{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:02:18Z","timestamp":1792098138959,"version":"4.4.0"},"reference-count":17,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"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":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2015,9]]},"abstract":"ABSTRACT<\/jats:title>\n \n Avibactam is a novel \u03b2-lactamase inhibitor with affinity for\n Klebsiella pneumoniae<\/jats:named-content>\n carbapenemases (KPCs). In combination with ceftazidime, the agent demonstrates activity against KPC-producing\n K. pneumoniae<\/jats:named-content>\n (KPC-Kp). KPC-Kp strains are genetically diverse and harbor multiple resistance determinants, including defects in outer membrane proteins and extended-spectrum \u03b2-lactamases (ESBLs). Mutations in porin gene\n ompK36<\/jats:italic>\n confer high-level carbapenem resistance to KPC-Kp strains. Whether specific mechanisms of antimicrobial resistance also influence the activity of ceftazidime-avibactam is unknown. We defined the effects of ceftazidime-avibactam against 72 KPC-Kp strains with diverse mechanisms of resistance, including various combinations of KPC subtypes and ESBL and\n ompK36<\/jats:italic>\n mutations. Ceftazidime MICs ranged from 64 to 4,096 \u03bcg\/ml and were lowered by a median of 512-fold with the addition of avibactam. All strains exhibited ceftazidime-avibactam MICs at or below the CLSI breakpoint for ceftazidime (\u22644 \u03bcg\/ml; range, 0.25 to 4). However, the MICs were within two 2-fold dilutions of the CLSI breakpoint against 24% of the strains, and those strains would be classified as nonsusceptible to ceftazidime by EUCAST criteria (MIC > 1 \u03bcg\/ml). Median ceftazidime-avibactam MICs were higher against KPC-3 than KPC-2 variants (\n P<\/jats:italic>\n = 0.02). Among KPC-2-Kp strains, the presence of both ESBL and porin mutations was associated with higher drug MICs compared to those seen with either factor alone (\n P<\/jats:italic>\n = 0.003 and\n P<\/jats:italic>\n = 0.02, respectively). In conclusion, ceftazidime-avibactam displays activity against genetically diverse KPC-Kp strains. Strains with higher-level drug MICs provide a reason for caution. Judicious use of ceftazidime-avibactam alone or in combination with other agents will be important to prevent the emergence of resistance.\n <\/jats:p>","DOI":"10.1128\/aac.00548-15","type":"journal-article","created":{"date-parts":[[2015,7,13]],"date-time":"2015-07-13T22:24:44Z","timestamp":1436826284000},"page":"5793-5797","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":113,"title":["Effects of Klebsiella pneumoniae Carbapenemase Subtypes, Extended-Spectrum \u03b2-Lactamases, and Porin Mutations on the\n In Vitro<\/i>\n Activity of Ceftazidime-Avibactam against Carbapenem-Resistant K. pneumoniae"],"prefix":"10.1128","volume":"59","author":[{"given":"Ryan K.","family":"Shields","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"},{"name":"Antibiotic Management Program, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA"},{"name":"XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelius J.","family":"Clancy","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"},{"name":"XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA"},{"name":"VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binghua","family":"Hao","sequence":"additional","affiliation":[{"name":"XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Chen","sequence":"additional","affiliation":[{"name":"Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen G.","family":"Press","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole M.","family":"Iovine","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Florida, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry N.","family":"Kreiswirth","sequence":"additional","affiliation":[{"name":"Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Hong","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"},{"name":"Antibiotic Management Program, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA"},{"name":"XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dku025"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.12424"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03894-14"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00099-14"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01069-13"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01949-13"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01588-10"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00316-12"},{"key":"e_1_3_2_10_2","volume-title":"Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard","author":"Clinical and Laboratory Standards Institute","year":"2009","unstructured":"Clinical and Laboratory Standards Institute. 2009. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard\u20148th ed: approved standard M07-A8. CLSI, Wayne, PA."},{"key":"e_1_3_2_11_2","volume-title":"Performance standards for antimicrobial susceptibility testing (M100-S24)","author":"Clinical and Laboratory Standard Institute","year":"2014","unstructured":"Clinical and Laboratory Standard Institute. 2014. Performance standards for antimicrobial susceptibility testing (M100-S24). Clinical and Laboratory Standards Institute, Wayne, PA."},{"key":"e_1_3_2_12_2","author":"The European Committee on Antimicrobial Susceptibility Testing","year":"2015","unstructured":"The European Committee on Antimicrobial Susceptibility Testing. 2015. Breakpoint tables for interpretation of MICs and zone diameters. Version 5.0. http:\/\/www.eucast.org\/.","journal-title":"Breakpoint tables for interpretation of MICs and zone diameters"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02429-13"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.11.4760-4762.2005"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04218-14"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01275-10"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00080-14"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03579-14"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00548-15","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00548-15","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T17:56:39Z","timestamp":1645466199000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.00548-15"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,9]]},"references-count":17,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2015,9]]}},"alternative-id":["10.1128\/AAC.00548-15"],"URL":"https:\/\/doi.org\/10.1128\/aac.00548-15","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,9]]},"assertion":[{"value":"2015-03-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-07-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-08-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}