SOFT-TISSUE INFECTION PROPHYLAXIS WITH GENTAMICIN ENCAPSULATED IN MULTIVESICULAR LIPOSOMES - RESULTS FROM A PROSPECTIVE, RANDOMIZED TRIAL

Objectives: Systemically administered antibiotic agents are not evenly distributed in the body, which frequently results in subtherapeutic r egional drug concentrations, particularly in areas of poor vasculariza tion, including wound sites. We have developed a lipid-based drug deli very 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 comp artments that can contain drug. The preparation may be effective for t he prevention and treatment of a variety of infections, including infe ctions associated with indwelling vascular catheters. Design: Prospect ive, randomized trial. Setting: Animal laboratory. Subjects: Mice, 6 t o 12 wks of age, weighing 20 to 30 g. Interventions: 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 i noculation. Measurements and Main Results: With a 10(7) cfu challenge, animals that received 2- and 4-day pretreatment with multivesicular l iposome/ gentamicin had a 4 log(10) reduction in cfu/g of tissue compa red with controls. When 10(5) cfu of Staphylococcus aureus were inocul ated after 2- and 4-day pretreatment with multivesicular liposome/gent amicin, a 6 log(10) reduction in bacteria colony-forming units was obs erved. Conclusion: Local injection of multivesicular liposome/gentamic in provides sustained drug concentrations in regional tissues that pro tect against a massive bacterial challenge for at least four subsequen t days.