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<title xml:lang="en">Interlaboratory Variability of Caspofungin MICs for
<named-content content-type="genus-species">Candida</named-content>
spp. Using CLSI and EUCAST Methods: Should the Clinical Laboratory Be Testing This Agent?</title>
<author>
<name sortKey="Espinel Ingroff, A" sort="Espinel Ingroff, A" uniqKey="Espinel Ingroff A" first="A." last="Espinel-Ingroff">A. Espinel-Ingroff</name>
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<name sortKey="Pfaller, M A" sort="Pfaller, M A" uniqKey="Pfaller M" first="M. A." last="Pfaller">M. A. Pfaller</name>
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<author>
<name sortKey="Bonfietti, L X" sort="Bonfietti, L X" uniqKey="Bonfietti L" first="L. X." last="Bonfietti">L. X. Bonfietti</name>
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<name sortKey="Bustamante, B" sort="Bustamante, B" uniqKey="Bustamante B" first="B." last="Bustamante">B. Bustamante</name>
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<name sortKey="Canton, E" sort="Canton, E" uniqKey="Canton E" first="E." last="Canton">E. Canton</name>
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<name sortKey="Chryssanthou, E" sort="Chryssanthou, E" uniqKey="Chryssanthou E" first="E." last="Chryssanthou">E. Chryssanthou</name>
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<name sortKey="Cuenca Estrella, M" sort="Cuenca Estrella, M" uniqKey="Cuenca Estrella M" first="M." last="Cuenca-Estrella">M. Cuenca-Estrella</name>
<affiliation>
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<name sortKey="Fuller, J" sort="Fuller, J" uniqKey="Fuller J" first="J." last="Fuller">J. Fuller</name>
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<name sortKey="Gaustad, P" sort="Gaustad, P" uniqKey="Gaustad P" first="P." last="Gaustad">P. Gaustad</name>
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</affiliation>
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<name sortKey="Gonzalez, G M" sort="Gonzalez, G M" uniqKey="Gonzalez G" first="G. M." last="Gonzalez">G. M. Gonzalez</name>
<affiliation>
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</affiliation>
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<author>
<name sortKey="Guarro, J" sort="Guarro, J" uniqKey="Guarro J" first="J." last="Guarro">J. Guarro</name>
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</affiliation>
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<author>
<name sortKey="Lass Florl, C" sort="Lass Florl, C" uniqKey="Lass Florl C" first="C." last="Lass-Flörl">C. Lass-Flörl</name>
<affiliation>
<nlm:aff id="aff15"></nlm:aff>
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<author>
<name sortKey="Lockhart, S R" sort="Lockhart, S R" uniqKey="Lockhart S" first="S. R." last="Lockhart">S. R. Lockhart</name>
<affiliation>
<nlm:aff id="aff16"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Meis, J F" sort="Meis, J F" uniqKey="Meis J" first="J. F." last="Meis">J. F. Meis</name>
<affiliation>
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<author>
<name sortKey="Moore, C B" sort="Moore, C B" uniqKey="Moore C" first="C. B." last="Moore">C. B. Moore</name>
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<author>
<name sortKey="Ostrosky Zeichner, L" sort="Ostrosky Zeichner, L" uniqKey="Ostrosky Zeichner L" first="L." last="Ostrosky-Zeichner">L. Ostrosky-Zeichner</name>
<affiliation>
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<author>
<name sortKey="Pelaez, T" sort="Pelaez, T" uniqKey="Pelaez T" first="T." last="Pelaez">T. Pelaez</name>
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<name sortKey="Pukinskas, S R B S" sort="Pukinskas, S R B S" uniqKey="Pukinskas S" first="S. R. B. S." last="Pukinskas">S. R. B. S. Pukinskas</name>
<affiliation>
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</affiliation>
</author>
<author>
<name sortKey="St Germain, G" sort="St Germain, G" uniqKey="St Germain G" first="G." last="St-Germain">G. St-Germain</name>
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<nlm:aff id="aff22"></nlm:aff>
