{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T00:27:12Z","timestamp":1793406432700,"version":"4.5.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The emergence of carbapenem-resistant\n                      <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                      (CRKP) co-producing KPC-2 and NDM-1 (K2N1-CRKP) has intensified a major public health threat and severely limited therapeutic options. Eravacycline, a novel tetracycline, shows potent\n                      <jats:italic>in vitro<\/jats:italic>\n                      activity against carbapenem-resistant Enterobacteriaceae. However, its efficacy and synergistic potential against K2N1-CRKP remain unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analyzed the molecular epidemiology of 42 K2N1-CRKP strains and evaluated their susceptibility to eravacycline. The\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      (using a\n                      <jats:italic>Galleria mellonella<\/jats:italic>\n                      model) synergistic effects of eravacycline combined with other antibiotics were determined.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      All 42 strains belonged to ST11. Among them, 92.8% (39\/42) were susceptible to eravacycline (MIC50\/90: 1 \u03bcg\/mL; range: 0.5\u20132 \u03bcg\/mL). Two strains (KP17, KP18) were resistant to both eravacycline and polymyxin B. The eravacycline-polymyxin B combination showed synergistic activity against 9.5% (4\/42) of isolates, including the two dual-resistant strains. No interaction was observed for eravacycline combined with ceftazidime-avibactam, meropenem, or amikacin. Time-kill assays confirmed the rapid, sustained bactericidal activity of the eravacycline-polymyxin B combination against K2N1-CRKP. In the\n                      <jats:italic>G. mellonella<\/jats:italic>\n                      infection model, this combination provided a significantly superior survival benefit compared to monotherapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Eravacycline demonstrates potent\n                      <jats:italic>in vitro<\/jats:italic>\n                      activity against ST11 K2N1-CRKP. While combinations with ceftazidime-avibactam, amikacin, or meropenem showed only additive effects, eravacycline plus polymyxin B exhibited strong synergistic and bactericidal activity both\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      , even against strains resistant to either agent alone. This regimen represents a promising evidence-based therapeutic option for these formidable infections.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1802577","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T06:53:40Z","timestamp":1774421620000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Eravacycline monotherapy and combination therapy against KPC-2- and NDM-1-co- producing Klebsiella pneumoniae: in vitro and in vivo activity analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiaojie","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou","place":["Jiangsu, China"]},{"name":"The Center for Clinical Research and Transformation of Pathogen Diagnosis, Xuzhou Medical University, Xuzhou","place":["Jiangsu, 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