{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:00:40Z","timestamp":1791327640402,"version":"4.3.1"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"publisher","award":["2022YFC2303201"],"award-info":[{"award-number":["2022YFC2303201"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Clinical Key Program of Peking University Third Hospital","award":["BYSYZD2022007"],"award-info":[{"award-number":["BYSYZD2022007"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82200012"],"award-info":[{"award-number":["82200012"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Peking University Clinical Scientist Training Program","award":["BMU2024PYJH011"],"award-info":[{"award-number":["BMU2024PYJH011"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Hypervirulent ceftazidime\/avibactam (CAZ\/AVI)-resistant Klebsiella pneumoniae (Kp) has emerged; however, its dynamic within-host evolution and competitive features are uncharacterized. This study aimed to clarify the systematic microevolution characteristics of the rapid transformation of blaKPC variants during long-term infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Thirty-nine Kp strains were isolated from a single patient with severe recurrent osteomyelitis during a 2-year period. Whole-genome sequencing and in vitro evolution assay was performed. Microbiological characteristics were examined through antimicrobial susceptibility testing, plasmid stability, growth curve, in vitro competition and Galleria mellonella larvae lethality assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among all the clinical Kp isolates, 37 were carbapenem-resistant Kp (CRKP), including 25 CAZ-\/AVI-resistant Kp. All isolates belonged to the ST11-K47. During in vivo evolution, the blaKPC variant and its amplification emerged. Twenty-four isolates (24\/39, 61.5%) harboured a novel blaKPC variant, blaKPC-144. All five Kp isolates carried blaKPC-2 in 2021. Surprisingly, 24 blaKPC-144-harbouring isolates (70.6%, 24\/34) and 10 blaKPC-2-harboring isolates were identified in 2023, indicating rapid changing of blaKPC. Kp4 carried two copies of blaKPC-2, and Kp10-1 exhibited a 1.94-fold increase in the blaKPC-144 copy number. Similarly, in vitro, the blaKPC copy number increased upon exposure to low CAZ\/AVI concentrations. However, at higher concentrations (4\/1\u2005mg\/L), the blaKPC copy number increased significantly, and blaKPC mutations emerged simultaneously. The competition assay indicated that the blaKPC-144-harboring isolates exhibited a superior competitive capacity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The blaKPC amplification and mutation emerged simultaneously or sequentially during in vivo and in vitro evolution. Kp isolates harbouring blaKPC-144, conferring resistance to CAZ\/AVI, exhibited a competitive advantage, promoting the rapid replacement of blaKPC-2.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkaf337","type":"journal-article","created":{"date-parts":[[2025,9,7]],"date-time":"2025-09-07T11:29:55Z","timestamp":1757244595000},"page":"3034-3042","source":"Crossref","is-referenced-by-count":2,"title":["Rapid replacement of\n                    <i>bla<\/i>\n                    KPC variant in ST11 carbapenem-resistant and hypervirulent\n                    <i>Klebsiella pneumoniae<\/i>\n                    contributed to ceftazidime\/avibactam resistance during severe\n                    <i>in vivo<\/i>\n                    infection"],"prefix":"10.1093","volume":"80","author":[{"given":"Ping","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Peking University Third Hospital , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5886-4264","authenticated-orcid":false,"given":"Chao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Peking University Third Hospital , Beijing ,","place":["China"]},{"name":"Center of Infectious Disease, Peking University Third Hospital , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajia","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Peking University Third Hospital , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Peking University Third Hospital , Beijing ,","place":["China"]},{"name":"Institute of Medical Technology, Peking University Health Science 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