{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:39:48Z","timestamp":1792798788464,"version":"4.5.0"},"reference-count":26,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Ministry of Science and Technology, taiwan","award":["111-2314-B-A49-044"],"award-info":[{"award-number":["111-2314-B-A49-044"]}],"id":[{"id":"https:\/\/ror.org\/02kv4zf79","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100011912","name":"Taipei Veterans General Hospital","doi-asserted-by":"publisher","award":["V112C-102, V113C-073, V114C-047"],"award-info":[{"award-number":["V112C-102, V113C-073, V114C-047"]}],"id":[{"id":"10.13039\/501100011912","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020950","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["112-2314-B-A49-029, 114-2314-B-A49-079-MY3"],"award-info":[{"award-number":["112-2314-B-A49-029, 114-2314-B-A49-079-MY3"]}],"id":[{"id":"10.13039\/501100020950","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,6,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The emergence of ceftazidime-avibactam-resistant\n                      <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n                      carbapenemase (KPC)-producing\n                      <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n                      (CZA-R KPC-Kp), primarily due to KPC variants, poses a growing challenge to clinical practice. We aimed to investigate risk factors for\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      development of CZA resistance in KPC-Kp and explore resistance mechanisms. A matched case-control study was conducted at Taipei Veterans General Hospital, including patients with sequential KPC-Kp isolates, between June 2019 and May 2025. Forty-five patients with CZA-R KPC-Kp and a prior CZA-susceptible KPC-Kp (i.e., cases) were matched 1:1 to controls with both the first and the second KPC-Kp isolates being CZA-susceptible, based on the interval between the first and second isolates. Logistic regression was used to determine risk factors for the emergence of CZA resistance. The median interval between the first and second isolates was 20 days. KPC variants accounted for 73.3% (33\/45) of CZA-R KPC-Kp isolates, with 20 variant types identified. The most common KPC variant was KPC-33 (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 11), followed by KPC-35 (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 3). Most KPC variants-producing strains (81.8%, 27\/33) exhibited restored imipenem susceptibility (minimum inhibitory concentration [MIC] \u2264 4 \u00b5g\/mL). CZA use was an independent risk factor for the development of resistance (odds ratio [OR] = 9.47,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.001), whereas carbapenem use was a protective factor (OR = 0.27,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.015). In conclusion, CZA exposure was the only risk factor for CZA resistance development in KPC-Kp, whereas the use of carbapenem may reduce the risk, possibly due to restored imipenem susceptibility in most KPC variant-producing strains.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        The emergence of ceftazidime-avibactam (CZA)-resistant\n                        <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n                        carbapenemase (KPC)-producing\n                        <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                        poses a new threat to public health. Our study found that 73.3% of CZA-resistant strains carried KPC variants, and KPC-33 was the most frequent. Most KPC variants (82%) regained imipenem susceptibility. Exposure to CZA independently predicted resistance in KPC-Kp, whereas carbapenem use was protective. These findings highlight the importance of antibiotic stewardship and warrant further comparative study of meropenem-vaborbactam or imipenem-cilastatin-relebactam versus CZA for KPC-producing\n                        <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                        infections.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.00972-26","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T13:06:48Z","timestamp":1777900008000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Risk factors for\n                    <i>in vivo<\/i>\n                    emergence of ceftazidime-avibactam resistance in KPC-producing\n                    <i>Klebsiella pneumoniae<\/i>\n                    and the associated resistance mechanisms: a case-control study"],"prefix":"10.1128","volume":"14","author":[{"given":"Chien","family":"Chuang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03ymy8z76","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital","place":["Taipei, Taiwan"]},{"id":[{"id":"https:\/\/ror.org\/00se2k293","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Medicine, College of Medicine, National Yang Ming Chiao Tung University","place":["Taipei, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szu-Yu","family":"Liu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03ymy8z76","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital","place":["Taipei, Taiwan"]},{"id":[{"id":"https:\/\/ror.org\/00se2k293","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Medicine, College of Medicine, National Yang Ming Chiao Tung University","place":["Taipei, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Chien","family":"Ho","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03ymy8z76","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital","place":["Taipei, Taiwan"]},{"id":[{"id":"https:\/\/ror.org\/00se2k293","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Medicine, College of Medicine, National Yang Ming Chiao Tung University","place":["Taipei, Taiwan"]},{"id":[{"id":"https:\/\/ror.org\/05dhw1e18","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Kinmen Hospital, Ministry of Health and