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-

Neisseria elongata subsp. nitroreducens, an usual commensal of the nasopharynx, can cause serious infections, usually endocarditis. A case of Neisseria elongata endocarditis complicating mitral valve prolapse in a patient allergic to penicillin is reported. Cure was obtained with a combination of ceftriaxone and gentamicin, there being no requirement for surgery during the acute phase of the disease.

No abstract

The activity of roxithromycin against three clinical isolates of Mycobacterium avium was compared with that of clarithromycin both in a model of infection of human monocyte-derived macrophages and in a model of established infection of C57BL/6 mice. In the cell culture model, roxithromycin and clarithromycin were bactericidal for strains MO-1 and N-92159 and bacteriostatic for strain N-93043. For the three strains, the differences between the intracellular activities of roxithromycin and clarithromycin were not significant after 7 days of treatment. Mice were infected with the MO-1 strain. Drugs were given by gavage at a dosage of 200 mg/kg of body weight 6 days per week for 16 weeks starting 5 weeks after infection. At the end of treatment, clarithromycin was more effective than roxithromycin in lungs; roxithromycin was as effective as clarithromycin in spleens. Thus, the activity of roxithromycin was comparable to that of clarithromycin both in vitro and in vivo.New macrolides are among the most active antibiotics against the Mycobacterium avium complex. Clarithromycin, in particular, has been proven to be effective in treating disseminated M. avium infection in AIDS patients (6, 10) and is now the reference macrolide for this indication. Among other macrolides, although roxithromycin has been shown to be active in vitro against M. avium (1, 2, 11, 14, 15), its activity has been neither compared with that of clarithromycin nor evaluated in vivo. The purpose of the present study was to evaluate the anti-M. avium activity of roxithromycin compared with that of clarithromycin both in vitro in a model of infection of human monocyte-derived macrophages and in vivo in a model of established infection in C57BL/6 mice. MO-1, N-93043, and N-92159, obtained from the blood of AIDS patients were used for the in vitro studies. Strain MO-1 was used for the in vivo studies; this strain has been used in our previous studies (3,4,12,13). Cell suspensions with predominantly (Ͼ95%) transparent colony morphologies cultivated in Middlebrook 7H9 broth (Difco Laboratories, Detroit, Mich.) supplemented with ADC enrichment (Difco) were used as described previously (13). The organisms were passaged through C57BL/6 mice to maintain the virulence of the organisms. MATERIALS AND METHODS Strains of M. avium. Three clinical isolates of M. avium,Antimicrobial agents. Roxithromycin (Roussel-Uclaf, Romainville, France) and clarithromycin (Abbott France, Rungis, Val de Marne, France) were provided as standard powders by the manufacturers. In the cell model, the lactobionate salt of clarithromycin was used and was dissolved in distilled water; roxithromycin was dissolved in methanol and was subsequently diluted in distilled water. For the in vivo studies, suspensions in carboxymethyl cellulose were used for both antibiotics tested.In vitro susceptibility. The MICs were determined by the agar macrodilution method by using Mueller-Hinton agar medium supplemented with 10% Middlebrook OADC enrichment (Difco) (17).Human macrophage model. (i) Human m...