{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T11:34:49Z","timestamp":1789990489089,"version":"4.0.1"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2019,6,21]],"date-time":"2019-06-21T00:00:00Z","timestamp":1561075200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"JMI Laboratories"},{"DOI":"10.13039\/100007819","name":"Allergan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007819","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To evaluate ceftazidime\/avibactam resistance mechanisms among Pseudomonas aeruginosa clinical isolates and compare with isolates susceptible to this combination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>During 2015, 2548 P. aeruginosa isolates were collected in 106 US hospitals and 46 (1.8%) were resistant to ceftazidime\/avibactam. These isolates were matched with 109 ceftazidime\/avibactam-susceptible isolates resistant to other antipseudomonal agents and were evaluated for the presence of \u03b2-lactam resistance mechanisms using WGS analysis and quantitative real-time PCR. Results were analysed using logistic regression comparing the isolate groups to understand the mechanisms of ceftazidime\/avibactam resistance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two isolates carried the MBLs blaVIM-1 and blaVIM-2 and another three had unique alterations or deletions in the chromosomal AmpC \u03a9-loop associated with ceftazidime\/avibactam resistance. Overexpression of mexA (+27.4%), disruptions in ampP (+21.7%), mexR (+17.1%) and mexZ (+14.6%) and alterations in ctpA (+13.0%), dnaK (+17.8%) and ftsI (+20.8%) were significantly more prevalent among ceftazidime\/avibactam-resistant isolates when compared with their susceptible counterparts independently or in combination. The combination of dnaK alterations and mexA overexpression was more common among ceftazidime\/avibactam-resistant by 82\u00d7; mexR disruptions and mexA overexpression by 45\u00d7; and other two- or three-genotype interactions that included alterations\/disruptions in dnaK, ftsI, nalD, mexR, mexZ and mexA overexpression by 6.5\u00d7 to 34\u00d7.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Resistance to ceftazidime\/avibactam among P. aeruginosa clinical isolates has been shown to be a complex interplay of resistance mechanisms that can affect ceftazidime and\/or avibactam and some similar findings were reported in laboratory isolates exposed to ceftazidime\u2009\u00b1\u2009avibactam.<\/jats:p><\/jats:sec>","DOI":"10.1093\/jac\/dkz243","type":"journal-article","created":{"date-parts":[[2019,6,10]],"date-time":"2019-06-10T19:13:46Z","timestamp":1560194026000},"page":"2588-2595","source":"Crossref","is-referenced-by-count":56,"title":["Combination of MexAB-OprM overexpression and mutations in efflux regulators, PBPs and chaperone proteins is responsible for ceftazidime\/avibactam resistance in Pseudomonas aeruginosa clinical isolates from US hospitals"],"prefix":"10.1093","volume":"74","author":[{"given":"Mariana","family":"Castanheira","sequence":"first","affiliation":[{"name":"JMI Laboratories, North Liberty, IA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy B","family":"Doyle","sequence":"additional","affiliation":[{"name":"JMI Laboratories, North Liberty, IA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin J","family":"Smith","sequence":"additional","affiliation":[{"name":"JMI Laboratories, North Liberty, IA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo E","family":"Mendes","sequence":"additional","affiliation":[{"name":"JMI Laboratories, North Liberty, IA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helio 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