EFFICACY OF GENTAMICIN OR CEFTAZIDIME ENTRAPPED IN LIPOSOMES WITH PROLONGED BLOOD-CIRCULATION AND ENHANCED LOCALIZATION IN KLEBSIELLA PNEUMONIAE-INFECTED LUNG-TISSUE

Polymer (PEG-PE)-coated liposomes exhibit prolonged circulation time i n 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 admin istered to rats experimentally infected with pneumonia: Relatively hig h and sustained concentrations of liposome-associated antibiotic in bl ood were observed. Compared with antibiotics alone, one dose of liposo me-entrapped gentamicin or ceftazidime increased the therapeutic effec t of the drugs, survival of rats, and bacterial killing in lungs. One dose of liposome-entrapped ceftazidime was as effective as a continuou s 2-day infusion of nonentrapped ceftazidime. Since antibiotic-contain ing liposomes are stable during circulation and liposome-entrapped cef tazidime and gentamicin have low bactericidal activity in vitro, the s uperior therapeutic effect of the liposome-encapsulated antibiotics re sults from localization and subsequent degradation of liposomes and th e resulting release of entrapped antibiotic at the infection site.