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  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
        <publisher-loc>S&#227;o Paulo, SP, Brazil</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">YR4sH8GbpKs3NHVm4xpX46z</article-id>
      <article-id pub-id-type="other">00016</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2011001400016</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(11)09700516</article-id>
      <article-id pub-id-type="doi">10.1590/S0066-782X2011001400016</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Relato de Caso</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Endocardite por lactococcus garvieae: primeiro relato de caso da Am&#233;rica Latina</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Hirakawa</surname>
            <given-names>Tatiana Franco</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Costa</surname>
            <given-names>Fernando Augusto Alves da</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Vilela</surname>
            <given-names>Marcos Cairo</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Rigon</surname>
            <given-names>Micheli</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Abensur</surname>
            <given-names>Henry</given-names>
          </name>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Ara&#250;jo</surname>
            <given-names>Maria Rita Elmor de</given-names>
          </name>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <addr-line>
          <named-content content-type="city">S&#227;o Paulo</named-content>
          <named-content content-type="state">S&#227;o Paulo</named-content>
        </addr-line>
        <institution content-type="orgname">Cl&#237;nica Paulista de Doen&#231;as Cardiovasculares Ltda</institution>
        <institution content-type="orgdiv1">Cl&#237;nica Paulista de Doen&#231;as Cardiovasculares </institution>
        <country country="BR">Brazil</country>
      </aff>
      <aff id="aff02">
        <addr-line>
          <named-content content-type="city">S&#227;o Paulo</named-content>
          <named-content content-type="state">S&#227;o Paulo</named-content>
        </addr-line>
        <institution content-type="orgname">Benem&#233;rita Sociedade de Benefic&#234;ncia Portuguesa de S&#227;o Paulo</institution>
        <country country="BR">Brazil</country>
      </aff>
      <pub-date date-type="collection" publication-format="electronic">
        <month>11</month>
        <year>2011</year>
      </pub-date>
      <volume>97</volume>
      <issue>5</issue>
      <fpage>e108</fpage>
      <lpage>e110</lpage>
      <history>
        <date date-type="rev-recd">
          <day>20</day>
          <month>08</month>
          <year>2010</year>
        </date>
        <date date-type="received">
          <day>05</day>
          <month>06</month>
          <year>2010</year>
        </date>
        <date date-type="accepted">
          <day>09</day>
          <month>09</month>
          <year>2010</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/" xml:lang="en">
          <license-p>This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.</license-p>
        </license>
      </permissions>
      <abstract>
        <p>Lactococcus garvieae, pat&#243;geno zoon&#243;tico emergente, &#233; respons&#225;vel por mastite em ruminantes e septicemia em peixes. Embora seja considerado oportunista e raramente causar infec&#231;&#245;es em humanos, sua incid&#234;ncia deve estar subestimada devido &#224; dificuldade do diagn&#243;stico. H&#225; pouqu&#237;ssimos relatos de osteomielite, abscesso hep&#225;tico e peritonite, e apenas nove casos descritos na literatura mundial de endocardite. Relatamos o primeiro caso de endocardite por Lactococcus garvieae da Am&#233;rica Latina em paciente portadora de pr&#243;tese valvar met&#225;lica, com quadro de febre di&#225;ria, calafrios, nodos de Osler e seis hemoculturas positivas para Lactococcus garvieae, que preenchiam os crit&#233;rios de Duke para o diagn&#243;stico de "endocardite infecciosa definitiva"</p>
      </abstract>
      <kwd-group xml:lang="pt" kwd-group-type="author-generated">
        <kwd>Endocardite bacteriana</kwd>
        <kwd>diagn&#243;stico</kwd>
        <kwd>Lactococcus garvieae</kwd>
        <kwd>pr&#243;teses valvares card&#237;acas</kwd>
      </kwd-group>
      <pub-date publication-format="electronic" date-type="pub">
        <day>20</day>
        <month>12</month>
        <year>2011</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>
      <bold>RELATO DE CASO</bold>
    </p>
    <p>
      <bold>Endocardite por <italic>lactococcus garvieae</italic>: primeiro relato de caso da Am&#233;rica Latina</bold>
    </p>
    <p>
      <bold>Tatiana Franco Hirakawa<sup>I,II</sup>; Fernando Augusto Alves da Costa<sup>I,II</sup>; Marcos Cairo Vilela<sup>I,II</sup>; Micheli Rigon<sup>I,II</sup>; Henry Abensur<sup>II</sup>; Maria Rita Elmor de Ara&#250;jo<sup>II</sup></bold>
    </p>
    <p><sup>I</sup>FGM - Cl&#237;nica Paulista de Doen&#231;as Cardiovasculares, S&#227;o Paulo, SP - Brasil </p>
    <p><sup>II</sup>Hospital Benefic&#234;ncia Portuguesa de S&#227;o Paulo, S&#227;o Paulo, SP - Brasil</p>
    <p>
      <xref ref-type="corresp" rid="end">Correspond&#234;ncia</xref>
    </p>
    <p>
      <bold>RESUMO</bold>
    </p>
