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<PubmedArticle><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">39468752</PMID><DateRevised><Year>2024</Year><Month>10</Month><Day>29</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1460-2091</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2024</Year><Month>Oct</Month><Day>28</Day></PubDate></JournalIssue><Title>The Journal of antimicrobial chemotherapy</Title><ISOAbbreviation>J Antimicrob Chemother</ISOAbbreviation></Journal><ArticleTitle>Efficacy of meropenem against ceftazidime-avibactam-resistant Klebsiella pneumoniae producing KPC-31, KPC-33, KPC-90, KPC-106 and KPC-114.</ArticleTitle><ELocationID EIdType="pii" ValidYN="Y">dkae389</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1093/jac/dkae389</ELocationID><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Klebsiella pneumoniae producing KPC variants conferring resistance to ceftazidime-avibactam often remain susceptible to meropenem, suggesting a potential therapeutic use of this antibiotic.</AbstractText><AbstractText Label="OBJECTIVES" NlmCategory="OBJECTIVE">In this study, the efficacy of clinically relevant concentrations of meropenem was evaluated against high-risk clones of ceftazidime-avibactam-resistant K. pneumoniae strains producing KPC variants, in a tandem in vitro time-kill/in vivo Galleria mellonella survival model.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">In vitro/in vivo efficacy of meropenem against ceftazidime-avibactam-resistant K. pneumoniae of CG16, CG25 and CG258, producing KPC-31, KPC-33, KPC-90, KPC-106 and KPC-114 variants, was evaluated using EUCAST dosing recommendation adjusted to the G. mellonella model. For in vivo assays, untreated, meropenem (40 mg/kg&#x200a;&#xd7;&#x200a;1)-treated and ceftazidime-avibactam (40 mg/kg ceftazidime-10 mg/kg avibactam&#x200a;&#xd7;&#x200a;1)-treated groups were established, with 60 larvae per group. Kaplan-Meier curves, log-rank tests, univariate Cox regression and hazard ratios (HR) were used to assess treatment effects (P&#x200a;&lt;&#x200a;0.05).</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">For all KPC-variant producers, time-kill assays showed &gt;3 log-kills reduction (-6.91&#x200a;&#xb1;&#x200a;1.28 SD) after 6 h interaction when exposed to 8-32 mg/L meropenem MIC values (i.e. &#x200a;&#x2265;&#x200a;&#x200a;&#xd7;&#x200a;4 MIC). In the assessment of in vivo efficacy of meropenem, at the 4-day follow-up, mortality rates were 96.7% (untreated), 83.3% (ceftazidime-avibactam-treated) and 13.3% (meropenem-treated) (P&#x200a;&lt;&#x200a;0.05). Univariate Cox regression analysis showed significantly lower risk in the meropenem group compared to untreated group [HR 0.02 (95% CI: 0.01-0.05)].</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">These pre-clinical results might support use of meropenem as a potential alternative for treatment of infections due to KPC-variant producers displaying in vitro susceptibility to meropenem.</AbstractText><CopyrightInformation>&#xa9; The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site&#x2014;for further information please contact journals.permissions@oup.com.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Pariona</LastName><ForeName>Jesus G M</ForeName><Initials>JGM</Initials><Identifier Source="ORCID">0000-0001-9174-0749</Identifier><AffiliationInfo><Affiliation>Department of Clinical Analysis, Faculty of Pharmaceutical Sciences, Universidade de S&#xe3;o Paulo, S&#xe3;o Paulo, Brazil.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Microbiology, Institute of Biomedical Sciences, University of S&#xe3;o Paulo, S&#xe3;o Paulo, Brazil.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>One Health Brazilian Resistance Project (OneBR), S&#xe3;o Paulo, Brazil.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>V&#xe1;squez-Ponce</LastName><ForeName>Felipe</ForeName><Initials>F</Initials><Identifier Source="ORCID">0000-0002-9447-8325</Identifier><AffiliationInfo><Affiliation>Department of Microbiology, Institute of Biomedical Sciences, University of S&#xe3;o Paulo, S&#xe3;o Paulo, Brazil.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>One Health Brazilian Resistance Project (OneBR), S&#xe3;o Paulo, Brazil.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pariona</LastName><ForeName>Eva M M</ForeName><Initials>EMM</Initials><Identifier Source="ORCID">0000-0001-9026-8366</Identifier><AffiliationInfo><Affiliation>Unidad de Investigaci&#xf3;n de Enfermedades Emergentes y Cambio Clim&#xe1;tico, Universidad Peruana Cayetano Heredia, Lima, Peru.