Treatment of toenail onychomycosis with 2% butenafine and 5% Melaleuca alternifolia (tea tree) oil in cream. Tazarotene 0.1% gel in the treatment of fingernail psoriasis: a double-blind, randomized, vehicle-controlled study. Ciclopirox nail lacquer topical solution 8% in the treatment of toenail onychomycosis. Comparison of two topical preparations for the treatment of onychomycosis: Melaleuca alternifolia (tea tree) oil and clotrimazole. A clinical trial of topical terbinafine (a new allylamine antifungal) in the treatment of tinea pedis. Dystrophic psoriatic fingernails treated with 1% 5-fluorouracil in a nail penetration-enhancing vehicle: a double-blind study. Randomised trial of 0.2% chlorhexidine gluconate and 2.5% natamycin for fungal keratitis in Bangladesh. Evaluation of the efficacy of methotrexate and cyclosporine therapies on psoriatic nails: a one-blind, randomized study. Treatment of psoriatic nails with topical cyclosporin: a prospective, randomized placebo-controlled study. Treatment of chronic tinea pedis (athlete's foot type) with topical terbinafine. Topical clotrimazole in tinea pedis. A double-blind, vehicle-controlled study of the safety and efficacy of Fungoid Tincture in patients with distal subungual onychomycosis of the toes. Placebo-controlled clinical trial of meglumine antimonate (glucantime) vs. localized controlled heat in the treatment of cutaneous leishmaniasis in Guatemala. Allopurinol in the treatment of American cutaneous leishmaniasis. Wound healing and infection in nail matrix phenolization wounds. Does topical medication make a difference? A randomized, double-blind, placebo-controlled clinical trial of itraconazole in the treatment of cutaneous leishmaniasis. Trial of chlorhexidine gluconate for fungal corneal ulcers. Comparison of an antifungal agent used alone with an antifungal used with a topical steroid in inflammatory tinea pedis. A double-blind, randomized, placebo-controlled trial of itraconazole capsules as antifungal prophylaxis for neutropenic patients. Baseline nail disease in patients with moderate to severe psoriasis and response to treatment with infliximab during 1 year. Ciclopirox gel in the treatment of patients with interdigital tinea pedis. Comparison of intralesionally injected zinc sulfate with meglumine antimoniate in the treatment of acute cutaneous leishmaniasis. [The antifungal agent naftifin. Placebo-controlled therapeutic comparison in tinea pedis]. Randomized, controlled, double-blind trial of topical treatment of cutaneous leishmaniasis with paromomycin plus methylbenzethonium chloride ointment in Guatemala. Efficacy of ketoconazole against Leishmania braziliensis panamensis cutaneous leishmaniasis. Fluconazole prophylaxis of fungal infections in patients with acute leukemia. Results of a randomized placebo-controlled, double-blind, multicenter trial. The beneficial toxicity paradox of antimicrobials in leg ulcer healing impaired by a polymicrobial flora: a proof-of-concept study. Antifungal prophylaxis during remission induction therapy for acute leukemia fluconazole versus intravenous amphotericin B. Evaluating the efficacy of allopurinol and meglumine antimoniate (Glucantime) in the treatment of cutaneous leishmaniasis. Are antibiotics necessary in the treatment of locally infected ingrown toenails? Prophylactic treatment with miconazole in patients highly predisposed to fungal infection. A placebo-controlled double-blind study. Efficacy of miconazole in the topical treatment of tinea pedis in sportsmen. Efficacy of topical and systemic itraconazole as a broad-spectrum antifungal agent in mycotic corneal ulcer. A preliminary study. Prevention and therapy of fungal infection in severe acute pancreatitis: A prospective clinical study. Miconazole as adjuvant therapy for oral lichen planus: a double-blind randomized controlled trial. Oral terbinafine versus griseofulvin in the treatment of moccasin-type tinea pedis. Systemic treatment of venous leg ulcers with high doses of pentoxifylline: efficacy in a randomized, placebo-controlled trial. Voriconazole versus natamycin as primary treatment in fungal corneal ulcers. Management of fungal infection in neutropenic patients with fluconazole. Fluconazole for the treatment of cutaneous leishmaniasis caused by Leishmania major. Efficacy of paromomycin ointment in the treatment of cutaneous leishmaniasis: results of a double-blind, randomized trial in Isfahan, Iran. Topical paromomycin/methylbenzethonium chloride plus parenteral meglumine antimonate as treatment for American cutaneous leishmaniasis: controlled study. Liposomal amphotericin (AmBisome) in the prophylaxis of fungal infections in neutropenic patients: a randomised, double-blind, placebo-controlled study.
