The Impact of Different Antibiotic Regimens on the Emergence of Antimicrobial-Resistant Bacteria
Identifieur interne : 000152 ( Pmc/Curation ); précédent : 000151; suivant : 000153The Impact of Different Antibiotic Regimens on the Emergence of Antimicrobial-Resistant Bacteria
Auteurs : Erika M. C. D'Agata [États-Unis] ; Myrielle Dupont-Rouzeyrol [France] ; Pierre Magal [France] ; Damien Olivier [France] ; Shigui Ruan [États-Unis]Source :
- PLoS ONE [ 1932-6203 ] ; 2008.
Abstract
The emergence and ongoing spread of antimicrobial-resistant bacteria is a major public health threat. Infections caused by antimicrobial-resistant bacteria are associated with substantially higher rates of morbidity and mortality compared to infections caused by antimicrobial-susceptible bacteria. The emergence and spread of these bacteria is complex and requires incorporating numerous interrelated factors which clinical studies cannot adequately address.
A model is created which incorporates several key factors contributing to the emergence and spread of resistant bacteria including the effects of the immune system, acquisition of resistance genes and antimicrobial exposure. The model identifies key strategies which would limit the emergence of antimicrobial-resistant bacterial strains. Specifically, the simulations show that early initiation of antimicrobial therapy and combination therapy with two antibiotics prevents the emergence of resistant bacteria, whereas shorter courses of therapy and sequential administration of antibiotics promote the emergence of resistant strains.
The principal findings suggest that (i) shorter lengths of antibiotic therapy and early interruption of antibiotic therapy provide an advantage for the resistant strains, (ii) combination therapy with two antibiotics prevents the emergence of resistance strains in contrast to sequential antibiotic therapy, and (iii) early initiation of antibiotics is among the most important factors preventing the emergence of resistant strains. These findings provide new insights into strategies aimed at optimizing the administration of antimicrobials for the treatment of infections and the prevention of the emergence of antimicrobial resistance.
Url:
DOI: 10.1371/journal.pone.0004036
PubMed: 19112501
PubMed Central: 2603320
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<front><div type="abstract" xml:lang="en"><sec><title>Backgroud</title>
<p>The emergence and ongoing spread of antimicrobial-resistant bacteria is a major public health threat. Infections caused by antimicrobial-resistant bacteria are associated with substantially higher rates of morbidity and mortality compared to infections caused by antimicrobial-susceptible bacteria. The emergence and spread of these bacteria is complex and requires incorporating numerous interrelated factors which clinical studies cannot adequately address.</p>
</sec>
<sec><title>Methods/Principal Findings</title>
<p>A model is created which incorporates several key factors contributing to the emergence and spread of resistant bacteria including the effects of the immune system, acquisition of resistance genes and antimicrobial exposure. The model identifies key strategies which would limit the emergence of antimicrobial-resistant bacterial strains. Specifically, the simulations show that early initiation of antimicrobial therapy and combination therapy with two antibiotics prevents the emergence of resistant bacteria, whereas shorter courses of therapy and sequential administration of antibiotics promote the emergence of resistant strains.</p>
</sec>
<sec><title>Conclusions/Significance</title>
<p>The principal findings suggest that (i) shorter lengths of antibiotic therapy and early interruption of antibiotic therapy provide an advantage for the resistant strains, (ii) combination therapy with two antibiotics prevents the emergence of resistance strains in contrast to sequential antibiotic therapy, and (iii) early initiation of antibiotics is among the most important factors preventing the emergence of resistant strains. These findings provide new insights into strategies aimed at optimizing the administration of antimicrobials for the treatment of infections and the prevention of the emergence of antimicrobial resistance.</p>
</sec>
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<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS ONE</journal-id>
<journal-id journal-id-type="publisher-id">plos</journal-id>
<journal-id journal-id-type="pmc">plosone</journal-id>
<journal-title>PLoS ONE</journal-title>
<issn pub-type="epub">1932-6203</issn>
<publisher><publisher-name>Public Library of Science</publisher-name>
<publisher-loc>San Francisco, USA</publisher-loc>
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<article-meta><article-id pub-id-type="pmid">19112501</article-id>
<article-id pub-id-type="pmc">2603320</article-id>
<article-id pub-id-type="publisher-id">08-PONE-RA-06813R1</article-id>
<article-id pub-id-type="doi">10.1371/journal.pone.0004036</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
</subj-group>
<subj-group subj-group-type="Discipline"><subject>Mathematics/Nonlinear Dynamics</subject>
