In vitro and in vivo activities of three acridine thioethers against Leishmania donovani.

The lack of definitive chemotherapeutic agents to fight against visceral leishmaniasis has lead to the testing of numerous compounds. In the present work, we carry out an in-depth study of the activity against Leishmania donovani of three acridine derivatives both in vitro and in vivo. These compounds have proven to be highly effective at medium and high concentrations of 10 microg/ml, against both flagellate and nonflagellate forms of the parasite, which, though obtained in vitro, closely resemble natural intracellular amastigotes. The in vivo assays showed a significant reduction in the percentage of parasitation versus control, for all the compounds tested. In addition, we have studied the possible mechanism by which these acridine derivatives act: they displayed a greater inhibitory effect against macromolecule synthesis in treated flagellates, yet alterations are also caused in the production of end metabolites and in the activity of different enzymes. The data obtained indicate that the acridine derivatives had several targets, one of them is the synthesis of nucleic acids and proteins, while the second one might be interaction with the carbohydrate and energy-production processes in the parasite. This conclusion is consistent with our observations concerning the ultrastructural changes induced in the parasite by these compounds principally at the mitochondrial level.

Medical management of pneumonia caused by Rhodococcus equi in a renal transplant recipient.

Rhodococcus equi is an animal pathogen that occasionally causes opportunistic infections in immunocompromised patients. The most common clinical picture is one of necrotizing pneumonia with a tendency toward cavitation and the formation of abscesses. We report a case of pneumonia caused by R equi in a renal transplant patient. An excellent response was shown to antibiotic treatment. Symptoms regressed, and the progressive disappearance of the lesion was confirmed on follow-up computed tomography scans. Surgical intervention or other invasive procedures were not required. To our knowledge, 14 cases of infection by R equi in solid-organ transplant patients have been described to date. Nine were recipients of a renal allograft. Surgery was required in many of these patients, and all the renal transplant recipients required the use of invasive therapeutic techniques, such as pleural drainage. This is the first case of a renal transplant recipient in whom radiologic presentation was as a solid nodule without ensuing cavitation that resolved exclusively with antibiotic treatment.