{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:52:38Z","timestamp":1791391958217,"version":"4.3.3"},"reference-count":28,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32370195, 82102411, 82260403"],"award-info":[{"award-number":["32370195, 82102411, 82260403"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Youth Project of Jiangxi Provincial Health Commission","award":["202510273"],"award-info":[{"award-number":["202510273"]}],"id":[{"id":"https:\/\/ror.org\/03vc7fb96","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004479","name":"Natural Science Foundation of Jiangxi Province","doi-asserted-by":"publisher","award":["20242BAB20428"],"award-info":[{"award-number":["20242BAB20428"]}],"id":[{"id":"10.13039\/501100004479","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2026,10,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Ceftazidime\u2013avibactam (CZA) is an important therapeutic option for infections caused by\n                      <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n                      carbapenemase (KPC)-producing\n                      <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n                      . However, CZA exposure also selects for emergent KPC variants. Their\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      evolutionary patterns, fitness consequences, and underlying molecular mechanisms remain unclear. We performed a longitudinal multiomics analysis of 35 clonally related ST11 KPC-producing\n                      <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                      isolates collected from eight hospitalized patients during clinical follow-up, most of whom had received CZA therapy. Whole-genome sequencing, antimicrobial susceptibility testing,\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      competition assays, enzyme kinetic analysis, and transcriptomic sequencing were used to systematically characterize the within-host evolutionary dynamics of KPC variants and the fitness heterogeneity of KPC-33. Multiple KPC variants were identified during longitudinal follow-up, among which KPC-33 was the most frequently detected. Among the seven patients who received CZA treatment, KPC-33 was detected in longitudinal isolates from four patients. It was also identified in patient P3, who had not received CZA, whereas other variants were only sporadically identified. Biochemical analysis showed that KPC-33 exhibited an altered kinetic profile relative to KPC-2, characterized by reduced catalytic turnover and altered substrate affinity. KPC-33 did not exhibit a uniform and pronounced fitness defect but instead showed marked strain-dependent heterogeneity. Strains with higher competitive fitness generally showed only limited transcriptional changes, whereas those with lower fitness were accompanied by broader transcriptional remodeling. In this longitudinal cohort, KPC-33 was repeatedly detected, predominantly under CZA-associated selective conditions. Its fitness consequences were clearly strain background dependent and may be associated with the extent of transcriptional remodeling. These findings provide new evidence for understanding the\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      evolution of CZA resistance.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00767-26","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T14:07:35Z","timestamp":1789049255000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Repeated emergence and fitness heterogeneity of KPC-33 in ST11\n                    <i>Klebsiella pneumoniae<\/i>\n                    under ceftazidime\u2013avibactam pressure"],"prefix":"10.1128","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-4333-2051","authenticated-orcid":true,"given":"Fangling","family":"Du","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/042v6xz23","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Laboratory, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University","place":["Nanchang, People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7156-7551","authenticated-orcid":true,"given":"Xinyue","family":"Dai","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/042v6xz23","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Laboratory, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University","place":["Nanchang, People's Republic of 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