{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T16:04:21Z","timestamp":1783699461909,"version":"3.55.0"},"reference-count":15,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2018,9,26]],"date-time":"2018-09-26T00:00:00Z","timestamp":1537920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,10,31]],"date-time":"2018-10-31T00:00:00Z","timestamp":1540944000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100007819","name":"Allergan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007819","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSphere"],"published-print":{"date-parts":[[2018,10,31]]},"abstract":"<jats:p>\n            The development of ceftazidime-avibactam resistance among KPC-producing isolates during treatment with this agent has been reported. Usually isolates that become resistant have a mutated\n            <jats:italic>bla<\/jats:italic>\n            <jats:sub>KPC<\/jats:sub>\n            gene that confers resistance to ceftazidime-avibactam and susceptibility to meropenem. We report a\n            <jats:named-content content-type=\"genus-species\">Citrobacter freundii<\/jats:named-content>\n            isolate that developed ceftazidime-avibactam resistance due to mutations within the coding region of the\n            <jats:italic>bla<\/jats:italic>\n            <jats:sub>KPC-2<\/jats:sub>\n            \u03a9-loop previously reported; however, in this case, only 11% of the whole-genome sequencing reads had mutations, making this alteration difficult to detect and the treatment of these isolates more challenging. In addition to\n            <jats:italic>bla<\/jats:italic>\n            <jats:sub>KPC<\/jats:sub>\n            , the initial and the follow-up patient isolates displayed hyperexpression of the AcrAB-TolC efflux system and disruption of the outer membrane protein (OMP) OmpF, which contribute to carbapenem resistance. Experiments performed to confirm our findings included generating mutant isolates from the initial patient isolate, passaging the isolates for purity in drug-free medium, resulting in a reversible phenotype, and cloning the mutations to demonstrate the resistance conferred.\n          <\/jats:p>","DOI":"10.1128\/msphere.00408-18","type":"journal-article","created":{"date-parts":[[2018,9,25]],"date-time":"2018-09-25T11:09:41Z","timestamp":1537873781000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":30,"title":["Analyses of a Ceftazidime-Avibactam-Resistant\n            <i>Citrobacter freundii<\/i>\n            Isolate Carrying\n            <i>bla<\/i>\n            <sub>KPC-2<\/sub>\n            Reveals a Heterogenous Population and Reversible Genotype"],"prefix":"10.1128","volume":"3","author":[{"given":"Mariana","family":"Castanheira","sequence":"first","affiliation":[{"name":"JMI Laboratories, North Liberty, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. J. Ryan","family":"Arends","sequence":"additional","affiliation":[{"name":"JMI Laboratories, North Liberty, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew P.","family":"Davis","sequence":"additional","affiliation":[{"name":"JMI Laboratories, North Liberty, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah N.","family":"Woosley","sequence":"additional","affiliation":[{"name":"JMI Laboratories, North Liberty, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amira A.","family":"Bhalodi","sequence":"additional","affiliation":[{"name":"Allergan plc, Irvine, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8019-2270","authenticated-orcid":false,"given":"Shawn H.","family":"MacVane","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Services, Medical University of South Carolina, Charleston, South Carolina, USA"},{"name":"Division of Infectious Diseases, College of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00883-17"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cix783"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw398"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01165-15"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00989-17"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02097-16"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00528-17"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00451-17"},{"key":"e_1_3_2_10_2","volume-title":"AVYCAZ (ceftazidime-avibactam)","author":"Allergan USA, Inc","year":"2017","unstructured":"Allergan USA, Inc. 2017. AVYCAZ (ceftazidime-avibactam). Allergan USA, Inc, Irvine, CA. https:\/\/www.allergan.com\/assets\/pdf\/avycaz_pi. Accessed February 2017."},{"key":"e_1_3_2_11_2","volume-title":"M100-S27. Performance standards for antimicrobial susceptibility testing: 27th informational supplement","author":"CLSI","year":"2017","unstructured":"CLSI. 2017. M100-S27. Performance standards for antimicrobial susceptibility testing: 27th informational supplement. Clinical and Laboratory Standards Institute, Wayne, PA."},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0136813"},{"key":"e_1_3_2_13_2","volume-title":"M07-A10. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard","author":"CLSI","year":"2015","unstructured":"CLSI. 2015. M07-A10. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard, 10th ed. Clinical and Laboratory Standards Institute, Wayne, PA.","edition":"10"},{"key":"e_1_3_2_14_2","volume-title":"M02-A12. Performance standards for antimicrobial disk susceptibility tests","author":"CLSI","year":"2015","unstructured":"CLSI. 2015. M02-A12. Performance standards for antimicrobial disk susceptibility tests, 12th ed. Clinical and Laboratory Standards Institute, Wayne, PA.","edition":"12"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkr081"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dku048"}],"container-title":["mSphere"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mSphere.00408-18","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mSphere.00408-18","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T04:16:32Z","timestamp":1646712992000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mSphere.00408-18"}},"subtitle":[],"editor":[{"given":"Patricia A.","family":"Bradford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2018,10,31]]},"references-count":15,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2018,10,31]]}},"alternative-id":["10.1128\/mSphere.00408-18"],"URL":"https:\/\/doi.org\/10.1128\/msphere.00408-18","relation":{},"ISSN":["2379-5042"],"issn-type":[{"value":"2379-5042","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,31]]},"assertion":[{"value":"2018-07-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00408-18"}}