抗真菌药在宿主细胞肺内药物分布与药效动力学（英文PPT）Intrapulmonary drug distribution pharmacodynamic interactions of antifungal drugs with host cells.ppt

* * * * So it is important to remember there are sites were the echinocandins do not achieve therapeutically-effective concentrations, especially in the setting of mild resistance. Echinocandins are not good choices for infection localized the the brain and CSF, eyes or bladder Agents cannot act unless they are bound * * Intrapulmonary drug distribution pharmacodynamic interactions of antifungal drugs with host cells Russell E. Lewis, Pharm.D., FCCP, BCPS Associate Professor University of Houston College of Pharmacy The University of Texas M.D. Anderson Cancer Center Houston, Texas UH Anti-Infective Research Laboratories Outline How does the pathophysiology of invasive pulmonary aspergillosis impair drug delivery to the site of infection? Are pharmacokinetic differences among antifungal agents important for the treatment of fungal pneumonia? Impaired by neutropenia, glucocorticoids, metabolic abnormalities, concomitant infections Pathology of acute mould infectionsneutropenic hosts Inhalation of conidia Conidia reach distal alveolar space and begin to germinate Mononuclear and polymorphonuclear cells clear germinating conidia and hyphal forms Angioinvasive growth In tissue with hemorrhage, thrombosis, hypoxia, necrosis, and dissemination Administer drugs to slow fungal proliferation; and reduce, angioinvasion, and dissemination Figure: R. Lewis Inhalation of conidia Conidia reach distal alveolar space and begin to germinate Mononuclear and polymorphonuclear cells clear germinating conidia and hyphal forms Angioinvasive growth In tissue with hemorrhage, thrombosis, hypoxia, necrosis, and dissemination Figure: R. Lewis Dysregulated inflammatory response Immunopathology hemorrhage, necrosis Pathology of acute mould infectionscorticosteroid and mixed immunosuppression? Figure: R. Lewis Progressive thrombosis- inflammation-necrosis impair drug activity in invasive aspergillosis Solid nodular consolidation with necrotic center Dense neutrophilic infiltrate on pe