Preclinical testing of the nitroimidazopyran PA-824 for activity against Mycobacterium tuberculosis in a series of in vitro and in vivo models

This study extends earlier reports regarding the in vitro and in vivo efficacies of the nitroimidazopyran PA-824 against Mycobacterium tuberculosis. PA-824 was tested in vitro against a broad panel of multidrug-resistant clinical isolates and was found to be highly active against all isolates (MIC<1 microg/ml). The activity of PA-824 against M. tuberculosis was also assessed grown under conditions of oxygen depletion. PA-824 showed significant activity at 2, 10, and 50 microg/ml, similar to that of metronidazole, in a dose-dependent manner. In a short-course mouse infection model, the efficacy of PA-824 at 50, 100, and 300 mg/kg of body weight formulated in methylcellulose or cyclodextrin/lecithin after nine oral treatments was compared with those of isoniazid, rifampin, and moxifloxacin. PA-824 at 100 mg/kg in cyclodextrin/lecithin was as active as moxifloxacin at 100 mg/kg and isoniazid at 25 mg/kg and was slightly more active than rifampin at 20 mg/kg. Long-term treatment with PA-824 at 100 mg/kg in cyclodextrin/lecithin reduced the bacterial load below 500 CFU in the lungs and spleen. No significant differences in activity between PA-824 and the other single drug treatments tested (isoniazid at 25 mg/kg, rifampin at 10 mg/kg, gatifloxacin at 100 mg/kg, and moxifloxacin at 100 mg/kg) could be observed. In summary, its good activity in in vivo models, as well as its activity against multidrug-resistant M. tuberculosis and against M. tuberculosis isolates in a potentially latent state, makes PA-824 an attractive drug candidate for the therapy of tuberculosis. These data indicate that there is significant potential for effective oral delivery of PA-824 for the treatment of tuberculosis.     

Two decades have passed ... and still it is her eyes that I remember: reflections of a pediatric nurse

A pediatric nurse reflects on her practice by recounting her experience while caring for a child with Guillian Barre 20 years ago. Principles and lessons relevant to guide pediatric nursing practice in today's health care environment are identified.     

Successful treatment of pure red cell aplasia associated with systemic lupus erythematosus with oral danazol and steroid

We describe a middle-aged Chinese systemic lupus erythematosus (SLE) patient developing steroid refractory and transfusion dependent red cell aplasia. Oral danazol 200 mg twice per day was started together with low-dose prednisolone therapy. There was no further recurrence of anemia 1 month after this combined therapy.     

Comparison of Campylobacter jejuni isolates implicated in Guillain-Barré syndrome and strains that cause enteritis by a DNA microarray

We asked whether Campylobacter jejuni isolated from patients with Guillain-Barré syndrome (GBS) differ from isolates isolated from patients with uncomplicated gastrointestinal infection using DNA microarray analysis. We found that specific GBS genes or regions were not identified, and microarray analysis confirmed significant genomic heterogeneity among the isolates.     

Reemerging leptospirosis, California

Leptospirosis is a reemerging infectious disease in California. Leptospirosis is the most widespread zoonosis throughout the world, though it is infrequently diagnosed in the continental United States. From 1982 to 2001, most reported California cases occurred in previously healthy young adult white men after recreational exposures to contaminated freshwater. We report five recent cases of human leptospirosis acquired in California, including the first documented common-source outbreak of human leptospirosis acquired in this state, and describe the subsequent environmental investigation. Salient features in the California cases include high fever with uniform renal impairment and mild hepatitis. Because leptospirosis can progress rapidly if untreated, this reemerging infection deserves consideration in febrile patients with a history of recreational freshwater exposure, even in states with a low reported incidence of infection.