It has been shown previously that
tobramycin encapsulated in fluid
liposomes (composed of
dipalmitoylphosphatidylcholine (DPPC) and
dimyristoylphosphatidylglycerol (
DMPG)) eradicated mucoid Pseudomonas aeruginosa in an animal model of chronic pulmonary
infection. Exponential cultures of P. aeruginosa, Stenotrophomonas maltophila, Burkholderia cepacia, Escherichia coli and Staphylococcus aureus were treated with (i) free
tobramycin, (ii) sub-MIC
tobramycin encapsulated in DPPC/
DMPG liposomes, (iii) control
liposomes without
antibiotic or (iv) control
liposomes combined with free
tobramycin. Bacterial colonies were counted 0, 1, 3, 6 and 16 h after addition of
antibiotic. After 3 h, the growth of B. cepacia, E. coli and S. aureus was reduced 129, 84 and 566 times respectively in cultures treated with encapsulated
antibiotic compared with those treated with free
antibiotic. Six hours and 16 h
after treatment, the maximal reduction of growth between strains treated with
liposome-encapsulated
tobramycin and free
tobramycin was 84, 129, 166, 10(5) and 10(4) times respectively for P. aeruginosa, B. cepacia, E. coli, S. maltophilia and S. aureus. The
liposomes were stable at 4 degrees C and at room temperature for the whole period studied. At 37 degrees C, equivalent stability was observed for the first 16 h of the study. Administration of
antibiotic encapsulated in DPPC/
DMPG liposomes may thus greatly improve the management of resistant
infections caused by a large range of microorganisms. The strong bactericidal activity of the encapsulated
antibiotic at sub-MIC doses of the strains tested cannot be explained only as a result of prolonged residence time of
liposome-encapsulated
tobramycin and the resulting release of entrapped
antibiotic at the bacterial site; rather, direct interaction of chemoliposomes and bacteria, probably by a fusion process, may explain the bactericidal effect of the sub-MIC
antibiotic doses used.