The prevalence of onychomycosis, a superficial fungal infection that destroys the entire nail unit, is rising, with no satisfactory cure. The objective of this randomized, double-blind, placebo-controlled study was to examine the clinical efficacy and tolerability of 2% butenafine hydrochloride and 5% Melaleuca alternifolia oil incorporated in a cream to manage toenail onychomycosis in a cohort. Sixty outpatients (39 M, 21 F) aged 18-80 years (mean 29.6) with 6-36 months duration of disease were randomized to two groups (40 and 20), active and placebo. After 16 weeks, 80% of patients using medicated cream were cured, as opposed to none in the placebo group. Four patients in the active treatment group experienced subjective mild inflammation without discontinuing treatment. During follow-up, no relapse occurred in cured patients and no improvement was seen in medication-resistant and placebo participants. A double-blind, randomized, vehicle-controlled, parallel-group trial was performed to compare the efficacy and tolerability of tazarotene 0.1% gel and vehicle gel in 31 patients with fingernail psoriasis. Patients were randomized to receive tazarotene or vehicle gel, which they applied each evening for up to 24 weeks to 2 target fingernails, one under occlusion and one unoccluded. The tazarotene treatment resulted in a significantly greater reduction in onycholysis in occluded nails (P < or = .05 at weeks 4 and 12) and a significantly greater reduction in onycholysis in nonoccluded nails (P < or = .05 at week 24). Tazarotene also resulted in a significantly greater reduction in pitting in occluded nails (P < or = .05 at week 24). There were no other significant between-group differences in pitting, subungual hyperkeratosis, leukonychia, nail plate crumbling/loss, splinter hemorrhage, or nail growth rate. Tazarotene 0.1% gel was well tolerated with only 5 of the 21 tazarotene-treated patients reporting a treatment-related adverse event (all mild or moderate). In conclusion, tazarotene 0.1% gel can significantly reduce onycholysis (in occluded and nonoccluded nails) and pitting (in occluded nails) and is well tolerated in the treatment of nail psoriasis. Onychomycosis is a relatively common condition affecting toenails more than fingernails. It is caused predominantly by dermatophytes. Onychomycosis can cause pain and discomfort and has the potential to be a source of morbidity.
                We evaluated the efficacy and safety of ciclopirox nail lacquer solution 8% used to treat onychomycosis of the toe in the United States and in centers worldwide.
                Two identically designed, double-blind, vehicle controlled, parallel group multicenter studies were performed in the United States to evaluate the use of ciclopirox nail lacquer to treat mild to moderate toe onychomycosis caused by dermatophytes. In the first study, 223 patients were randomized to treatment (ciclopirox group: 112, vehicle group: 111), and in the second study, 237 subjects were randomized (ciclopirox group: 119, vehicle group: 118). Before randomization, patients were to have clinical features of onychomycosis in at least one great toe with positive light microscopic examination and a positive dermatophyte culture. The test material was applied daily for a period of 48 weeks to all toenails and affected fingernails, covering the entire nail plate and approximately 5 mm of surrounding skin. At baseline, subjects had between 20% to 65% area of target nail involved. Physician's assessments were carried out every 4 weeks, and mycologic evaluation and photographic planimetry using standardized photographs were performed every 12 weeks during the 48 weeks of treatment. In studies conducted outside the United States, patients were also to have clinical, microscopic, and culture evidence of onychomycosis. However, these studies included some patients infected with nondermatophyte organisms (eg, Candida species), and the area of nail involvement was generally greater than observed in the US studies. Treatment regimens also varied in the non-US studies with lacquer applications that were sometimes less frequent than the once daily treatment used in the US studies (eg, alternate day or twice weekly). In addition, the typical duration of treatment was 6 months in the non-US studies as compared with 48 weeks in the United States. Outcome measures were similar to those used in the US trials, although a non-photographic planimetric method was used to quantify disease extent.
