Kinetics and toxicity of liposomal and conventional amikacin in a patient with multidrug-resistant tuberculosis

The pharmacokinetics and toxicity of liposomal amikacin in a patient treated for advanced pulmonary multidrug-resistant tuberculosis are described. A dose of 20 mg/kg of liposomal amikacin was given on alternate days for 14 days and weekly thereafter for 9 weeks, for a total dose of 20.1 g in 17 divided doses. Accumulation occurred with alternate-day, but not weekly, dosing. The serum levels of amikacin obtained with the liposomal preparation were considerably greater than those obtained with the conventional preparation (range, 81-457 mg/l vs. 4.1-37.7 mg/l). The liposomal amikacin was well tolerated and led to clinical improvement, but it failed to achieve a microbiological response. The patient's sputum remained smear- and culture-positive during the treatment period with liposomal amikacin and for 9 months afterward.