    <p><italic>Lactococcus garvieae</italic>, pat&#243;geno zoon&#243;tico emergente, &#233; respons&#225;vel por mastite em ruminantes e septicemia em peixes. Embora seja considerado oportunista e raramente causar infec&#231;&#245;es em humanos, sua incid&#234;ncia deve estar subestimada devido &#224; dificuldade do diagn&#243;stico. H&#225; pouqu&#237;ssimos relatos de osteomielite, abscesso hep&#225;tico e peritonite, e apenas nove casos descritos na literatura mundial de endocardite. Relatamos o primeiro caso de endocardite por <italic>Lactococcus garvieae </italic>da Am&#233;rica Latina em paciente portadora de pr&#243;tese valvar met&#225;lica, com quadro de febre di&#225;ria, calafrios, nodos de <italic>Osler</italic> e seis hemoculturas positivas para <italic>Lactococcus garvieae</italic>, que preenchiam os crit&#233;rios de <italic>Duke</italic> para o diagn&#243;stico de "endocardite infecciosa definitiva".</p>
    <p><bold>Palavras-chave:</bold> Endocardite bacteriana, diagn&#243;stico, <italic>Lactococcus garvieae</italic>, pr&#243;teses valvares card&#237;acas.</p>
    <p>
      <bold>Introdu&#231;&#227;o</bold>
    </p>
    <p><italic>Lactococcus garvieae</italic>, pat&#243;geno zoon&#243;tico emergente, originalmente isolado em mastites de ruminantes e respons&#225;vel por septicemias em peixes, &#233; considerado oportunista e de baixa virul&#234;ncia em humanos, com rar&#237;ssimos casos descritos de endocardite (nove casos na literatura mundial)<sup>1-7</sup>, osteomielite<sup>8</sup>, abscesso hep&#225;tico<sup>9</sup>, septicemia e peritonite<sup>5</sup>. Entretanto, a dificuldade do diagn&#243;stico para diferenci&#225;-lo do <italic>Enterococcus</italic> pode subestimar uma incid&#234;ncia maior e desvalorizar sua real import&#226;ncia. Neste estudo, relatamos o primeiro caso de endocardite por <italic>Lactococcus garvieae</italic> da Am&#233;rica Latina e d&#233;cimo caso mundial.</p>
    <p>
      <bold>Relato de caso</bold>
    </p>
    <p>Paciente do sexo feminino, 58 anos, branca, previamente hipertensa, diab&#233;tica tipo 2, dislipid&#234;mica e ex-tabagista, foi submetida &#224; troca de valva mitral por pr&#243;tese met&#225;lica h&#225; seis meses, devido a uma estenose mitral severa de etiologia reum&#225;tica. Com hist&#243;rico de febre di&#225;ria h&#225; seis dias (38,5&#186; C), calafrios, sudorese, n&#243;dulos eritematosos nas m&#227;os e nos membros inferiores, mialgia e fraqueza, deu entrada no hospital. Como h&#225;bito alimentar, consumia diversos tipos de peixes com frequ&#234;ncia e referia ter ingerido um queijo branco recentemente. Apesar de negar tratamento odontol&#243;gico nos &#250;ltimos meses, &#233; portadora de pr&#243;tese dent&#225;ria e perfurou sua gengiva com uma "espinha de peixe" cinco dias antes do in&#237;cio dos sintomas.</p>
    <p>Na admiss&#227;o, apresentava-se febril (38,2&#186; C), com nodos de <italic>Osler</italic> na m&#227;o esquerda, membros inferiores e denti&#231;&#227;o com estado de conserva&#231;&#227;o prec&#225;rio, sem outras altera&#231;&#245;es no exame f&#237;sico. Exames laboratoriais evidenciaram altera&#231;&#245;es de provas inflamat&#243;rias, PCR = 81,9 e VHS = 47,1, sem leucocitose. Nenhum foco de infec&#231;&#227;o foi identificado, apesar de exaustiva investiga&#231;&#227;o diagn&#243;stica.</p>
    <p>Hemoculturas colhidas em tr&#234;s s&#237;tios diferentes isolaram cocos gram-positivos, identificados como <italic>Lactococcus garvieae</italic> por meio de exame bioqu&#237;mico e confirmado com estudo gen&#233;tico. Foi novamente isolado em outras tr&#234;s amostras de hemoculturas, colhidas com intervalo de cinco dias. O antibiograma demonstrou resist&#234;ncia apenas &#224; clindamicina, com sensibilidade &#224; penicilina, gentamicina, vancomicina e demais antibi&#243;ticos.</p>
    <p>Foram realizados dois ecocardiogramas transesof&#225;gicos, por&#233;m, n&#227;o se visibilizou vegeta&#231;&#227;o, e a pr&#243;tese mitral apresentava-se competente. No entanto, segundo os crit&#233;rios modificados de <italic>Duke</italic>, a paciente recebeu o diagn&#243;stico de endocardite e foi medicada com vancomicina 1 g de 12 em 12 horas durante 28 dias, devido &#224; alergia confirmada &#224; penicilina. Evoluiu com remiss&#227;o completa dos sinais e dos sintomas, normaliza&#231;&#227;o dos exames laboratoriais e negativa&#231;&#227;o das hemoculturas.</p>
    <p>Na tentativa de identificar a origem da infec&#231;&#227;o, o queijo branco consumido pela paciente foi enviado para exame microbiol&#243;gico. Na busca por uma "porta de entrada", devido &#224; hist&#243;ria familiar de polipose intestinal, a paciente foi submetida a um enema opaco. Todavia, ambos os exames pareciam dentro da normalidade.</p>
    <p>A paciente recebeu alta assintom&#225;tica ap&#243;s 30 dias de interna&#231;&#227;o, e foi encaminhada para acompanhamento ambulatorial com cardiologista.</p>
    <p>
      <bold>Discuss&#227;o</bold>
    </p>
    <p><italic>Lactococcus garvieae</italic> &#233; uma das oito esp&#233;cies pertencentes ao g&#234;nero <italic>Lactococcus</italic>, originalmente conhecido como o grupo l&#225;tico do g&#234;nero <italic>Streptococcus</italic>, sendo separado deste em 1985, ap&#243;s an&#225;lise gen&#233;tica<sup>10</sup>.</p>
    <p>Formado por cocos gram-positivos, catalase negativa e de crescimento anaer&#243;bio facultativo, s&#227;o bact&#233;rias produtoras de &#225;cido l&#225;tico, que lhes atribui capacidade de fermenta&#231;&#227;o e propriedade bactericida, sendo utilizadas pela ind&#250;stria aliment&#237;cia para fermenta&#231;&#227;o e como conservantes de alimentos<sup>10</sup>.</p>