</affiliation>
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<name sortKey="Szeszs, M W" sort="Szeszs, M W" uniqKey="Szeszs M" first="M. W." last="Szeszs">M. W. Szeszs</name>
<affiliation>
<nlm:aff id="aff23"></nlm:aff>
</affiliation>
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<author>
<name sortKey="Turnidge, J" sort="Turnidge, J" uniqKey="Turnidge J" first="J." last="Turnidge">J. Turnidge</name>
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<nlm:aff id="aff24"></nlm:aff>
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<idno type="pmid">24018263</idno>
<idno type="pmc">3837874</idno>
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<idno type="RBID">PMC:3837874</idno>
<idno type="doi">10.1128/AAC.01519-13</idno>
<date when="2013">2013</date>
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<title xml:lang="en" level="a" type="main">Interlaboratory Variability of Caspofungin MICs for
<named-content content-type="genus-species">Candida</named-content>
spp. Using CLSI and EUCAST Methods: Should the Clinical Laboratory Be Testing This Agent?</title>
<author>
<name sortKey="Espinel Ingroff, A" sort="Espinel Ingroff, A" uniqKey="Espinel Ingroff A" first="A." last="Espinel-Ingroff">A. Espinel-Ingroff</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Arendrup, M C" sort="Arendrup, M C" uniqKey="Arendrup M" first="M. C." last="Arendrup">M. C. Arendrup</name>
<affiliation>
<nlm:aff id="aff2"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Pfaller, M A" sort="Pfaller, M A" uniqKey="Pfaller M" first="M. A." last="Pfaller">M. A. Pfaller</name>
<affiliation>
<nlm:aff id="aff3"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Bonfietti, L X" sort="Bonfietti, L X" uniqKey="Bonfietti L" first="L. X." last="Bonfietti">L. X. Bonfietti</name>
<affiliation>
<nlm:aff id="aff4"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Bustamante, B" sort="Bustamante, B" uniqKey="Bustamante B" first="B." last="Bustamante">B. Bustamante</name>
<affiliation>
<nlm:aff id="aff5"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Canton, E" sort="Canton, E" uniqKey="Canton E" first="E." last="Canton">E. Canton</name>
<affiliation>
<nlm:aff id="aff6"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Chryssanthou, E" sort="Chryssanthou, E" uniqKey="Chryssanthou E" first="E." last="Chryssanthou">E. Chryssanthou</name>
<affiliation>
<nlm:aff id="aff7"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Cuenca Estrella, M" sort="Cuenca Estrella, M" uniqKey="Cuenca Estrella M" first="M." last="Cuenca-Estrella">M. Cuenca-Estrella</name>
<affiliation>
<nlm:aff id="aff8"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Dannaoui, E" sort="Dannaoui, E" uniqKey="Dannaoui E" first="E." last="Dannaoui">E. Dannaoui</name>
<affiliation>
<nlm:aff id="aff9"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Fothergill, A" sort="Fothergill, A" uniqKey="Fothergill A" first="A." last="Fothergill">A. Fothergill</name>
<affiliation>
<nlm:aff id="aff10"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Fuller, J" sort="Fuller, J" uniqKey="Fuller J" first="J." last="Fuller">J. Fuller</name>
<affiliation>
<nlm:aff id="aff11"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Gaustad, P" sort="Gaustad, P" uniqKey="Gaustad P" first="P." last="Gaustad">P. Gaustad</name>
<affiliation>
<nlm:aff id="aff12"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Gonzalez, G M" sort="Gonzalez, G M" uniqKey="Gonzalez G" first="G. M." last="Gonzalez">G. M. Gonzalez</name>
<affiliation>
<nlm:aff id="aff13"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Guarro, J" sort="Guarro, J" uniqKey="Guarro J" first="J." last="Guarro">J. Guarro</name>
<affiliation>
<nlm:aff id="aff14"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Lass Florl, C" sort="Lass Florl, C" uniqKey="Lass Florl C" first="C." last="Lass-Flörl">C. Lass-Flörl</name>
<affiliation>
<nlm:aff id="aff15"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Lockhart, S R" sort="Lockhart, S R" uniqKey="Lockhart S" first="S. R." last="Lockhart">S. R. Lockhart</name>
<affiliation>
