{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:16:16Z","timestamp":1791504976457,"version":"4.3.4"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP23K16313"],"award-info":[{"award-number":["JP23K16313"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Cefiderocol is an important treatment option for infections caused by multidrug-resistant Gram-negative bacteria; however, resistance among New Delhi metallo-\u03b2-lactamase-producing Enterobacterales (NDME) is increasingly reported, leaving limited therapeutic alternatives. This study evaluated the in vitro activity of the minocycline\u2013biapenem combination against cefiderocol-resistant NDME.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Twenty-three non-duplicate clinical NDME isolates with cefiderocol MIC\u200a\u2265\u200a16\u2005mg\/L determined by reference broth microdilution in iron-depleted cation-adjusted Mueller\u2013Hinton broth were analysed. Checkerboard assays were performed to assess combination activity using fractional inhibitory concentration indices (FICIs), sub-MIC interaction analysis and cumulative inhibition heatmaps. Time\u2013kill assays were conducted using three representative isolates producing NDM-1 or NDM-5.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Susceptibility rates for minocycline and biapenem tested alone were 52% and 13%, respectively. The minocycline\u2013biapenem combination demonstrated synergistic activity (FICI\u200a\u2264\u200a0.5) in 22 of 23 isolates (96%), with a median FICI of 0.063. Synergy was consistently observed across Escherichia coli, Enterobacter cloacae and Klebsiella pneumoniae. Sub-MIC analyses revealed asymmetric pharmacodynamic interactions, with sustained reductions in biapenem MIC at minocycline exposures as low as 1\/512\u00d7 baseline MIC. Cumulative inhibition heatmaps showed growth inhibition in 100% of isolates at the susceptible breakpoint concentrations of minocycline (4\u2005mg\/L) and biapenem (1\u2005mg\/L). Time\u2013kill assays confirmed rapid and exposure-dependent bactericidal activity at clinically achievable concentration pairs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The minocycline\u2013biapenem combination showed consistent in vitro synergistic and bactericidal activity against cefiderocol-resistant NDME across multiple species and NDM variants. These findings support further pharmacodynamic and translational evaluation of this combination as a potential therapeutic option for cefiderocol-refractory infections.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkag128","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T12:46:01Z","timestamp":1774615561000},"source":"Crossref","is-referenced-by-count":2,"title":["<i>In vitro<\/i>\n                    synergistic activity of minocycline and biapenem against cefiderocol-resistant New Delhi metallo-\u03b2-lactamase-producing Enterobacterales"],"prefix":"10.1093","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5640-5811","authenticated-orcid":false,"given":"Takashi","family":"Okanda","sequence":"first","affiliation":[{"name":"Department of Microbiology, St.Marianna University School of Medicine , Kanagawa 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