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 journalArticle

23 Citations (Scopus)

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

Fingerprint

Soft Tissue Infections
Gentamicins
Liposomes
Stem Cells
Staphylococcus aureus
Pharmaceutical Preparations
Vascular Access Devices
Indwelling Catheters
Subcutaneous Tissue
Laboratory Animals
Lipid Bilayers
Drug Delivery Systems
Infection
Microspheres
Anti-Bacterial Agents
Bacteria
Lipids
Injections
Membranes
Wounds and Injuries

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

Cite this

Soft tissue infection prophylaxis with gentamicin encapsulated in multivesicular liposomes : Results from a prospective, randomized trial. / Grayson, L. S.; Hansbrough, J. F.; Zapata Sirvent, Ramon; Roehrborn, A. J.; Kim, T.; Kim, S.

In: Critical Care Medicine, Vol. 23, No. 1, 13.01.1995, p. 84-91.

Research output: Contribution to journalArticle

@article{bb80943e9ed04fc7989c9d8d0d339b64,
title = "Soft tissue infection prophylaxis with gentamicin encapsulated in multivesicular liposomes: Results from a prospective, randomized trial",
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.",
keywords = "abscess, animal model, antibiotics, bacterial infection, drug delivery systems, drug toxicity, gentamicin, liposomes, liposomes, prophylaxis, sustained release preparations",
author = "Grayson, {L. S.} and Hansbrough, {J. F.} and {Zapata Sirvent}, Ramon and Roehrborn, {A. J.} and T. Kim and S. Kim",
year = "1995",
month = "1",
day = "13",
doi = "10.1097/00003246-199501000-00016",
language = "English (US)",
volume = "23",
pages = "84--91",
journal = "Critical Care Medicine",
issn = "0090-3493",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - Soft tissue infection prophylaxis with gentamicin encapsulated in multivesicular liposomes

T2 - Results from a prospective, randomized trial

AU - Grayson, L. S.

AU - Hansbrough, J. F.

AU - Zapata Sirvent, Ramon

AU - Roehrborn, A. J.

AU - Kim, T.

AU - Kim, S.

PY - 1995/1/13

Y1 - 1995/1/13

N2 - 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.

AB - 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.

KW - abscess

KW - animal model

KW - antibiotics

KW - bacterial infection

KW - drug delivery systems

KW - drug toxicity

KW - gentamicin

KW - liposomes

KW - liposomes

KW - prophylaxis

KW - sustained release preparations

UR - http://www.scopus.com/inward/record.url?scp=0028896156&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028896156&partnerID=8YFLogxK

U2 - 10.1097/00003246-199501000-00016

DO - 10.1097/00003246-199501000-00016

M3 - Article

C2 - 8001392

AN - SCOPUS:0028896156

VL - 23

SP - 84

EP - 91

JO - Critical Care Medicine

JF - Critical Care Medicine

SN - 0090-3493

IS - 1

ER -