We showed herein in a rabbit model of MRSA pneumonia that, although LNZ was efficient in keeping in check bacterial growth within the lung of both SB and MV animals, infection could be considered as more severe in the latter, since pulmonary-to-systemic translocation of S. aureus was apparently not prevented by LNZ in the ventilated animals. The lung inflammatory response was in part dampened by LNZ in both SB and MV rabbits, but interestingly, an additive effect was achieved by pre-treatment with atorvastatin. Similarly, we showed that LNZ alone failed to completely abrogate the systemic release of inflammatory mediators subsequent to pneumonia, whereas its combination with atorvastatin succeeded in doing so. This anti-inflammatory effect, however, could have hampered the host’s ability to control systemic diffusion of S. aureus, thereby promoting bacterial spillover into the bloodstream in MV animals.