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

J Antimicrob Chemother. 2012 Sep;67(9):2191-4. doi: 10.1093/jac/dks212. Epub 2012 Jun 2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / pharmacokinetics
  • Bacteremia / drug therapy
  • Bacteremia / microbiology
  • Drug Carriers / administration & dosage
  • Drug Carriers / pharmacokinetics
  • Liposomes / administration & dosage*
  • Liposomes / pharmacokinetics
  • Male
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Mice
  • Microbial Sensitivity Tests
  • Microbial Viability / drug effects
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / microbiology
  • Treatment Outcome
  • Vancomycin / administration & dosage*
  • Vancomycin / pharmacokinetics

Substances

  • Anti-Bacterial Agents
  • Drug Carriers
  • Liposomes
  • Vancomycin