                Data from the pivotal US trials have demonstrated that ciclopirox nail lacquer 8% topical solution is significantly more effective than placebo in the treatment of onychomycosis caused by Trichophyton rubrum, and of mild to moderate toe onychomycosis without lunula involvement. At the end of the 48-week treatment period, the mycologic cure rate (negative culture and negative light microscopy) in study I was 29% vs 11% in the ciclopirox and vehicle groups, respectively. Similarly, the mycologic cure rate for study II was 36% vs 9%, respectively. In the non-US studies, the mycologic cure rates ranged from 46.7% to 85.7%. In addition, ciclopirox nail lacquer has demonstrated a broad spectrum of activity with efficacy against Candida species and some nondermatophytes in non-US studies. Ciclopirox nail lacquer is considered extremely safe regarding causally related treatment emergent adverse-effects (TEAEs), with most TFAEs transient and localized to the site of action (eg, erythema and application site reaction). In the US studies, TFAEs were generally mild and cleared while the patient continued to use the nail lacquer.
                Studies conducted worldwide demonstrate the efficacy of ciclopirox nail lacquer for the treatment of finger and toe onychomycosis. Both controlled and open-label studies confirm the excellent safety profile of this topical therapy. Thus, the nail lacquer provides a treatment choice with a favorable benefit-to-risk ratio. With its novel mechanism of action and its topical route of administration, ciclopirox nail lacquer offers an innovative approach to the treatment of this often difficult-to-manage disease The prevalence of onychomycosis, the most frequent cause of nail disease, ranges from 2% to 13%. Standard treatments include debridement, topical medications, and systemic therapies. This study assesses the efficacy and tolerability of topical application of 1% clotrimazole solution compared with that of 100% Melaleuca alternifolia (tea tree) oil for the treatment of toenail onychomycosis.
                A double-blind, multicenter, randomized controlled trial was performed at two primary care health and residency training centers and one private podiatrist's office. The participants included 117 patients with distal subungual onychomycosis proven by culture. Patients received twice-daily application of either 1% clotrimazole (CL) solution or 100% tea tree (TT) oil for 6 months. Debridement and clinical assessment were performed at 0, 1, 3, and 6 months. Cultures were obtained at 0 and 6 months. Each patient's subjective assessment was also obtained 3 months after the conclusion of therapy.
                The baseline characteristics of the treatment groups did not differ significantly. After 6 months of therapy, the two treatment groups were comparable based on culture cure (CL = 11%, TT = 18%) and clinical assessment documenting partial or full resolution (CL = 61%, TT = 60%). Three months later, about one half of each group reported continued improvement or resolution (CL = 55%; TT = 56%).
