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Treatment with rifampicin (RFP) is considered only in meticillin\u2010resistant and multidrug\u2010resistant<jats:italic>S.\u00a0pseudintermedius<\/jats:italic>(MDR\u2010MRSP).<\/jats:p><\/jats:sec><jats:sec><jats:title>Hypothesis\/Objectives<\/jats:title><jats:p>To determine an optimal RFP dosing for MDR\u2010MRSP treatment without induction of RFP resistance and identify causal mutations for antimicrobial resistance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and materials<\/jats:title><jats:p>Time\u2013kill assays were performed in a control isolate and three MDR\u2010MRSP isolates at six clinically relevant concentrations [32 to 1,024\u00a0\u00d7\u00a0MIC (the minimum inhibitory concentration)]. Whole\u2010genome resequencing and bioinformatic analysis were performed in the resistant strains developed in this assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The genomic analysis identified nine antimicrobial resistance genes (ARGs) in MDR\u2010MRSP isolates, which are responsible for resistance to seven classes of antibiotics. RFP activity against all four isolates was consistent with a time\u2010dependent and bacteriostatic response. RFP resistance was observed in six of the 28 time\u2013kill assays, including concentrations 64\u00a0\u00d7\u00a0MIC in MDR\u2010MRSP1 isolates at 24\u00a0h, 32\u00a0\u00d7\u00a0MIC in MDR\u2010MRSP2 at 48\u00a0h, 32\u00a0\u00d7\u00a0MIC in MDR\u2010MRSP3 at 48\u00a0h and 256\u00a0\u00d7\u00a0MIC in MDR\u2010MRSP3 at 24\u00a0h. Genome\u2010wide mutation analyses in these RFP\u2010resistant strains discovered the causal mutations in the coding region of the<jats:italic>rpoB<\/jats:italic>gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and clinical relevance<\/jats:title><jats:p>A study has shown that 6\u00a0mg\/kg per os results in plasma concentrations of 600\u20131,000\u00a0\u00d7\u00a0MIC of<jats:italic>S.\u00a0pseudintermedius<\/jats:italic>. Based on our data, this dose should achieve the minimum MIC (\u00d7512) to prevent RFP resistance development; therefore, we recommend a minimum daily dose of 6\u00a0mg\/kg for MDR\u2010MRSP pyoderma treatment when limited antibiotic options are available.<\/jats:p><\/jats:sec>","DOI":"10.1111\/vde.12959","type":"journal-article","created":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T03:23:25Z","timestamp":1619061805000},"page":"219","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Genomic and<i>in vitro<\/i>pharmacodynamic analysis of rifampicin resistance in multidrug\u2010resistant canine<i>Staphylococcus pseudintermedius<\/i>isolates"],"prefix":"10.1111","volume":"32","author":[{"given":"Karly","family":"Hicks","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences Auburn University Auburn AL 36849 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