Figure 5: Tamoxifen reduces mortality and enhances clearance of USA300 MRSA in an in vivo model of acute infection.

(a) At 1 h following intraperitoneal (i.p.) treatment with tamoxifen (TAM; 250 mg kg⁻¹) or vehicle control (VEH; corn oil), CD-1 background mice were infected i.p. with a lethal dose of USA300 MRSA (5 × 10⁸ CFU ml⁻¹, 200 μl). Mice were subsequently treated with tamoxifen or vehicle control at 1 and 8 h post infection and monitored for 5 days. Tamoxifen significantly protected against mortality. (b) To assess bacterial dissemination, CD-1 background mice received i.p. injections of tamoxifen (250 mg kg⁻¹) or vehicle control 2 h before and 6 h following i.p. injection of enhanced green fluorescent protein (EGFP)-expressing USA300 MRSA (5 × 10⁸ CFU ml⁻¹, 200 μl). Bacterial counts were determined in the peritoneal lavage fluid and blood, kidney, liver and spleen tissue samples. (c) Light microscopy revealed that neutrophils in the vehicle control samples often appeared damaged and contained multiple intact bacteria (scale bar, 25 μm). (d) Quantitative analysis of fixed peritoneal lavage samples confirmed the presence of elevated EGFP-USA300 MRSA levels in vehicle- versus tamoxifen-treated animals. Results were analysed by the log-rank test (survival curve comparison) or one-way analysis of variance and post hoc Newman Keuls test. *P<0.05, **P<0.01 versus control values.