{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T13:22:36Z","timestamp":1780320156420,"version":"3.54.1"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T00:00:00Z","timestamp":1713916800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,10,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Klebsiella pneumoniae is capable of resistance to \u03b2-lactam antibiotics through expression of \u03b2-lactamases (both chromosomal and plasmid-encoded) and downregulation of outer membrane porins. However, the extent to which these mechanisms interplay in a resistant phenotype is not well understood. The purpose of this study was to determine the extent to which \u03b2-lactamases and outer membrane porins affected \u03b2-lactam resistance.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Minimum inhibitory concentrations (MICs) to \u03b2-lactams and inhibitor combinations were determined by agar dilution or Etest. Outer membrane porin production was evaluated by Western blot of outer membrane fractions. \u03b2-lactamase carriage was determined by whole genome sequencing and expression evaluated by real-time reverse-transcription polymerase chain reaction.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Plasmid-encoded \u03b2\u00ad-lactamases were important for cefotaxime and ceftazidime resistance. Elevated expression of chromosomal SHV was important for ceftolozane-tazobactam resistance. Loss of outer membrane porins was predictive of meropenem resistance. Extended-spectrum \u03b2-lactamases and plasmid-encoded AmpCs (pAmpCs) in addition to porin loss were sufficient to confer resistance to the third-generation cephalosporins, piperacillin-tazobactam, ceftolozane-tazobactam, and meropenem. pAmpCs (CMY-2 and DHA) alone conferred resistance to piperacillin-tazobactam.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Detection of a resistance gene by whole genome sequencing was not sufficient to predict resistance to all antibiotics tested. Some \u03b2-lactam resistance was dependent on the expression of both plasmid-encoded and chromosomal \u03b2-lactamases and loss of porins.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiae204","type":"journal-article","created":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T03:14:06Z","timestamp":1713928446000},"page":"e777-e788","source":"Crossref","is-referenced-by-count":7,"title":["What Contributes to the Minimum Inhibitory Concentration? Beyond \u03b2-Lactamase Gene Detection in <i>Klebsiella pneumoniae<\/i>"],"prefix":"10.1093","volume":"230","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7076-5875","authenticated-orcid":false,"given":"Alyssa K W","family":"Maclean","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Immunology, CRISS 2"},{"name":"Center for Antimicrobial Resistance and Epidemiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey","family":"Morrow","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, CRISS 2"},{"name":"Center for Antimicrobial Resistance and Epidemiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Clinical Research and Evaluative Sciences, Creighton University School of Medicine , Omaha, Nebraska"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy D","family":"Hanson","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, CRISS 2"},{"name":"Center for Antimicrobial Resistance and Epidemiology"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,4,24]]},"reference":[{"key":"2024101612593824600_jiae204-B1","volume-title":"Antimicrobial resistance threats in the United States","author":"Centers for Disease Control and Prevention","year":"2019"},{"key":"2024101612593824600_jiae204-B2","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1093\/femsre\/fux013","article-title":"Klebsiella pneumoniae: a major worldwide source and shuttle for antibiotic resistance","volume":"41","author":"Navon-Venezia","year":"2017","journal-title":"FEMS Microbiol Rev"},{"key":"2024101612593824600_jiae204-B3","doi-asserted-by":"crossref","first-page":"e169","DOI":"10.1093\/cid\/ciaa1478","article-title":"Infectious Diseases Society of America 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