    <p>No entanto, sabe-se que algumas esp&#233;cies podem ser patog&#234;nicas a animais e humanos, principalmente o <italic>Lactococcus garvieae</italic> e o <italic>Lactococcus Lactis</italic><sup>10</sup>.</p>
    <p>Considerado um pat&#243;geno zoon&#243;tico emergente, o <italic>Lactococcus garvieae </italic>&#233; respons&#225;vel por mastites de ruminantes e septicemia em peixes. Peixes infectados que n&#227;o desenvolvem a doen&#231;a podem contribuir com a dissemina&#231;&#227;o<sup>5</sup>.</p>
    <p>&#201; considerado pat&#243;geno raro em humanos, oportunista e de baixa virul&#234;ncia. H&#225; pouqu&#237;ssimos casos descritos na literatura, nos quais o <italic>Lactococcus garvieae </italic>&#233; o agente causal de endocardite<sup>1-7</sup>, osteomielite<sup>8</sup>, abscesso hep&#225;tico<sup>9</sup>, septicemia e peritonite<sup>5</sup>. Existem nove casos de endocardite relatados na literatura mundial, dos quais quatro acometem pr&#243;teses valvares<sup>1,3</sup> e cinco valvas nativas<sup>2,4,5,7</sup>.</p>
    <p>Este &#233; o primeiro relato de caso de endocardite causada por <italic>Lactococcus garvieae </italic>na Am&#233;rica Latina em paciente portadora de pr&#243;tese valvar met&#225;lica em posi&#231;&#227;o mitral que preencheu os crit&#233;rios modificados de <italic>Duke</italic> para o diagn&#243;stico de "endocardite definitiva" (<xref ref-type="table" rid="tab1">Tabela 1</xref>).</p>
    <table-wrap id="tab1">
      <graphic xlink:href="1678-4170-abc-97-05-e108-00016-gt01.jpg"/></table-wrap>
    <p>A patogenicidade e infectividade do <italic>Lactococcus garvieae</italic> ainda permanecem inconclusivas. Sabe-se que os <italic>Lactococcus</italic> tipicamente n&#227;o fazem parte da flora humana<sup>3</sup>, mas o consumo de leite ou peixes contaminados podem ser fontes de infec&#231;&#227;o<sup>5</sup>. Tamb&#233;m foram isolados em alimentos manufaturados, devido &#224; sua utiliza&#231;&#227;o em produtos aliment&#237;cios. No entanto, acidez g&#225;strica, enzimas pancre&#225;ticas, secre&#231;&#245;es biliares e intestinais, peristalse e integridade das c&#233;lulas epiteliais s&#227;o fatores protetores da infec&#231;&#227;o oral e gastrointestinal. A exist&#234;ncia de desordens gastrointestinais como &#250;lceras, p&#243;lipos ou divert&#237;culos podem atuar como facilitadoras da infectividade bacteriana.</p>
    <p>No caso descrito, &#233; poss&#237;vel que a fonte de infec&#231;&#227;o seja os peixes consumidos rotineiramente pela paciente e a porta de entrada seja o ferimento perfurante causado pela "espinha de peixe", bem como sua denti&#231;&#227;o prec&#225;ria. Por&#233;m, n&#227;o h&#225; dados que confirmem essa hip&#243;tese.</p>
    <p>H&#225; dificuldade na distin&#231;&#227;o com os <italic>Enterococcus</italic>, pois seus fen&#243;tipos s&#227;o semelhantes. Outro desafio est&#225; em isolar o <italic>Lactococcus garvieae </italic>do<italic> lactis</italic>. Alguns estudos sugerem a utiliza&#231;&#227;o do antibiograma, caracterizando o g<italic>arvieae</italic> como resistente &#224; clindamicina, enquanto o <italic>lactis</italic> &#233; sempre sens&#237;vel; hip&#243;tese sustentada nesse caso.</p>
    <p>Em rela&#231;&#227;o ao ecocardiograma, encontramos na literatura escassos relatos de pacientes que apresentavam vegeta&#231;&#245;es em valva nativa<sup>2</sup> e casos com aus&#234;ncia de altera&#231;&#245;es, tanto no exame transtor&#225;cico quanto no transesof&#225;gico, de pacientes com endocardite em pr&#243;teses valvares<sup>8</sup>, semelhante ao aqui descrito.</p>
    <p>O exame padr&#227;o ouro para o isolamento do <italic>Lactococcus garvieae,</italic> apesar do alto custo, &#233; o estudo gen&#233;tico, com o reconhecimento de seu seq&#252;enciamento de DNA<sup>10</sup>.</p>
    <p>
      <bold>Conclus&#227;o</bold>
    </p>
    <p>Endocardite causada por <italic>Lactococcus garvieae</italic> &#233; extremamente rara, sendo esse o d&#233;cimo caso descrito na literatura mundial, e sua patogenia ainda permanece inconclusiva. Poss&#237;veis fontes de infec&#231;&#227;o s&#227;o leite e peixes contaminados, com relatos de crescimento dessa bact&#233;ria em alimentos manufaturados. Comorbidades gastrointestinais e condi&#231;&#227;o bucal prec&#225;ria podem facilitar a infectividade desse pat&#243;geno, assim como pr&#243;teses valvares s&#227;o fatores predisponentes, o que demanda a necessidade de orientar os pacientes sobre a import&#226;ncia da higiene oral e do tratamento dent&#225;rio na preven&#231;&#227;o de endocardite, bem como investigar dist&#250;rbios gastrointestinais quando necess&#225;rio.</p>
    <p>As semelhan&#231;as fenot&#237;picas entre o <italic>Lactococcus</italic> e o <italic>Enterococcus</italic> dificultam muito seu diagn&#243;stico microbiol&#243;gico, sendo ainda necess&#225;rio o estudo gen&#233;tico para o isolamento de certeza do <italic>Lactococcus garvieae. </italic>A indisponibilidade desses exames na maioria dos centros m&#233;dicos do mundo provavelmente gera um subdiagn&#243;stico do <italic>Lactococcus garvieae, </italic>que pode representar uma signific&#226;ncia cl&#237;nica muito al&#233;m do que lhe &#233; atribu&#237;da.</p>
    <p>
