{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T07:04:33Z","timestamp":1767164673332,"version":"build-2238731810"},"reference-count":26,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:00:00Z","timestamp":1722902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:00:00Z","timestamp":1722902400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2024,8,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      To monitor the resistance rate and gain a deeper understanding of the resistance mechanisms, we conducted over a 2-year surveillance focusing on the\n                      <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                      associated with the clinical usage of ceftazidime-avibactam (CZA) in a teaching hospital. A total of 4,641\n                      <jats:italic>K<\/jats:italic>\n                      .\n                      <jats:italic>pneumoniae<\/jats:italic>\n                      isolates were screened to identify the CZA resistance through antimicrobial susceptibility testing. Comprehensive analyses, including homology analysis, conjugation experiments, clone assays, and whole genome sequencing, were furtherly performed on the CZA-resistant strains. In total, four CZA-resistant\n                      <jats:italic>K. pneumoniae<\/jats:italic>\n                      (CZA-R-Kp) strains were separated from four patients, in which three of them received CZA treatment during the hospitalization, accounting for a 4% (3\/75) resistance development rate of\n                      <jats:italic>K. pneumoniae<\/jats:italic>\n                      under CZA stress. All CZA-R-Kp isolates were found to possess variants of\n                      <jats:italic>bla<\/jats:italic>\n                      <jats:sub>KPC-2<\/jats:sub>\n                      . The identified mutations included\n                      <jats:italic>bla<\/jats:italic>\n                      <jats:sub>KPC-33<\/jats:sub>\n                      ,\n                      <jats:italic>bla<\/jats:italic>\n                      <jats:sub>KPC-86<\/jats:sub>\n                      , and a novel variant designated as\n                      <jats:italic>bla<\/jats:italic>\n                      <jats:sub>KPC-129<\/jats:sub>\n                      , all of which were located in the \u03a9 loop of the KPC enzyme. These mutations were found to impact the amino acid sequence and spatial structure of the enzyme\u2019s active center, consequently affecting KPC carbapenemase activity. This study underscores the importance of active surveillance to monitor the emergence of resistance to CZA, highlighting the need for ongoing research to develop effective strategies for combating antimicrobial resistance. Understanding the mechanisms behind resistance is crucial in maintaining the efficacy of CZA, a vital tool in the battle against multidrug-resistant infections.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        As an effective drug for the treatment of carbapenem-resistant\n                        <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                        , ceftazidime-avibactam (CZA) began to develop resistance in recent years and showed an increasing trend. In order to effectively monitor the resistance rate of CZA and understand its resistance mechanism, we monitored\n                        <jats:italic>K. pneumoniae<\/jats:italic>\n                        for more than 2 years to find CZA-resistant strains. Through comprehensive analysis of the selected CZA-resistant strains, it was found that all the CZA-resistant strains had mutation, which could affect the activity of KPC carbapenemase. This study highlights the importance of proactive surveillance to monitor the emergence of CZA resistance, which highlights the need for ongoing research to develop effective strategies to combat antimicrobial resistance. Understanding the mechanisms behind resistance is critical to maintaining the effectiveness of CZA, an important tool in the fight against multidrug-resistant infections.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.00258-24","type":"journal-article","created":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T09:02:27Z","timestamp":1719997347000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["A large-scale surveillance revealed that KPC variants mediated ceftazidime-avibactam resistance in clinically isolated\n                    <i>Klebsiella pneumoniae<\/i>"],"prefix":"10.1128","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7542-484X","authenticated-orcid":true,"given":"Sai","family":"Qiao","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China"},{"name":"Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Sir Run Run Shaw Hospital, Hangzhou, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaojun","family":"Xin","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China"},{"name":"Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Sir Run Run Shaw Hospital, Hangzhou, Zhejiang, China"},{"name":"Department of Clinical Laboratory, Huzhou Central Hospital, Affiliated Huzhou Hospital, School of Medicine, Zhejiang University, Huzhou, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yufeng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Sir Run Run Shaw 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