Efficacy of liposomal gentamicin against Rhodococcus equi in a mouse infection model and colocalization with R. equi in equine alveolar macrophages
2015
Burton, Alexandra J. | Giguère, S. (Steeve) | Berghaus, Londa J. | Hondalus, Mary K. | Arnold, Robert D.
Rhodococcus equi, a facultative intracellular pathogen and an important cause of pneumonia in foals, is highly susceptible to killing by gentamicin in vitro. However, gentamicin is not effective in vivo, due to its poor cellular penetration. Encapsulation of drugs in liposomes enhances cellular uptake. The objectives of this study were to compare liposomal gentamicin and free gentamicin with respect to their uptake by equine macrophages and intracellular colocalization with R. equi and to compare the efficacies of liposomal gentamicin, free gentamicin and clarithromycin with rifampin for the reduction of R. equi CFU in a mouse model of infection. After ex vivo exposure, a significantly higher mean (±SD) percentage of equine alveolar macrophages contained liposomal gentamicin (91.9±7.6%) as opposed to free gentamicin (16.8±12.5%). Intracellular colocalization of drug and R. equi, as assessed by confocal microscopy, occurred in a significantly higher proportion of cells exposed to liposomal gentamicin (81.2±17.8%) compared to those exposed to free gentamicin (10.4±8.7%). The number of R. equi CFU in the spleen was significantly lower in mice treated with liposomal gentamicin compared to that of mice treated with free gentamicin or to untreated control mice. Treatment with liposomal gentamicin also resulted in a significantly greater reduction in the number of R. equi CFU in the liver compared to treatment with clarithromycin in combination with rifampin. These results support further investigation of liposomal gentamicin as a new treatment for infections caused by R. equi.
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