{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T19:32:26Z","timestamp":1777923146163,"version":"3.51.4"},"reference-count":35,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Microbial Drug Resistance"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:p>\n                    Antibiotic combinations remain the frontline therapy for severe infections to reduce mortality. However, conventional antibiotic combinations have some limitations such as the low bioavailability and the rise of resistant strains. Nanoparticles are increasingly used as antibiotic delivery systems to promote bioavailability and hence improve efficacy of antibiotics. In this work, we hypothesize that the simultaneous delivery of two antibiotic-loaded nanoparticles will improve the intracellular bioavailability and thus inhibit emergence of resistance. Accordingly, Chitosan\u2013pluronic nanoparticles were used to construct nanosized ciprofloxacin and meropenem and the antibacterial activity of nanosized combined antibiotics were compared versus unloaded single, unloaded combined, and nanosized single antibiotics. Thirty-six stepwise mutants were selected by exposing two\n                    <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                    strains to increasing concentrations of free-unloaded and nanosized antibiotics, and mutants were tested for antimicrobial susceptibilities using broth microdilution and disc diffusion methods. The change in expression levels of\n                    <jats:italic toggle=\"yes\">acrB<\/jats:italic>\n                    efflux pump and porins (\n                    <jats:italic toggle=\"yes\">ompC<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">ompF<\/jats:italic>\n                    ) was assessed by real-time reverse transcription\u2013PCR. The\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    evaluation of combined ciprofloxacin and meropenem-loaded nanoparticles demonstrated that this nanosystem exhibited enhanced antibacterial effect. Step mutants selected with nanosized combined antibiotics showed higher sensitivity to both drugs, exhibited lower mutation frequencies, and less cross-resistance to other antimicrobial classes. Moreover, for all steps of selection, nanosized combined antibiotic mutants expressed significantly lower levels of\n                    <jats:italic toggle=\"yes\">acrB<\/jats:italic>\n                    as well as higher levels of\n                    <jats:italic toggle=\"yes\">ompC<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">ompF<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">p-<\/jats:italic>\n                    value &lt;0.01). In view of these results, the use of nanosized combined antibiotics may be considered among the new promising strategies to combat infections through their potential efficacy in reducing microorganisms' ability to form resistant mutants.\n                  <\/jats:p>","DOI":"10.1089\/mdr.2022.0095","type":"journal-article","created":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T17:40:36Z","timestamp":1663263636000},"page":"972-979","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Nanosized Combined Antimicrobial Drugs Decreased Emergence of Resistance in\n                    <i>Escherichia coli<\/i>\n                    : A Future Promise"],"prefix":"10.1177","volume":"28","author":[{"given":"Safy","family":"Hadiya","sequence":"first","affiliation":[{"name":"Assiut International Center of Nanomedicine, Al-Rajhy Liver Hospital, Assiut University, Assiut, Egypt."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reham A.","family":"Ibrahem","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Minia University, Minia, Egypt."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rehab M.","family":"Abd El-Baky","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Minia University, Minia, Egypt."},{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Deraya University, Minia, Egypt."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahmoud","family":"Elsabahy","sequence":"additional","affiliation":[{"name":"School of Biotechnology and Science Academy, Badr University in Cairo, Badr City, Cairo, Egypt."},{"name":"Department of Chemistry, Texas A&amp;M University, College Station, Texas, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sherine A.","family":"Aly","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2022,10,14]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2012.12.006"},{"issue":"3","key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/s41579-018-0141-x","article-title":"Drug combinations: A strategy to extend the life of antibiotics in the 21st century","volume":"17","author":"Tyers M","year":"2019","unstructured":"Tyers M, , Wright GD. 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