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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Carbapenems: Past, Present, and Future <xref ref-type="fn" rid="FN1"><sup>▿</sup>
</xref>
</title>
<author><name sortKey="Papp Wallace, Krisztina M" sort="Papp Wallace, Krisztina M" uniqKey="Papp Wallace K" first="Krisztina M." last="Papp-Wallace">Krisztina M. Papp-Wallace</name>
<affiliation><nlm:aff id="aff1">Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio 44106</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">Departments of Medicine</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Endimiani, Andrea" sort="Endimiani, Andrea" uniqKey="Endimiani A" first="Andrea" last="Endimiani">Andrea Endimiani</name>
<affiliation><nlm:aff id="aff1">Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio 44106</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">Departments of Medicine</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff3">Institute for Infectious Diseases, University of Bern 3010, Bern, Switzerland</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Taracila, Magdalena A" sort="Taracila, Magdalena A" uniqKey="Taracila M" first="Magdalena A." last="Taracila">Magdalena A. Taracila</name>
<affiliation><nlm:aff id="aff2">Departments of Medicine</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bonomo, Robert A" sort="Bonomo, Robert A" uniqKey="Bonomo R" first="Robert A." last="Bonomo">Robert A. Bonomo</name>
<affiliation><nlm:aff id="aff1">Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio 44106</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">Departments of Medicine</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff4">Pharmacology</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff5">Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, Ohio 44106</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">21859938</idno>
<idno type="pmc">3195018</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3195018</idno>
<idno type="RBID">PMC:3195018</idno>
<idno type="doi">10.1128/AAC.00296-11</idno>
<date when="2011">2011</date>
<idno type="wicri:Area/Pmc/Corpus">000481</idno>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Carbapenems: Past, Present, and Future <xref ref-type="fn" rid="FN1"><sup>▿</sup>
</xref>
</title>
<author><name sortKey="Papp Wallace, Krisztina M" sort="Papp Wallace, Krisztina M" uniqKey="Papp Wallace K" first="Krisztina M." last="Papp-Wallace">Krisztina M. Papp-Wallace</name>
<affiliation><nlm:aff id="aff1">Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio 44106</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">Departments of Medicine</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Endimiani, Andrea" sort="Endimiani, Andrea" uniqKey="Endimiani A" first="Andrea" last="Endimiani">Andrea Endimiani</name>
<affiliation><nlm:aff id="aff1">Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio 44106</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">Departments of Medicine</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff3">Institute for Infectious Diseases, University of Bern 3010, Bern, Switzerland</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Taracila, Magdalena A" sort="Taracila, Magdalena A" uniqKey="Taracila M" first="Magdalena A." last="Taracila">Magdalena A. Taracila</name>
<affiliation><nlm:aff id="aff2">Departments of Medicine</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bonomo, Robert A" sort="Bonomo, Robert A" uniqKey="Bonomo R" first="Robert A." last="Bonomo">Robert A. Bonomo</name>
<affiliation><nlm:aff id="aff1">Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio 44106</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">Departments of Medicine</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff4">Pharmacology</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff5">Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, Ohio 44106</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="2011">2011</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
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<profileDesc><textClass></textClass>