      <bold>Potencial Conflito de Interesses</bold>
    </p>
    <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
    <p>
      <bold>Fontes de Financiamento</bold>
    </p>
    <p>O presente estudo n&#227;o teve fontes de financiamento externas.</p>
    <p>
      <bold>Vincula&#231;&#227;o Acad&#234;mica</bold>
    </p>
    <p>N&#227;o h&#225; vincula&#231;&#227;o deste estudo a programas de p&#243;s-gradua&#231;&#227;o.</p>
    <p>
      <fn id="end" fn-type="corresp">
        <label>
          <bold> Correspond&#234;ncia:</bold>
        </label>
        <p> Fernando Augusto Alves da Costa </p>
        <p> Pra&#231;a Amadeu Amaral, 47 cj 12A - Bela Vista </p>
        <p> 01327-010 - S&#227;o Paulo, SP - Brasil </p>
        <p> E-mail: </p>
        <p><email xlink:href="alvesdacosta@uol.com.br">alvesdacosta@uol.com.br</email>, </p>
        <p>
          <email xlink:href="faacosta@cardiol.br">faacosta@cardiol.br</email>
        </p>
      </fn>
    </p>
    <p> Artigo recebido em 05/06/10; revisado recebido em 20/08/10; aceito em 09/09/10.</p>
  </body>
  <back>
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  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Case Report</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title xml:lang="en">Lactococcus garvieae endocarditis: first case report in Latin America</article-title>
      </title-group>
      <abstract xml:lang="en">
        <p>Lactococcus garvieae, an emerging zoonotic pathogen, is responsible for mastitis in rodents and sepsis in fish. Although deemed opportunistic and hardly ever causing infections in humans, its incidence is probably underestimated due to the difficulty in diagnosis. There are very few reports of osteomyelitis, liver abscess, and peritonitis, and only nine cases of endocarditis described in worldwide literature. We describe the first case of Lactococcus garvieae endocarditis in Latin America, in a female patient with metallic prosthetic heart valve who presented with daily fever, chills, Osler nodes and six positive blood cultures for Lactococcus garvieae, which met Duke's criteria for the diagnosis of "definitive infective endocarditis"</p>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Endocarditis, bacterial</kwd>
        <kwd>diagnosis</kwd>
        <kwd>Lactococus garvieae</kwd>
        <kwd>heart valve prosthesis</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <bold>CASE REPORT</bold>
      </p>
      <p>
        <fn id="enda-body2">
          <label>
            <bold>Lactococcus garvieae <italic>endocarditis:</italic> first case report in Latin America</bold>
          </label>
          <p>
            <bold>Tatiana Franco Hirakawa<sup>I,II</sup>; Fernando Augusto Alves da Costa<sup>I,II</sup>; Marcos Cairo Vilela<sup>I,II</sup>; Micheli Rigon<sup>I,II</sup>; Henry Abensur<sup>II</sup>; Maria Rita Elmor de Ara&#250;jo<sup>II</sup></bold>
          </p>
        </fn>
      </p>
      <p><sup>I</sup>FGM - Cl&#237;nica Paulista de Doen&#231;as Cardiovasculares, S&#227;o Paulo, SP - Brasil </p>
      <p><sup>II</sup>Hospital Benefic&#234;ncia Portuguesa de S&#227;o Paulo, S&#227;o Paulo, SP - Brasil</p>
      <p>Mailing address</p>
      <p>
        <bold>ABSTRACT</bold>
      </p>
      <p><italic>Lactococcus garvieae</italic>, an emerging zoonotic pathogen, is responsible for mastitis in rodents and sepsis in fish. Although deemed opportunistic and hardly ever causing infections in humans, its incidence is probably underestimated due to the difficulty in diagnosis. There are very few reports of osteomyelitis, liver abscess, and peritonitis, and only nine cases of endocarditis described in worldwide literature. We describe the first case of <italic>Lactococcus garvieae</italic> endocarditis in Latin America, in a female patient with metallic prosthetic heart valve who presented with daily fever, chills, Osler nodes and six positive blood cultures for <italic>Lactococcus garvieae</italic>, which met Duke's criteria for the diagnosis of "definitive infective endocarditis".</p>
      <p><bold>Keywords:</bold> Endocarditis, bacterial; diagnosis; <italic>Lactococus garvieae</italic>; heart valve prosthesis.</p>
      <p>
        <bold>Introduction</bold>
      </p>
      <p><italic>Lactococcus garvieae, </italic>an emerging zoonotic pathogen, was originally isolated in mastitis in rodents and is responsible for sepsis in fish; it is deemed opportunistic and shows low virulence in humans, with very few reports of endocarditis (nine cases in the worldwide literature)<sup>1-7</sup>, osteomyelitis<sup>8</sup>, liver abscess<sup>9</sup>, sepsis, and peritonitis<sup>5</sup>. However, the difficult differential diagnosis with <italic>Enterococcus</italic> may lead to underestimation of its incidence and real importance. In the present study, we report the first case of <italic>Lactococcus garvieae</italic> endocarditis in Latin America, the tenth in the worldwide literature.</p>
      <p>
        <bold>Case report</bold>
      </p>
      <p>A 58-year-old female Caucasian patient, a former smoker previously hypertensive, with type-2 diabetes, dyslipidemia, underwent mitral valve replacement by a metallic prosthetic valve six months earlier due to severe mitral stenosis of rheumatic etiology. Upon arrival at the hospital, the patient had a history of daily fever for six days (38.5&#186; C), chills, diaphoresis, erythematous nodules in hands and legs, myalgia and weakness. As regards her nutritional habits, she often consumed several types of fish and reported having eaten white cheese recently. Despite denying dental treatment in the past few months, the patient had a dental prosthesis and had had a gingival perforation with a "fish bone" five days prior to the onset of symptoms.</p>
