{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T20:57:17Z","timestamp":1790456237507,"version":"4.1.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T00:00:00Z","timestamp":1764720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100003009","name":"Science, Technology & Innovative Funding Authority","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003009","id-type":"DOI","asserted-by":"publisher"}]},{"name":"One Health Grant","award":["48362"],"award-info":[{"award-number":["48362"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Despite the growing concern over MDR hypervirulent Klebsiella pneumoniae (MDR-hvKP), effective treatments remain limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>This study explores the potential of co-loading ciprofloxacin and meropenem into a nano-polymeric matrix to enhance their synergistic activity against MDR-hvKP and improve treatment outcomes in a hvKP-infected rat model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Ten clinical K. pneumoniae isolates were tested for virulence genes (p-rmpA, iucA) to confirm the presence of hvKP. The synergistic activity of free-ciprofloxacin\/meropenem and nanosized ciprofloxacin\/meropenem was evaluated using checkerboard and time\u2013kill assays. Survival rates and bacterial burden were assessed in a rat sepsis model after receiving either nano- or free-ciprofloxacin\/meropenem.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>HvKP strains exhibited significantly lower MICs for nanosized drugs compared with free drugs. MICs of nano-ciprofloxacin ranged from 2 to 32\u2005mg\/L, and nano-meropenem from 0.125 to 64\u2005mg\/L, reflecting 2\u20134- and 4\u201316-fold reductions compared with free drugs. Nano- ciprofloxacin\/meropenem combination displayed synergistic activity against 7 out of 10 hvKP strains and additive activity against three strains. By contrast, free-ciprofloxacin\/meropenem showed synergy in only two strains, additive effects in two strains and indifferent activity in six strains. Time\u2013kill assays demonstrated that monotherapies failed to inhibit bacterial growth, while nanosized combination exhibited bactericidal activity at 1\u00d7MIC. Nano-ciprofloxacin\/meropenem significantly improved survival and reduced bacterial load compared with free drugs combination (P\u200a\u2264\u200a0.0001).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Dual antibiotic-loaded nanoparticles represent an innovative therapeutic approach against hvKP infections and highlight nanotechnology's potential in overcoming MDR pathogens for future clinical application.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkaf422","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T12:44:37Z","timestamp":1761655477000},"source":"Crossref","is-referenced-by-count":1,"title":["Nanoparticle-based co-delivery of ciprofloxacin and meropenem enhances synergistic activity against multidrug-resistant hypervirulent\n                    <i>Klebsiella pneumoniae<\/i>\n                    clinical isolates"],"prefix":"10.1093","volume":"81","author":[{"given":"Reham","family":"Mostafa","sequence":"first","affiliation":[{"name":"Chest Hospital, Ministry of Health , Assiut ,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shereen","family":"Mohammed","sequence":"additional","affiliation":[{"name":"Medical Microbiology and Immunology Department, Faculty of Medicine, Assiut University , Assiut ,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed S","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Medical Microbiology and Immunology Department, Faculty of Medicine, Assiut University , Assiut ,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherine A","family":"Aly","sequence":"additional","affiliation":[{"name":"Medical Microbiology and Immunology Department, Faculty of Medicine, Assiut University , Assiut 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