<nlm:aff id="aff16"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Meis, J F" sort="Meis, J F" uniqKey="Meis J" first="J. F." last="Meis">J. F. Meis</name>
<affiliation>
<nlm:aff id="aff17"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Moore, C B" sort="Moore, C B" uniqKey="Moore C" first="C. B." last="Moore">C. B. Moore</name>
<affiliation>
<nlm:aff id="aff18"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Ostrosky Zeichner, L" sort="Ostrosky Zeichner, L" uniqKey="Ostrosky Zeichner L" first="L." last="Ostrosky-Zeichner">L. Ostrosky-Zeichner</name>
<affiliation>
<nlm:aff id="aff19"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Pelaez, T" sort="Pelaez, T" uniqKey="Pelaez T" first="T." last="Pelaez">T. Pelaez</name>
<affiliation>
<nlm:aff id="aff20"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Pukinskas, S R B S" sort="Pukinskas, S R B S" uniqKey="Pukinskas S" first="S. R. B. S." last="Pukinskas">S. R. B. S. Pukinskas</name>
<affiliation>
<nlm:aff id="aff21"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="St Germain, G" sort="St Germain, G" uniqKey="St Germain G" first="G." last="St-Germain">G. St-Germain</name>
<affiliation>
<nlm:aff id="aff22"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Szeszs, M W" sort="Szeszs, M W" uniqKey="Szeszs M" first="M. W." last="Szeszs">M. W. Szeszs</name>
<affiliation>
<nlm:aff id="aff23"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Turnidge, J" sort="Turnidge, J" uniqKey="Turnidge J" first="J." last="Turnidge">J. Turnidge</name>
<affiliation>
<nlm:aff id="aff24"></nlm:aff>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Antimicrobial Agents and Chemotherapy</title>
<idno type="ISSN">0066-4804</idno>
<idno type="eISSN">1098-6596</idno>
<imprint>
<date when="2013">2013</date>
</imprint>
</series>
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<front>
<div type="abstract" xml:lang="en">
<p>Although Clinical and Laboratory Standards Institute (CLSI) clinical breakpoints (CBPs) are available for interpreting echinocandin MICs for
<named-content content-type="genus-species">Candida</named-content>
spp., epidemiologic cutoff values (ECVs) based on collective MIC data from multiple laboratories have not been defined. While collating CLSI caspofungin MICs for 145 to 11,550
<named-content content-type="genus-species">Candida</named-content>
isolates from 17 laboratories (Brazil, Canada, Europe, Mexico, Peru, and the United States), we observed an extraordinary amount of modal variability (wide ranges) among laboratories as well as truncated and bimodal MIC distributions. The species-specific modes across different laboratories ranged from 0.016 to 0.5 μg/ml for
<named-content content-type="genus-species">C. albicans</named-content>
and
<named-content content-type="genus-species">C. tropicalis</named-content>
, 0.031 to 0.5 μg/ml for
<named-content content-type="genus-species">C. glabrata</named-content>
, and 0.063 to 1 μg/ml for
<named-content content-type="genus-species">C. krusei</named-content>
. Variability was also similar among MIC distributions for
<named-content content-type="genus-species">C. dubliniensis</named-content>
and
<named-content content-type="genus-species">C. lusitaniae</named-content>
. The exceptions were
<named-content content-type="genus-species">C. parapsilosis</named-content>
and
<named-content content-type="genus-species">C. guilliermondii</named-content>
MIC distributions, where most modes were within one 2-fold dilution of each other. These findings were consistent with available data from the European Committee on Antimicrobial Susceptibility Testing (EUCAST) (403 to 2,556 MICs) for
<named-content content-type="genus-species">C. albicans</named-content>
,
<named-content content-type="genus-species">C. glabrata</named-content>
,
<named-content content-type="genus-species">C. krusei</named-content>
, and
<named-content content-type="genus-species">C. tropicalis</named-content>
