{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,21]],"date-time":"2025-09-21T17:56:59Z","timestamp":1758477419916},"reference-count":33,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2012,8,1]],"date-time":"2012-08-01T00:00:00Z","timestamp":1343779200000},"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":[[2012,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Methicillin-resistant\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            (MRSA) isolates that are susceptible to vancomycin but are tolerant to its killing effect may present a potential challenge for effective treatment. This study compared the microbiologic characteristics of clinical vancomycin-tolerant (VT-MRSA) and vancomycin-susceptible (VS-MRSA) strains using phenotypic and gene regulation studies. MRSA isolates collected from vancomycin-treated patients with bacteremia over a 5-year period were analyzed for vancomycin, daptomycin, and telavancin susceptibility, as well as accessory gene regulator (\n            <jats:italic>agr<\/jats:italic>\n            ) group and function. Vancomycin tolerance was defined by a minimum bactericidal concentration (MBC)\/minimum inhibitor concentration (MIC) ratio of \u226532 mg\/liter. VT-MRSA isolates were compared to VS-MRSA isolates for differences in antimicrobial susceptibility, time-kill activity, and gene expression of key cell envelope response genes\n            <jats:italic>vraSR<\/jats:italic>\n            ,\n            <jats:italic>dltA<\/jats:italic>\n            , and\n            <jats:italic>mprF<\/jats:italic>\n            . All 115 isolates evaluated were susceptible to vancomycin, daptomycin, and telavancin. Seven isolates (6%) were VT-MRSA.\n            <jats:italic>agr<\/jats:italic>\n            group II was more prevalent in isolates with vancomycin MBC\/MIC ratios of \u22658. In time-kill analyses, VT-MRSA had reduced vancomycin killing, but daptomycin and telavancin activities were maintained. Significantly greater gene expression was observed in VT-MRSA after 72 h of subinhibitory antibiotic exposures. Vancomycin most notably increased\n            <jats:italic>vraSR<\/jats:italic>\n            expression (\n            <jats:italic>P<\/jats:italic>\n            = 0.002 versus VS-MRSA strains). Daptomycin and telavancin increased expression of all genes studied, most significantly\n            <jats:italic>mprF<\/jats:italic>\n            expression (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.001). Longer durations of antibiotic exposure (72 h versus 24 h) resulted in substantial increases in gene expression in VT-MRSA. Although the clinical impact of VT-MRSA is not fully recognized, these data suggest that VT-MRSA strains, while still susceptible, have altered gene regulation to adapt to the antimicrobial effects of glyco- and lipopeptides that may emerge during prolonged durations of exposure.\n          <\/jats:p>","DOI":"10.1128\/aac.00676-12","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T05:39:27Z","timestamp":1339479567000},"page":"4422-4427","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":25,"title":["Vancomycin Tolerance in Methicillin-Resistant Staphylococcus aureus: Influence of Vancomycin, Daptomycin, and Telavancin on Differential Resistance Gene Expression"],"prefix":"10.1128","volume":"56","author":[{"given":"Warren E.","family":"Rose","sequence":"first","affiliation":[{"name":"Pharmacy Practice Division, University of Wisconsin\u2014Madison School of Pharmacy, Madison, Wisconsin, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Fallon","sequence":"additional","affiliation":[{"name":"University of Wisconsin Hospital and Clinics, Madison, Wisconsin, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John J. M.","family":"Moran","sequence":"additional","affiliation":[{"name":"Pharmacy Practice Division, University of Wisconsin\u2014Madison School of Pharmacy, Madison, Wisconsin, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua P.","family":"Vanderloo","sequence":"additional","affiliation":[{"name":"Pharmacy Practice Division, University of Wisconsin\u2014Madison School of Pharmacy, Madison, Wisconsin, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0029573"},{"key":"e_1_3_2_3_2","unstructured":"Clinical and Laboratory Standards Institute. 2010. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically: approved standard 10th ed. Clinical and Laboratory Standards Institute Wayne PA."},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.9.2276-2285.2000"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01173-08"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkr195"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00039-06"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.3.1127-1134.2005"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir270"},{"key":"e_1_3_2_10_2","doi-asserted-by":"crossref","unstructured":"HondaH\nDoernCD\nMichael-DunneWJr\nWarrenDK. 2011. The impact of vancomycin susceptibility on treatment outcomes among patients with methicillin resistant Staphylococcus aureus bacteremia. BMC Infect. 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Teicoplanin pharmacodynamics in reference to the accessory gene regulator (agr) in Staphylococcus aureus using an in vitro pharmacodynamic model. J. Antimicrob. Chemother. 61:1099\u20131102.","journal-title":"J. Antimicrob. Chemother."},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkq292"},{"key":"e_1_3_2_25_2","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1093\/jac\/dkp319","article-title":"Occurrence of vancomycin-tolerant and heterogeneous vancomycin-intermediate strains (hVISA) among Staphylococcus aureus causing bloodstream infections in nine USA hospitals","volume":"64","author":"Sader HS","year":"2009","unstructured":"SaderHS JonesRN RossiKL RybakMJ. 2009. Occurrence of vancomycin-tolerant and heterogeneous vancomycin-intermediate strains (hVISA) among Staphylococcus aureus causing bloodstream infections in nine USA hospitals. J. Antimicrob. Chemother. 64:1024\u20131028.","journal-title":"J. Antimicrob. 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