{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:10:13Z","timestamp":1791897013837,"version":"4.3.4"},"reference-count":23,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:00:00Z","timestamp":1722902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FUR2024"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>We investigated the activity of cefiderocol\/\u03b2-lactamase inhibitor combinations against clinical strains with different susceptibility profiles to cefiderocol to explore the potentiality of antibiotic combinations as a strategy to contain the major public health problem of multidrug-resistant (MDR) pathogens. Specifically, we evaluated the synergistic activity of cefiderocol with avibactam, sulbactam, or tazobactam on three of the most \u201cCritical Priority\u201d group of MDR bacteria (carbapenem-resistant Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii). Clinical isolates were genomically characterized by Illumina iSeq 100. The synergy test was conducted with time-kill curve assays. Specifically, cefiderocol\/avibactam, \/sulbactam, or \/tazobactam combinations were analyzed. Synergism was assigned if bacterial grow reduction reached 2 log10 CFU\/mL. We reported the high antimicrobial activity of the cefiderocol\/sulbactam combination against carbapenem-resistant Enterobacterales, P. aeruginosa, and A. baumannii; of the cefiderocol\/avibactam combination against carbapenem-resistant Enterobacterales; and of the cefiderocol\/tazobactam combination against carbapenem-resistant Enterobacterales and P. aeruginosa. Our results demonstrate that all \u03b2-lactamase inhibitors (BLIs) tested are able to enhance cefiderocol antimicrobial activity, also against cefiderocol-resistant isolates. The cefiderocol\/sulbactam combination emerges as the most promising combination, proving to highly enhance cefiderocol activity in all the analyzed carbapenem-resistant Gram-negative isolates, whereas the Cefiderocol\/tazobactam combination resulted in being active only against carbapenem-resistant Enterobacterales and P. aeruginosa, and cefiderocol\/avibactam was only active against carbapenem-resistant Enterobacterales.<\/jats:p>","DOI":"10.3390\/cells13161315","type":"journal-article","created":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T08:42:28Z","timestamp":1723020148000},"page":"1315","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Synergistic Activity of Cefiderocol in Combination with Avibactam, Sulbactam or Tazobactam against Carbapenem-Resistant Gram-Negative Bacteria"],"prefix":"10.3390","volume":"13","author":[{"given":"Russell E.","family":"Lewis","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, University of Padova, 35122 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Palombo","sequence":"additional","affiliation":[{"name":"IRCCS Azienda Ospedaliero, Universitaria di Bologna, 40135 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1373-7533","authenticated-orcid":false,"given":"Erica","family":"Diani","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Public Health, Microbiology Section, Verona University, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedetta","family":"Secci","sequence":"additional","affiliation":[{"name":"IRCCS Azienda Ospedaliero, Universitaria di Bologna, 40135 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Gibellini","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Public Health, Microbiology Section, Verona University, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3791-8635","authenticated-orcid":false,"given":"Paolo","family":"Gaibani","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Public Health, Microbiology Section, Verona University, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1007\/s10096-021-04296-1","article-title":"Treatment for carbapenem-resistant Enterobacterales infections: Recent advances and future directions","volume":"40","author":"Tompkins","year":"2021","journal-title":"Eur. 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