{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T10:26:21Z","timestamp":1759227981141},"reference-count":27,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2011,2,1]],"date-time":"2011-02-01T00:00:00Z","timestamp":1296518400000},"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":[[2011,2]]},"abstract":"ABSTRACT<\/jats:title>\n \n The antibacterial effects of telavancin, vancomycin, and teicoplanin against six\n Staphylococcus aureus<\/jats:italic>\n strains (1 methicillin-susceptible\n S. aureus<\/jats:italic>\n [MSSA] strain, 4 methicillin-resistant\n S. aureus<\/jats:italic>\n [MRSA] strains, and 1 vancomycin-intermediate\n S. aureus<\/jats:italic>\n [VISA] strain) and three\n Enterococcus<\/jats:italic>\n sp. strains (1\n Enterococcus faecalis<\/jats:italic>\n strain, 1\n Enterococcus faecium<\/jats:italic>\n strain, and 1 vancomycin-resistant\n E. faecium<\/jats:italic>\n [VREF] strain) were compared using an\n in vitro<\/jats:italic>\n pharmacokinetic model of infection. Analyzing the data from all five vancomycin-susceptible\n S. aureus<\/jats:italic>\n (VSSA) strains or all 4 MRSA strains showed that telavancin was superior in its antibacterial effect as measured by the area under the bacterial kill curve at 24 h (AUBKC\n 24<\/jats:sub>\n ) and 48 h (AUBKC\n 48<\/jats:sub>\n ) in comparison to vancomycin or teicoplanin (\n P<\/jats:italic>\n < 0.05). Telavancin was also superior to vancomycin and teicoplanin in terms of its greater early killing effect (\n P<\/jats:italic>\n < 0.05). Against the three\n Enterococcus<\/jats:italic>\n spp. tested, telavancin was superior to vancomycin in terms of its AUBKC\n 24<\/jats:sub>\n , AUBKC\n 48<\/jats:sub>\n , and greater early bactericidal effect (\n P<\/jats:italic>\n < 0.05). Dose-ranging studies were performed to provide free-drug area under the concentration-time curve over 24 h in the steady state divided by the MIC (fAUC\/MIC) exposures from 0 to 1,617 (7 to 14 exposures per strain) for 5 VSSA, 4 VISA, and the 3\n Enterococcus<\/jats:italic>\n strains. The fAUC\/MIC values for a 24-h bacteriostatic effect and a 1-log-unit drop in the viable count were 43.1 \u00b1 38.4 and 50.0 \u00b1 39.0 for VSSA, 3.2 \u00b1 1.3 and 4.3 \u00b1 1.3 for VISA, and 15.1 \u00b1 8.8 and 40.1 \u00b1 29.4 for the\n Enterococcus<\/jats:italic>\n spp., respectively. The reason for the paradoxically low fAUC\/MIC values for VISA strains is unknown. There was emergence of resistance to telavancin in the dose-ranging studies, as indicated by subpopulations able to grow on plates containing 2\u00d7 MIC telavancin concentrations compared to the preexposure population analysis profiles. Changes in population analysis profiles were less likely with enterococci than with\n S. aureus<\/jats:italic>\n , and the greatest risk of changed profiles occurred for both species at fAUC\/MIC ratios of 1 to 10. Maintaining a fAUC\/MIC ratio of >50 reduced the risk of subpopulations able to grow on antibiotic-containing media emerging. These data help explain the clinical effectiveness of telavancin against MRSA and indicate that telavancin may have clinically useful activity against\n Enterococcus<\/jats:italic>\n spp., and perhaps also VISA, at human doses of 10 mg\/kg of body weight\/day. In addition, they support a clinical breakpoint of sensitive at \u22641 mg\/liter for both\n S. aureus<\/jats:italic>\n and\n Enterococcus<\/jats:italic>\n spp.\n <\/jats:p>","DOI":"10.1128\/aac.00933-10","type":"journal-article","created":{"date-parts":[[2010,11,16]],"date-time":"2010-11-16T04:14:55Z","timestamp":1289880895000},"page":"867-873","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":26,"title":["Pharmacodynamics of Telavancin Studied in an\n In Vitro<\/i>\n Pharmacokinetic Model of Infection"],"prefix":"10.1128","volume":"55","author":[{"given":"Alasdair P.","family":"MacGowan","sequence":"first","affiliation":[{"name":"Bristol Centre for Antimicrobial Research and Evaluation (BCARE), University of Bristol and North Bristol NHS Trust, Department of Medical Microbiology, Lime Walk Building, Southmead Hospital, Westbury-on-Trym, Bristol, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan R.","family":"Noel","sequence":"additional","affiliation":[{"name":"Bristol Centre for Antimicrobial Research and Evaluation (BCARE), University of Bristol and North Bristol NHS Trust, Department of Medical Microbiology, Lime Walk Building, Southmead Hospital, Westbury-on-Trym, Bristol, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon","family":"Tomaselli","sequence":"additional","affiliation":[{"name":"Bristol Centre for Antimicrobial Research and Evaluation (BCARE), University of Bristol and North Bristol NHS Trust, Department of Medical Microbiology, Lime Walk Building, Southmead