{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:13:18Z","timestamp":1787029998653,"version":"build-2736575974"},"reference-count":51,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,10,2]],"date-time":"2022-10-02T00:00:00Z","timestamp":1664668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["TropicalMed"],"abstract":"<jats:p>Introduction: The emergence of multidrug-resistant (MDR) E. coli has developed worldwide; therefore, the use of antibiotic combinations may be an effective strategy to target resistant bacteria and fight life-threatening infections. The current study was performed to evaluate the in vitro and in vivo efficacy of amikacin and imipenem alone and in combination against multidrug-resistant E. coli. Methods: The combination treatment was assessed in vitro using a checkerboard technique and time-killing curve and in vivo using a peritonitis mouse model. In resistant isolates, conventional PCR and quantitative real-time PCR techniques were used to detect the resistant genes of Metallo-\u03b2-lactamase gene Imipenemase (bla-IMP) and aminoglycoside 6\u2032-N-acetyltransferase (aac (6\u2032)-Ib). Scanning electron microscopy was used to detect the morphological changes in the resistant isolates after treatment with each drug alone and in combination. In vitro and in vivo studies showed a synergistic effect using the tested antibiotic combinations, showing fractional inhibitory concentration indices (FICIs) of \u22640.5. Regarding the in vivo study, combination therapy indicated a bactericidal effect after 24 h. E. coli isolates harboring the resistant genes Metallo-\u03b2-lactamase gene Imipenemase (bla-IMP) and aminoglycoside 6\u2032-N-acetyltransferase (aac (6\u2032)-Ib) represented 80% and 66.7%, respectively, which were mainly isolated from wound infections. The lowest effect on Metallo-\u03b2-lactamase gene Imipenemase (bla-IMP) and aminoglycoside 6\u2032-N-acetyltransferase (aac (6\u2032)-Ib) gene expression was shown in the presence of 0.25 \u00d7 MIC of imipenem and 0.5 \u00d7 MIC of amikacin. The scanning electron microscopy showed cell shrinkage and disruption in the outer membrane of E. coli in the presence of the antibiotic combination. Amikacin and imipenem combination can be expected to be effective in the treatment and control of serious infections caused by multidrug-resistant (MDR) E. coli and the reduction in bacterial resistance emergence.<\/jats:p>","DOI":"10.3390\/tropicalmed7100281","type":"journal-article","created":{"date-parts":[[2022,10,11]],"date-time":"2022-10-11T06:13:27Z","timestamp":1665468807000},"page":"281","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["In Vitro and In Vivo Effect of Amikacin and Imipenem Combinations against Multidrug-Resistant E. coli"],"prefix":"10.3390","volume":"7","author":[{"given":"Sara Mahmoud","family":"Farhan","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt 2 Department of Microbiology and Immunology, Faculty of Pharmacy, Deraya University, Minia 11566, Egypt 3 Department of Microbiology and Immunology, Faculty of Pharmacy, Minia University, Minia 61519, Egypt 4 Department of Microbiology and Immunology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt 5 Department of Microbiology and Immunology, Faculty of Pharmacy, Sohag University, Sohag 82524, Egypt 6 Department of Plant and Microbiology, Faculty of Science, Damanhour University, Damanhour 22511, Egypt 7 Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, USA"},{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Deraya University, Minia 11566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6094-5653","authenticated-orcid":false,"given":"Rehab Mahmoud Abd","family":"El-Baky","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Deraya University, Minia 11566, Egypt"},{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Minia University, Minia 61519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5550-8352","authenticated-orcid":false,"given":"Salah","family":"Abdalla","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0980-5185","authenticated-orcid":false,"given":"Ahmed Osama","family":"EL-Gendy","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt 2 Department of Microbiology and Immunology, Faculty of Pharmacy, Deraya University, Minia 11566, Egypt 3 Department of Microbiology and Immunology, Faculty of Pharmacy, Minia University, Minia 61519, Egypt 4 Department of Microbiology and Immunology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt 5 Department of Microbiology and Immunology, Faculty of Pharmacy, Sohag University, Sohag 82524, Egypt 6 Department of Plant and Microbiology, Faculty of Science, Damanhour University, Damanhour 22511, Egypt 7 Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hala Rady","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Minia University, Minia 61519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doaa Safwat","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Sohag University, Sohag 82524, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amr El","family":"El Zawily","sequence":"additional","affiliation":[{"name":"Department of Plant and Microbiology, Faculty of Science, Damanhour University, Damanhour 22511, Egypt"},{"name":"Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed Farag","family":"Azmy","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt 2 Department of Microbiology and Immunology, Faculty of Pharmacy, Deraya University, Minia 11566, Egypt 3 Department of Microbiology and Immunology, Faculty of Pharmacy, Minia University, Minia 61519, Egypt 4 Department of Microbiology and Immunology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt 5 Department of Microbiology and Immunology, Faculty of Pharmacy, Sohag University, Sohag 82524, Egypt 6 Department of Plant and Microbiology, Faculty of Science, Damanhour University, Damanhour 22511, Egypt 7 Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107479","DOI":"10.1016\/j.foodcont.2020.107479","article-title":"Inactivation of Listeria monocytogenes and Escherichia coli O157: H7 inoculated on fresh-cut romaine lettuce by peanut skin extract\/benzethonium chloride emulsion washing","volume":"119","author":"Lee","year":"2021","journal-title":"Food Control"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13099-019-0290-0","article-title":"Virulence factors, prevalence and potential transmission of extraintestinal pathogenic Escherichia coli isolated from different sources: Recent 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