{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T02:17:44Z","timestamp":1782958664540,"version":"3.54.5"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T00:00:00Z","timestamp":1730073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cienti\u0301fico e Tecnolo\u0301gico","doi-asserted-by":"publisher","award":["314336\/2021-4"],"award-info":[{"award-number":["314336\/2021-4"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cienti\u0301fico e Tecnolo\u0301gico","doi-asserted-by":"publisher","award":["422984\/2021-3"],"award-info":[{"award-number":["422984\/2021-3"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Klebsiella pneumoniae producing KPC variants conferring resistance to ceftazidime\u2013avibactam often remain susceptible to meropenem, suggesting a potential therapeutic use of this antibiotic.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>In this study, the efficacy of clinically relevant concentrations of meropenem was evaluated against high-risk clones of ceftazidime\u2013avibactam-resistant K. pneumoniae strains producing KPC variants, in a tandem in vitro time-kill\/in vivo Galleria mellonella survival model.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In vitro\/in vivo efficacy of meropenem against ceftazidime\u2013avibactam-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\u200a\u00d7\u200a1)-treated and ceftazidime\u2013avibactam (40 mg\/kg ceftazidime\u201310 mg\/kg avibactam\u200a\u00d7\u200a1)-treated groups were established, with 60 larvae per group. Kaplan\u2013Meier curves, log-rank tests, univariate Cox regression and hazard ratios (HR) were used to assess treatment effects (P\u200a&amp;lt;\u200a0.05).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>For all KPC-variant producers, time-kill assays showed &amp;gt;3 log-kills reduction (\u22126.91\u200a\u00b1\u200a1.28 SD) after 6 h interaction when exposed to 8\u201332 mg\/L meropenem MIC values (i.e. \u200a\u2265\u200a\u200a\u00d7\u200a4 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\u2013avibactam-treated) and 13.3% (meropenem-treated) (P\u200a&amp;lt;\u200a0.05). Univariate Cox regression analysis showed significantly lower risk in the meropenem group compared to untreated group [HR 0.02 (95% CI: 0.01\u20130.05)].<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkae389","type":"journal-article","created":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T06:03:03Z","timestamp":1730181783000},"page":"162-168","source":"Crossref","is-referenced-by-count":2,"title":["Efficacy of meropenem against ceftazidime\u2013avibactam-resistant <i>Klebsiella pneumoniae<\/i> producing KPC-31, KPC-33, KPC-90, KPC-106 and KPC-114"],"prefix":"10.1093","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9174-0749","authenticated-orcid":false,"given":"Jesus G M","family":"Pariona","sequence":"first","affiliation":[{"name":"Department of Clinical Analysis, Faculty of Pharmaceutical Sciences, Universidade de S\u00e3o Paulo , S\u00e3o Paulo ,","place":["Brazil"]},{"name":"Department of Microbiology, Institute of Biomedical Sciences, University of S\u00e3o Paulo , S\u00e3o Paulo ,","place":["Brazil"]},{"name":"One Health Brazilian Resistance Project (OneBR) , S\u00e3o Paulo ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9447-8325","authenticated-orcid":false,"given":"Felipe","family":"V\u00e1squez-Ponce","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Institute of Biomedical Sciences, University of S\u00e3o Paulo , S\u00e3o Paulo ,","place":["Brazil"]},{"name":"One Health Brazilian Resistance Project 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,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4320-3089","authenticated-orcid":false,"given":"Thais","family":"Martins-Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Institute of Biomedical Sciences, University of S\u00e3o Paulo , S\u00e3o Paulo ,","place":["Brazil"]},{"name":"One Health Brazilian Resistance Project (OneBR) , S\u00e3o Paulo ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9813-1556","authenticated-orcid":false,"given":"Johana","family":"Becerra","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Institute of Biomedical Sciences, University of S\u00e3o Paulo , S\u00e3o Paulo ,","place":["Brazil"]},{"name":"One Health Brazilian Resistance Project (OneBR) , S\u00e3o Paulo ,","place":["Brazil"]},{"name":"Antimicrobial Resistance Institute of S\u00e3o Paulo (ARIES) , S\u00e3o Paulo ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6325-1446","authenticated-orcid":false,"given":"Aline V","family":"de Lima","sequence":"additional","affiliation":[{"name":"Department of Clinical Analysis, Faculty of Pharmaceutical Sciences, Universidade de S\u00e3o Paulo , S\u00e3o Paulo ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7359-3095","authenticated-orcid":false,"given":"Gustavo","family":"Queiroga","sequence":"additional","affiliation":[{"name":"Department of Clinical Analysis, Faculty of Pharmaceutical Sciences, Universidade de S\u00e3o Paulo , S\u00e3o Paulo ,","place":["Brazil"]},{"name":"One Health Brazilian Resistance Project (OneBR) , S\u00e3o Paulo ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7789-3028","authenticated-orcid":false,"given":"Jorge 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