Journal of Antimicrobial Chemotherapy, Vol 41, 35-41, Copyright © 1998 by The British Society for Antimicrobial Chemotherapy
C Beaulac, S Sachetelli and J Lagace
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.
ORIGINAL ARTICLES
In-vitro bactericidal efficacy of sub-MIC concentrations of liposome- encapsulated antibiotic against gram-negative and gram-positive bacteria
Department of Microbiology and Immunology, Faculty of Medicine, Universite de Montreal, Quebec, Canada.
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