Hospital, Westbury-on-Trym, Bristol, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather C.","family":"Elliott","sequence":"additional","affiliation":[{"name":"Bristol Centre for Antimicrobial Research and Evaluation (BCARE), University of Bristol and North Bristol NHS Trust, Department of Medical Microbiology, Lime Walk Building, Southmead Hospital, Westbury-on-Trym, Bristol, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen E.","family":"Bowker","sequence":"additional","affiliation":[{"name":"Bristol Centre for Antimicrobial Research and Evaluation (BCARE), University of Bristol and North Bristol NHS Trust, Department of Medical Microbiology, Lime Walk Building, Southmead Hospital, Westbury-on-Trym, Bristol, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"45","year":"1999","unstructured":"Andrews, J. M. 1999. Microbiological assays, p. 45-63. In D. S. Reeves, R. Wise, J. M. Andrews, and L. O. White (ed.), Clinical microbiological assays. Oxford University Press, Oxford, United Kingdom.","journal-title":"Clinical microbiological assays"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkp289"},{"key":"e_1_3_2_4_2","unstructured":"Performance standards for antimicrobial susceptibility testing. 2005"},{"key":"e_1_3_2_5_2","first-page":"16","year":"2006","unstructured":"Craig, W. A., and D. R. Andes. 2006. In vivo pharmacodynamics of vancomycin against VISA, heteroresistant VISA and VSSA in the neutropenic murine thigh infection model, abstr. A-644, p. 16. Abstr. 46th Intersci. Conf. Antimicrob. Agents Chemother. American Society for Microbiology, Washington, DC.","journal-title":"In vivo pharmacodynamics of vancomycin against VISA, heteroresistant VISA and VSSA in the neutropenic murine thigh infection model"},{"key":"e_1_3_2_6_2","first-page":"49","year":"1999","unstructured":"Dudley, M., D. Griffith, E. Corcoran, C. Liu, K. Sorensen, V. Tembe, D. Cotter, S. Chamberland, and S. Chen. 1999. Pharmacokinetic-pharmacodynamic indices for vancomycin treatment of susceptible and intermediate S. aureus in the neutropenic mouse thigh model, abstr. 2031, p. 49. Abstr. 39th Intersci. Conf. Antimicrob. Agents Chemother. American Society for Microbiology, Washington, DC.","journal-title":"Pharmacokinetic-pharmacodynamic indices for vancomycin treatment of susceptible and intermediate S. aureus in the neutropenic mouse thigh model"},{"key":"e_1_3_2_7_2","unstructured":"Teicoplanin. 2010"},{"key":"e_1_3_2_8_2","unstructured":"Vancomycin. 2010"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.8.3043-3050.2004"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00100-07"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkh156"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01544-08"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkl235"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01110-07"},{"key":"e_1_3_2_15_2","first-page":"1","year":"1999","unstructured":"MacGowan, A. P., D. S. Reeves, and R. Wise. 1999. Clinical interpretation of antimicrobial assays, p. 1-11. In D. S. Reeves, R. Wise, J. M. Andrews, and L. O. White (ed.), Clinical antibiotic assays. Oxford University Press, Oxford, United Kingdom.","journal-title":"Clinical antibiotic assays"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.3.1088-1095.2003"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01153-07"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.8.3163-3165.2005"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01266-06"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01470-06"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.11.3602-3604.2003"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01244-08"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.10.4344-4346.2005"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkl222"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.1.195-201.2005"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.50.3.862-867.2006"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/48.5.727"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/47.4.399"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00933-10","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00933-10","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T23:21:36Z","timestamp":1645485696000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.00933-10"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,2]]},"references-count":27,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2011,2]]}},"alternative-id":["10.1128\/AAC.00933-10"],"URL":"https:\/\/doi.org\/10.1128\/aac.00933-10","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,2]]},"assertion":[{"value":"2010-07-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2010-11-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-01-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}