{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T05:38:49Z","timestamp":1791005929966,"version":"4.1.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T00:00:00Z","timestamp":1672963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Intravenous vancomycin (VAN) is the primary treatment for systemic infections due to methicillin-resistant <jats:italic>Staphylococcus aureus<\/jats:italic> (MRSA). Pharmacokinetic\/pharmacodynamic target (PK\/PD) indices for VAN therapies are more difficult to achieve for MRSA isolates with a minimum inhibitory concentration (MIC) greater than 1 \u00b5g mL<jats:sup>-1<\/jats:sup>. This research investigated the <jats:italic>in vitro<\/jats:italic> antimicrobial PD interaction of disulfiram (DSF) with VAN as a potential adjuvant therapy for infections due to these bacteria.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The antimicrobial interaction was assessed by differential analysis using checkerboard titration testing, time-kill studies, flow cytometry, and the post-antibiotic effect (PAE) experiment. Ten MRSA strains with MICs ranging from 1 to &amp;gt;256\u2006\u00b5g mL<jats:sup>-1<\/jats:sup> for VAN were evaluated. A comprehensive PD assessment of the VAN\/DSF interaction was performed using the VAN-intermediate (VISA) strain Mu50 (MIC 8\u2006\u00b5g mL<jats:sup>-1<\/jats:sup>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The addition of DSF lowered the MIC and minimum bactericidal concentration (MBC) of VAN in either a synergistic or additive manner for the MRSA panel. Optimal bactericidal effects and suppression of VISA Mu50 growth were observed with a 4\/8\u2006\u00b5g mL<jats:sup>-1<\/jats:sup> combination of VAN\/DSF, but not the individual drugs. Flow cytometry further confirmed the enhanced killing action on a cellular level; however, the addition of DSF had an overall antagonistic effect on the PAEs for VAN.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This research established that DSF exhibits additive to synergistic killing action with VAN for MRSA. Conversely, antagonism was observed on the PAE of VAN with DSF addition for the Mu50 strain. Flow cytometry further confirmed the enhanced bactericidal effect on a cellular level while revealing that DSF may counteract the muropeptide fortification mechanism against VAN in VISA.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2022.1092257","type":"journal-article","created":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T22:29:17Z","timestamp":1673044157000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Antimicrobial pharmacodynamics of vancomycin and disulfiram (Antabuse\u00ae) in Staphylococcus aureus"],"prefix":"10.3389","volume":"13","author":[{"given":"Hasitha","family":"Chavva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yogesh","family":"Meka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy E.","family":"Long","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,6]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1914","DOI":"10.1128\/AAC.43.8.1914","article-title":"Analysis of vancomycin population susceptibility profiles, killing activity, and postantibiotic effect against vancomycin-intermediate Staphylococcus aureus","volume":"43","author":"Aeschlimann","year":"1999","journal-title":"Antimicrob. 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