<subject>Microbiology/Immunity to Infections</subject>
<subject>Infectious Diseases/Antimicrobials and Drug Resistance</subject>
<subject>Infectious Diseases/Bacterial Infections</subject>
<subject>Infectious Diseases/Nosocomial and Healthcare-Associated Infections</subject>
<subject>Public Health and Epidemiology/Nosocomial and Healthcare-Associated Infections</subject>
</subj-group>
</article-categories>
<title-group><article-title>The Impact of Different Antibiotic Regimens on the Emergence of Antimicrobial-Resistant Bacteria</article-title>
<alt-title alt-title-type="running-head">Antimicrobial-Resistance</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>D'Agata</surname>
<given-names>Erika M. C.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="yes"><name><surname>Dupont-Rouzeyrol</surname>
<given-names>Myrielle</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Magal</surname>
<given-names>Pierre</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Olivier</surname>
<given-names>Damien</given-names>
</name>
<xref ref-type="aff" rid="aff4"><sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ruan</surname>
<given-names>Shigui</given-names>
</name>
<xref ref-type="aff" rid="aff5"><sup>5</sup>
</xref>
<xref ref-type="corresp" rid="cor1"><sup>*</sup>
</xref>
</contrib>
</contrib-group>
<aff id="aff1"><label>1</label>
<addr-line>Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America</addr-line>
</aff>
<aff id="aff2"><label>2</label>
<addr-line>Laboratoire d'Ecotoxicologie des Milieux Aquatiques, Université du Havre, Le Havre, France</addr-line>
</aff>
<aff id="aff3"><label>3</label>
<addr-line>Laboratoire de Mathématiques Appliquées, Université du Havre, Le Havre, France</addr-line>
</aff>
<aff id="aff4"><label>4</label>
<addr-line>Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes, Université du Havre, Le Havre, France</addr-line>
</aff>
<aff id="aff5"><label>5</label>
<addr-line>Department of Mathematics, University of Miami, Coral Gables, Florida, United States of America</addr-line>
</aff>
<contrib-group><contrib contrib-type="editor"><name><surname>Bereswill</surname>
<given-names>Stefan</given-names>
</name>
<role>Editor</role>
<xref ref-type="aff" rid="edit1"></xref>
</contrib>
</contrib-group>
<aff id="edit1">Charité-Universitätsmedizin Berlin, Germany</aff>
<author-notes><corresp id="cor1">* E-mail: <email>ruan@math.miami.edu</email>
</corresp>
<fn fn-type="con"><p>Conceived and designed the experiments: ED MMDR PM DO. Analyzed the data: ED MMDR PM SR. Contributed reagents/materials/analysis tools: ED MMDR PM DO SR. Wrote the paper: ED MMDR PM SR.</p>
</fn>
</author-notes>
<pub-date pub-type="collection"><year>2008</year>
</pub-date>
<pub-date pub-type="epub"><day>29</day>
<month>12</month>
<year>2008</year>
</pub-date>
<volume>3</volume>
<issue>12</issue>
<elocation-id>e4036</elocation-id>
<history><date date-type="received"><day>10</day>
<month>10</month>
<year>2008</year>
</date>
<date date-type="accepted"><day>17</day>
<month>11</month>
<year>2008</year>
</date>
</history>
<copyright-statement>D'Agata et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</copyright-statement>
<copyright-year>2008</copyright-year>
<abstract><sec><title>Backgroud</title>
<p>The emergence and ongoing spread of antimicrobial-resistant bacteria is a major public health threat. Infections caused by antimicrobial-resistant bacteria are associated with substantially higher rates of morbidity and mortality compared to infections caused by antimicrobial-susceptible bacteria. The emergence and spread of these bacteria is complex and requires incorporating numerous interrelated factors which clinical studies cannot adequately address.</p>
</sec>
<sec><title>Methods/Principal Findings</title>
<p>A model is created which incorporates several key factors contributing to the emergence and spread of resistant bacteria including the effects of the immune system, acquisition of resistance genes and antimicrobial exposure. The model identifies key strategies which would limit the emergence of antimicrobial-resistant bacterial strains. Specifically, the simulations show that early initiation of antimicrobial therapy and combination therapy with two antibiotics prevents the emergence of resistant bacteria, whereas shorter courses of therapy and sequential administration of antibiotics promote the emergence of resistant strains.</p>
</sec>
<sec><title>Conclusions/Significance</title>
<p>The principal findings suggest that (i) shorter lengths of antibiotic therapy and early interruption of antibiotic therapy provide an advantage for the resistant strains, (ii) combination therapy with two antibiotics prevents the emergence of resistance strains in contrast to sequential antibiotic therapy, and (iii) early initiation of antibiotics is among the most important factors preventing the emergence of resistant strains. These findings provide new insights into strategies aimed at optimizing the administration of antimicrobials for the treatment of infections and the prevention of the emergence of antimicrobial resistance.</p>
</sec>
</abstract>
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