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Ceftazidime-avibactam (CZA) is a novel \u03b2-lactam\/\u03b2-lactamase inhibitor recently approved for the treatment of limited infectious diseases. Here, we describe a novel CMY variant, CMY-192, that confers high-level resistance to CZA. This gene was detected in a clinical MDR\n              <jats:italic>Escherichia coli<\/jats:italic>\n              strain (Ec73552) isolated from an outpatient with a community-acquired urinary tract infection who had not received prior CZA treatment. Ec73552 was typed as O101:H9-ST10, a high-risk clone associated with human and animal diseases. Ec73552 was able to colonize the bladder in a mouse model, suggesting that this strain was uropathogenic. CMY-192 shared the highest amino acid identity (98.95%) with CMY-172 and conferred at least a 32-fold increase in CZA MIC (from \u22640.125\/4 to 8\/4 mg\/L) when cloned into a CZA-susceptible\n              <jats:italic>E. coli<\/jats:italic>\n              DH5\u03b1 strain. Knockout of CMY-192 in Ec73552 resulted in a 256-fold reduction in CZA MIC (from 64\/4 to 0.25\/4 mg\/L). CMY-192 was encoded on an IncB\/O\/K\/Z-type plasmid (pCMY192). Conjugation assays confirmed that pCMY192 was self-transmissible, resulting in a 256-fold increase in the CZA MIC of the recipient. Notably, pCMY192 cured in Ec73552 did not confer a growth advantage, while the conjugant exhibited reduced biomass and growth rate, indicating that fitness costs imposed by pCMY192 may have been compensated in Ec73552. Our findings highlight the importance of continuous monitoring of CZA susceptibility to prevent the spread of resistance in clinical settings.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.00906-24","type":"journal-article","created":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T13:00:38Z","timestamp":1730206838000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["Novel plasmid-mediated CMY variant (CMY-192) conferring ceftazidime-avibactam resistance in multidrug-resistant\n            <i>Escherichia coli<\/i>"],"prefix":"10.1128","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2913-2133","authenticated-orcid":false,"given":"Tingting","family":"Xu","sequence":"first","affiliation":[{"name":"Shenzhen Institute of Respiratory Diseases, Shenzhen People\u2019s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology)","place":["Shenzhen, China"]},{"name":"Department of Pathogen Biology, Shenzhen University Medicine School","place":["Shenzhen, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiyuan","family":"Wu","sequence":"additional","affiliation":[{"name":"Clinical Laboratory, Second Clinical Medical College (Shenzhen People\u2019s Hospital), Jinan University; the First Af\ufb01liated Hospital (Shenzhen People\u2019s Hospital), Southern University of Science and Technology","place":["Shenzhen, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lili","family":"Huang","sequence":"additional","affiliation":[{"name":"Shenzhen Institute of Respiratory Diseases, Shenzhen People\u2019s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology)","place":["Shenzhen, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Microbiology and Technology, Nankai University, Ministry of Education","place":["Tianjin, China"]},{"name":"Nankai International Advanced Research Institute, Nankai University","place":["Shenzhen, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiaodong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanghai Frontiers Science Center for Drug Target Identification and Delivery, and the Engineering Research Center of Cell and Therapeutic Antibody of the Ministry of Education, School of Pharmaceutical Sciences, National Key Laboratory of Innovative Immunotherapy, Shanghai Jiao Tong University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingjie","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Fifth Affiliated Hospital, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jialong","family":"Liu","sequence":"additional","affiliation":[{"name":"Shenzhen Institute of Respiratory Diseases, Shenzhen People\u2019s Hospital (The Second Clinical Medical College, Jinan University; 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