      <p>On admission, she had fever (38.2&#186; C), Osler nodes on her left hand and legs, and poor dentition. The remainder of her physical examination was unremarkable. Laboratory tests showed alterations in inflammatory tests, with PCR = 81.9 and VHS = 47.1, with no leukocytosis. No focus of infection was identified, despite extensive diagnostic investigation.</p>
      <p>In samples for blood cultures drawn from three different sites, Gram-positive cocci were isolated and further identified as <italic>Lactococcus garvieae</italic> by means of biochemical tests and confirmed by genetic studies. The pathogen was isolated again in three other blood cultures samples drawn five days later. The antibiotic susceptibility test showed resistance only to clindamycin, and sensitivity to penicillin, gentamicin, vancomycin and other antibiotics.</p>
      <p>Two transesophageal echocardiograms were performed, revealing absence of vegetation and competent mitral valve prosthesis. However, according to Duke's modified criteria, the patient was diagnosed with endocarditis and was treated with vancomycin 1 g every 12 hours for 28 days, due to confirmed penicillin allergy. There was complete remission of signs and symptoms, as well as normalization of laboratory tests; control blood cultures were negative.</p>
      <p>In an attempt to identify the source of the infection, the white cheese consumed by the patient was sent for microbiologic testing. In the search for an "entrance door", due to the family history of intestinal polyposis, the patient also underwent barium enema. However, both tests were normal.</p>
      <p>The patient was discharged with no symptoms after 30 days of hospitalization, and was referred for cardiology outpatient follow-up.</p>
      <p>
        <bold>Discussion</bold>
      </p>
      <p><italic>Lactococcus garvieae</italic> is one of the eight species belonging to the <italic>Lactococcus</italic> genus, originally known as the lactic group of the <italic>Streptococcus</italic> genus, from which it was split in 1985, after genetic analysis<sup>10</sup>.</p>
      <p>Formed by facultatively anaerobic catalase-negative Gram-positive cocci, these bacteria produce lactic acid, which provide them with fermentation ability and bactericidal property; thus, it is used in the food industry for fermentation and preservation of food<sup>10</sup>.</p>
      <p>However, it is known that some species may be pathogenic to animals and humans, especially <italic>Lactococcus garvieae</italic> and <italic>Lactococcus Lactis</italic><sup>10</sup>.</p>
      <p>Considered an emerging zoonotic pathogen, <italic>Lactococcus garvieae</italic> is responsible for mastitis in rodents, and sepsis in fish. Infected fish which do not develop the disease may contribute to dissemination<sup>5</sup>.</p>
      <p>It is considered an uncommon pathogen in humans; it is opportunistic and shows low virulence. Very few cases have been described in the literature with <italic>Lactococcus garvieae</italic> being the causal agent of endocarditis<sup>1-7</sup>, osteomyelitis<sup>8</sup>, liver abscess<sup>9</sup>, sepsis and peritonitis<sup>5</sup>. There are nine cases of endocarditis reported in worldwide literature: in four of them prosthetic valves<sup>1,3</sup> are affected, and in the other five, native heart valves are<sup>2,4,5,7</sup>.</p>
      <p>This is the first case report of <italic>Lactococcus garvieae</italic> endocarditis in Latin America in a patient with metallic prosthetic valve in the mitral position who met the modified Duke criteria for the diagnosis of "definitive endocarditis" (<xref ref-type="table" rid="tab1-body2">Table 1</xref>).</p>
      <table-wrap id="tab1-body2">
        <graphic xlink:href="1678-4170-abc-97-05-e108-00016-gt01-en.jpg"/></table-wrap>
      <p>Pathogenicity and infectivity of <italic>Lactococcus garvieae</italic> remain inconclusive. <italic>It is known that lactococci </italic>are not typically a part of the human flora<sup>3</sup>, but the intake of milk or contaminated fish may be sources of infection<sup>5</sup>. They have also been isolated in manufactured food due to their use in food products. However, gastric acidity, pancreatic enzymes, gallbladder and intestinal secretions, peristalsis, and epithelial cell integrity are protective factors against oral and gastrointestinal infections. The existence of gastrointestinal disorders such as ulcers, polyps or diverticula may act as facilitators of bacterial infectivity.</p>
      <p>In the case described, the source of infection may have been the fish routinely consumed by the patient; the wound may have been caused by the "fish bone" and her poor dentition which may both been the entrance door. However, no data confirm this hypothesis.</p>
      <p>It is difficult to distinguish <italic>L. garvieae</italic> from <italic>Enterococcus</italic>, because their phenotypes are similar. It is also challenging to distinguish <italic>Lactococcus garvieae</italic> from <italic>L. lactis</italic>. Some studies suggest the use of antibiotic susceptibility tests, because <italic>L. garvieae</italic> is resistant to clindamycin, whereas <italic>L. lactis</italic> is always sensitive to this antibiotic: this proved true in the present case.</p>
