{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T13:46:31Z","timestamp":1791985591864,"version":"4.4.0"},"reference-count":37,"publisher":"American Society for Microbiology","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"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"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Automated antimicrobial susceptibility testing (AST) may generate carbapenem minimum inhibitory concentration (MIC) results differing from reference methods, complicating recognition of carbapenemase-producing\n                      <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n                      complex isolates. We characterized carbapenem susceptibility discordance in a retrospective discovery cohort of 133 carbapenemase-producing isolates collected in Shenzhen (2004\u20132017) by comparing imipenem (IPM) and meropenem (MEM) MICs obtained by VITEK 2 and broth microdilution (BMD). Confirmed discordance was defined as repeat-confirmed raw MIC differences of \u22652 log\n                      <jats:sub>2<\/jats:sub>\n                      dilutions. Features were assessed by whole-genome sequencing, mCIM\/eCIM, and exploratory phenotypic assays. Cross-card reproducibility was assessed using an alternative VITEK 2 AST card. A separate retrospectively enriched cohort of 166\n                      <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                      isolates (2018\u20132024) was used to evaluate a phenotype-guided reflex-testing workflow. Twenty-nine isolates showed confirmed carbapenem AST discordance, including 28 with IPM discordance. Of these, 27 had raw VITEK 2 IPM MICs at least 2 log\u2082 dilutions higher than those obtained by BMD, whereas one was reported as resistant after system adjustment despite a low raw MIC. All discrepant isolates carried\n                      <jats:italic toggle=\"yes\">bla<\/jats:italic>\n                      <jats:sub>IMP-4<\/jats:sub>\n                      as the sole detected carbapenemase gene, had relatively low carbapenem MICs by BMD, and were distributed across 14 sequence types. Cross-card retesting reproduced the direction of IPM elevation, although the magnitude varied. In a combined internal analysis set of 275 isolates, the phenotype-guided workflow identified unflagged \u22652 log\u2082 MIC discrepancies with 81.4% sensitivity (95% CI, 67.4%\u201390.3%) and 92.2% specificity (95% CI, 88.1%\u201395.0%). These findings define a repeat-confirmed\n                      <jats:italic toggle=\"yes\">bla<\/jats:italic>\n                      <jats:sub>IMP-4<\/jats:sub>\n                      -associated, IPM-predominant discordance between VITEK 2 and BMD and support phenotype-guided reflex-testing to identify unflagged MIC discrepancies and prioritize confirmatory testing in routine laboratories.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Clinical microbiology laboratories rely on automated systems to support antimicrobial susceptibility interpretation, but these systems may not always recognize method-dependent carbapenem susceptibility discordance. In this study, we show that a specific group of bacteria carrying the\n                        <jats:italic toggle=\"yes\">bla<\/jats:italic>\n                        <jats:sub>IMP-4<\/jats:sub>\n                        gene can produce potentially misleading carbapenem susceptibility results, particularly for imipenem, when tested by automated methods. These discrepancies may not be flagged by the instrument and could therefore be overlooked in routine practice. By combining routine laboratory data with genetic analysis and additional testing, we identify a recognizable pattern associated with these hidden discrepancies and examine a phenotype-guided confirmatory workflow to support their laboratory recognition. Our findings highlight the importance of targeted confirmatory testing and provide a framework for local validation of laboratory-actionable carbapenem susceptibility discrepancies, thereby supporting more reliable AST interpretation and antimicrobial resistance surveillance.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.01493-26","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T13:00:30Z","timestamp":1791982830000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["<i>bla<\/i>\n                    <sub>IMP-4<\/sub>\n                    -associated imipenem susceptibility discordance in the\n                    <i>Klebsiella pneumoniae<\/i>\n                    complex: characterization and a phenotype-guided confirmatory workflow"],"prefix":"10.1128","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9212-4048","authenticated-orcid":true,"given":"Haoyun","family":"Lin","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/049tv2d57","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Laboratory Medicine, Shenzhen Key Laboratory of Pathogenic Microbiology and Antimicrobial Resistance Surveillance, Shenzhen People\u2019s Hospital, The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University","place":["Shenzhen, China"]},{"name":"Guangdong Provincial Clinical Research Center for Laboratory Medicine","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danxuan","family":"Lin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/049tv2d57","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Laboratory Medicine, Shenzhen Key Laboratory of Pathogenic Microbiology and Antimicrobial Resistance Surveillance, Shenzhen People\u2019s Hospital, The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University","place":["Shenzhen, China"]},{"name":"Guangdong Provincial Clinical Research Center for Laboratory Medicine","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanchen","family":"Li","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/049tv2d57","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Laboratory Medicine, Shenzhen Key Laboratory of Pathogenic Microbiology and Antimicrobial Resistance Surveillance, Shenzhen People\u2019s Hospital, The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University","place":["Shenzhen, China"]},{"name":"Guangdong Provincial Clinical Research Center for Laboratory Medicine","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihan","family":"Zhao","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/049tv2d57","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Laboratory Medicine, Shenzhen Key Laboratory of Pathogenic Microbiology and Antimicrobial Resistance Surveillance, Shenzhen People\u2019s Hospital, The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University","place":["Shenzhen, China"]},{"name":"Guangdong Provincial Clinical Research Center for Laboratory Medicine","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingsong","family":"Wu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/049tv2d57","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Laboratory Medicine, Shenzhen Key Laboratory of Pathogenic Microbiology and Antimicrobial Resistance Surveillance, Shenzhen People\u2019s Hospital, The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University","place":["Shenzhen, China"]},{"name":"Guangdong Provincial Clinical Research Center for Laboratory Medicine","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Xu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01vy4gh70","id-type":"ROR","asserted-by":"publisher"}],"name":"Guangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology and Immunology, Shenzhen University Medical School, Shenzhen University","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayu","family":"Wu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01f8qvj05","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Life Science, Bengbu Medical College","place":["Bengbu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4896-9317","authenticated-orcid":false,"given":"Jine","family":"Cheng","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/049tv2d57","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Laboratory Medicine, Shenzhen Key Laboratory of Pathogenic Microbiology and Antimicrobial Resistance Surveillance, Shenzhen People\u2019s Hospital, The First Affiliated Hospital, Southern University of Science and Technology; 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