="sec-2">
   <title>Case Presentation</title>
   <p id="b-2">A 38-year-old woman presented with painful deformity of the right elbow and right ankle, and severe abdominal pain after an accidental 3-story fall onto her right side. She denied any history of significant medical illness. Her body temperature on arrival was 37    <sup>o</sup>
C, pulse rate 85 beats per minute, respiratory rate 20 per minute, and blood pressure of 90/58 mmHg. Physical examination showed cubitus valgus deformity of the right elbow with an open wound and bone exposure (Figure-1), varus deformity of the right ankle, and tenderness in the lower pelvis. Radiography of the right elbow revealed a comminuted fracture of the right supracondylar humerus, Gustilo type-II (Figure- 2). In addition, radiography of the pelvis and lower limbs disclosed a comminuted fracture of the right femoral inter/sub-trochanter, right bimalleolar fracture, fractures of the bilateral pubic rami, right transverse process of the L5, and left distal tibia, and a displaced fracture of the left middle fibular shaft. Laboratory studies were as follows: white blood cell count, 21.5 x 10    <sup>9</sup>
 /L with neutrophil predominance (83.8%); serum creatinine, 0.82 mg/dL; alanine aminotransferase, 179 U/L; sodium, 141.3 mmol/L; and C-reactive protein, 103.7 mg/dL (reference value, &lt; 0.8 mg/dL).</p>
   <fig id="fig-1" position="float">
    <label>Figure 1</label>
    <caption>
     <p>Deformity of the right elbow with an open wound and bone exposure.</p>
    </caption>
    <graphic xlink:href="fig-1.png">
     <alt-text>Figure 1: Deformity of the right elbow with an open wound and bone exposure.</alt-text>
    </graphic>
   </fig>
   <p id="b-3">revealed liver and spleen lacerations, pelvic fracture and hemoperitoneum. Because of her unstable hemodynamic status and progressive dyspnea, she received aggressive fluid resuscitation, massive blood transfusions and intubation for acute respiratory failure. Emergency angiography showed petechial hemorrhage in the bilateral internal iliac arteries and liver, and she received successful transarterial embolization to stop the bleeding. Empirical antibiotic treatment with flomoxef was prescribed for traumatic wound infection over the right elbow. After her hemodynamic status stabilized, surgical intervention with repeated wound debridement of the right elbow was done.</p>
   <fig id="fig-2" position="float">
    <label>Figure 2</label>
    <caption>
     <p>Radiography of the right elbow shows as a comminuted fracture of right supracondylar humerus and soft tissue swelling.</p>
    </caption>
    <graphic xlink:href="fig-2.png">
     <alt-text>Figure 2: Radiography of the right elbow shows as a comminuted fracture of right supracondylar humerus and soft tissue swelling.</alt-text>
    </graphic>
   </fig>
   <p id="b-4">A sample of the gross turbid discharge with wound tissue was sent for cul-ture, and the wound specimen grew Graphium spp. The fungus which was identified by *MALDI-TOF Mass Spectrometer and had a best identification score of 1.841, which indicated genus-level identification. Thus, amphotericin was added into antimicrobial regimen for better coverage of the fungus. The postoperative course was smooth, and she was discharged uneventfully. Follow-up in the outpatient clinic showed that the wound healed well.</p>
  </sec>
  <sec id="sec-3">
   <title>Discussion</title>
   <p id="b-5">The present report demonstrated an unusual fungus - Graphium spp. which caused a traumatic wound infection in an immunocompetent patient. The source of infection could have been the soil where the patient fell. To the best of our knowledge, definite Graphium spp.- associated human infections are rare, and only two human cases have been reported previously. In 2007, Kumar reported a case of Graphium basitruncatum with a presentation of persistent fungemia and skin lesions in a patient with acute leukemia (    <xref ref-type="bibr" rid="ref2">2</xref>
). In 2012, El Feghaly reported a case of G. basitruncatum fungemia in a child post stem-cell transplantation.(    <xref ref-type="bibr" rid="ref3">3</xref>
) In contrast to previous reports (    <xref ref-type="bibr" rid="ref2">2</xref>
,    <xref ref-type="bibr" rid="ref3">3</xref>
), our patient had a traumatic would infection and no significant immunocompromised condition. As seen in this case, Graphium spp. can cause traumatic wound infection in an immunocompetent patient, further expanding the disease spectrum of Graphium spp. infections.</p>
   <p id="b-6">In vitro antifungal susceptibility tests showed the MICs for the isolates in Kumar et al ’s report were amphotericin B, 0.5 µg/ml; itraconazole, &gt;16 µg/ml; voriconazole, 8 µg/ml; caspofungin, 2 µg/ml; fluconazole, &gt;64µg/ml (    <xref ref-type="bibr" rid="ref2">2</xref>
), and in El Feghaly et al’s report, were amphotericin B, 8µg/ml; itraconazole, &gt;16 µg/ml; voriconazole, &gt;16 µg/ml; posaconazole &gt;16 µg/ml (    <xref ref-type="bibr" rid="ref3">3</xref>
). The patient with leukemia was post chemotherapy, and had clinical improvement with liposomal amphotericin B, but the improvement coincided with recovery of neutrophils and was temporary (    <xref ref-type="bibr" rid="ref2">2</xref>
). The stem cell transplantation recipient died under treatment with amphotericin and anidulafungin (    <xref ref-type="bibr" rid="ref3">3</xref>
). Our patient had a favorable clinical response to amphotericin B and repeated surgical debridement. In summary, the clinical response was different between our case and previous reports, probably because of the significantly different immune status. Because of limited experience with Graphium spp. infections, the optimal antifungal treatment remains unclear. Therefore, further largescale in vitro and in vivo studies are warranted to establish the appropriate treatment guidelines for this unusual fungus.</p>
  </sec>
  <sec id="sec-4">
   <title>Conclusion</title>
   <p id="b-7">In conclusion, we describe the first case of a traumatic wound infection caused by Graphium spp. in an immunocompetent patient. Her clinical condition responded well to antibiotics and wound debridement.</p>
  </sec>
 </body>
 <back>
  <ref-list>
   <title>References</title>
   <ref id="ref1">
    <label>1</label>
    <mixed-citation publication-type="journal">Okada, G. Genus Graphium. J Antibact Antifung Agents 1994; 22: 45-54.</mixed-citation>
   </ref>
   <ref id="ref2">
    <label>2</label>
    <mixed-citation publication-type="journal">Kumar D, Sigler L, Gibas CF, Mohan S, Schuh A, Medeiros BC, et al. Graphium basitruncatum fungemia in a patient with acute leukemia. J Clin Microbiol 2007;45:1644 -1647.</mixed-citation>
   </ref>
   <ref id="ref3">
    <label>3</label>
    <mixed-citation publication-type="journal">El Feghaly RE, Sutton DA, Thompson EH, Fu J, Wickes BL, Al-Zubeidi D, et al. Graphium basitruncatum fungemia in an immunosuppressed child post stem-cell transplantation. Med Mycol Case Rep 2012;1:35-38.</mixed-citation>
   </ref>
   <ref id="ref4">
    <label>4</label>
    <mixed-citation publication-type="journal">Apostol JG, Meyer SL. Graphium endophthalmitis. Am J Ophthalmol 1972;73:566-569.</mixed-citation>
   </ref>
  </ref-list>
 </back>
</article>