Welfare","place":["Kinmen, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-Hua","family":"Chou","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03ymy8z76","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital","place":["Taipei, Taiwan"]},{"id":[{"id":"https:\/\/ror.org\/00se2k293","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Emergency and Critical Care Medicine, National Yang Ming Chiao Tung University","place":["Taipei, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Ru","family":"Huang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03ymy8z76","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital","place":["Taipei, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan","family":"Chin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03ymy8z76","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital","place":["Taipei, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiang-Ling","family":"Ho","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03ymy8z76","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital","place":["Taipei, Taiwan"]},{"id":[{"id":"https:\/\/ror.org\/00se2k293","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biotechnology and Laboratory Science in Medicine, National Yang Ming Chiao Tung University","place":["Taipei, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Chen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01y64my43","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo","place":["Buffalo, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9940-7529","authenticated-orcid":true,"given":"Yi-Tsung","family":"Lin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03ymy8z76","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital","place":["Taipei, Taiwan"]},{"id":[{"id":"https:\/\/ror.org\/00se2k293","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Emergency and Critical Care Medicine, National Yang Ming Chiao Tung University","place":["Taipei, Taiwan"]},{"id":[{"id":"https:\/\/ror.org\/03ymy8z76","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Infection Control, Taipei Veterans General Hospital","place":["Taipei, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_6_2_2","first-page":"10","volume-title":"WHO bacterial priority pathogens list, 2024: bacterial pathogens of public health importance, to guide research, development, and strategies to prevent and control antimicrobial resistance","author":"World Health Organization","year":"2024","unstructured":"World Health Organization2024. WHO bacterial priority pathogens list, 2024: bacterial pathogens of public health importance, to guide research, development, and strategies to prevent and control antimicrobial resistance, p 10\u201315. https:\/\/iris.who.int\/bitstream\/handle\/10665\/376776\/9789240093461-eng.pdf?sequence=1&isAllowed=y."},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40121-020-00395-2"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.02888"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciae403"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2021.11.025"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmii.2022.02.001"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgar.2021.04.001"},{"key":"e_1_3_6_9_2","unstructured":"National Centre for Biotechnology Information (NCBI). Reference sequence database. Available from: https:\/\/www.ncbi.nlm.nih.gov\/pathogens\/refgene\/#KPC. Accessed 10 April 2025"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/cmr.00008-23"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofad327"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-023-04712-8"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12941-025-00797-5"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00574-21"},{"key":"e_1_3_6_15_2","volume-title":"M100-S34Performance standards for antimicrobial susceptibility testing: 34th informational supplement","author":"Clinical and Laboratory Standards Institute","year":"2024","unstructured":"Clinical and Laboratory Standards Institute. 2024. M100-S34. Performance standards for antimicrobial susceptibility testing: 34th informational supplement. CLSI, Wayne, PA."},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2024.107244"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00731-18"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2022.106624"},{"key":"e_1_3_6_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.33.9.2233-2239.1995"},{"key":"e_1_3_6_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciac791"},{"key":"e_1_3_6_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02497-17"},{"key":"e_1_3_6_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02313-19"},{"key":"e_1_3_6_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02048-18"},{"key":"e_1_3_6_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2022.01.025"},{"key":"e_1_3_6_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkae450"},{"key":"e_1_3_6_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01551-18"},{"key":"e_1_3_6_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofab141"}],"container-title":["Microbiology Spectrum"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.00972-26","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.00972-26","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T13:11:06Z","timestamp":1781701866000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/spectrum.00972-26"}},"subtitle":[],"editor":[{"given":"Joanna B.","family":"Goldberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,6,2]]},"references-count":26,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6,2]]}},"alternative-id":["10.1128\/spectrum.00972-26"],"URL":"https:\/\/doi.org\/10.1128\/spectrum.00972-26","relation":{},"ISSN":["2165-0497"],"issn-type":[{"value":"2165-0497","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,2]]},"assertion":[{"value":"2026-03-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00972-26"}}