{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T06:11:12Z","timestamp":1780553472013,"version":"3.54.1"},"reference-count":15,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2018,7,1]],"date-time":"2018-07-01T00:00:00Z","timestamp":1530403200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Spero Therapeutics, Inc."},{"DOI":"10.13039\/100006127","name":"DOE | NNSA | Office of Defense Programs","doi-asserted-by":"publisher","award":["W81XWH-16-2-0019"],"award-info":[{"award-number":["W81XWH-16-2-0019"]}],"id":[{"id":"10.13039\/100006127","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            SPR741 is a novel agent with structural similarity to polymyxins that is capable of potentiating the activities of various classes of antibiotics. Previously published studies indicated that although\n            <jats:named-content content-type=\"genus-species\">Enterobacteriaceae<\/jats:named-content>\n            isolates had minimal susceptibilities to azithromycin (AZM), the\n            <jats:italic>in vitro<\/jats:italic>\n            antimicrobial activity of AZM against\n            <jats:named-content content-type=\"genus-species\">Enterobacteriaceae<\/jats:named-content>\n            was enhanced when it was combined with SPR741. The current study evaluated the\n            <jats:italic>in vivo<\/jats:italic>\n            activity of human-simulated regimens (HSR) of AZM equivalent to clinical doses of 500 mg given intravenously (i.v.) every 24 h (q24h) and SPR741 equivalent to clinical doses of 400 mg q8h i.v. (1-h infusion), alone and in combination, against multidrug-resistant (MDR)\n            <jats:named-content content-type=\"genus-species\">Enterobacteriaceae<\/jats:named-content>\n            . We studied 30 MDR\n            <jats:named-content content-type=\"genus-species\">Enterobacteriaceae<\/jats:named-content>\n            isolates expressing a wide spectrum of \u03b2-lactamases (ESBL, NDM, VIM, and KPC), including a subset of isolates positive for genes conferring macrolide resistance (\n            <jats:italic>mphA<\/jats:italic>\n            ,\n            <jats:italic>mphE<\/jats:italic>\n            ,\n            <jats:italic>ermB<\/jats:italic>\n            , and\n            <jats:italic>msr<\/jats:italic>\n            ).\n            <jats:italic>In vivo<\/jats:italic>\n            activity was assessed as the change in log\n            <jats:sub>10<\/jats:sub>\n            CFU per thigh at 24 h compared with 0 h. Treatment with AZM alone was associated with net growth of 2.60 \u00b1 0.83 log\n            <jats:sub>10<\/jats:sub>\n            CFU\/thigh. Among isolates with AZM MICs of \u226416 mg\/liter, treatment with AZM-SPR741was associated with an average reduction in bacterial burden of \u22120.53 \u00b1 0.82 log\n            <jats:sub>10<\/jats:sub>\n            CFU\/thigh, and stasis to 1-log kill was observed in 9\/11 isolates (81.8%). Combination therapy with an AZM-SPR741 HSR showed promising\n            <jats:italic>in vivo<\/jats:italic>\n            activity against MDR\n            <jats:named-content content-type=\"genus-species\">Enterobacteriaceae<\/jats:named-content>\n            isolates with AZM MICs of \u226416 mg\/liter, including those producing a variety of \u03b2-lactamases. These data support a potential role for AZM-SPR741 in the treatment of infections due to MDR\n            <jats:named-content content-type=\"genus-species\">Enterobacteriaceae<\/jats:named-content>\n            .\n          <\/jats:p>","DOI":"10.1128\/aac.00239-18","type":"journal-article","created":{"date-parts":[[2018,6,13]],"date-time":"2018-06-13T09:49:30Z","timestamp":1528883370000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":24,"title":["Assessment of the\n            <i>In Vivo<\/i>\n            Activity of SPR741 in Combination with Azithromycin against Multidrug-Resistant Enterobacteriaceae Isolates in the Neutropenic Murine Thigh Infection Model"],"prefix":"10.1128","volume":"62","author":[{"given":"Sean M.","family":"Stainton","sequence":"first","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamilia","family":"Abdelraouf","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke","family":"Utley","sequence":"additional","affiliation":[{"name":"Spero Therapeutic, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Pucci","sequence":"additional","affiliation":[{"name":"Spero Therapeutic, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Troy","family":"Lister","sequence":"additional","affiliation":[{"name":"Spero Therapeutic, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P.","family":"Nicolau","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA"},{"name":"Division of Infectious Diseases, Hartford Hospital, Hartford, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2011.03570.x"},{"key":"e_1_3_2_3_2","volume-title":"Antibiotic resistance threats in the United States, 2013","author":"Centers for Disease Control and Prevention","year":"2013","unstructured":"Centers for Disease Control and Prevention. 2013. Antibiotic resistance threats in the United States, 2013. Centers for Disease Control and Prevention, Atlanta, GA. https:\/\/www.cdc.gov\/drugresistance\/threat-report-2013\/."},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra041359"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10156-012-0451-2"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2014.02.016"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2008.11.005"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00200-17"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01439-09"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01239-17"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00491-17"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01208-16"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00486-17"},{"key":"e_1_3_2_14_2","volume-title":"CLSI document M100-S17","author":"Clinical and Laboratory Standards Institute","year":"2017","unstructured":"Clinical and Laboratory Standards Institute. 2017. Performance standards for antimicrobial susceptibility testing; seventeenth informational supplement. CLSI document M100-S17. CLSI, Wayne, PA."},{"key":"e_1_3_2_15_2","volume-title":"Azithromycin intravenous package insert","author":"Sagent Pharmaceuticals","year":"2013","unstructured":"Sagent Pharmaceuticals. March 2013. Azithromycin intravenous package insert. Sagent Pharmaceuticals, Schaumburg, IL."},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.1.276-280.2005"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00239-18","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00239-18","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T21:17:32Z","timestamp":1645478252000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.00239-18"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7]]},"references-count":15,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2018,7]]}},"alternative-id":["10.1128\/AAC.00239-18"],"URL":"https:\/\/doi.org\/10.1128\/aac.00239-18","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7]]},"assertion":[{"value":"2018-02-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-06-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00239-18"}}