                All current therapies have high recurrence rates. Oral therapy has the added disadvantages of high cost and potentially serious adverse effects. Topical therapy, including the two preparations presented in this paper, provide improvement in nail appearance and symptomatology. The use of a topical preparation in conjunction with debridement is an appropriate initial treatment strategy. Twenty-three patients were enrolled in a randomized, double-blind trial of terbinafine 1% cream compared with placebo vehicle in the treatment of tinea pedis. Of the 20 patients who were evaluated for efficacy, 10 received terbinafine and 10 received placebo. Except for the terbinafine-treated patients being an average of 11 years older than the patients receiving placebo and the median duration of disease being 6 weeks longer in the placebo group, the two groups were demographically and clinically similar. Results of mycologic tests and clinical findings showed terbinafine to be significantly more effective than placebo in the treatment of tinea pedis. Significantly more terbinafine-treated patients than placebo-treated patients showed conversion to negative culture and microscopy at end of therapy and a significant reduction in scored signs and symptoms. Overall efficacy at follow-up (combined mycologic and clinical findings) was also significantly greater in the terbinafine group (78%) than in the placebo group (zero) (p less than 0.001). Unexplained elevation of liver function test results was noted in three placebo-treated patients and in one terbinafine-treated patient, but these changes were not considered clinically relevant or drug related. Topically applied nail therapeutics need to permeate the nail plate to reach the nail bed or nail matrix and exert their potential beneficial effect at these locations to obtain a therapeutic benefit. So far only topically applied 5-fluorouracil on affected nails of psoriatic patients has been shown to produce a notable clearance. Vehicle formulations enhancing nail permeation processes are thought to increase the concentration of the active agent and therefore therapeutic efficacy, possibly enabling the use of a low concentration of the active agent thereby lowering the incidence of adverse effects.
                This study was designed to verify whether a recently developed nail penetration enhancer in a lotion formulation, Belanyx((R)) (urea, propylene glycol), improves the efficacy of a low concentration of 5-fluorouracil (1%) in psoriatic fingernail lesions.
                In a randomised, double-blind, left-right study the efficacy of 1% 5-fluorouracil in the Belanyx vehicle was compared to the vehicle preparation Belanyx in dystrophic fingernails of 57 psoriatic patients. Both preparations were applied in a once daily regimen for 12 weeks. Responses and adverse effects of one selected target nail were recorded at screening, at baseline and at weeks 2, 4, 8 and 12 of treatment with a final assessment at week 16: 4 weeks after the end of treatment. As parameter of efficacy was chosen the total nail area severity (NAS) score, consisting of the separate parameters nail pitting area, number of nail pits, subungual keratosis, onycholysis, oil spots and the various scores of overall improvement.
                The efficacy of 1% 5-fluorouracil in lotion and that of the vehicle in suppressing the parameters of dystrophy were shown to be similar at the end of treatment (p = 0.063) or follow-up (p = 0.130). Both preparations produced statistically significant improvements (p </= 0.05) for almost all assessed parameters after 12 weeks of treatment and after the 4 weeks of follow-up. For Belanyx lotion this applied to the nail pitting area, the number of nail pits, subungual keratosis, onycholysis and oil spots. The investigators' and patients' opinion of overall improvement of severity as well as the total NAS score of one target nail likewise showed a statistically significant improvement at the end of treatment and at the end of the observation period (p </= 0.05). With the 1% 5-fluorouracil lotion the same statistically significant improvements were obtained in all of the assessed symptoms with the exception of the number of pits and onycholysis at week 12 and week 16. Possible treatment-related adverse effects were established in 6 patients showing inflammation and infection (3 patients) or discoloration (5 patients); 3 patients on 5-fluorouracil lotion showed onycholysis.
                Addition of 1% 5-fluorouracil to the nail permeation enhancer Belanyx does not increase the efficacy of the active agent in psoriatic nail dystrophy of this study population. The obtained results also suggest that Belanyx lotion can be used in this indication since it has shown a favourable efficacy-safety ratio.
                Copyright (R) 2000 S. Karger AG, Basel The management of suppurative keratitis due to filamentous fungi presents severe problems in tropical countries. The aim was to demonstrate the efficacy of chlorhexidine 0.2% drops as an inexpensive antimicrobial agent, which could be widely distributed for fungal keratitis.
                Successive patients presenting to the Chittagong Eye Institute and Training Complex with corneal ulcers were admitted to the trial when fungal hyphae had been seen on microscopy. They were randomised to drop treatment with chlorhexidine gluconate 0.2% or the standard local treatment natamycin 2.5%. The diameters, depths, and other features of the ulcers were measured and photographed at regular intervals. The outcome measures were healing at 21 days and presence or absence of toxicity. If there was not a favourable response at 5 days, "treatment failure" was recorded and the treatment was changed to one or more of three options, which included econazole 1% in the latter part of the trial.
