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[link] shows the various therapeutic classes of antifungal drugs, categorized by mode of action, with examples of each.
| Common Antifungal Drugs | |||
|---|---|---|---|
| Mechanism of Action | Drug Class | Specific Drugs | Clinical Uses |
| Inhibit ergosterol synthesis | Imidazoles | Miconazole, ketoconazole, clotrimazole | Fungal skin infections and vaginal yeast infections |
| Triazoles | Fluconazole | Systemic yeast infections, oral thrush, and cryptococcal meningitis | |
| Allylamines | Terbinafine | Dermatophytic skin infections (athlete’s foot, ring worm, jock itch), and infections of fingernails and toenails | |
| Bind ergosterol in the cell membrane and create pores that disrupt the membrane | Polyenes | Nystatin | Used topically for yeast infections of skin, mouth, and vagina; also used for fungal infections of the intestine |
| Amphotericin B | Variety systemic fungal infections | ||
| Inhibit cell wall synthesis | Echinocandins | Caspofungin | Aspergillosis and systemic yeast infections |
| Not applicable | Nikkomycin Z | Coccidioidomycosis (Valley fever) and yeast infections | |
| Inhibit microtubules and cell division | Not applicable | Griseofulvin | Dermatophytic skin infections |
Jack, a 48-year-old engineer, is HIV positive but generally healthy thanks to antiretroviral therapy (ART) . However, after a particularly intense week at work, he developed a fever and a dry cough. He assumed that he just had a cold or mild flu due to overexertion and didn’t think much of it. However, after about a week, he began to experience fatigue, weight loss, and shortness of breath. He decided to visit his physician, who found that Jack had a low level of blood oxygenation. The physician ordered blood testing, a chest X-ray, and the collection of an induced sputum sample for analysis. His X-ray showed a fine cloudiness and several pneumatoceles (thin-walled pockets of air), which indicated Pneumocystis pneumonia (PCP), a type of pneumonia caused by the fungus Pneumocystis jirovecii . Jack’s physician admitted him to the hospital and prescribed Bactrim , a combination of sulfamethoxazole and trimethoprim , to be administered intravenously.
P. jirovecii is a yeast-like fungus with a life cycle similar to that of protozoans. As such, it was classified as a protozoan until the 1980s. It lives only in the lung tissue of infected persons and is transmitted from person to person, with many people exposed as children. Typically, P. jirovecii only causes pneumonia in immunocompromised individuals. Healthy people may carry the fungus in their lungs with no symptoms of disease. PCP is particularly problematic among HIV patients with compromised immune systems.
PCP is usually treated with oral or intravenous Bactrim, but atovaquone or pentamidine (another antiparasitic drug) are alternatives. If not treated, PCP can progress, leading to a collapsed lung and nearly 100% mortality. Even with antimicrobial drug therapy, PCP still is responsible for 10% of HIV-related deaths.
The cytological examination, using direct immunofluorescence assay (DFA), of a smear from Jack’s sputum sample confirmed the presence of P. jirovecii ( [link] ). Additionally, the results of Jack’s blood tests revealed that his white blood cell count had dipped, making him more susceptible to the fungus. His physician reviewed his ART regimen and made adjustments. After a few days of hospitalization, Jack was released to continue his antimicrobial therapy at home. With the adjustments to his ART therapy, Jack’s CD4 counts began to increase and he was able to go back to work.
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