Intracellular vancomycin delivery targets hepatic MRSA reservoir clearance and suppresses bacterial dissemination. (a) SD-IVM images from mouse livers from untreated mice or mice treated with 50 mg/kg vancomycin i.v. 1 h before or after infection with MRSA (MW2–GFP; green). Images were taken 8 h after infection. Bar, 50 µm. Quantification of stitched SD-IVM images (b) or liver bacterial load (c) of mice treated with 50 mg/kg vancomycin 1 h before or after i.v. infection with MRSA (MW2-GFP). (b) n = 4 or (c) n = 10 per condition. Error bars, SEM. *, P < 0.05, one-way ANOVA with Bonferroni’s posttest. Data shown are compiled from two independent experiments. (d) SD-IVM image of Bodipy-vancomycin staining (green) of MRSA (MW2-AF555, red) injected 15 m before infection (left) or 15 m after infection (right) in mouse (Videos 8 and 9). (e, left) SD-IVM image of mouse liver infected with MRSA (MW2-AF555, red) co-localizing with KC (F4/80, purple) and (right) 15 min after injection of Did-labeled vancosomes (blue; Corresponding Video 10). (d and e) Bar, 25 µm. (f) Representative images of the healthy uninfected liver (control), MRSA-infected liver (24 h; untreated), and MRSA-infected liver treated 1 h after infection with 50 mg/kg vancomycin or vancosomes i.v. (g) Serum ALT levels at 24 h after infection (n = 8 per treatment group, error bars, SEM; *, P < 0.05, one-way ANOVA with Bonferroni’s posttest). (h) CFU levels at 24 and 96 h in mice i.v. infected with MRSA (MW2) with or without treatment 1 h after infection with 50 mg/kg vancomycin or vancosomes. n = 10–15 per treatment group. *, P < 0.05; **, P < 0.05; ***, P < 0.001, one-way ANOVA with Bonferroni’s posttest). Data shown are compiled from 3 independent experiments. (i) Survival of a lethal dose of MRSA (10⁸ CFU MW2)-infected mice with or without treatment 1 h after infection with 50 mg/kg vancomycin or vancosomes. n = 10 per treatment group, Log-rank test versus vancosomes. Data shown are compiled from two independent experiments.