The control of microorganisms is critical for the prevention and treatment of disease. Microorganisms also grow on and within other organisms, and microbial colonization can lead to disease, disability, and death. Thus the control or destruction of microorganisms residing within the bodies of humans and other animals is of great importance.
The most successful drugs interfere with processes that differ between the pathogen and host, and seriously damage the target microorganism while harming its host as little as possible.
Treatment of fungal infections generally has been less successful than that of bacterial infections largely because eukaryotic fungal cells are much more similar to human cells than are bacteria. Many drugs that inhibit or kill fungi are therefore quite toxic for humans. In addition, most fungi have a detoxification systems that modifies many antibiotics, probably by hydroxylation. As a result the added antibiotics are fungistactic only as long as repeated application maintains high levels of unmodified antibiotic. Despite their relatively low therapeutic index, a few drugs are useful in treating many major fungal diseases. Effective antifungal agents frequently either extract membrane sterols or prevent their synthesis. Similarly, because animal cells do not have cell walls, the enzyme chitin synthase is the target for fungal active antibiotics such as polyoxin D and nikkomycin.
Fungal infections are divided into infections of superficial tissues or superficial mycoses and systemic mycoses. Treatment for these two types of diseases is very different.
Several drugs are used to treat superficial mycoses. Three drugs containing imidazole- miconazole, ketoconazole, and clotrimazole- are broad spectrum agents available as creams and solutions for the treatment of dermatophyte infections such as athlete�s foot, and oral and vaginal candidiasis. They are thought to disrupt fungal membrane permeability and inhibit sterol synthesis. Tolnaftate is used topically for the treatment of cutaneous infections, but is not as effective against infections of the skin and hair. Nystatin, a polyene antibiotic from Streptomyces, is used to control Candida infections of the skin, vagina, or alimentary tract. Griesofulvin, an antibiotic formed by Penicillium, is given orally to treat chronic dermatophyte infections. It is thought to disrupt the mitotic spindle and inhibit cell division; it also may inhibit protein and nucleic acid synthesis. Side effects of griseofulvin include headaches, gastrointestinal upset, and allergic reactions.
Systemic infections are very difficult to control and can be fatal. Three drugs commonly used against systemic mycoses are amphotericin B, 5-flucystosine, and fluconazole. Amphotericin B from Streptomyces spp. binds to the sterols in fungal membranes, disrupting membrane permeability and causing leakage of cell constituents. It is quite toxic and used only for serious, life threatening infections. The synthetic oral antimycoctic agent 5-flucytosine is effective against most systemic fungi, although drug resistance often develops rapidly. The drug is converted to 5-fluorouracil by the fungi, incorporated into RNA in place of uracil, and disrupts the RNA function. Its side effects include skin rashes, diarrhea, nausea, aplastic anemia, and liver damage. Fluconazole is used in the treatment of candidiasis, cryptococcal meningitis, and coccidioidal meningitis. Adverse effects are relatively uncommon.
Overuse of Antifungal agents leads to an increase in drug resistance. For example, Candida infections are becoming more frequent and drug resistant.