. Although many factors (caspofungin powder source, stock solution solvent, powder storage time length and temperature, and MIC determination testing parameters) were examined as a potential cause of such unprecedented variability, a single specific cause was not identified. Therefore, it seems highly likely that the use of the CLSI species-specific caspofungin CBPs could lead to reporting an excessive number of wild-type (WT) isolates (e.g.,
<named-content content-type="genus-species">C. glabrata</named-content>
and
<named-content content-type="genus-species">C. krusei</named-content>
) as either non-WT or resistant isolates. Until this problem is resolved, routine testing or reporting of CLSI caspofungin MICs for
<named-content content-type="genus-species">Candida</named-content>
is not recommended; micafungin or anidulafungin data could be used instead.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article">
<pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Antimicrob Agents Chemother</journal-id>
<journal-id journal-id-type="iso-abbrev">Antimicrob. Agents Chemother</journal-id>
<journal-id journal-id-type="hwp">aac</journal-id>
<journal-id journal-id-type="pmc">aac</journal-id>
<journal-id journal-id-type="publisher-id">AAC</journal-id>
<journal-title-group>
<journal-title>Antimicrobial Agents and Chemotherapy</journal-title>
</journal-title-group>
<issn pub-type="ppub">0066-4804</issn>
<issn pub-type="epub">1098-6596</issn>
<publisher>
<publisher-name>American Society for Microbiology</publisher-name>
<publisher-loc>1752 N St., N.W., Washington, DC</publisher-loc>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">24018263</article-id>
<article-id pub-id-type="pmc">3837874</article-id>
<article-id pub-id-type="publisher-id">01519-13</article-id>
<article-id pub-id-type="doi">10.1128/AAC.01519-13</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Susceptibility</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Interlaboratory Variability of Caspofungin MICs for
<named-content content-type="genus-species">Candida</named-content>
spp. Using CLSI and EUCAST Methods: Should the Clinical Laboratory Be Testing This Agent?</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Espinel-Ingroff</surname>
<given-names>A.</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Arendrup</surname>
<given-names>M. C.</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Pfaller</surname>
<given-names>M. A.</given-names>
</name>
<xref ref-type="aff" rid="aff3">
<sup>c</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Bonfietti</surname>
<given-names>L. X.</given-names>
</name>
<xref ref-type="aff" rid="aff4">
<sup>d</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Bustamante</surname>
<given-names>B.</given-names>
</name>
<xref ref-type="aff" rid="aff5">
<sup>e</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Canton</surname>
<given-names>E.</given-names>
</name>
<xref ref-type="aff" rid="aff6">
<sup>f</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Chryssanthou</surname>
<given-names>E.</given-names>
</name>
<xref ref-type="aff" rid="aff7">
<sup>g</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Cuenca-Estrella</surname>
<given-names>M.</given-names>
</name>
<xref ref-type="aff" rid="aff8">
<sup>h</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Dannaoui</surname>
<given-names>E.</given-names>
</name>
<xref ref-type="aff" rid="aff9">
<sup>i</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Fothergill</surname>
<given-names>A.</given-names>
</name>
<xref ref-type="aff" rid="aff10">
<sup>j</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Fuller</surname>
<given-names>J.</given-names>
</name>
<xref ref-type="aff" rid="aff11">
<sup>k</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Gaustad</surname>
<given-names>P.</given-names>
</name>
<xref ref-type="aff" rid="aff12">
<sup>l</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Gonzalez</surname>
<given-names>G. M.</given-names>
</name>
<xref ref-type="aff" rid="aff13">
<sup>m</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Guarro</surname>
<given-names>J.</given-names>
</name>
<xref ref-type="aff" rid="aff14">
<sup>n</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lass-Flörl</surname>
<given-names>C.</given-names>
</name>