      <p>In relation to the echocardiogram, few reports are found in the literature of patients presenting with vegetations in the native valve<sup>2</sup>, and cases without abnormalities both in the transthoracic and transesophageal test of patients with endocarditis in prosthetic valves<sup>8</sup>, as in the present case report.</p>
      <p>The gold-standard test for the identification of <italic>Lactococcus gavieae</italic>, despite its high cost, is the genetic study with confirmation of its DNA sequence<sup>10</sup>.</p>
      <p>
        <bold>Conclusion</bold>
      </p>
      <p><italic>Lactococcus garvieae</italic> endocarditis is extremely uncommon, this being the tenth case described in worldwide literature, and its pathogenesis remains inconclusive. Possible sources of infection are contaminated milk and fish, with reports of growth of these bacteria in manufactured food. Gastrointestinal comorbidities and poor oral conditions may facilitate infectivity of this pathogen. Prosthetic heart valves are also predisposing factors, and this implies the need to advise patients on the importance of oral hygiene and dental treatment in the prevention of endocarditis. Gastrointestinal disorders should also be investigated whenever necessary.</p>
      <p>Phenotypic similarities between <italic>Lactococcus</italic> and <italic>Enterococcus</italic> make it difficult to establish a microbiological diagnosis, so that genetic studies are still necessary for the definite identification of <italic>Lactococcus garvieae</italic>. The fact that these tests are unavailable in most of the medical centers worldwide probably cause <italic>Lactococcus garvieae</italic> to be underdiagnosed, so its clinical significance may be far greater than is thought.</p>
      <p>
        <bold>Potential Conflict of Interest</bold>
      </p>
      <p>No potential conflict of interest relevant to this article was reported.</p>
      <p>
        <bold>Sources of Funding</bold>
      </p>
      <p>There were no external funding sources for this study.</p>
      <p>
        <bold>Study Association</bold>
      </p>
      <p>This study is not associated with any post-graduation program.</p>
      <p>
        <bold>References</bold>
      </p>
    </body>
  </sub-article>
  <sub-article article-type="translation" id="TRes" xml:lang="es">
    <front-stub>
      <article-categories/>
      <title-group>
        <article-title xml:lang="es">Endocarditis por lactococcus garvieae: primer relato de caso de Am&#233;rica Latina</article-title>
      </title-group>
      <abstract xml:lang="es">
        <p>Lactococcus garvieae, pat&#243;geno zoon&#243;tico emergente, es responsable por mastitis en rumiantes y septicemia en peces. Aunque sea considerado oportunista y raramente cause infecciones en humanos, su incidencia debe estar subestimada debido a la dificultad del diagn&#243;stico. Hay poqu&#237;simos relatos de osteomielitis, absceso hep&#225;tico y peritonitis, y apenas nueve casos descriptos en la literatura mundial de endocarditis. Relatamos el primer caso de endocarditis por Lactococcus garvieae de Am&#233;rica Latina en paciente portadora de pr&#243;tesis valvar met&#225;lica, con cuadro de fiebre diaria, escalofr&#237;os, n&#243;dulos de Osler y seis hemocultivos positivos para Lactococcus garvieae, que llenaban los criterios de Duke para el diagn&#243;stico de "endocarditis infecciosa definitiva"</p>
      </abstract>
      <kwd-group xml:lang="es">
        <kwd>Endocarditis bacteriana</kwd>
        <kwd>diagn&#243;stico</kwd>
        <kwd>Lactococcus garvieae</kwd>
        <kwd>pr&#243;tesis valvares card&#237;acas</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <bold>CASO CL&#205;NICO</bold>
      </p>
      <p>
        <fn id="enda-body3">
          <label>
            <bold>Endocarditis por <italic>lactococcus garvieae</italic>: primer relato de caso de Am&#233;rica Latina</bold>
          </label>
          <p>
            <bold>Tatiana Franco Hirakawa<sup>I,II</sup>; Fernando Augusto Alves da Costa<sup>I,II</sup>; Marcos Cairo Vilela<sup>I,II</sup>; Micheli Rigon<sup>I,II</sup>; Henry Abensur<sup>II</sup>; Maria Rita Elmor de Ara&#250;jo<sup>II</sup></bold>
          </p>
        </fn>
      </p>
      <p><sup>I</sup>FGM - Cl&#237;nica Paulista de Doen&#231;as Cardiovasculares, S&#227;o Paulo, SP - Brasil </p>
      <p><sup>II</sup>Hospital Benefic&#234;ncia Portuguesa de S&#227;o Paulo, S&#227;o Paulo, SP - Brasil</p>
      <p>Correspondencia</p>
      <p>
        <bold>RESUMEN</bold>
      </p>
      <p><italic>Lactococcus garvieae</italic>, pat&#243;geno zoon&#243;tico emergente, es responsable por mastitis en rumiantes y septicemia en peces. Aunque sea considerado oportunista y raramente cause infecciones en humanos, su incidencia debe estar subestimada debido a la dificultad del diagn&#243;stico. Hay poqu&#237;simos relatos de osteomielitis, absceso hep&#225;tico y peritonitis, y apenas nueve casos descriptos en la literatura mundial de endocarditis. Relatamos el primer caso de endocarditis por <italic>Lactococcus garvieae </italic>de Am&#233;rica Latina en paciente portadora de pr&#243;tesis valvar met&#225;lica, con cuadro de fiebre diaria, escalofr&#237;os, n&#243;dulos de <italic>Osler</italic> y seis hemocultivos positivos para <italic>Lactococcus garvieae</italic>, que llenaban los criterios de <italic>Duke</italic> para el diagn&#243;stico de "endocarditis infecciosa definitiva".</p>
