Antifungals

Fungi often infect the skin surface and subsequently invade the stratum corneum to avoid being shed from the skin surface by desquamation. Pharmacologic agents applied to the surface of the skin in the form of creams, lotions, or sprays, readily penetrate into the stratum corneum to kill the fungi (fungicidal agents), or at least render them unable to grow or divide (fungistatic agents). Thus, topical therapies work well to rid the skin of topical fungi and yeasts. Azole drugs such as miconazole, clotrimazole, and ketoconazole are fungistatic, limiting fungal growth but depending on epidermal turnover to shed the still-living fungus from the skin surface. Allylamines and benzylamines such as terbinafine, naftifine, and butenafine are fungicidal, actually killing the fungal organisms. Fungicidal drugs are often preferred over fungistatic drugs for treatment of dermatophytic fungal infections, since treatment times as short as one application daily for 1 week are associated with high cure rates. Furthermore, patients often stop treatments when the skin appears healed, usually after about a week of treatment. If this short-term treatment is stopped, fungi recur more often when fungistatic, rather than fungicidal, drugs have been used. Yeast infections such as those caused by Candida albicans respond less well to allylamine drugs. The azole drugs are often preferred for these types of infections. Nail infections are difficult to cure with topical therapies because the infections usually occur under the nail instead of on top of it and products penetrate poorly, if at all, through the nail plate. Infections of hair follicles, nails, and widespread infections often require systemic treatments. Antifungal agents are compounded into many different types of vehicles. Patients often prefer to treat weeping infections with spray formulations. Most physicians prescribe branded products in cream or lotion bases. Cost is a factor dictating prescription choice, especially since most products work well regardless of mechanism of action. Cost becomes especially important when infections involve large areas of the body surface. This article reviews various treatments of cutaneous fungal infections, with special emphasis on cure rates and rationales for choosing particular products.

The use of the agar diffusion Neo-Sensitabs method to determine antifungal susceptibility of 59 isolates of dermatophytes, namely Epidermophyton floccosum, Microsporum canis, M. gypseum, Trichophyton mentagrophytes, T. rubrum and T. tonsurans to Clotrimazole (CLZ), Itraconazole (ITZ) and Terbinafine (TBF) is described. Results obtained are compared to the minimum inhibitory concentrations (MIC) determined by an adaptation of the NCCLS-M38-A procedure. Using the diffusion method, all strains showed a broad zone of inhibition at the first available reading time (3 or 7 days). Using the broth microdilution method, the geometric mean MIC (microg/ml) with regard to all isolates was < or = 0.03 for TBF, < or = 0.069 for CLZ and < or = 0.919 for ITZ. In both methods, TBF was the most active antifungal agent against all isolates tested. The two methods evaluated were able to detect the resistance of the quality control strains of Aspergillus fumigatus to ITZ. Even though a reference method for testing dermatophytes still has not been developed, our data suggest that the Neo-Sensitabs diffusion method could provide a simple procedure for the antifungal susceptibility testing of dermatophytes in the routine clinical laboratory.

The frequency of invasive fungal infections has increased dramatically in recent decades because of an expanding population at risk. Until now, treatment options for invasive mycoses have been primarily amphotericin B and the azoles, fluconazole and itraconazole. Traditional agents are limited by an inadequate spectrum of activity, drug resistance, toxicities, and drug-drug interactions. The recent approval of caspofungin and voriconazole clearly has expanded the number of existing antifungal drugs available. However, the enthusiasm that accompanies their availability is counterbalanced by limited clinical experience, high drug acquisition costs, and distinctive toxicities. The pharmacologic characteristics, extent of clinical experience (efficacy and toxicity), and drug acquisition costs among available systemic antifungal agents are compared, with emphasis on the new agents. Also, recommendations on the role of each agent are provided according to the most common indications for systemic antifungal therapy: invasive candidiasis, invasive aspergillosis, and febrile neutropenia.

Clin Cornerstone. 2001;4(1):33-8.
Topical medications: a focus on antifungals and topical steroids.
Webster GF.
Department of Dermatology and Cutaneous Biology, Center for Cutaneous Pharmacology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

Because skin disease is accessible, it can be treated with locally applied medication, which offers great advantages--exposure to a drug is limited to the affected skin and systemic effects of potentially toxic drugs are minimized. Ointments, creams, antifungals, and antibiotics all have their place in treating various skin diseases. Topical steroids, the largest group of topical medications, are effective but present the potential for side effects. This article discusses current and new topical medications that can be used to treat a range of skin diseases.

Profound and prolonged neutropenia following chemotherapy is a major risk factor for systemic fungal infections. Mortality associated with disseminated fungal infection is high, and treatment with conventional amphotericin B is complicated by renal toxicity. Candida and Aspergillus are among the major pathogens in these patients. Many patients remaining neutropenic over a prolonged period of time will receive empirical antifungal therapy. The clinical and laboratory diagnoses of these infections are neither sensitive nor specific and are generally limited in the early detection of invasive fungal infection. However, several new approaches to diagnosis are being developed, which should be translated into routine practice, based on a greater understanding of the pathogenesis of systemic fungal infection and virulence determinants of fungal pathogens. These include antigen detection and polymerase chain reaction. Patients with presumed fungal infection require more intense and accurate monitoring for signs of disseminated infection. Early diagnosis may guide appropriate treatment and prevent mortality. Continued development of commercial tests should help achieve the objective of definitive diagnostic tests for systemic fungal infections.