                71 patients were recruited to the trial, of which 35 were randomised to chlorhexidine and 36 to natamycin. One allocated to natamycin grew bacteria and therefore was excluded from the analysis. None of the severe ulcers was fully healed at 21 days of treatment, but three of those allocated to chlorhexidine eventually healed in times up to 60 days. Of the nonsevere ulcers, 66.7% were healed at 21 days with chlorhexidine and 36.0% with natamycin, a relative efficacy (RE) of 1.85 (CL 1.01-3.39, p = 0.04). If those ulcers were excluded where fungi were seen in the scraping but did not grow on culture, the estimated efficacy ratio does not change but becomes less precise because of smaller numbers. Equal numbers of Aspergillus (22) and Fusarium (22) were grown. The Aspergillus were the most resistant to either primary treatment.
                Chlorhexidine may have potential as an inexpensive topical agent for fungal keratitis and warrants further assessment as a first line treatment in situations where microbiological facilities and a range of antifungal agents are not available. Treatment of psoriatic nail is difficult.
                The aim of this study was to evaluate and compare the efficacy and safety of methotrexate and cyclosporine in psoriatic nail.
                Thirty-seven psoriatic patients with nail involvement were randomized to treatment with methotrexate (initial dose, 15 mg per week) or cyclosporine (initial dose, 5 mg per kg of bodyweight per day) for 24 weeks. The primary outcome was the Nail Psoriasis Severity Index (NAPSI). The Psoriasis Area and Severity Index (PASI), doctor and patient global score were also measured. The scores were determined by a blinded observer.
                Seventeen patients completed the study in each group. The mean percentages of reduction of the NAPSI score after methotrexate and cyclosporine treatments were 43.3% and 37.2%, respectively. No significant differences between the treatment groups was found for in the NAPSI, PASI, physician's and patient's global score at the end of the study period. The methotrexate group showed a significant improvement in nail matrix scores and the cyclosporine group in nail bed score.
                Moderate effectiveness on psoriatic nail was found in the two treatment agents and there were no significant differences in efficacy between the groups. A significant improvement was detected in methotrexate group for the nail matrix findings, and in cyclosporine group for the nail bed findings.
                © 2010 The Authors. Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology. Nail involvement is a frequent event in the course of psoriasis causing severe distress. While systemic cyclosporin (CsA) represents a well-established therapy of psoriasis, its topical use is limited by the difficult penetration of the molecule through the skin and the nail because of its highly lipophilic nature.
                We carried out a prospective randomized placebo-controlled study in order to analyze the effectiveness and tolerability of topical oil-dissolved 70% CsA solution in nail psoriasis.
                Sixteen adult patients with nail psoriasis, divided randomly into two groups of 8 patients (group A and group B), were treated respectively with a 70% maize-oil-dissolved oral CsA solution and maize oil alone. To compare the therapeutic effectiveness, all patients were evaluated, before starting the treatment and after 12 weeks of therapy, by the same dermatologists. The patients were also asked to assess the severity of their nail involvement at baseline and at the end of the treatment.
                In group A, 3 patients came to a complete resolution of nail lesions and 5 showed a substantial improvement of the overall severity score. In group B, a slight improvement was noted in only 1 patient. All the patients of group A judged positively the results of the therapy, while in group B only 1 patient reported a moderate improvement.
                Our results show that topical therapy with oral CsA solution is a safe, effective and cosmetically highly acceptable treatment modality for nail psoriasis. The ability of CsA to influence keratinocyte proliferation and T-cell lymphokine release, reducing the cornification of the upper layers of the epidermis, may prevent the typical alterations observed in nail psoriasis.