      <p><bold>Palabras clave:</bold> Endocarditis bacteriana, diagn&#243;stico, <italic>Lactococcus garvieae</italic>, pr&#243;tesis valvares card&#237;acas.</p>
      <p>
        <bold>Introducci&#243;n</bold>
      </p>
      <p><italic>Lactococcus garvieae</italic>, pat&#243;geno zoon&#243;tico emergente, originalmente aislado en mastitis de rumiantes y responsable por septicemias en peces, es considerado oportunista y de baja virulencia en humanos, con rar&#237;simos casos descriptos de endocarditis (nueve casos en la literatura mundial)<sup>1-7</sup>, osteomielitis<sup>8</sup>, absceso hep&#225;tico<sup>9</sup>, septicemia y peritonitis<sup>5</sup>. Entre tanto, la dificultad del diagn&#243;stico para diferenciarlo del <italic>Enterococcus</italic> puede subestimar una incidencia mayor y desvalorizar su real importancia. En este estudio, relatamos el primer caso de endocarditis por <italic>Lactococcus garvieae</italic> de Am&#233;rica Latina y d&#233;cimo caso mundial.</p>
      <p>
        <bold>Caso cl&#237;nico</bold>
      </p>
      <p>Paciente del sexo femenino, 58 a&#241;os, blanca, previamente hipertensa, diab&#233;tica tipo 2, dislipid&#233;mica y ex tabaquista, fue sometida a reemplazo de v&#225;lvula mitral por pr&#243;tesis met&#225;lica hac&#237;a seis meses, debido a una estenosis mitral severa de etiolog&#237;a reum&#225;tica. Con historia de fiebre diaria hac&#237;a seis d&#237;as (38,5&#186; C), escalofr&#237;os, sudoraci&#243;n, n&#243;dulos eritematosos en las manos y en los miembros inferiores, mialgia y debilidad, dio entrada al hospital. Como h&#225;bito alimentario, consum&#237;a diversos tipos de peces con frecuencia y refer&#237;a haber ingerido un queso blanco recientemente. A pesar de negar tratamiento odontol&#243;gico en los &#250;ltimos meses, es portadora de pr&#243;tesis dentaria y perfor&#243; su enc&#237;a con una "espina de pescado" cinco d&#237;as antes del comienzo de los s&#237;ntomas.</p>
      <p>En la admisi&#243;n, se presentaba febril (38,2&#186; C), con n&#243;dulos de <italic>Osler</italic> en la mano izquierda, miembros inferiores y dentici&#243;n con estado de conservaci&#243;n precario, sin otras alteraciones en el examen f&#237;sico. Ex&#225;menes de laboratorio evidenciaron alteraciones de pruebas inflamatorias, PCR = 81,9 y VHS = 47,1, sin leucocitosis. Ning&#250;n foco de infecci&#243;n fue identificado, a pesar de exhaustiva investigaci&#243;n diagn&#243;stica.</p>
      <p>Hemocultivos recogidos en tres lugares diferentes aislaron cocos gram-positivos, identificados como <italic>Lactococcus garvieae</italic> por medio de examen bioqu&#237;mico y confirmado con estudio gen&#233;tico. Fue nuevamente aislado en otras tres muestras de hemocultivos, recogidas con intervalo de cinco d&#237;as. El antibiograma demostr&#243; resistencia apenas a la clindamicina, con sensibilidad a la penicilina, gentamicina, vancomicina y dem&#225;s antibi&#243;ticos.</p>
      <p>Fueron realizados dos ecocardiogramas transesof&#225;gicos, sin embargo, no se visibiliz&#243; vegetaci&#243;n, y la pr&#243;tesis mitral se presentaba competente. Mientras tanto, seg&#250;n los criterios modificados de <italic>Duke</italic>, la paciente recibi&#243; el diagn&#243;stico de endocarditis y fue medicada con vancomicina 1g de 12 en 12 horas durante 28 d&#237;as, debido a la alergia confirmada a la penicilina. Evolucion&#243; con remisi&#243;n completa de las se&#241;ales y de los s&#237;ntomas, normalizaci&#243;n de los ex&#225;menes de laboratorio y negativaci&#243;n de los hemocultivos.</p>
      <p>En la tentativa de identificar el origen de la infecci&#243;n, el queso blanco consumido por la paciente fue enviado para examen microbiol&#243;gico. En la b&#250;squeda de una "puerta de entrada", debido a la historia familiar de p&#243;lipos intestinales, la paciente fue sometida a un enema opaco. Sin embargo, ambos ex&#225;menes parec&#237;an dentro de la normalidad.</p>
      <p>La paciente recibi&#243; alta asintom&#225;tica despu&#233;s de 30 d&#237;as de internaci&#243;n, y fue encaminada para control ambulatorio por cardi&#243;logo.</p>
      <p>
        <bold>Discusi&#243;n</bold>
      </p>
      <p><italic>Lactococcus garvieae</italic> es una de las ocho especies pertenecientes al g&#233;nero <italic>Lactococcus</italic>, originalmente conocido como el grupo l&#225;ctico del g&#233;nero <italic>Streptococcus</italic>, siendo separado de &#233;ste en 1985, despu&#233;s de an&#225;lisis gen&#233;tico<sup>10</sup>.</p>
      <p>Formado por cocos Gram positivos, catalasa negativa y de crecimiento anaer&#243;bico facultativo, son bacterias productoras de &#225;cido l&#225;ctico, que les atribuye capacidad de fermentaci&#243;n y propiedad bactericida, siendo utilizadas por la industria alimenticia para fermentaci&#243;n y como conservantes de alimentos<sup>10</sup>.</p>
      <p>Mientras tanto, se sabe que algunas especies pueden ser patog&#233;nicas a animales y humanos, principalmente el <italic>Lactococcus garvieae</italic> y el <italic>Lactococcus Lactis</italic><sup>10</sup>.</p>
