{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T08:20:50Z","timestamp":1787732450073,"version":"build-2784847793"},"reference-count":26,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["MicrobiologyOpen"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The emergence of novel\n                    <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                    carbapenemase (KPC) variants contributing to clinical treatment failure poses a substantial threat to public health. To inform the clinical management of infections caused by KPC\u2010variant\u2010harboring\n                    <jats:italic>K. pneumoniae<\/jats:italic>\n                    , this study reports the complex evolutionary trajectory of ceftazidime\u2010avibactam (CAZ\u2010AVI)\u2010resistant KPC\u2010variant\u2010harboring\n                    <jats:italic>K. pneumoniae<\/jats:italic>\n                    in a single patient during CAZ\u2010AVI treatment. Three KPC\u2010producing\n                    <jats:italic>K. pneumoniae<\/jats:italic>\n                    (KPC\u2010KP) isolates were obtained from a patient with\n                    <jats:italic>K. pneumoniae<\/jats:italic>\n                    infection who received sequential treatment with imipenem followed by CAZ\u2010AVI. Isolate K2, harboring\n                    <jats:italic>bla<\/jats:italic>\n                    <jats:sub>KPC\u20102<\/jats:sub>\n                    , exhibited carbapenem resistance. After 12 days of CAZ\u2010AVI administration, isolate K25 (carrying\n                    <jats:italic>bla<\/jats:italic>\n                    <jats:sub>KPC\u201025<\/jats:sub>\n                    ) showed CAZ\u2010AVI resistance but remained susceptible to imipenem. In contrast, isolate K127 (harboring\n                    <jats:italic>bla<\/jats:italic>\n                    <jats:sub>KPC\u2010127<\/jats:sub>\n                    firstly identified by our group), recovered after combined CAZ\u2010AVI and imipenem therapy, displayed dual resistance to both CAZ\u2010AVI and carbapenems; this carbapenem resistance was attributed to outer membrane protein mutations combined with\n                    <jats:italic>bla<\/jats:italic>\n                    <jats:sub>KPC\u2010127<\/jats:sub>\n                    overexpression. Analysis of the genetic regions revealed that all subtypes were located within a conserved genetic background: IS\n                    <jats:italic>26<\/jats:italic>\n                    \u2010IS\n                    <jats:italic>Kpn8<\/jats:italic>\n                    \u2010\n                    <jats:italic>bla<\/jats:italic>\n                    <jats:sub>KPC<\/jats:sub>\n                    \u2010\u0394IS\n                    <jats:italic>Kpn6<\/jats:italic>\n                    \u2010\u0394\n                    <jats:italic>tnpR<\/jats:italic>\n                    \u2010Tn\n                    <jats:italic>1721<\/jats:italic>\n                    . Cloning and heterologous expression of the KPC variants, followed by enzymatic kinetic analyses and minimum inhibitory concentration (MIC) determinations, confirmed that the variants altered the MICs of CAZ\u2010AVI and carbapenems. Compared with the KPC\u20102 protein, both variant proteins exhibited reduced hydrolytic activity against ceftazidime. Additionally, the half\u2010maximal inhibitory concentration (IC\n                    <jats:sub>50<\/jats:sub>\n                    ) of avibactam against the KPC variants was significantly higher than that of the wild\u2010type KPC\u20102 protein. These results indicate that the KPC variant proteins have low affinity for avibactam, thereby reducing susceptibility to this inhibitor.\n                  <\/jats:p>","DOI":"10.1002\/mbo3.70363","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T20:40:04Z","timestamp":1782938404000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Emergence of Ceftazidime\u2010Avibactam\u2010Induced KPC Variants (KPC\u201025\/127) in Intracranial Infection and Implications for Clinical Management"],"prefix":"10.1002","volume":"15","author":[{"given":"Ke","family":"Lei","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoliang","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangni","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory XD Group Hospital Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohd H.","family":"Abdul\u2010Aziz","sequence":"additional","affiliation":[{"name":"University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine The University of Queensland Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7115-829X","authenticated-orcid":false,"given":"Jiao","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeshi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01108-23"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02412-14"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(16)30004-4"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2014.09.003"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/cmr.00008-23"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics11050604"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1099\/mgen.0.000748"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.00276-21"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00447-22"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01836-19"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00213-21"},{"issue":"12","key":"e_1_2_11_13_1","first-page":"1116","article-title":"[Multilocus Sequence Typing (MLST) Analysis]","volume":"61","author":"Matsumura Y.","year":"2013","journal-title":"Rinsho Byori. 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