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<front><div type="abstract" xml:lang="en"><p>In this review, we summarize the current “state of the art” of carbapenem antibiotics and their role in our antimicrobial armamentarium. Among the β-lactams currently available, carbapenems are unique because they are relatively resistant to hydrolysis by most β-lactamases, in some cases act as “slow substrates” or inhibitors of β-lactamases, and still target penicillin binding proteins. This “value-added feature” of inhibiting β-lactamases serves as a major rationale for expansion of this class of β-lactams. We describe the initial discovery and development of the carbapenem family of β-lactams. Of the early carbapenems evaluated, thienamycin demonstrated the greatest antimicrobial activity and became the parent compound for all subsequent carbapenems. To date, more than 80 compounds with mostly improved antimicrobial properties, compared to those of thienamycin, are described in the literature. We also highlight important features of the carbapenems that are presently in clinical use: imipenem-cilastatin, meropenem, ertapenem, doripenem, panipenem-betamipron, and biapenem. In closing, we emphasize some major challenges and urge the medicinal chemist to continue development of these versatile and potent compounds, as they have served us well for more than 3 decades.</p>
</div>
</front>
</TEI>
<pmc article-type="review-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="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">21859938</article-id>
<article-id pub-id-type="pmc">3195018</article-id>
<article-id pub-id-type="publisher-id">0296-11</article-id>
<article-id pub-id-type="doi">10.1128/AAC.00296-11</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Minireview</subject>
</subj-group>
</article-categories>
<title-group><article-title>Carbapenems: Past, Present, and Future <xref ref-type="fn" rid="FN1"><sup>▿</sup>
</xref>
</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Papp-Wallace</surname>
<given-names>Krisztina M.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Endimiani</surname>
<given-names>Andrea</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Taracila</surname>
<given-names>Magdalena A.</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bonomo</surname>
<given-names>Robert A.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
<xref ref-type="aff" rid="aff4"><sup>4</sup>
</xref>
<xref ref-type="aff" rid="aff5"><sup>5</sup>
</xref>
<xref ref-type="corresp" rid="cor1">*</xref>
</contrib>
<aff id="aff1"><label>1</label>
Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio 44106</aff>
<aff id="aff3"><label>3</label>
Institute for Infectious Diseases, University of Bern 3010, Bern, Switzerland</aff>
<aff id="aff2"><label>2</label>
Departments of Medicine</aff>
<aff id="aff4"><label>4</label>
Pharmacology</aff>
<aff id="aff5"><label>5</label>
Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, Ohio 44106</aff>
</contrib-group>
<author-notes><corresp id="cor1"><label>*</label>
Corresponding author. Mailing address:
<addr-line>Infectious Diseases Section, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, 10701 East Blvd., Cleveland, OH 44106</addr-line>
. Phone:
<phone>(216) 791-3800, ext. 4801</phone>
. Fax:
<fax>(216) 231-3482</fax>
. E-mail: <email>robert.bonomo@med.va.gov</email>
.</corresp>
</author-notes>
<pub-date pub-type="ppub"><month>11</month>
<year>2011</year>
</pub-date>
<volume>55</volume>
<issue>11</issue>
<fpage>4943</fpage>
<lpage>4960</lpage>
<permissions><copyright-statement>Copyright © 2011, American Society for Microbiology. All Rights Reserved.</copyright-statement>
<copyright-year>2011</copyright-year>
<copyright-holder>American Society for Microbiology</copyright-holder>
</permissions>
<self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zac01111004943.pdf"></self-uri>
<abstract><p>In this review, we summarize the current “state of the art” of carbapenem antibiotics and their role in our antimicrobial armamentarium. Among the β-lactams currently available, carbapenems are unique because they are relatively resistant to hydrolysis by most β-lactamases, in some cases act as “slow substrates” or inhibitors of β-lactamases, and still target penicillin binding proteins. This “value-added feature” of inhibiting β-lactamases serves as a major rationale for expansion of this class of β-lactams. We describe the initial discovery and development of the carbapenem family of β-lactams. Of the early carbapenems evaluated, thienamycin demonstrated the greatest antimicrobial activity and became the parent compound for all subsequent carbapenems. To date, more than 80 compounds with mostly improved antimicrobial properties, compared to those of thienamycin, are described in the literature. We also highlight important features of the carbapenems that are presently in clinical use: imipenem-cilastatin, meropenem, ertapenem, doripenem, panipenem-betamipron, and biapenem. In closing, we emphasize some major challenges and urge the medicinal chemist to continue development of these versatile and potent compounds, as they have served us well for more than 3 decades.</p>
</abstract>
</article-meta>
</front>
</pmc>
</record>
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