title: Efficacy of gentamicin or ceftazidime entrapped in liposomes with prolonged blood circulation and enhanced localization in Klebsiella pneumoniae-infected lung tissue.
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.
authors.affiliation: Department of Clinical Microbiology, Erasmus University, Rotterdam, Netherlands.
authors.forename: I A
authors.initials: IA
authors.lastname: Bakker-Woudenberg
authors.forename: M T
authors.initials: MT
authors.lastname: ten Kate
authors.forename: L E
authors.initials: LE
authors.lastname: Stearne-Cullen
authors.forename: M C
authors.initials: MC
authors.lastname: Woodle
mesh_terms: D000818:Animals; D002442:Ceftazidime / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D004337:Drug Carriers; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D007710:Klebsiella Infections / Q000188:drug therapy*; D007711:Klebsiella pneumoniae / Q000187:drug effects; D008081:Liposomes / Q000633:toxicity; D008168:Lung / Q000382:microbiology; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D018410:Pneumonia, Bacterial / Q000188:drug therapy*; D011092:Polyethylene Glycols; D051381:Rats; D013047:Specific Pathogen-Free Organisms
chemical_list: D004337:Drug Carriers; D005839:Gentamicins; D008081:Liposomes; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C038089:1,2-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols; D002442:Ceftazidime