                Copyright 2003 S. Karger AG, Basel Twenty-seven patients with chronic tinea pedis, athlete's foot type, were enrolled in a randomized, double-blind trial of topical treatment with terbinafine 1% cream versus its vehicle (placebo). Patients were examined weekly during 4 weeks of twice-daily treatment and at follow-up 2 weeks after the conclusion of therapy. No adverse events were reported in either treatment group. Drug efficacy was evaluated in 22 patients, of whom nine (41%) were treated with terbinafine and 13 (59%) with placebo. Analysis of combined mycologic and clinical results showed that terbinafine was significantly more effective than placebo at the end of therapy (78% vs zero) and at the 2-week follow-up (89% vs zero) (p less than or equal to 0.001 at both intervals. Clotrimazole is a new antifungal agent which is effective topically in dermatophytosis, cutaneous candidiasis, and tinea vesicolor. The authors performed a controlled double-blind clinical trial comparing topical clotrimazole with its vehicle in the treatment of 66 patients with dermatophytic infections of the skin of the feet. Clotrimazole proved to be effective in the treatment of tinea pedis of both the interdigital and the plantar hyperkeratotic types. Onychomycosis is one of the most common causes of nail disease and one of the hardest to treat among fungal infections. A double-blind, vehicle-controlled study has been conducted to evaluate the safety and efficacy of Fungoid Tincture (Pedinol Pharmacal, Inc), for the treatment of fungal infection of the toenails. Ten patients with distal subungual onychomycosis were treated for twelve months with topical Fungoid Tincture. Another ten patients with the same ailment were treated with the vehicle alone. Once a month, clinical and global evaluation of the target nail was done, in addition to trimming and debridement of the nails. After twelve months of treatment, 90 percent of patients applying Fungoid Tincture showed negative results on culture. There were minimal adverse effects. Sixty-six Guatemalans with parasitologically proven cutaneous leishmaniasis were randomly and equally divided into 3 treatment groups: those receiving meglumine antimonate (Glucantime), 850 mg antimony/day im for 15 days; those receiving localized controlled heat from a radio-frequency generator, 50 degrees C for 30 sec, 3 treatments at 7 day intervals; and those receiving treatment with a placebo. Of 53 isolates identified, 40 were Leishmania braziliensis braziliensis and 13 were L. mexicana mexicana. Thirteen weeks after beginning treatment, the number of patients from each group with completely healed and parasitologically negative lesions were as follows: meglumine antimonate, 16 (73%); localized heat, 16 (73%); and placebo, 6 (27%). The cure rate for those with infections due to L. b. braziliensis in each group was as follows: meglumine antimonate, 11 out of 14 (79%); controlled heat, 9 out of 14 (64%); and placebo, 0 out of 11. Pentavalent antimony, the generally accepted treatment for leishmaniasis, is given parenterally, and it is expensive and not readily available in developing countries. An inexpensive, orally administered compound would be a substantial advance in treatment. Previous studies in vitro have shown synergism between allopurinol and pentavalent antimony in tissue-culture systems. We designed this clinical study to determine whether synergism could be demonstrated in patients.
                We performed a randomized, controlled study of the efficacy of allopurinol plus meglumine antimoniate (Glucantime), as compared with meglumine antimoniate alone, in patients with cutaneous leishmaniasis, who were recruited from a village in southeastern Colombia. In addition, those who declined injections were treated with allopurinol alone, and those who declined any treatment were considered controls. All the patients were followed for one year after the completion of treatment. Lesions that healed completely at three months and remained healed during follow-up were considered to be cured.
                The cure rate for patients treated with meglumine antimoniate was 36 percent; the addition of allopurinol increased the rate to 74 percent (P less than 0.001). Treatment with allopurinol alone yielded a cure rate of 80 percent (P less than 0.001). There were no cures among the untreated patients. There was no significant difference between the cure rate with allopurinol plus meglumine antimoniate and that with allopurinol alone. No major toxic effects were observed.
