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Excerpt
Previously we reported the effects of three new immunosuppressive drugs used for organ transplantation compared with dexamethasone in provocation of Pneumocystis carinii pneumonitis, in virus-free Sprague Dawley rats (1). This model has been found remarkably similar to the human disease. The tropism of the organism, histology, pathogenesis, and response to drugs in the animal model are almost identical to those parameters in humans. Twenty-nine percent of rats treated with 4 mg/kg of rapamycin (sirolimus) for 4 weeks developed P carinii pneumonitis. Rats treated with tacrolimus showed a dose-dependent response to the point of severe Pneumocystis carinii pneumonitis similar to those treated with high-dose dexamethasone. In contrast mycophenolate mofetil alone or combined with dexamethasone had a novel protective effect, and 0% of animals became infected with P carinii (Table 1).
In the recent issue of Transplantation, Dominguez and colleagues evaluated the effects of 5 mg/kg of rapamycin in 20 patients after renal transplantation from 0 to 204 months (2). Of the 12 patients treated with rapamycin, 2 (17%) developed pneumonitis due to P carinii infection. These patients were not on P carinii prophylaxis. The pneumonia persisted until rapamycin was withdrawn. The authors conclude that rapamycin drug levels should be monitored to avoid overimmunosuppression and P carinii pneumonia prophylaxis should be given.
We found this study to be of major interest. However, these findings could have been anticipated based on our previously published work in the rat model.
