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The most common mechanism that develops drug resistance is the overexpression of the efflux pump, especially Resistance-nodulation-cell division (RND) family, to almost most antibiotics. The study is designed to detect RND efflux pump genes in <jats:italic>A. baumannii<\/jats:italic>, and its correlation to multidrug resistance, in particular, the carbapenems resistance <jats:italic>Acinetobacter<\/jats:italic><jats:italic>baumannii<\/jats:italic>\u00a0(CRAB), and using different inhibitors that restore the antibiotic susceptibility of imipenem. Clinical <jats:italic>A. baumannii<\/jats:italic> isolates were recovered from different Egyptian hospitals in Intensive care unit (ICU). The expression of genes in two strains was analyzed using RT-PCR before and after inhibitor treatment. About 100 clinical <jats:italic>A. baumannii<\/jats:italic> isolates were recovered and identified and recorded as MDR strains with 75% strains resistant to imipenem. <jats:italic>adeB, adeC, adeK,<\/jats:italic> and <jats:italic>adeJ<\/jats:italic> were detected in thirty- seven the carbapenems resistance <jats:italic>Acinetobacter<\/jats:italic><jats:italic>baumannii<\/jats:italic> (CRAB) strains. <jats:italic>Cinnamomum verum<\/jats:italic> oil, Trimethoprim, and Omeprazole was promising inhibitor against 90% of the carbapenems resistance <jats:italic>Acinetobacter<\/jats:italic><jats:italic>baumannii<\/jats:italic>\u00a0(CRAB) strains with a 2-6-fold decrease in imipenem MIC. Downregulation of four genes was associated with the addition of those inhibitors to imipenem for two the carbapenems resistance <jats:italic>Acinetobacter<\/jats:italic><jats:italic>baumannii<\/jats:italic>\u00a0(CRAB) (ACN15 and ACN99) strains, and the effect was confirmed in 24 h killing kinetics. Our investigation points to the carbapenems resistance <jats:italic>Acinetobacter<\/jats:italic><jats:italic>baumannii<\/jats:italic>\u00a0(CRAB) strain\u2019s prevalence in Egyptian hospitals with the idea to revive the imipenem activity using natural and chemical drugs as inhibitors that possessed high synergistic activity.<\/jats:p>","DOI":"10.1186\/s12866-024-03194-8","type":"journal-article","created":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T06:02:34Z","timestamp":1707372154000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Regulation of overexpressed efflux pump encoding genes by cinnamon oil and trimethoprim to abolish carbapenem-resistant Acinetobacter baumannii clinical strains"],"prefix":"10.1186","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7985-3644","authenticated-orcid":false,"given":"Neveen M.","family":"Saleh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadeer","family":"Ezzat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5410-7936","authenticated-orcid":false,"given":"Gharieb S.","family":"El-Sayyad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamdallah","family":"Zedan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,8]]},"reference":[{"key":"3194_CR1","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1128\/CMR.00058-07","volume":"21","author":"AY Peleg","year":"2008","unstructured":"Peleg AY, Seifert H, Paterson DL. 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