Except for management of Pseudomonas aeruginosa (PA) in cystic fibrosis, there are no approved inhaled antibiotic treatments for any other diseases or for infections from other pathogenic microorganisms such as tuberculosis, non-tuberculous mycobacteria, fungal infections or potential inhaled biowarfare agents including Francisella tularensis, Yersinia pestis and Coxiella burnetii (which cause pneumonic tularemia, plague and Q fever, respectively). Delivery of an antibiotic formulation via the inhalation route has the potential to provide high concentrations at the site of infection with reduced systemic exposure to limit side effects. A liposomal formulation may improve tolerability, increase compliance by reducing the dosing frequency, and enhance penetration of biofilms and treatment of intracellular infections. Two liposomal ciprofloxacin formulations (Lipoquin® and Pulmaquin®) that are in development by Aradigm Corporation are described here.

Infection with human or simian immunodeficiency virus (SIV) is characterized by the rapid turnover of both viral particles and productively infected cells. It has recently been reported that the clearance of SIV in vivo is exceedingly fast, with half-lives on the order of minutes. The underlying mechanism or site responsible for this rapid clearance, however, remains unknown. To investigate this issue, we chose to infuse infectious SIVmac239 grown from autologous peripheral blood mononuclear cells that were radioactively labeled by [35 S]methionine and [ 35 S]cysteine. This approach eliminates from the viral membrane alloantigens that may have a significant impact on viral clearance. In addition, this approach also permits identification of the sites of viral clearance by measuring the radioactive intensity, even if degradation of SIV RNA occurs in tissues. We now report that the half-life of infused SIV in blood is extremely close to estimates from a previous study, in which unlabeled SIV grown in a heterologous cell line was used. The allogeneic effect due to the presence of human antigens on the surfaces of virions may, therefore, play a minimal role in the high rate of virion clearance. Moreover, close to 30% of infused radioactivity was found in the liver and measureable amounts were detected in the lungs (5.4%), lymph nodes (3.0%), and spleen (0.4%). The detection of a significant proportion of infused virus in the liver suggests that viral clearance from circulation is mediated by a common, nonspecific mechanism, such as the phagocytic functions of the reticuloendothelial system. The rapid clearance and degradation of exogenously infused virions may pose a major obstacle for gene therapy with viral vectors, unless strategies to overcome the rapid in vivo elimination of these particles are developed.

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Histopathological preparations of cecum and colon from monkeys naturally infected with invasive Entamoeba histolytica were examined to determine the distribution of amebae in the tissues and the types of lesions, if any, associated with them. Infections were studied in 3 New World species (10 Callicebus moloch, 1 C. torquatus, and 2 Aotus trivirgatus) and 3 Old World species (8 Macaca mulatta, 6 Erythrocebus patas, and 1 Cercopithecus aethiops). Amebiasis was recorded as the principal or a contributing cause of death of all of the 13 New World monkeys and in 6 of the 15 Old World monkeys; amebiasis was detected in the rest of the monkeys only after tissues were re-examined specifically for amebae. Amebae causing no apparent damage were found in the lamina propriae, mainly at the muscularis mucosae. Most frequent were colonies or aggregates of amebae in the crypts between the epithelium and basement membrane, causing either no evident necrosis or changes ranging from necrosis and disarrangement of adjacent cells to complete destruction of the epithelium and reduction of the cells to pyknotic bodies. A lesion interpreted as possibly characteristic of carrier-state invasive amebiasis was destruction of the epithelium in patches of mucosal crypts, not leading to ulceration. Uncommon but present in both New and Old World monkeys were typical areas of surface erosion and classical flask-shaped ulcers. The observations show that in some species of Old World monkeys amebiasis can be invasive without causing clinical disease.