                For the treatment of American cutaneous leishmaniasis, the combination of allopurinol and meglumine antimoniate is significantly more effective than meglumine antimoniate alone, probably because of the efficacy of allopurinol alone, which appears to be as good as the combination. After nail matrix ablation using phenolization, a medicated wound dressing (10% povidone iodine), an amorphous hydrogel dressing (Intrasite Gel), and a control dressing (paraffin gauze) were evaluated. Forty-two participants, randomly divided into three dressing groups, were evaluated. Healing time did not differ between the 10% povidone iodine (33 days), amorphous hydrogel (33 days), and the control dressing (34 days). For all groups, the clinical infection rate was lower than in previous studies, and there was no clinical difference between groups (one infection in the povidone iodine and control groups; none in the amorphous hydrogel group). However, in the amorphous hydrogel group, other complications, such as hypergranulation, were more likely. This investigation indicated that medicated or hydrogel dressings did not enhance the rate of healing or decrease infection rates. Several modalities have been used for the treatment of cutaneous leishmaniasis (CL) with various results. In vitro and in vivo studies have shown inhibitory effects of azole drugs on Leishmania parasites.
                To evaluate the efficacy and tolerability of oral itraconazole in the treatment of CL caused by L. major.
                A total of 200 patients with parasitologically confirmed CL with a duration of less than 45 days from a well known L. major endemic area were included in a randomized, double-blind, placebo-controlled clinical trial. The patients received either itraconazole 200 mg daily (100 patients) or placebo (100 patients) for 8 weeks. The primary outcome measures were clinical cure (complete re-epithelization of all lesions) and parasitological cure at the end of the treatment.
                Eighty-three patients in the itraconazole and 75 patients in the placebo group completed the treatment course. After 8 weeks of treatment, clinical cure was observed in 59% and 53% and parasitological cure was observed in 83% and 76% of patients in the itraconazole and placebo groups, respectively, which were not significantly different. There was no difference in the rate of adverse events.
                An 8-week course of oral itraconazole was not more effective than placebo in the treatment of CL. Suppurative corneal ulcers due to filamentous fungi are a serious and intractable problem in many tropical developing countries. In vitro studies and a small pilot study have shown that chlorhexidine gluconate is effective. The aim was to establish the optimum concentration which would be appropriate to use in a larger randomized clinical trial.
                A masked randomized clinical trial of three concentrations of chlorhexidine compared with natamycin 5% was carried out in consecutive patients with established corneal ulcers shown by microscopy to contain fungal hyphae and later proven to be culture positive. Topical treatments were applied 1/2-hourly to 2-hourly for up to 5 days, with reduced frequency thereafter, and all patients were re-assessed at 21 days.
                Of 60 patients entered in the trial, 2 were lost to follow-up, and 12 were classified as 'severe' with little prospect of recovery. At 5 days the response was related to the concentration of chlorhexidine, with 0.2% giving the best results. Compared with the response to natamycin as the referent, the relative efficacy was 1.17 with chlorhexidine 0.05%, 1.43 with 0.1%, and 2.00 with 0.2%. The superiority of 0.2% chlorhexidine over natamycin was statistically significant (relative efficacy 2.20, p = 0.043) in patients not having had prior antifungal treatment.
                This preliminary study justifies further trials of chlorhexidine as a primary treatment for fungal corneal ulcers in circumstances where specific antifungal agents are not available. The efficacy and safety of monotherapy with oxiconazole nitrate cream, 1 percent, a topical broadspectrum antifungal agent, were compared with those of combination therapy with oxiconazole nitrate cream, 1 percent, and fluticasone propionate cream, 0.05 percent, in a multicenter, randomized, double-blind, vehicle-controlled, parallel-group study of patients with inflammatory tinea pedis. Both combination therapy and monotherapy were associated with significantly greater proportions of mycologic and clinical cure, and a better global response than vehicle. An unexpected finding in this study was that more than 70 percent of patients with interdigital tinea pedis also had plantar or plantar plus vesiculobullous infection. To evaluate the efficacy of itraconazole capsules in prophylaxis for fungal infections in neutropenic patients, we conducted a prospective, double-blind, placebo-controlled, randomized trial. Patients with hematologic malignancies or those who received autologous bone marrow transplants were assigned either a regimen of itraconazole (100 mg orally twice daily; n=104) or of placebo (n=106). Overall, fungal infections (superficial or systemic) occurred more frequently in the placebo group (15% vs. 6%; P=.03). There were no differences in the empirical use of amphotericin B or systemic fungal infections. Among patients with neutropenia that was profound (<100 neutrophils/mm3) and prolonged (for at least 7 days), those receiving itraconazole used less empirical amphotericin B (22% vs. 61%; P=.0001) and developed fewer systemic fungal infections (6% vs. 19%; P=.04). For patients with profound and prolonged neutropenia, itraconazole capsules at the dosage of 100 mg every 12 h reduce the frequency of systemic fungal infections and the use of empirical amphotericin B. Although nail psoriasis occurs frequently in patients with psoriatic skin lesions, effective treatments are limited.
