Briefly describe 3 different ways antifungal chemotherapeutic agents may affect fungi and give an example of an antibiotic for each way.
Remember that like human cells, fungal cells are eukaryotic. Since fungal cells, unlike prokaryotic bacterial cells, are not that different from human cells, it is more difficult to find a chemotherapeutic agent that is selectively toxic for fungi, that is, will inhibit or kill fungal cells without also inhibiting or killing human cells. Some of the common antifungal chemotherapeutic agents are listed below.
- One antibiotic, griseofulvin (Fulvicin, Grifulvin, Gris-PEG), interferes with nuclear division by preventing the aggregation of microtubules needed for mitosis in superficial mycelial fungi. It is used only for severe dermatophyte infections.
- The antimetabolites trimethoprim + sulfomethoxazole , trimetrexate, atovaquone, and flucytosine interfere with normal nucleic acid synthesis. Trimethoprim/sulfomethoxazole (Septra, Bactrim), atovaquone (Mepron), and trimetrexate (Neutrexin) are used to treat Pneumocystis pneumonia. Flucytosine (Ancobon) is used for more serious Candida infections.
- Polyene antibiotics such as amphotericin B, pimaricin, and nystatin are fungicidal drugs that bind to ergosterol in the fungal cytoplasmic membrane thus altering its structure and function and causing leakage of cellular needs. Nystatin (Mycostatin) is used to treat superficial Candida infections (thrush, vaginitis, cutaneous infections), amphotericin B (Abelcet, Fungizone) is used for systemic Candida infections, Cryptococcus infections, and dimorphic fungal infections.
- The azole derivative antibiotics such as clotrimazole, miconazole, itraconazole, fluconazole, and ketoconazole, are fungistatic drugs used to treat many fungal infections. They interfere with ergosterol biosynthesis and thus alter the structure of the cytoplasmic membrane as well as the function of several membrane-bound enzymes like those involved in nutrient transport and chitin synthesis. Clotrimazole (Lotramin, Mycelex), miconazole (Monistat), and econazole (Spectazole) are used to treat superficial Candida and dermatophyte infections; oxiconazole (Oxistat) and sulconazole (Exelderm) are used for dermatophyte infections; butaconazole (Femstat-3), terconazole (Terazole), and tioconazole (Vagistat-1) are used for Candida vaginitis; ketoconazole (Nizoral) and itraconazole (Sporanox) are used for systemic Candida, Cryptococcus, and dimorphic fungal infections; and fluconazole (Diflucan) is used for Candida infections. Voriconazole (VFEND) is a triazole is used to treat Candida infections such as candidemia, disseminated infections in skin and infections in abdomen, kidney, bladder wall, and wounds. It is also used for invasive aspergillosis.
- Echinocandins, including caspofungin (Cancidas) and micafungin (Mycamine) are intravenous antifungals that inhibits glucan synthesis in fungal cell walls. It is used in the treatment of candidemia , Candida intra-abdominal abscesses, peritonitis, esophageal candidiasis, and pleural space infections.
- Naftifine (Naftin) and terbinafine (Lamisil) are allylamines that block synthesis of ergosterol as does the topical thiocarbonate tolnaftate. They are used to treat dermatophyte infections.
Exercise: Think-Pair-Share Questions
- Why are there so few antifungal chemotherapeutic agents compared to the number of antibacterial agents?
- Most of the antifungal agents interfere with the synthesis of ergosterol in the fungal cytoplasmic membrane.
- How does this harm the fungus?
- Why don’t these agents work on bacterial and viral infections?
For a more detailed description of any specific antimicrobial agent, see the website of RxList - The Internet Drug Index.
Contributors and Attributions
Dr. Gary Kaiser (COMMUNITY COLLEGE OF BALTIMORE COUNTY, CATONSVILLE CAMPUS)