{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T13:10:50Z","timestamp":1788527450945,"version":"build-2803163510"},"reference-count":35,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T00:00:00Z","timestamp":1700006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T00:00:00Z","timestamp":1700006400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32141001"],"award-info":[{"award-number":["32141001"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"MOST | National Key Research and Development Program of China","award":["2018YFE0101800"],"award-info":[{"award-number":["2018YFE0101800"]}]},{"name":"MOST | National Key Research and Development Program of China","award":["2018YFE0102100"],"award-info":[{"award-number":["2018YFE0102100"]}]},{"name":"Merck"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2023,11,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n            high-risk clones pose severe threats to public health. Here, we characterize the imipenem\/relebactam (IR) resistance mechanisms in\n            <jats:italic>P. aeruginosa<\/jats:italic>\n            high-risk clones sequence type 235 (ST235) and ST463 in China. Minimum inhibitory concentrations (MICs) were determined, and Illumina short-read sequencing was performed for 1,168 clinical carbapenem-resistant\n            <jats:italic>P. aeruginosa<\/jats:italic>\n            (CRPA) isolates. The gene copy number and expression level were analyzed by Illumina sequencing depth and reverse transcription-quantitative PCR, respectively. Resistance conferred by\n            <jats:italic>bla<\/jats:italic>\n            <jats:sub>GES-5<\/jats:sub>\n            was evaluated by cloning experiments. ST463 and ST235 accounted for 9.8% (115\/1,168) and 4.5% (53\/1,168) of total isolates, respectively, and showed high frequencies of extensively drug-resistant and difficult-to-treat resistant phenotypes. The overall IR-resistant rate in CRPA was 21.0% (245\/1,168). However, the IR resistance rate was 81.7% (94\/115) in ST463-PA and 52.8% (28\/53) in ST235-PA. Of the ST463 isolates, 92.2% (106\/115) were\n            <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n            carbapenemase-producing\n            <jats:italic>P. aeruginosa<\/jats:italic>\n            (KPC-PA), and all 94 IR-resistant ST463-PA produced KPC-2. Compared to IR-susceptible ST463 KPC-2-PA, IR-resistant ST463 KPC-2-PA exhibited significantly higher\n            <jats:italic>bla<\/jats:italic>\n            <jats:sub>KPC-2<\/jats:sub>\n            copy numbers and expression levels. In ST463 KPC-2-PA, 16 mg\/L relebactam resulted in additional fourfold reductions in imipenem MIC\n            <jats:sub>50\/90<\/jats:sub>\n            values compared to 4 mg\/L relebactam. In ST235, 1.9% (1\/53) carried\n            <jats:italic>bla<\/jats:italic>\n            <jats:sub>IMP<\/jats:sub>\n            carbapenemase and 54.7% (29\/53) carried\n            <jats:italic>bla<\/jats:italic>\n            <jats:sub>GES<\/jats:sub>\n            carbapenemase. Other than the IMP producer, all 27 IR-resistant ST235-PA produced GES-5. Cloning experiments revealed that imipenem resistance in\n            <jats:italic>bla<\/jats:italic>\n            <jats:sub>GES-5<\/jats:sub>\n            -carrying PAO1 transformants was generally unaffected by relebactam. In conclusion, IR-resistant CRPA isolates in China were mainly distributed in\n            <jats:italic>P. aeruginosa<\/jats:italic>\n            high-risk clones ST463 and ST235. The major underlying IR resistance mechanisms were\n            <jats:italic>bla<\/jats:italic>\n            <jats:sub>KPC-2<\/jats:sub>\n            overexpression and\n            <jats:italic>bla<\/jats:italic>\n            <jats:sub>GES-5<\/jats:sub>\n            carriage.\n          <\/jats:p>","DOI":"10.1128\/aac.00675-23","type":"journal-article","created":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T13:00:36Z","timestamp":1697029236000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":19,"title":["<i>bla<\/i>\n            <sub>KPC-2<\/sub>\n            overexpression and\n            <i>bla<\/i>\n            <sub>GES-5<\/sub>\n            carriage as major imipenem\/relebactam resistance mechanisms in\n            <i>Pseudomonas aeruginosa<\/i>\n            high-risk clones ST463 and ST235, respectively, in China"],"prefix":"10.1128","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6161-1196","authenticated-orcid":false,"given":"Yue","family":"Li","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine , Hangzhou, China"},{"name":"Regional Medical Center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine , Hangzhou, China"},{"name":"Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province , Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine , Hangzhou, China"},{"name":"Regional Medical Center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine , Hangzhou, China"},{"name":"Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province , Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengqian","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine , Hangzhou, China"},{"name":"Regional Medical Center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine , Hangzhou, China"},{"name":"Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province , Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine , Hangzhou, China"},{"name":"Regional Medical Center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine , Hangzhou, China"},{"name":"Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province , Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8215-916X","authenticated-orcid":true,"given":"Xiaoting","family":"Hua","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine , Hangzhou, China"},{"name":"Regional Medical Center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine , Hangzhou, China"},{"name":"Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province , Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang 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