{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T03:20:03Z","timestamp":1771125603004,"version":"3.50.1"},"reference-count":26,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2017,10,1]],"date-time":"2017-10-01T00:00:00Z","timestamp":1506816000000},"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":[[2017,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The recent escalation of occurrences of carbapenem-resistant\n            <jats:named-content content-type=\"genus-species\">Pseudomonas aeruginosa<\/jats:named-content>\n            has been recognized globally and threatens to erode the widespread clinical utility of the carbapenem class of compounds for this prevalent health care-associated pathogen. Here, we compared the\n            <jats:italic>in vitro<\/jats:italic>\n            inhibitory activity of ceftazidime-avibactam and ceftolozane-tazobactam against 290 meropenem-nonsusceptible\n            <jats:named-content content-type=\"genus-species\">Pseudomonas aeruginosa<\/jats:named-content>\n            nonduplicate clinical isolates from 34 U.S. hospitals using reference broth microdilution methods. Ceftazidime-avibactam and ceftolozane-tazobactam were active, with ceftolozane-tazobactam having significantly higher inhibitory activity than ceftazidime-avibactam. The heightened inhibitory activity of ceftolozane-tazobactam was sustained when the site of origin (respiratory, blood, or wound) and nonsusceptibility to other \u03b2-lactam antimicrobials was considered. An extensive genotypic search for enzymatically driven \u03b2-lactam resistance mechanisms revealed the exclusive presence of the VIM metallo-\u03b2-lactamase among only 4% of the subset of isolates nonsusceptible to ceftazidime-avibactam, ceftolozane-tazobactam, or both. These findings suggest an important role for both ceftazidime-avibactam and ceftolozane-tazobactam against carbapenem-nonsusceptible\n            <jats:named-content content-type=\"genus-species\">Pseudomonas aeruginosa<\/jats:named-content>\n            . Further\n            <jats:italic>in vitro<\/jats:italic>\n            and\n            <jats:italic>in vivo<\/jats:italic>\n            studies are needed to better define the clinical utility of these novel therapies against the increasingly prevalent threat of multidrug-resistant\n            <jats:named-content content-type=\"genus-species\">Pseudomonas aeruginosa<\/jats:named-content>\n            .\n          <\/jats:p>","DOI":"10.1128\/aac.00875-17","type":"journal-article","created":{"date-parts":[[2017,7,25]],"date-time":"2017-07-25T00:20:23Z","timestamp":1500942023000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":75,"title":["Multicenter Evaluation of Ceftazidime-Avibactam and Ceftolozane-Tazobactam Inhibitory Activity against Meropenem-Nonsusceptible Pseudomonas aeruginosa from Blood, Respiratory Tract, and Wounds"],"prefix":"10.1128","volume":"61","author":[{"given":"Mordechai","family":"Grupper","sequence":"first","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Sutherland","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David P.","family":"Nicolau","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","unstructured":"Centers for Disease Control and Prevention. 2016. Antibiotic\/antimicrobial resistance. http:\/\/www.cdc.gov\/drugresistance\/biggest_threats.html. Accessed 15 September 2016."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/MCP.0b013e32835f27be"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/jhm.2080"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw243"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2015.05.003"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02969-15"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.3343\/alm.2017.37.2.174"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12941-016-0155-z"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02252-16"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01802-13"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00267-10"},{"key":"e_1_3_2_13_2","unstructured":"US Food and Drug Administration Anti-Infective Drugs Advisory Committee. 2014. Cerexa Ia subsidiary of Actavis plc ceftazidime-avibactam for injection. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2015\/206494Orig1s000CllinPharmR.pdf. Accessed 27 July 2017."},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.566"},{"key":"e_1_3_2_15_2","unstructured":"Cubist Pharmaceuticals LLC. 2000. A prospective randomized double-blind multicenter phase 3 study to assess the safety and efficacy of intravenous ceftolozane\/tazobactam compared with meropenem in adult patients with ventilated nosocomial pneumonia. ClinicalTrials.gov NLM identifier NCT02070757. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02070757."},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2015.07.004"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1089\/mdr.2011.0174"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2007.01681.x"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04238-14"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkv131"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02462-13"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03681-14"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03057-14"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00912-09"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2007.05.019"},{"key":"e_1_3_2_26_2","volume-title":"CLSI document M100-S24 U","author":"Clinical and Laboratory Standards Institute","year":"2016","unstructured":"Clinical and Laboratory Standards Institute. 2016. Performance standards for antimicrobial susceptibility testing; twenty-fourth informational supplement. CLSI document M100-S24 U. Clinical and Laboratory Standards Institute, Wayne, PA."},{"key":"e_1_3_2_27_2","unstructured":"Allergan USA Inc. 2015. Avycaz\u00ae (ceftazidime-avibactam) package insert. http:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2015\/206494s000lbl.pdf. Accessed 23 February 2017."}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00875-17","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00875-17","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:46:59Z","timestamp":1645476419000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.00875-17"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10]]},"references-count":26,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2017,10]]}},"alternative-id":["10.1128\/AAC.00875-17"],"URL":"https:\/\/doi.org\/10.1128\/aac.00875-17","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,10]]},"assertion":[{"value":"2017-04-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-07-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-09-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00875-17"}}