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

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 investigat...

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Bibliographic Details
Published in:	Journal of antimicrobial chemotherapy Vol. 67; no. 9; pp. 2191 - 2194
Main Authors:	Sande, Linette, Sanchez, Marisel, Montes, Joy, Wolf, Andrea J, Morgan, Margie A, Omri, Abdelwahab, Liu, George Y
Format:	Journal Article
Language:	English
Published:	England Oxford Publishing Limited (England) 01-09-2012
Subjects:	Animal models Animals Anti-Bacterial Agents - administration & dosage Anti-Bacterial Agents - pharmacokinetics Antibiotics Bacteremia - drug therapy Bacteremia - microbiology Disseminated infection Drug Carriers - administration & dosage Drug Carriers - pharmacokinetics Drug resistance Encapsulation Kidney Kinetics Lipids Liposomes Liposomes - administration & dosage Liposomes - pharmacokinetics Male Methicillin-Resistant Staphylococcus aureus - drug effects Mice Microbial Sensitivity Tests Microbial Viability - drug effects Minimum inhibitory concentration Morbidity Psychotherapy Public health Staphylococcal Infections - drug therapy Staphylococcal Infections - microbiology Staphylococcus aureus Staphylococcus infections Treatment Outcome Vancomycin Vancomycin - administration & dosage Vancomycin - pharmacokinetics
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Summary:	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. 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. 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. Our findings suggest that entrapment within liposomes could improve the antistaphylococcal efficacy of vancomycin.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	0305-7453 1460-2091
DOI:	10.1093/jac/dks212