{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T01:43:51Z","timestamp":1789523031207,"version":"build-2803163510"},"reference-count":17,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2004,8,1]],"date-time":"2004-08-01T00:00:00Z","timestamp":1091318400000},"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":[[2004,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            We previously observed marked synergy between daptomycin and both rifampin and ampicillin against vancomycin-resistant enterococci (VRE). Because the synergy between daptomycin and ampicillin was observed for 100% of VRE strains with high-level ampicillin resistance (ampicillin MIC of \u2265128 \u03bcg\/ml), we looked for synergy between daptomycin and other \u03b2-lactams against 18 strains of methicillin-resistant\n            <jats:italic>Staphylococcus aureus<\/jats:italic>\n            (MRSA) by employing a time-kill method using Mueller-Hinton broth supplemented to 50 mg of Ca\n            <jats:sup>2+<\/jats:sup>\n            \/liter. All strains were resistant to oxacillin (16 of 18 strains were resistant at drug concentrations of \u2265256 \u03bcg\/ml), and all strains were susceptible to daptomycin (the MIC at which 90% of the tested isolates were inhibited was 1 \u03bcg\/ml). Daptomycin was tested at concentrations of 2, 1, 0.5, 0.25, 0.125, and 0.0625 \u03bcg\/ml alone or in combination with oxacillin at a fixed concentration of 32 \u03bcg\/ml. Synergy was found for all 18 strains with daptomycin at one-half the MIC in combination with 32 \u03bcg of oxacillin\/ml, and synergy was found for 11 of 18 strains (61%) with daptomycin at one-fourth the MIC or less in combination with oxacillin. At 24 h, the daptomycin-oxacillin combination with daptomycin at one-half the MIC showed bactericidal activity against all 18 strains, and the combination with one-fourth the daptomycin MIC showed bactericidal activity against 9 of 18 strains. We also used a novel screening method to look for synergy between daptomycin and other \u03b2-lactams. In this approach, daptomycin was incorporated into Ca\n            <jats:sup>2+<\/jats:sup>\n            -supplemented Mueller-Hinton agar at subinhibitory concentrations, and synergy was screened by comparing test antibiotic Kirby-Bauer disks on agar with and without daptomycin. By this method, daptomycin with ampicillin-sulbactam, ticarcillin-clavulanate, or piperacillin-tazobactam showed synergy comparable to or greater than daptomycin with oxacillin. For seven of the eight strains tested, time-kill studies confirmed synergy between daptomycin and ampicillin-sulbactam with ampicillin in the range of 2 to 8 \u03bcg\/ml. The combination of daptomycin and \u03b2-lactams may be useful for the treatment of MRSA infection, but further studies are needed to elucidate the mechanisms and to determine the in vivo efficacy of the combination.\n          <\/jats:p>","DOI":"10.1128\/aac.48.8.2871-2875.2004","type":"journal-article","created":{"date-parts":[[2004,7,23]],"date-time":"2004-07-23T18:45:20Z","timestamp":1090608320000},"page":"2871-2875","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":131,"title":["Synergy of Daptomycin with Oxacillin and Other \u03b2-Lactams against Methicillin-Resistant\n            <i>Staphylococcus aureus<\/i>"],"prefix":"10.1128","volume":"48","author":[{"given":"Kenneth H.","family":"Rand","sequence":"first","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herbert J.","family":"Houck","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"1972","volume":"31","year":"1981","unstructured":"Adam, D., K. Wilhelm, and V. Chysky. 1981. Antibiotic concentrations in blood and tissue. Intraoperative ischemia as a model for the determination of tissue concentrations using mezlocillin and oxacillin as examples. Arzneim.-Forsch.31:1972-1976.","journal-title":"Arzneim.-Forsch."},{"key":"e_1_3_2_3_2","first-page":"33","volume":"29","year":"1981","unstructured":"Bergan, T. 1981. Overview of acylureidopenicillin pharmacokinetics. Scand. J. Infect. Dis. Suppl.29:33-48.","journal-title":"Scand. J. Infect. Dis. Suppl."},{"key":"e_1_3_2_4_2","first-page":"63","volume":"37","year":"1999","unstructured":"de la Pena, A., and H. Derendorf. 1999. Pharmacokinetic properties of beta-lactamase inhibitors. Int. J. Clin. Pharm. Ther.37:63-75.","journal-title":"Int. J. Clin. Pharm. Ther."},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.20.4.481"},{"key":"e_1_3_2_6_2","first-page":"330","year":"1996","unstructured":"Eliopoulos, G. M., and R. C. Moellering, Jr. 1996. Antimicrobial combinations, p. 330-396. In V. Lorian (ed.), Antibiotics in laboratory medicine. Williams & Wilkins, Baltimore, Md.","journal-title":"Antibiotics in laboratory medicine"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1592\/phco.22.7.471.33665"},{"key":"e_1_3_2_8_2","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1023\/A:1025309604656","volume":"17","year":"2003","unstructured":"Hall, L. M., L. H. Hall, and L. B. Kier. 2003. QSAR modeling of beta-lactam binding to human serum proteins. J. Comput.-Aided Mol. Des.17:103-118.","journal-title":"J. Comput.-Aided Mol. 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National Committee for Clinical Laboratory Standards Wayne Pa."},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkh104"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/39.suppl_1.47"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.8.2538-2544.2003"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/46.4.523"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0196-4399(02)80007-1"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.48.8.2871-2875.2004","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.48.8.2871-2875.2004","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T18:27:28Z","timestamp":1645468048000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.48.8.2871-2875.2004"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,8]]},"references-count":17,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2004,8]]}},"alternative-id":["10.1128\/AAC.48.8.2871-2875.2004"],"URL":"https:\/\/doi.org\/10.1128\/aac.48.8.2871-2875.2004","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,8]]},"assertion":[{"value":"2003-10-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2004-04-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2004-08-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}