Soft tissue infection prophylaxis with gentamicin encapsulated in multivesicular liposomes: Results from a prospective, randomized trial

L. S. Grayson, J. F. Hansbrough, Ramon Zapata Sirvent, A. J. Roehrborn, T. Kim, S. Kim

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Objectives: 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. Design: Prospective, randomized trial. Setting: Animal laboratory. Subjects: Mice, 6 to 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 105 to 107 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. Measurements and Main Results: With a 107 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 105 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)84-91
Number of pages8
JournalCritical Care Medicine
Volume23
Issue number1
DOIs
StatePublished - Jan 13 1995
Externally publishedYes

Keywords

  • abscess
  • animal model
  • antibiotics
  • bacterial infection
  • drug delivery systems
  • drug toxicity
  • gentamicin
  • liposomes
  • liposomes
  • prophylaxis
  • sustained release preparations

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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