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Journal of Antimicrobial Chemotherapy (2001) 48, 877-880
© 2001 The British Society for Antimicrobial Chemotherapy

The early bactericidal activity of a low-clearance liposomal amikacin in pulmonary tuberculosis

Peter R. Donalda, Frederick A. Sirgelb, Amour Venterb, Elizabeth Smita, Donald P. Parkina, Bernard W. Van de Wala and Denis A. Mitchisonc,*

a Departments of Paediatrics and Child Health, Pharmacology, Medical Biochemistry and Internal Medicine, University of Stellenbosch, Cape Town; b Medical Research Council, Tygerberg, South Africa; c St George's Hospital Medical School, London SW17 0RE, UK

The early bactericidal activity (EBA) of a liposomal preparation of amikacin (MiKasome) with a long plasma half-life of 120–200 h was examined in seven patients with newly diagnosed, smear-positive pulmonary tuberculosis. Liposomal amikacin was given in slow iv infusions of 30 mg total amikacin/kg body weight on three successive days. Cfu counts were set up on 16 h sputum collections preceding the first dose and following each dose and were used for calculating the EBA. Despite the high concentrations of total amikacin, >1000 mg/L, obtainable in plasma, no evidence of EBA was obtained. In view of the considerable activity of liposomal amikacin in experimental murine tuberculosis, this finding indicates that liberation of amikacin from the long-life liposomes occurs only in macrophages that are not usually present in the vicinity of the large extracellular clumps of bacilli in the cavity caseum.

* Corresponding author. Tel: +44-20-8725-5704; Fax: +44-20-8672-0234; E-mail: dmitchis{at}sghms.ac.uk


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J. Dhillon, R. Fielding, J. Adler-Moore, R. L. Goodall, and D. Mitchison
The activity of low-clearance liposomal amikacin in experimental murine tuberculosis
J. Antimicrob. Chemother., December 1, 2001; 48(6): 869 - 876.
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