Eradication of mucoid Pseudomonas aeruginosa with fluid liposome-encapsulated tobramycin in an animal model of chronic pulmonary infection

Despite controversies associated with forms and value of antibiotic therapy for cystic \ufb01brosis patients, antibiotherapy remains a cornerstone in the management of those patients. Locally administered liposome-encapsulated antibiotics may offer advantages over free antibiotics, including sustained concentration of the antibiotic, minimal systemic absorption, reduced toxicity, and increased ef\ufb01cacy. We evaluated the ef\ufb01cacy of free and encapsulated tobramycin in \ufb02uid and rigid liposomal formulations administered to rats chronically infected with Pseudomonas aeruginosa. Chronic infection in lungs was established by intratracheal administration of 10\u2075 CFU of a mucoid variant of P. aeruginosa PA 508 prepared in agar beads. Antibiotic treatments were given intratracheally at time intervals of 16 h. After the last treatment, lung bacterial counts were determined and tobramycin levels in the lungs and kidneys were evaluated by high-performance liquid chromatographic analysis and microbiological assay. Two independent experiments showed that animals treated with encapsulated tobramycin in \ufb02uid liposomes had a number of CFU less than the minimal CFU number required to be statistically acceptable compared with 6710\u2076 CFU per pair of lungs for animals treated with encapsulated tobramycin in rigid liposomes, free antibiotic, or liposomes without tobramycin. Tobramycin measured in the lungs at 16 h after the last treatment following the administration of encapsulated antibiotic was still active, and its concentration was 6727 \u3bcg/mg of tissue. Low levels of tobramycin were detected in the kidneys (0.59 to 0.87 \u3bcg/mg of tissue) after the administration of encapsulated antibiotic, while 5.31 \u3bcg/mg of tissue was detected in the kidneys following the administration of free antibiotic. These results suggest that the local administration of \ufb02uid liposomes with encapsulated tobramycin could greatly improve the management of chronic pulmonary infection in cystic \ufb01brosis patientsNRC publication: Ye