<xref ref-type="aff" rid="aff15">
<sup>o</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lockhart</surname>
<given-names>S. R.</given-names>
</name>
<xref ref-type="aff" rid="aff16">
<sup>p</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Meis</surname>
<given-names>J. F.</given-names>
</name>
<xref ref-type="aff" rid="aff17">
<sup>q</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Moore</surname>
<given-names>C. B.</given-names>
</name>
<xref ref-type="aff" rid="aff18">
<sup>r</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ostrosky-Zeichner</surname>
<given-names>L.</given-names>
</name>
<xref ref-type="aff" rid="aff19">
<sup>s</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Pelaez</surname>
<given-names>T.</given-names>
</name>
<xref ref-type="aff" rid="aff20">
<sup>t</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Pukinskas</surname>
<given-names>S. R. B. S.</given-names>
</name>
<xref ref-type="aff" rid="aff21">
<sup>u</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>St-Germain</surname>
<given-names>G.</given-names>
</name>
<xref ref-type="aff" rid="aff22">
<sup>v</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Szeszs</surname>
<given-names>M. W.</given-names>
</name>
<xref ref-type="aff" rid="aff23">
<sup>w</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Turnidge</surname>
<given-names>J.</given-names>
</name>
<xref ref-type="aff" rid="aff24">
<sup>x</sup>
</xref>
</contrib>
<aff id="aff1">Virginia Commonwealth University Medical Center, Richmond, Virginia, USA
<label>a</label>
</aff>
<aff id="aff2">Unit of Mycology, Department of Microbiological Surveillance and Research, Statens Serum Institut, Copenhagen, Denmark
<label>b</label>
</aff>
<aff id="aff3">JMI Laboratories and the University of Iowa, Iowa City, Iowa, USA
<label>c</label>
</aff>
<aff id="aff4">Adolfo Lutz Institute, Araçatuba City, Brazil
<label>d</label>
</aff>
<aff id="aff5">Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru
<label>e</label>
</aff>
<aff id="aff6">Unidad de Microbiologia Experimental, Centro de Investigacion, Hospital Universitario La Fe, Valencia, Spain
<label>f</label>
</aff>
<aff id="aff7">Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden
<label>g</label>
</aff>
<aff id="aff8">Department of Mycology, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain
<label>h</label>
</aff>
<aff id="aff9">Institut Pasteur, Centre National de Reference Mycoses and Antifongiques, Unite de Mycologie Moleculaire, Paris, France
<label>i</label>
</aff>
<aff id="aff10">University of Texas Health Science Center, San Antonio, Texas, USA
<label>j</label>
</aff>
<aff id="aff11">The University of Alberta, Edmonton, Alberta, Canada
<label>k</label>
</aff>
<aff id="aff12">Institute of Medical Microbiology, Rikshospitalet University Hospital, Oslo, Norway
<label>l</label>
</aff>
<aff id="aff13">Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, México
<label>m</label>
</aff>
<aff id="aff14">Facultat de Medicina, IISPV, URV, Reus, Spain
<label>n</label>
</aff>
<aff id="aff15">The Innsbruck Medical University, Division of Hygiene and Medical Microbiology, Innsbruck, Austria
<label>o</label>
</aff>
<aff id="aff16">Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
<label>p</label>
</aff>
<aff id="aff17">Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital and Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
<label>q</label>
</aff>
<aff id="aff18">Mycology Reference Centre, Education and Research Centre, University Hospital of South Manchester, Manchester, United Kingdom
<label>r</label>
</aff>
<aff id="aff19">University of Texas Health Science Center, Houston, Texas, USA
<label>s</label>
</aff>
<aff id="aff20">Hospital General Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense, Madrid, Spain
<label>t</label>
</aff>
<aff id="aff21">Fungal Taxonomy Laboratories, Adolfo Lutz Institute, São Paulo City, Brazil
<label>u</label>
</aff>
<aff id="aff22">Laboratoire de Santé Publique du Québec, Institut National de Santé Publique du Québec, Québec, Canada
<label>v</label>
</aff>
