Prior to surgery, mice were randomized to one of two treatment groups or a control group (n = 10 per group). Mice in the vancomycin group were subcutaneously administered a therapeutic dose of vancomycin (110 mg/kg twice daily) (Mylan, Cannonsburg, PA), which approximated the area under the curve (AUC) of 440 μg⋅h/ml for typical human exposure for vancomycin (1g twice daily).[29 (link)–31 (link)] Mice in the combination therapy group were administered a therapeutic subcutaneous mouse dose of rifampin (25 mg/kg daily) (Fresenius Kabi, Lake Zurich, IL) in addition to vancomycin therapy (110 mg/kg twice daily).[32 (link)] This rifampin dose was chosen based on previously published studies of various mouse models of staphylococcal infection.[32 (link)–36 (link)] All antibiotic therapy and sham injections of sterile saline were initiated on postoperative day 7 and continued through postoperative day 14 to mimic the treatment of an established SII. The MICs for Xen36 were ≤0.5 μg/ml for vancomycin and ≤0.5 μg/ml for rifampin.
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