Mycological cure

The final choice of a suitable antimycotic and the route of adniinistration are deterrnined by many factors safety of the antimycotic, easy adniinistration, broad-spectmm activity, and rapid clinical improvement associated with mycological cure. 

Twenty percent of HIV-infected patients develop fluconazole-resistant Candida albicans isolates after repeated exposure to fluconazole.33 To treat fluconazole-resistant oropharyngeal candidiasis, daily itraconazole for 2 to 4 weeks may be used. Oral itraconazole solution exhibits a mycological cure rate of 88% and a clinical cure rate of 97% in immunocompromised patients.34 Fluconazole-resistant esophageal candidiasis should be treated with intravenous amphotericin B or caspofungin. 

Onychomycosis is a chronic infection that rarely remits spontaneously. Adequate treatment is essential to prevent spread to other sites, secondary bacterial infections, cellulitis, or gangrene. Due to the chronic nature and impenetrability of nails, topical agents have low efficacy rates for treating onychomycosis. Oral agents that can penetrate the nail matrix and nail base, such as itraconazole and terbinafine, are more effective than ciclopirox lacquer. Itraconazole and terbinafine demonstrate mycological cure rates of 62%37 and 76%,38 respectively, while ciclopirox has a cure rate of 29% to 36%.39... 

The optimal clinical effect is seen some months after mycological cure and cessation of treatment. This is related to the period required for outgrowth of healthy nail. 

The safety and efficacy of terbinafine 250 mg/day and itraconazole 200 mg/day given for 12 weeks for toenail onychomycosis have been compared in a randomized, double-blind study in 372 patients (19). Adverse events were reported in 39% of the terbinafine-treated patients and in 35% of the itraconazole-treated patients. The mean values of biochemical parameters of liver and kidney function did not change significantly. Terbinafine produced higher rates of clinical cure (76 versus 58%) and mycological cure (73 versus 46%) than itraconazole. 

In a randomized, double-blind comparison of terbinafine 250 mg/day n — 146) with itraconazole 200 mg/day n — 146), administered for 12 weeks for toenail onychomycosis, mycological cure rates at the 36-week follow-up end-point (67 versus 61%) and the proportion of patients with adverse effects (23 versus 22%) were similar in both study arms. However, more patients taking terbinafine... 

In a double-blind, randomized, multicenter comparison of terbinafine (250 mg/day for 12 or 16 weeks) or itraconazole capsules (200 mg bd for 1 week every 4 weeks for 12 or 16 weeks), 236 patients reported at least one adverse event. All were within the known safety profile of both drugs, and there were no significant differences among the four treatment regimens. Continuous terbinafine was significantly more effective than intermittent itraconazole (mycological cure rates at week 72 76, 81, 38, and 49% significant for all comparisons between terbinafine and itraconazole) (21,22). 

In an open, non-comparative study of the use of terbinafine for 14 days to treat tinea capitis in 50 children and adolescents (mean age 7.6 years range 24 months to 18 years), the clinical and mycological cure rates were 86%. The drug appeared to be well tolerated. Two children had reversible neutropenia, thought to be due to a preceding viral illness other adverse effects were not observed (18). 

Data is also available suggesting efficacy of topical garlic on fungal infections. For tinea pedis, 1-week topical treatment with ajoene 1% twice daily resulted in mycological cure 60 days later in 100% of patients, compared to 94% for 1% topical terbinafine and 72% for 0.6% topical ajoene (43). Another study showed that 0.6% topical ajoene was as effective as 1% terbinafine cream, both applied twice daily for 1 week, for the treatment of tinea cruris and corposis. After 60 days, effectiveness (clinical plus mycological cure) was 73 vs 71 %,respectively (44). In addition, a0.4% cream was also shown to be effective (45). Although a topical preparation is not available commercially, it could likely be compounded. 

Systemic oral azoles should be reserved for use in the more severe episodes of OPC unresponsive to topical agents or in patients with concurrent esophageal involvement. Although clinical response in more than 80% of patients can be obtained with 50 to 200 mg/day of fluconazole, response occurs within 10 days with the 50-mg daily dose compared to within 5 days for 100- to 200-mg daily doses even for the most intractable forms of OPC. The lower dose potentially may contribute to selection of resistance. Itraconazole oral solution with an improved absorption profile compared with the capsule formulation is comparable with fluconazole with respect to clinical and mycologic response and relapse rates. A 14-day treatment course of itraconazole seems to be more effective than a 7-day course—the shorter course is associated with lower rates of mycologic cure and higher relapse rates. Itraconazole solution can be used as first-line therapy for OPC, and it may be used for cases... 

In the treatment of tinea pedis, tinea cruris, and tinea versicolor the cure rate may be over 90%. In the treatment of vulvovaginal candidiasis, the mycologic cure rate at the end of 1 month is about 80 to 95%. Pruritus sometimes is relieved after a single application. Some vaginal infections caused by Candida glabrata also respond. 

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]. 

Microemulsion produced many folds increase in drug permeation. Treatment resulted in a complete clinical and mycological cure in 7 days. Formulation was observed to be nonsensitizing and histopathologically safe. 

The ointments were applied daily for a maximum of 3 weeks, according to summary of product characteristics. After assessment of the infected nail debridement, topical antifxmgal bifonazole cream was applied daily in both groups for 8 weeks. A total of 102 patients were evaluated, i.e. 51 in the 40% urea ointment with plastic dressing group and 51 in the bifonazole urea group. The primary end point was complete removal of the nail plate at day 21. Secondary end points were complete cure and mycological cure evaluated at day 105. Ease of use and local tolerability were also assessed. 

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