Activities of clarithromycin, sulfisoxazole, and rifabutin against Mycobacterium avium complex multiplication within human macrophages

Perronne, Christian; Gikas, Achille; Truffot-Pernot, C.; Grosset, J; Pocidalo, J J; Vildé, J. L.

doi:10.1128/aac.34.8.1508

Cited by 76 publications

(58 citation statements)

References 17 publications

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“…Amikacin and clarithromycin have proved to be the most active agents both in vitro and in vivo (18,21,34,46). However, to date only clarithromycin has been demonstrated to have curative efficacy in humans in a controlled clinical trial (12).…”

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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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confidence: 99%

“…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 combination.…”

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confidence: 99%

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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show abstract

“…Relapse with resistant strains was seen with both agents (18,19,20). Although the in vitro minimum inhibitory concentrations are not as low as with clarithromycin , the high degree of penetration of azithromycin into phagocytes makes this drug uniquely effective (21). In combination with other agents, clarithromycin and azithromycin have now assumed a central role in the treatment and prophylaxis of MAC (18).…”

Section: Macrolides Available In the Unitedmentioning

confidence: 99%

“…avium complex (MAC) infections (18)(19)(20)(21)(22). Both clarithromycin and azithromycin penetrate phagocytes and have been shown to effectively inhibit the replication of MAC in macrophage cell lines (21). Used alone, clarithromycin and azithromycin were initially very effective in treating disseminated MAC in AIDS (18,19,20).…”

Section: Macrolides Available In the Unitedmentioning

confidence: 99%