title: Liposomal amikacin: improved treatment of Mycobacterium avium complex infection in the beige mouse model.
abstract: Disseminated Mycobacterium avium complex (MAC) infection has reached epidemic proportions and is a major cause of morbidity and mortality in AIDS patients. We have developed a liposomal preparation of amikacin, VS107, which incorporates the drug in 54-65 nm diameter unilameller phospholipid vesicles and is stable at 4 degrees C for more than 4 months. VS107 exhibits superior microbiological and pharmacological activity over the free amikacin and improves the survival of mice in the established model for MAC infection. The serum half-life of VS107 in mice was 9.1 h and a peak serum level of 730 mg/L was obtained after administering three doses of 160 mg/kg. For the therapeutic study, beige mice infected with 10(7) cfu M. avium complex strain 101 were randomised to be treated with placebo liposomes, buffer, free amikacin or VS107 The drugs were administered via the caudal vein thrice weekly for 1, 3, 5 or 7 weeks beginning 5 days after infection. After 51 days of treatment with VS107, the number of viable M. avium in the liver and spleen was a 100 fold lower than was achieved with conventional amikacin (P < 0.01), and more than six decimal logarithms lower than was found untreated controls (P < 0.001). VS107 was well tolerated and might be a suitable candidate for treating human MAC infections.
authors.affiliation: Department of Medicine, University of Arizona College of Medicine, Tucson, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Petersen
authors.forename: J B
authors.initials: JB
authors.lastname: Grayson
authors.forename: E M
authors.initials: EM
authors.lastname: Hersh
authors.forename: R T
authors.initials: RT
authors.lastname: Dorr
authors.forename: S M
authors.initials: SM
authors.lastname: Chiang
authors.forename: M
authors.initials: M
authors.lastname: Oka
authors.forename: R T
authors.initials: RT
authors.lastname: Proffitt
mesh_terms: D000583:Amikacin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008081:Liposomes; D008099:Liver / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D015269:Mycobacterium avium Complex / Q000187:drug effects*; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy* / Q000382:microbiology; D011897:Random Allocation; D013154:Spleen / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D008081:Liposomes; D000583:Amikacin