{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T01:28:38Z","timestamp":1792200518141,"version":"4.4.0"},"reference-count":29,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2018,2,1]],"date-time":"2018-02-01T00:00:00Z","timestamp":1517443200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 HD070886"],"award-info":[{"award-number":["R01 HD070886"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01 GM068968"],"award-info":[{"award-number":["R01 GM068968"]}],"id":[{"id":"10.13039\/100000002","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":[[2018,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    We hypothesized that dosing vancomycin to achieve trough concentrations of &gt;15 mg\/liter overdoses many adults compared to area under the concentration-time curve (AUC)-guided dosing. We conducted a 3-year, prospective study of vancomycin dosing, plasma concentrations, and outcomes. In year 1, nonstudy clinicians targeted trough concentrations of 10 to 20 mg\/liter (infection dependent) and controlled dosing. In years 2 and 3, the study team controlled vancomycin dosing with BestDose Bayesian software to achieve a daily, steady-state AUC\/MIC ratio of \u2265400, with a maximum AUC value of 800 mg \u00b7 h\/liter, regardless of trough concentration. For Bayesian estimation of AUCs, we used trough samples in years 1 and 2 and optimally timed samples in year 3. We enrolled 252 adults who were \u226518 years old with \u22651 available vancomycin concentration. Only 19% of all trough concentrations were therapeutic versus 70% of AUCs (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.0001). After enrollment, median trough concentrations by year were 14.4, 9.7, and 10.9 mg\/liter (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.005), with 36%, 7%, and 6% over 15 mg\/liter (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.0001). Bayesian AUC-guided dosing in years 2 and 3 was associated with fewer additional blood samples per subject (3.6, 2.0, and 2.4;\n                    <jats:italic>P<\/jats:italic>\n                    = 0.003), shorter therapy durations (8.2, 5.4, and 4.7 days;\n                    <jats:italic>P<\/jats:italic>\n                    = 0.03), and reduced nephrotoxicity (8%, 0%, and 2%;\n                    <jats:italic>P<\/jats:italic>\n                    = 0.01). The median inpatient stay was 20 days among nephrotoxic patients versus 6 days (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.002). There was no difference in efficacy by year, with 42% of patients having microbiologically proven infections. Compared to trough concentration targets, AUC-guided, Bayesian estimation-assisted vancomycin dosing was associated with decreased nephrotoxicity, reduced per-patient blood sampling, and shorter length of therapy, without compromising efficacy. These benefits have the potential for substantial cost savings. (This study has been registered at ClinicalTrials.gov under registration no. NCT01932034.)\n                  <\/jats:p>","DOI":"10.1128\/aac.02042-17","type":"journal-article","created":{"date-parts":[[2017,12,4]],"date-time":"2017-12-04T11:46:07Z","timestamp":1512387967000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":320,"title":["Prospective Trial on the Use of Trough Concentration versus Area under the Curve To Determine Therapeutic Vancomycin Dosing"],"prefix":"10.1128","volume":"62","author":[{"given":"Michael N.","family":"Neely","sequence":"first","affiliation":[{"name":"University of Southern California, Keck School of Medicine, Los Angeles, California, USA"},{"name":"Laboratory of Applied Pharmacokinetics and Bioinformatics (LAPKB), Saban Research Institute, and Division of Infectious Diseases, Children's Hospital of Los Angeles, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Kato","sequence":"additional","affiliation":[{"name":"University of Southern California School of Pharmacy, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilmer","family":"Youn","sequence":"additional","affiliation":[{"name":"University of Southern California, Keck School of Medicine, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lironn","family":"Kraler","sequence":"additional","affiliation":[{"name":"University of Southern California, Keck School of Medicine, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Bayard","sequence":"additional","affiliation":[{"name":"Laboratory of Applied Pharmacokinetics and Bioinformatics (LAPKB), Saban Research Institute, and Division of Infectious Diseases, Children's Hospital of Los Angeles, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"van Guilder","sequence":"additional","affiliation":[{"name":"Laboratory of Applied Pharmacokinetics and Bioinformatics (LAPKB), Saban Research Institute, and Division of Infectious Diseases, Children's Hospital of Los Angeles, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Schumitzky","sequence":"additional","affiliation":[{"name":"Laboratory of Applied Pharmacokinetics and Bioinformatics (LAPKB), Saban Research Institute, and Division of Infectious Diseases, Children's Hospital of Los Angeles, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Yamada","sequence":"additional","affiliation":[{"name":"Laboratory of Applied Pharmacokinetics and Bioinformatics (LAPKB), Saban Research Institute, and Division of Infectious Diseases, Children's Hospital of Los Angeles, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda","family":"Jones","sequence":"additional","affiliation":[{"name":"University of Southern California, Keck School of Medicine, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emi","family":"Minejima","sequence":"additional","affiliation":[{"name":"University of Southern California School of Pharmacy, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.2146\/ajhp080434"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2014.05.016"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01653-13"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01568-12"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/38.4.589"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.10.2739"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1086\/491712"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05664-11"},{"key":"e_1_3_2_10_2","volume-title":"aureus in the neutropenic murine thigh model, p 49","author":"Dudley M","year":"1999","unstructured":"Dudley M, Griffith D, Corcoran E, Liu C, Sorensen K, Tembe V, Cotter D. 1999. Pharmacokinetic-pharmacodynamic (PK-PD) indices for vancomycin treatment of susceptible (VSSA) and intermediate (VISA) S. aureus in the neutropenic murine thigh model, p 49. Abstr 39th Intersci Conf Antimicrob Agents Chemother, Washington, DC."},{"key":"e_1_3_2_11_2","volume-title":"In vivo pharmacodynamics of vancomycin against VISA, heteroresistant VISA (hVISA) and VSSA in the neutropenic murine thigh-infection model, abstr A-644","author":"Craig WA","year":"2006","unstructured":"Craig WA, Andes DR. 2006. In vivo pharmacodynamics of vancomycin against VISA, heteroresistant VISA (hVISA) and VSSA in the neutropenic murine thigh-infection model, abstr A-644. 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Successful growth of Staphylococcus epidermidis in the neutropenic mouse thigh infection model (NMTIM) without the use of a foreign body, abstr A-1320. 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