The increased use of antibacterial and antifungal agents in recent years has resulted in the development of resistance to these drugs. The significant clinical implication of resistance has led to heightened interest in the study of antimicrobial resistance from different angles. Areas addressed include mechanisms underlying this resistance, improved methods to detect resistance when it occurs, alternate options for the treatment of infections caused by resistant organisms, and strategies to prevent and control the emergence and spread of resistance. 

 

Antifungals can be grouped into three classes based on their site of action: azoles, which inhibit the synthesis of ergosterol (the main fungal sterol); polyenes, which interact with fungal membrane sterols physicochemically; and 5-fluorocytosine, which inhibits macromolecular synthesis. Many different types of mechanisms contribute to the development of resistance to antifungals. These mechanisms include alteration in drug target, alteration in sterol biosynthesis, reduction in the intercellular concentration of target enzyme, and overexpression of the antifungal drug target. Although the comparison between the mechanisms of resistance to antifungals and antibacterials is necessarily limited by several factors , a correlation between the two exists. For example, modification of enzymes which serve as targets for antimicrobial action and the involvement of membrane pumps in the extrusion of drugs are well characterized in both the eukaryotic and prokaryotic cells.

 

Fungal infections range from superficial skin infections to life-threatening systemic infections. Systemic fungal infections are serious infections that occur when fungi gain entrance into the interior of the body. A fungus is a colorless plant that lacks chlorophyll. Fungi that cause disease in humans may be yeast like or mold like; the resulting infections are called mycotic infections or fungal infections.

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Mycotic (fungal) infections may be one of two types:

1. Superficial mycotic infections

2. Deep (systemic) mycotic infections

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The superficial mycotic infections occur on the surface of, or just below, the skin or nails. Superficial infections include tinea pedis (athlete’s foot), tinea cruris (jock itch), tinea corporis (ringworm), onychomycosis (nail fungus), and yeast infections, such as those caused by Candida albicans. Yeast infections or those caused by C. albicans affect women in the vulvovaginal area and can be difficult to control. Women who are at increased risk for vulvovaginal yeast infections are those who have diabetes, are pregnant, or are taking oral contraceptives, antibiotics, or corticosteroids.Deep mycotic infections develop inside the body, such as in the lungs. Treatment for deep mycotic infections is often difficult and porlonged.

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How antifungal medicines work

Antifungal medicines work by either:

• killing the fungal cells – for example, by affecting a substance in the cell walls, causing the contents of the fungal cells to leak out and the cells to die

• preventing the fungal cells from growing and reproducing

 

Antifungal drugs may be fungicidal (able to destroy fungi) or fungistatic (able to slow or retard the multiplication of fungi). Amphotericin B (Fungizone IV), miconazole (Monistat), nystatin (Mycostatin), and ketoconazole (Nizoral) are thought to have an effect on the cell membrane of the fungus, resulting in a fungicidal or fungistatic effect. The fungicidal or fungistatic effect of these drugs appears to be related to their concentration in body tissues. Fluconazole (Diflucan) has fungistatic activity that appears to result from the depletion of sterols (a group of substances related to fats) in the fungus cells. Griseofulvin (Grisactin) exerts its effect by beingdeposited in keratin precursor cells, which are then gradually lost (due to the constant shedding of top skin cells), and replaced by new, noninfected cells. The mode of action of flucytosine (Ancobon) is notclearly understood. Clotrimazole (Lotrimin, Mycelex) binds with phospholipids in the fungal cell membrane, increasing permeability of the cell and resulting in loss of intercellular components.