<aff id="aff23">Mycology Department, Adolfo Lutz Institute, São Paulo City, Brazil
<label>w</label>
</aff>
<aff id="aff24">University of Adelaide, Adelaide, Australia
<label>x</label>
</aff>
</contrib-group>
<author-notes>
<corresp id="cor1">Address correspondence to A. Espinel-Ingroff,
<email>avingrof@vcu.edu</email>
.</corresp>
</author-notes>
<pub-date pub-type="ppub">
<month>12</month>
<year>2013</year>
</pub-date>
<volume>57</volume>
<issue>12</issue>
<fpage>5836</fpage>
<lpage>5842</lpage>
<history>
<date date-type="received">
<day>16</day>
<month>7</month>
<year>2013</year>
</date>
<date date-type="rev-request">
<day>22</day>
<month>8</month>
<year>2013</year>
</date>
<date date-type="accepted">
<day>2</day>
<month>9</month>
<year>2013</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright © 2013, American Society for Microbiology. All Rights Reserved.</copyright-statement>
<copyright-year>2013</copyright-year>
<copyright-holder>American Society for Microbiology</copyright-holder>
</permissions>
<self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zac01213005836.pdf"></self-uri>
<abstract>
<p>Although Clinical and Laboratory Standards Institute (CLSI) clinical breakpoints (CBPs) are available for interpreting echinocandin MICs for
<named-content content-type="genus-species">Candida</named-content>
spp., epidemiologic cutoff values (ECVs) based on collective MIC data from multiple laboratories have not been defined. While collating CLSI caspofungin MICs for 145 to 11,550
<named-content content-type="genus-species">Candida</named-content>
isolates from 17 laboratories (Brazil, Canada, Europe, Mexico, Peru, and the United States), we observed an extraordinary amount of modal variability (wide ranges) among laboratories as well as truncated and bimodal MIC distributions. The species-specific modes across different laboratories ranged from 0.016 to 0.5 μg/ml for
<named-content content-type="genus-species">C. albicans</named-content>
and
<named-content content-type="genus-species">C. tropicalis</named-content>
, 0.031 to 0.5 μg/ml for
<named-content content-type="genus-species">C. glabrata</named-content>
, and 0.063 to 1 μg/ml for
<named-content content-type="genus-species">C. krusei</named-content>
. Variability was also similar among MIC distributions for
<named-content content-type="genus-species">C. dubliniensis</named-content>
and
<named-content content-type="genus-species">C. lusitaniae</named-content>
. The exceptions were
<named-content content-type="genus-species">C. parapsilosis</named-content>
and
<named-content content-type="genus-species">C. guilliermondii</named-content>
MIC distributions, where most modes were within one 2-fold dilution of each other. These findings were consistent with available data from the European Committee on Antimicrobial Susceptibility Testing (EUCAST) (403 to 2,556 MICs) for
<named-content content-type="genus-species">C. albicans</named-content>
,
<named-content content-type="genus-species">C. glabrata</named-content>
,
<named-content content-type="genus-species">C. krusei</named-content>
, and
<named-content content-type="genus-species">C. tropicalis</named-content>
. Although many factors (caspofungin powder source, stock solution solvent, powder storage time length and temperature, and MIC determination testing parameters) were examined as a potential cause of such unprecedented variability, a single specific cause was not identified. Therefore, it seems highly likely that the use of the CLSI species-specific caspofungin CBPs could lead to reporting an excessive number of wild-type (WT) isolates (e.g.,
<named-content content-type="genus-species">C. glabrata</named-content>
and
<named-content content-type="genus-species">C. krusei</named-content>
) as either non-WT or resistant isolates. Until this problem is resolved, routine testing or reporting of CLSI caspofungin MICs for
<named-content content-type="genus-species">Candida</named-content>
is not recommended; micafungin or anidulafungin data could be used instead.</p>
</abstract>
</article-meta>
</front>
</pmc>
</record>

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