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sousa-Carmo</LastName><ForeName>Rubens R</ForeName><Initials>RR</Initials><Identifier Source="ORCID">0000-0001-7135-7531</Identifier><AffiliationInfo><Affiliation>Department of Microbiology, Institute of Biomedical Sciences, University of S&#xe3;o Paulo, S&#xe3;o Paulo, Brazil.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>One Health Brazilian Resistance Project (OneBR), S&#xe3;o Paulo, Brazil.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Martins-Gon&#xe7;alves</LastName><ForeName>Thais</ForeName><Initials>T</Initials><Identifier Source="ORCID">0000-0003-4320-3089</Identifier><AffiliationInfo><Affiliation>Department of Microbiology, Institute of Biomedical Sciences, University of S&#xe3;o Paulo, S&#xe3;o Paulo, Brazil.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>One Health Brazilian Resistance Project (OneBR), S&#xe3;o Paulo, Brazil.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Becerra</LastName><ForeName>Johana</ForeName><Initials>J</Initials><Identifier Source="ORCID">0000-0002-9813-1556</Identifier><AffiliationInfo><Affiliation>Department of Microbiology, Institute of Biomedical Sciences, University of S&#xe3;o Paulo, S&#xe3;o Paulo, Brazil.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>One Health Brazilian Resistance Project (OneBR), S&#xe3;o Paulo, Brazil.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Antimicrobial Resistance Institute of S&#xe3;o Paulo (ARIES), S&#xe3;o Paulo, Brazil.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>de Lima</LastName><ForeName>Aline V</ForeName><Initials>AV</Initials><Identifier Source="ORCID">0000-0001-6325-1446</Identifier><AffiliationInfo><Affiliation>Department of Clinical Analysis, Faculty of Pharmaceutical Sciences, Universidade de S&#xe3;o Paulo, S&#xe3;o Paulo, Brazil.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Queiroga</LastName><ForeName>Gustavo</ForeName><Initials>G</Initials><Identifier Source="ORCID">0000-0001-7359-3095</Identifier><AffiliationInfo><Affiliation>Department of Clinical Analysis, Faculty of Pharmaceutical Sciences, Universidade de S&#xe3;o Paulo, S&#xe3;o Paulo, Brazil.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>One Health Brazilian Resistance Project (OneBR), S&#xe3;o Paulo, Brazil.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sampaio</LastName><ForeName>Jorge L M</ForeName><Initials>JLM</Initials><Identifier Source="ORCID">0000-0001-7789-3028</Identifier><AffiliationInfo><Affiliation>Department of Clinical Analysis, Faculty of Pharmaceutical Sciences, Universidade de S&#xe3;o Paulo, S&#xe3;o Paulo, Brazil.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lincopan</LastName><ForeName>Nilton</ForeName><Initials>N</Initials><Identifier Source="ORCID">0000-0003-0161-5800</Identifier><AffiliationInfo><Affiliation>Department of Clinical Analysis, Faculty of Pharmaceutical Sciences, Universidade de S&#xe3;o Paulo, S&#xe3;o Paulo, Brazil.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Microbiology, Institute of Biomedical Sciences, University of S&#xe3;o Paulo, S&#xe3;o Paulo, Brazil.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>One Health Brazilian Resistance Project (OneBR), S&#xe3;o Paulo, Brazil.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Antimicrobial Resistance Institute of S&#xe3;o Paulo (ARIES), S&#xe3;o Paulo, Brazil.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>314336/2021-4</GrantID><Agency>Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico</Agency><Country/></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2024</Year><Month>10</Month><Day>28</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>J Antimicrob Chemother</MedlineTA><NlmUniqueID>7513617</NlmUniqueID><ISSNLinking>0305-7453</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2024</Year><Month>7</Month><Day>17</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2024</Year><Month>10</Month><Day>12</Day></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2024</Year><Month>10</Month><Day>29</Day><Hour>6</Hour><Minute>23</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2024</Year><Month>10</Month><Day>29</Day><Hour>6</Hour><Minute>23</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2024</Year><Month>10</Month><Day>29</Day><Hour>2</Hour><Minute>13</Minute></PubMedPubDate></History><PublicationStatus>aheadofprint</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">39468752</ArticleId><ArticleId IdType="doi">10.1093/jac/dkae389</ArticleId><ArticleId IdType="pii">7848485</ArticleId></ArticleIdList></PubmedData></PubmedArticle></PubmedArticleSet>