{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T16:18:17Z","timestamp":1772209097539,"version":"3.50.1"},"reference-count":38,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T00:00:00Z","timestamp":1610582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>We report the emergence of an isolate belonging to the sequence type (ST)131-Escherichia coli high-risk clone with ceftazidime-avibactam resistance recovered from a patient with bacteremia in 2019. Antimicrobial susceptibility was determined and whole genome sequencing (Illumina-NovaSeq6000) and cloning experiments were performed to investigate its resistance phenotype. A KPC-3-producing E. coli isolate susceptible to ceftazidime-avibactam (MIC = 0.5\/4 mg\/L) and with non-wild type MIC of meropenem (8 mg\/L) was detected in a blood culture performed at hospital admission. Following 10-days of standard ceftazidime-avibactam dose treatment, a second KPC-producing E. coli isolate with a phenotype resembling an extended-spectrum \u03b2-lactamase (ESBL) producer (meropenem 0.5 mg\/L, piperacillin-tazobactam 16\/8 mg\/L) but resistant to ceftazidime-avibactam (16\/4 mg\/L) was recovered. Both E. coli isolates belonged to ST131, serotype O25:H4 and sublineage H30R1. Genomics analysis showed a core genome of 5,203,887 base pair with an evolutionary distance of 6 single nucleotide polymorphisms. A high content of resistance and virulence genes was detected in both isolates. The novel KPC-49 variant, an Arg-163-Ser mutant of blaKPC-3, was detected in the isolate with resistance to ceftazidime-avibactam. Cloning experiments revealed that blaKPC-49 gene increases ceftazidime-avibactam MIC and decreases carbapenem MICs when using a porin deficient Klebsiella pneumoniae strain as a host. Both blaKPC-3 and blaKPC-49 genes were located on the transposon Tn4401a as a part of an IncF [F1:A2:B20] plasmid. The emergence of novel blaKPC genes conferring decreased susceptibility to ceftazidime-avibactam and resembling ESBL production in the epidemic ST131-H30R1-E. coli high-risk clone presents a new challenge in clinical practice.<\/jats:p>","DOI":"10.3390\/pathogens10010067","type":"journal-article","created":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T21:50:54Z","timestamp":1610574654000},"page":"67","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Emergence of the New KPC-49 Variant Conferring an ESBL Phenotype with Resistance to Ceftazidime-Avibactam in the ST131-H30R1 Escherichia coli High-Risk Clone"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2857-2572","authenticated-orcid":false,"given":"Marta","family":"Hern\u00e1ndez-Garc\u00eda","sequence":"first","affiliation":[{"name":"Servicio de Microbiolog\u00eda, Hospital Universitario Ram\u00f3n y Cajal and Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), 28034 Madrid, Spain"},{"name":"Red Espa\u00f1ola de Investigaci\u00f3n en Patolog\u00eda Infecciosa (REIPI), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2631-4492","authenticated-orcid":false,"given":"Javier","family":"S\u00e1nchez-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda, Hospital Universitario Ram\u00f3n y Cajal and Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), 28034 Madrid, Spain"},{"name":"Red Espa\u00f1ola de Investigaci\u00f3n en Patolog\u00eda Infecciosa (REIPI), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Mart\u00ednez-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda, Hospital Universitario Ram\u00f3n y Cajal and Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), 28034 Madrid, Spain"},{"name":"Red Espa\u00f1ola de Investigaci\u00f3n en Patolog\u00eda Infecciosa (REIPI), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0948-0958","authenticated-orcid":false,"given":"Federico","family":"Becerra-Aparicio","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda, Hospital Universitario Ram\u00f3n y Cajal and Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), 28034 Madrid, Spain"},{"name":"Red Espa\u00f1ola de Investigaci\u00f3n en Patolog\u00eda Infecciosa (REIPI), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Isabel","family":"Morosini","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda, Hospital Universitario Ram\u00f3n y Cajal and Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), 28034 Madrid, Spain"},{"name":"Red Espa\u00f1ola de Investigaci\u00f3n en Patolog\u00eda Infecciosa (REIPI), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Ruiz-Garbajosa","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda, Hospital Universitario Ram\u00f3n y Cajal and Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), 28034 Madrid, Spain"},{"name":"Red Espa\u00f1ola de Investigaci\u00f3n en Patolog\u00eda Infecciosa (REIPI), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1675-3173","authenticated-orcid":false,"given":"Rafael","family":"Cant\u00f3n","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda, Hospital Universitario Ram\u00f3n y Cajal and Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), 28034 Madrid, Spain"},{"name":"Red Espa\u00f1ola de Investigaci\u00f3n en Patolog\u00eda Infecciosa (REIPI), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1086\/653932","article-title":"Escherichia coli Sequence Type ST131 as the Major Cause of Serious Multidrug-Resistant, E. coli Infections in the United States","volume":"51","author":"Johnson","year":"2010","journal-title":"Clin. 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