Liposome-encapsulated-amikacin therapy of Mycobacterium avium complex infection in beige mice

Cynamon, Michael H.; Swenson, Christine E.; Palmer, G S; Ginsberg, Rick

doi:10.1128/aac.33.8.1179

Cited by 64 publications

(41 citation statements)

References 14 publications

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“…The concentrations in serum and especially tissue differed with both forms, tending to be rather stable in spleen and to decrease more progressively in lungs with the liposomal form, as has been reported in other studies in mice in which aminoglycosides were used (11,15,48). In the kidney, an increase in the capreomycin concentrations was noted from 0 to 6 h, which may be explained by the renal route of elimination (5).…”

Section: Discussionmentioning

confidence: 50%

“…In all studies, both types of liposomes reduced the number of CFU similarly, although the concentrations in tissues were different. Furthermore, a study performed with amikacin and the same type of liposomes used in the present study reported 23% encapsulation but did not clearly specify the measurement method used (11).…”

Section: Discussionmentioning

confidence: 99%

“…However, it is impossible to conclude if encapsulation of capreomycin into liposomes reduces the long-term nephrotoxicity. (11,15,48) and can be attributed to the richness of cells in the reticuloendothelial system (which take up liposomes preferentially) in the organs studied (lungs and spleen) (1).…”

Section: Discussionmentioning

confidence: 99%

“…Liposomes containing aminoglycosides (amikacin, gentamicin, streptomycin, kanamycin) used in a mouse model of disseminated MAC infection have proved to be more efficient than free aminoglycosides in reducing the number of viable MAC organisms in organs (2,10,11,15,16,19,37). Liposome encapsulation reduces acute antibiotic toxicity and improves therapeutic activity by increasing the drug concentration at the infection site.…”

mentioning

confidence: 99%

“…Prophylactic treatment consisting of a daily injection of 120 mg of free or liposomal capreomycin per kg for 4 days was begun on the day before infection (11,37).…”

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confidence: 99%

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Pharmacokinetics, toxicity, and efficacy of liposomal capreomycin in disseminated Mycobacterium avium beige mouse model

Conte¹,

Gallou²,

Potel³

et al. 1994

Antimicrob Agents Chemother

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Capreomycin was incorporated into multilamellar vesicles of pure dipalmitoylphosphatidylcholine. The pharmacokinetics and nephrotoxicity of capreomycin in the free and liposomal forms were studied in normal mice. The efficacies of the two forms were evaluated by using the Mycobacterium avium complex beige mouse model. Approximately 107 viable M. avium cells were injected intravenously. Seven days later, treatment with either liposomal or free capreomycin at 60 or 120 mg/kg of body weight was administered daily for 5 days. Mice were sacrificed 5 days after the end of treatment, and the viable bacteria in liver, spleen, lungs, and blood were counted. After 5 days of treatment with dosages of 60 or 120 mg/kg/day, the level of blood urea nitrogen increased in the group treated with free capreomycin but not in the group treated with liposomal capreomycin. After intravenous injection of 120 mg/kg, liposomes enhanced the diffusion of capreomycin in the spleen, lungs, and kidneys and increased the half-life in serum. The 120-mg/kg dose of liposomal capreomycin significantly reduced the number of viable mycobacteria in the liver, spleen, and blood compared with those in the controls. Although these results are promising, further studies are needed to assess the efficacy of liposomal capreomycin for the treatment of M. avium complex infections.Since the appearance of the human immunodeficiency virus (HIV), the incidence of Mycobacterium avium complex (MAC) infections has increased considerably and has involved between 18 and 50% of HIV-infected patients (17,24,33). Treatment is difficult because of the weakened immune defense system of the host and the resistance of MAC strains to many classic antituberculous agents. Moreover, the phenotypes of resistance of these strains are very heterogeneous (25,26,49).Experimental infection models involving animal or human macrophage cultures and acute or chronic infections in the mouse have been developed to assess the activities of antiinfectious agents against MAC (32). Numerous studies have been performed either in vitro (25,28,36,49) or on macrophages (46) and in animal models (6,21,34,38,39) with classic or more recent antituberculous agents (ciprofloxacin, sparfloxacin, azithromycin, and clarithromycin) alone or in combi-

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Section: Discussionmentioning

confidence: 50%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

“…Prophylactic treatment consisting of a daily injection of 120 mg of free or liposomal capreomycin per kg for 4 days was begun on the day before infection (11,37).…”

mentioning

confidence: 99%

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