      <p>Considerado un pat&#243;geno zoon&#243;tico emergente, el <italic>Lactococcus garvieae </italic>es responsable por mastitis de rumiantes y septicemia en peces. Peces infectados que no desarrollan la enfermedad pueden contribuir a la diseminaci&#243;n<sup>5</sup>.</p>
      <p>Es considerado pat&#243;geno raro en humanos, oportunista y de baja virulencia. Hay poqu&#237;simos casos descriptos en la literatura, en los cuales el <italic>Lactococcus garvieae </italic>es el agente causal de endocarditis<sup>1-7</sup>, osteomielitis<sup>8</sup>, absceso hep&#225;tico<sup>9</sup>, septicemia y peritonitis<sup>5</sup>. Existen nueve casos de endocarditis relatados en la literatura mundial, de los cuales cuatro atacan pr&#243;tesis valvulares<sup>1,3</sup> y cinco v&#225;lvulas nativas<sup>2,4,5,7</sup>.</p>
      <p>Este es el primer relato de caso de endocarditis causada por <italic>Lactococcus garvieae </italic>en Am&#233;rica Latina en paciente portadora de pr&#243;tesis valvular met&#225;lica en posici&#243;n mitral que llen&#243; los criterios modificados de <italic>Duke</italic> para el diagn&#243;stico de "endocarditis definitiva" (<xref ref-type="table" rid="tab1-body3">Tabla 1</xref>).</p>
      <table-wrap id="tab1-body3">
        <graphic xlink:href="1678-4170-abc-97-05-e108-00016-gt01-es.jpg"/></table-wrap>
      <p>La patogenicidad e infectividad del <italic>Lactococcus garvieae</italic> aun permanecen inconclusivas. Se sabe que los <italic>Lactococcus</italic> t&#237;picamente no hacen parte de la flora humana<sup>3</sup>, pero el consumo de leche o peces contaminados pueden ser fuentes de infecci&#243;n<sup>5</sup>. Tambi&#233;n fueron aislados en alimentos manufacturados, debido a su utilizaci&#243;n en productos alimenticios. Mientras tanto, acidez g&#225;strica, enzimas pancre&#225;ticas, secreciones biliares e intestinales, peristalsis e integridad de las c&#233;lulas epiteliales son factores protectores de la infecci&#243;n oral y gastrointestinal. La existencia de des&#243;rdenes gastrointestinales como &#250;lceras, p&#243;lipos o divert&#237;culos puede actuar como facilitadoras de la infectividad bacteriana.</p>
      <p>En el caso descripto, es posible que la fuente de infecci&#243;n sean los peces consumidos habitualmente por la paciente y la puerta de entrada sea la herida perforante causada por la "espina de pescado", as&#237; como su dentici&#243;n precaria. Sin embargo, no hay datos que confirmen esa hip&#243;tesis.</p>
      <p>Hay dificultad en la distinci&#243;n con los <italic>Enterococcus</italic>, pues sus fenotipos son semejantes. Otro desaf&#237;o est&#225; en aislar el <italic>Lactococcus garvieae </italic>del<italic> lactis</italic>. Algunos estudios sugieren la utilizaci&#243;n del antibiograma, caracterizando el g<italic>arvieae</italic> como resistente a la clindamicina, en cuanto el <italic>lactis</italic> es siempre sensible; hip&#243;tesis sostenida en ese caso.</p>
      <p>En relaci&#243;n al ecocardiograma, encontramos en la literatura escasos relatos de pacientes que presentaban vegetaciones en v&#225;lvula nativa<sup>2</sup> y casos con ausencia de alteraciones, tanto en el examen transtor&#225;cico como en el transesof&#225;gico, de pacientes con endocarditis en pr&#243;tesis valvulares<sup>8</sup>, semejante al aqu&#237; descripto.</p>
      <p>El examen <italic>gold standard</italic> para el aislamiento del <italic>Lactococcus garvieae,</italic> a pesar del alto costo, es el estudio gen&#233;tico, con el reconocimiento de su secuenciamiento de DNA<sup>10</sup>.</p>
      <p>
        <bold>Conclusi&#243;n</bold>
      </p>
      <p>Endocarditis causada por <italic>Lactococcus garvieae</italic> es extremadamente rara, siendo este el d&#233;cimo caso descripto en la literatura mundial, y su patogenia aun permanece inconclusiva. Posibles fuentes de infecci&#243;n son leche y peces contaminados, con relatos de crecimiento de esa bacteria en alimentos manufacturados. Comorbilidades gastrointestinales y condici&#243;n bucal precaria pueden facilitar la infectividad de ese pat&#243;geno, as&#237; como pr&#243;tesis valvulares son factores predisponentes, lo que demanda la necesidad de orientar a los pacientes sobre la importancia de la higiene oral y del tratamiento dentario en la prevenci&#243;n de endocarditis, as&#237; como investigar disturbios gastrointestinales cuando sea necesario.</p>
      <p>Las semejanzas fenot&#237;picas entre el <italic>Lactococcus</italic> y el <italic>Enterococcus</italic> dificultan mucho su diagn&#243;stico microbiol&#243;gico, siendo aun necesario el estudio gen&#233;tico para el aislamiento de seguridad del <italic>Lactococcus garvieae. </italic>La indisponibilidad de esos ex&#225;menes en la mayor&#237;a de los centros m&#233;dicos del mundo probablemente genera un subdiagn&#243;stico del <italic>Lactococcus garvieae, </italic>que puede representar una significaci&#243;n cl&#237;nica mucho mayor de la que le es atribuida.</p>
      <p>
        <bold>PotencialConflicto de Intereses</bold>
      </p>
      <p>Declaro no haber conflicto de intereses pertinentes.</p>
      <p>
        <bold>Fuentes de Financiaci&#243;n</bold>
      </p>
      <p>El presente estudio no tuve fuentes de financiaci&#243;n externas.</p>
      <p>
        <bold>Vinculaci&#243;n Acad&#233;mica</bold>
      </p>
      <p>No hay vinculaci&#243;n de este estudio a programas de postgrado.</p>
      <p>
        <bold>Referencias</bold>
      </p>
    </body>
  </sub-article>
</article>
