Liposomal encapsulation of vancomycin improves killing of methicillin-resistant Staphylococcus aureus in a murine infection model

Abstract

OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) poses a major problem to public health worldwide. MRSA strains with increased resistance to vancomycin cause infections that are associated with greater morbidity and threaten the use of this once gold-standard antistaphylococcal drug. We investigated whether encapsulation of vancomycin within liposomes could improve its antistaphylococcal activity. METHODS: Two liposomal formulations of vancomycin were prepared using a rehydration-dehydration method. MICs and MBCs of the liposomal vancomycin for strains of MRSA were determined. The efficacy of one of the liposomal vancomycin formulations was also investigated in a time-kill assay in vitro and in a murine systemic infection model. RESULTS: Encapsulation in either liposome preparation decreased the vancomycin MICs and MBCs for MRSA strains by approximately 2-fold. Liposomal vancomycin increased killing of MRSA in vitro in a kinetic study. In a systemic murine infection model, treatment with a 50 mg/kg intraperitoneal injection of liposomal vancomycin improved kidney clearance of a USA300 strain by 1 log compared with an injection of 50 mg/kg of free vancomycin. CONCLUSIONS: Our findings suggest that entrapment within liposomes could improve the antistaphylococcal efficacy of vancomycin.