{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T15:32:15Z","timestamp":1784302335200,"version":"3.55.0"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2012,11,1]],"date-time":"2012-11-01T00:00:00Z","timestamp":1351728000000},"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":[[2012,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Daptomycin-nonsusceptible (DNS)\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Staphylococcus aureus<\/jats:named-content>\n            is found in difficult-to-treat infections, and the optimal therapy is unknown. We investigated the activity of high-dose (HD) daptomycin plus trimethoprim-sulfamethoxazole de-escalated to HD daptomycin or trimethoprim-sulfamethoxazole against 4 clinical DNS methicillin-resistant\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus<\/jats:named-content>\n            (MRSA) isolates in an\n            <jats:italic>in vitro<\/jats:italic>\n            pharmacokinetic\/pharmacodynamic model of simulated endocardial vegetations (10\n            <jats:sup>9<\/jats:sup>\n            CFU\/g). Simulated regimens included HD daptomycin at 10 mg\/kg\/day for 14 days, trimethoprim-sulfamethoxazole at 160\/800 mg every 12 h for 14 days, HD daptomycin plus trimethoprim-sulfamethoxazole for 14 days, and the combination for 7 days de-escalated to HD daptomycin for 7 days and de-escalated to trimethoprim-sulfamethoxazole for 7 days. Differences in CFU\/g (at 168 and 336 h) were evaluated by analysis of variance (ANOVA) with a Tukey's\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">post hoc<\/jats:named-content>\n            test. Daptomycin MICs were 4 \u03bcg\/ml (SA H9749-1, vancomycin-intermediate\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Staphylococcus aureus<\/jats:named-content>\n            ; R6212, heteroresistant vancomycin-intermediate\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Staphylococcus aureus<\/jats:named-content>\n            ) and 2 \u03bcg\/ml (R5599 and R5563). Trimethoprim-sulfamethoxazole MICs were \u22640.06\/1.19 \u03bcg\/ml. HD daptomycin plus trimethoprim-sulfamethoxazole displayed rapid bactericidal activity against SA H9749-1 (at 7 h) and R6212 (at 6 h) and bactericidal activity against R5599 (at 72 h) and R5563 (at 36 h). A \u22658 log\n            <jats:sub>10<\/jats:sub>\n            CFU\/g decrease was observed with HD daptomycin plus trimethoprim-sulfamethoxazole against all strains (at 48 to 144 h), which was maintained with de-escalation to HD daptomycin or trimethoprim-sulfamethoxazole at 336 h. The combination for 14 days and the combination for 7 days de-escalated to HD daptomycin or trimethoprim-sulfamethoxazole was significantly better than daptomycin monotherapy (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.05) and trimethoprim-sulfamethoxazole monotherapy (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.05) at 168 and 336 h. Combination therapy followed by de-escalation offers a novel bactericidal therapeutic alternative for high-inoculum, serious DNS MRSA infections.\n          <\/jats:p>","DOI":"10.1128\/aac.01185-12","type":"journal-article","created":{"date-parts":[[2012,8,21]],"date-time":"2012-08-21T04:22:25Z","timestamp":1345522945000},"page":"5709-5714","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":34,"title":["Evaluation of the Novel Combination of High-Dose Daptomycin plus Trimethoprim-Sulfamethoxazole against Daptomycin-Nonsusceptible Methicillin-Resistant Staphylococcus aureus Using an\n            <i>In Vitro<\/i>\n            Pharmacokinetic\/Pharmacodynamic Model of Simulated Endocardial Vegetations"],"prefix":"10.1128","volume":"56","author":[{"given":"Molly E.","family":"Steed","sequence":"first","affiliation":[{"name":"Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA"},{"name":"University of Kansas School of Pharmacy, Lawrence, Kansas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J.","family":"Werth","sequence":"additional","affiliation":[{"name":"Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cortney E.","family":"Ireland","sequence":"additional","affiliation":[{"name":"Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Rybak","sequence":"additional","affiliation":[{"name":"Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA"},{"name":"School of Medicine, Wayne State University, Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.2.454-459.2001"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.7.1925-1929.2000"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.165564"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00247-06"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/15.suppl_A.125"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1086\/520655"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2008.01.016"},{"key":"e_1_3_2_9_2","volume-title":"Approved standard M7-A9.","author":"Clinical and Laboratory Standards Institute","year":"2011","unstructured":"Clinical and Laboratory Standards Institute. 2011. 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Conf. Antimicrob. Agents Chemother.","author":"Steed M","year":"2011","unstructured":"SteedM AveryL WoodruffA RybakM. September 17, 2011. Evaluation of daptomycin (DAP) plus trimethoprim-sulfamethoxazole (TMP\/SMX) or rifampin activity in an in vitro pharmacokinetic\/pharmacodynamic (PK\/PD) model against VISA and daptomycin non-susceptible Staphylococcus aureus (SA) isolates from osteomyelitis cases, abstr. A2-019. Abstr. 51st Intersci. Conf. Antimicrob. Agents Chemother. American Society for Microbiology, Washington, DC."},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00536-10"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1086\/648473"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01415-08"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01185-12","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01185-12","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T21:59:33Z","timestamp":1645480773000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.01185-12"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,11]]},"references-count":37,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2012,11]]}},"alternative-id":["10.1128\/AAC.01185-12"],"URL":"https:\/\/doi.org\/10.1128\/aac.01185-12","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,11]]},"assertion":[{"value":"2012-06-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-08-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-10-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}