造血干细胞移植后的感染黄晓军2.pptVIP

* * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * Various antifungal agents target different parts of fungal cells as illustrated here. The antifungal agents in yellow are those currently approved by the FDA; those in white are in varying stages of development. The polyenes, amphotericin B, its lipid formulations, and nystatin interfere with membrane function. They are derived from Streptomyces species, are fungicidal, and have a broader range of action than other types of antifungal agents. They bind to membrane sterols causing increased membrane leakage and cell death. Those that are clinically useful have a higher affinity for ergosterol than for its mammalian equivalent, cholesterol, thereby limiting their toxicity in mammalian cells. Amphotericin B is the only polyene used to treat deep mycoses in severely immunocompromised patients, but its effectiveness is limited by its toxic side effects. Delivery of this agent in lipid formulations helps to reduce the toxicity. They can be used for patients unable to tolerate amphotericin B’s toxicity. The azole agents are synthetic compounds with a broad antifungal activity that encompasses more yeasts and filamentous fungi. Azoles are classified as imidazoles or triazoles, depending on whether the azole has 2 or 3 nitrogens in the 5-membered azole ring. Both groups of azoles act on ergosterol biosynthesis at the C-14 demethylation step, a cytochrome P-450-dependent reaction. The effect is alteration of the plasma membrane structure and is fungistatic rather than fungicidal. The older imidazoles can interact with and damage the cell membrane directly, making them fungicidal and toxic, and therefore they are used only topically. The azoles do not produce serious toxicity, but they influence the endocrine system by inhibiting mammalian cytochrome P-450–dependent enzymes that synthesize steroid hormones. The effect is far more pronounced in the older imidazoles. The effect of 5-fluorocytosine as an antifungal age