Antimycotic therapy

Borgers M, Degreef H, Cauwenbergh G. Fungal infections of the skin infection process and antimycotic therapy. Curr Drug Targets. 2005 6 849-862. 

Management Besides measures as boiling or disinfecting clothes, topical antimycotic therapy is the treatment of choice. Ointments should be applied several centimeters beyond the border of the lesion and treatment should be continued over at least 1 week after clearance of the lesions. However, these recommendations are seldom followed, resulting in chronic or recurrent disease (apart from the problem of resistance). In these cases, and when multilocular lesions or an infection of extensive spread have to be treated, systemic antifun-gals usually for 1-2 weeks are necessary, terbinafine usually giving the best results in dermatophytosis. 

Candida Leukoplakia (Chronic Plaque-Like or Hyperplastic Candidiasis). Here the plaques, most commonly on the cheeks and on the tongue, are not easily removable and may clear with prolonged antimycotic therapy. This condition is difficult to differentiate from other types of leukoplakia. 

Management Topical antimycotic therapy is sufficient for skin infection, whereas systemic infection demands systemic therapy with amphotericin B and/or fluconazole. 

Management For intertrigo, local antimycotic therapy has to be combined with drying of this region (e.g. linen strips, use of an antimycotic paste), local therapy with potassium permanganate deals with this aspect and is effective against concomitant bacteria as well. In the treatment of diaper candidiasis these points of view are important as well (e.g. frequent changes of napkins) steroids should be avoided if possible. 

Oral mucositis with ulceration caused by propolis has been reported in an HIV-negative man (3). Infectious stomatitis is common in HIV-positive patients. Therefore, the first approach is usually the administration of antiviral therapy, antimycotic therapy, or both. However, other causes, such as contact allergy, should be suspected if the patient is exposed to a potentially allergenic substance. 

In addition to topical antimycotic therapy, systemic NSAIDs and topical atropine sulfate are used to the control pain and ameliorate the effects of anterior segment injury associated with the iridocyclitis that inevitably accompanies ker-atomycosis. Topical proteinase inhibitor therapy is of significant clinical benefit in controlling stromal breakdown and, since potentially pathogenic bacteria contaminate most mycotic lesions, concurrent broad-spectrum, topical antibacterial agents should be used. 

The course of infectious aneurysms is unpredictable. Under antibiotic or antimycotic therapy they may shrink, or completely disappear. However, enlargement during treatment has also been reported (Brust et al. 1990). Septic aneurysms can be obliterated surgically or by endovascular treatment (Chapot et al. 2002 Phuong et al. 2002 Steinberg et al. 1992). The theoretical assumption that implantation of foreign material - like platinum coils - into an infectious lesion might worsen the problem is not true for infectious intracranial aneurysms. Mortality due to rupture of bacterial cerebral aneurysms is reported to be up to 60% (Barrow and Prats 1990 Bohmfalk et al. 1978 Clare and Barrow 1992). 

Because of the outbreak of antimony-resistant leishmania sis and the need to develop an oraky-adrninistered therapy, the use of many other compounds has been considered. Those that appear to have clinical utility ate aHoputinol (62), ketoconazole (63), and both systemicaHy and topically applied paromomycin (8) (see Antiparasitic agents, antimycotics). 

Face creme Inflammation, pain Joint and muscle pain Rheumatoid diseases Venous microcirculation Anti-inflammatory Sport injuries Antimycotic Hormone therapy Hormone therapy... 

Resistance Resistance can develop during therapy and is the reason that flucytosine is not used as a single antimycotic drug except for chromoblastomycosis. The rate of emergence of resistant fungal cells is lower with the combination of amphotericin B and flucytosine than it is with flucytosine alone. Decreased levels of any of the enzymes in the conversion of 5-FC to 5-FU and beyond, or increased synthesis of cytosine, can confer resistance. 

In acute myeloid leukaemia or lymphatic leukaemia as well as in acute leukaemic episodes in non-Hodgkin lymphoma, involvement of the liver may only be detectable clinically by the presence of hepatomegaly and subicterus. Laboratory parameters usually show slightly elevated transaminase as well as bilirubin values, and distinct cholestasis is occasionally observed. (7) Acute hepatic failure can occur during the course of acute leukaemia, (l, 8,26,65) Histologically, there are massive, yet uniform blast-cell infiltrates these are found mainly within the portal fields in acute lymphatic leukaemia (about 95%) and within the sinusoids in acute myeloid leukaemia (about 75%). Involvement of the liver is of no consequence with regard to the underlying disease and its therapy. Secondary infections require systemic treatment with antibiotics and/or antimycotics. 

Table 11.2 Recommended doses for intrauterine administration of antimycotic agents for the therapy of uterine fungal Infections In mares...

The approach to therapy is to remove or improve any predisposing factors if they can be identified. A pharmacologic agent should have limited local and systemic side effects, a high cure rate, and easy administration. Additionally, it would be advantageous to use a therapy that is able to resolve symptoms within 24 hours, that has broad antimycotic activity (to cover increasing rates on non-albicans Candida), that prevents recurrence, and that can be used over a shortened period of time such as 1 to 3 days. 

Starting from the hypothesis that azo compounds with an ability to form active carbonium ions in vivo are biologically active, Biichel et al. (1972,1975) synthesised several derivatives of 1-trityl azoles. They established in extensive research work that the derivatives particularly active are those which contain only one substituent in one of the phenol rings, and in which the azole ring remains unsubstituted. This led to the very active antimycotic clotrimazole (see Section 5.7.1), which nowadays plays an important role in the local therapy of human mycoses, and to fluo-trimazole, of specific activity against powdery mildews. 

Ajoene was also studied for short-term therapy of Tinea pedis. The use of ajoene as a 0.4% (w/w) cream resulted in complete clinical and mycological cure in 27 of 34 patients (79%) after 7 days of treatment. The remaining seven patients (21%) achieved complete cure after seven additional days of treatment. All patients were evaluated for recurrence of mycotic infections 90 days after the end of treatment, yielding negative cultures for fungus. These results show that ajoene is an alternative, efficient and low-cost antimycotic drug for short-term therapy of Tinea pedis [97]. 

How long a cutaneous preparation has to be used depends on the disorder and the typical period in which an active substance reaches its therapeutic effect. Usually corticosteroids or antibiotics should be applied for only a few days if applied every day. The treatment with an antimycotic may take a longer time. In general the physician should see the patient regularly to assess the effectiveness of the therapy. The preparation should therefore be prescribed in a limited amoimt appropriate to the treatment scheme. 

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