Soft tissue infection prophylaxis with gentamicin encapsulated in multivesicular liposomes: results from a prospective, randomized trial.
OBJECTIVE
Systemically administered antibiotic agents are not evenly distributed in the body, which frequently results in subtherapeutic regional drug concentrations, particularly in areas of poor vascularization, including wound sites. We have developed a lipid-based drug delivery system to provide prolonged levels of gentamicin in local tissues after local administration. Multivesicular liposomes are microspheres composed of lipid bilayer membranes surrounding multiple aqueous compartments that can contain drug. The preparation may be effective for the prevention and treatment of a variety of infections, including infections associated with indwelling vascular catheters.


METHODS
Prospective, randomized trial.


METHODS
Animal laboratory.


METHODS
Mice, 6 to 12 wks of age, weighing 20 to 30 g.


METHODS
We administered 0.5 mg of gentamicin encapsulated in multivesicular liposomes to dorsal subcutaneous tissue in mice. Animals were inoculated with 10(5) to 10(7) colony-forming units (cfu) of Staphylococcus aureus 2, 4, 6, and 8 days later. The cfu/g of tissue values were determined 2 days after inoculation.


RESULTS
With a 10(7) cfu challenge, animals that received 2- and 4-day pretreatment with multivesicular liposome/gentamicin had a 4 log10 reduction in cfu/g of tissue compared with controls. When 10(5) cfu of Staphylococcus aureus were inoculated after 2- and 4-day pretreatment with multivesicular liposome/gentamicin, a 6 log10 reduction in bacteria colony-forming units was observed.


CONCLUSIONS
Local injection of multivesicular liposome/gentamicin provides sustained drug concentrations in regional tissues that protect against a massive bacterial challenge for at least four subsequent days.
Grayson
L S
LS
Department of Surgery, University of California, San Diego Medical Center.
Hansbrough
J F
JF
Zapata-Sirvent
R
R
Roehrborn
A J
AJ
Kim
T
T
Kim
S
S
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage*; D008051:Lipid Bilayers; D008081:Liposomes; D051379:Mice; D011292:Premedication; D011897:Random Allocation; D018461:Soft Tissue Infections / Q000517:prevention & control*; D013203:Staphylococcal Infections / Q000517:prevention & control; D013211:Staphylococcus aureus
D004337:Drug Carriers; D005839:Gentamicins; D008051:Lipid Bilayers; D008081:Liposomes