Liposomal encapsulation of vancomycin improves killing of methicillin-resistant Staphylococcus aureus in a murine infection model.
OBJECTIVE
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.
Division of Pediatric Infectious Diseases, David Geffen School of Medicine, Mattel Children's Hospital UCLA, Los Angeles, CA 90095, USA.
Linette
L
Sande
Marisel
M
Sanchez
Joy
J
Montes
Andrea J
AJ
Wolf
Margie A
MA
Morgan
Abdelwahab
A
Omri
George Y
GY
Liu
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016470:Bacteremia / Q000188:drug therapy / Q000382:microbiology; D004337:Drug Carriers / Q000008:administration & dosage / Q000493:pharmacokinetics; D008081:Liposomes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D051379:Mice; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D016896:Treatment Outcome; D014640:Vancomycin / Q000008:administration & dosage* / Q000493:pharmacokinetics
D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D008081:Liposomes; D014640:Vancomycin