Efficacy of gentamicin or ceftazidime entrapped in liposomes with prolonged blood circulation and enhanced localization in Klebsiella pneumoniae-infected lung tissue

J Infect Dis. 1995 Apr;171(4):938-47. doi: 10.1093/infdis/171.4.938.

Abstract

Polymer (PEG-PE)-coated liposomes exhibit prolonged circulation time in blood and substantial localization in Klebsiella pneumoniae-infected lung tissue in rats. Therefore, to determine the therapeutic effect, gentamicin and ceftazidime were entrapped in these liposomes and administered to rats experimentally infected with pneumonia: Relatively high and sustained concentrations of liposome-associated antibiotic in blood were observed. Compared with antibiotics alone, one dose of liposome-entrapped gentamicin or ceftazidime increased the therapeutic effect of the drugs, survival of rats, and bacterial killing in lungs. One dose of liposome-entrapped ceftazidime was as effective as a continuous 2-day infusion of nonentrapped ceftazidime. Since antibiotic-containing liposomes are stable during circulation and liposome-entrapped ceftazidime and gentamicin have low bactericidal activity in vitro, the superior therapeutic effect of the liposome-encapsulated antibiotics results from localization and subsequent degradation of liposomes and the resulting release of entrapped antibiotic at the infection site.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ceftazidime / administration & dosage*
  • Ceftazidime / blood
  • Ceftazidime / pharmacology
  • Ceftazidime / therapeutic use
  • Drug Carriers
  • Female
  • Gentamicins / administration & dosage*
  • Gentamicins / blood
  • Gentamicins / pharmacology
  • Gentamicins / therapeutic use
  • Klebsiella Infections / drug therapy*
  • Klebsiella pneumoniae* / drug effects
  • Liposomes / toxicity
  • Lung / microbiology
  • Phosphatidylcholines
  • Phosphatidylethanolamines
  • Pneumonia, Bacterial / drug therapy*
  • Polyethylene Glycols
  • Rats
  • Specific Pathogen-Free Organisms

Substances

  • Drug Carriers
  • Gentamicins
  • Liposomes
  • Phosphatidylcholines
  • Phosphatidylethanolamines
  • 1,2-distearoylphosphatidylethanolamine
  • Polyethylene Glycols
  • Ceftazidime