                Occurrence of nail psoriasis by type and incidence of nail clearance using the Nail Psoriasis Severity Index were evaluated.
                This was a 50-week, phase III study in which 378 patients with moderate to severe psoriasis were randomized 4:1 to infliximab (5 mg/kg) or placebo at weeks 0, 2, 6, and every 8 weeks through week 46, with placebo crossover to infliximab at week 24.
                Of the 373 evaluated patients, 305 (81.8%) had baseline nail psoriasis. The right thumbnail was most often the worst involved nail, and pitting and onycholysis were the most common lesions. Among patients with baseline nail psoriasis, 6.9%, 26.2%, and 44.7% in the infliximab group had nail disease clearance at weeks 10, 24, and 50, respectively, versus 5.1% in the placebo group at week 24 (P < .001). Mean percent improvements in Nail Psoriasis Severity Index score at weeks 10 and 24 were 26.8% and 57.2%, respectively, in the infliximab group versus -7.7% and -4.1%, respectively, in the placebo group (both P < .001). At week 24, mean percent improvements in nail matrix and nail bed features were 52.9% and 69.2%, respectively (vs -1.9% and 18.4% for placebo; P < .001).
                The study did not evaluate nail response beyond 1 year.
                Patients with psoriasis receiving infliximab experienced marked and sustained nail improvement. BACKGROUND Tinea pedis (athlete's foot) is the most common fungal infection in the general population. Ciclopirox, a broad-spectrum hydroxypyridone antifungal, has proven efficacy against the organisms commonly implicated in tinea pedis; Trichophyton rubrum, T.mentagrophytes and Epidermophyton floccosum.
                Two multicenter, double-blind, clinical studies compared the efficacy and safety of ciclopirox gel with that of its vehicle base in subjects with moderate interdigital tinea pedis with or without plantar involvement.
                Three hundred and seventy-four subjects were enrolled and randomized to one of two treatment groups: ciclopirox gel 0.77%, or ciclopirox gel vehicle, applied twice daily for 28 days, with a final visit up to day 50. The primary efficacy variable was Treatment Success defined as combined mycological cure and clinical improvement >/= 75%. Secondary measures of effectiveness were Global Clinical Response, Sign and Symptom Severity Scores, Mycological Evaluation (KOH examination and final culture result), Mycological Cure (negative KOH and negative final culture results) and Treatment Cure (combined clinical and mycological cure).
                At endpoint (final post-baseline visit), 60% of the ciclopirox subjects achieved treatment success compared to 6% of the vehicle subjects. At the same time point, 66% of ciclopirox subjects compared with 19% of vehicle subjects were either cleared or had excellent improvement. Pooled data showed that 85% of ciclopirox subjects were mycologically cured, compared to only 16% of vehicle subjects at day 43, 2 weeks post-treatment.
                Ciclopirox gel 0.77% applied twice daily for 4 weeks is an effective treatment of moderate interdigital tinea pedis due to T. rubrum, T. mentagrophytes and E. floccosum and is associated with a low incidence of minor adverse effects. Cutaneous leishmaniasis is an endemic disease in developing countries. The first-line drugs for its treatment are the pentavalent antimony compounds such as meglumine antimoniate (MA). High cost, side effects, multiple injections and incomplete efficacy are limitations of this therapy. Zinc sulfate (ZS) has been reported to be effective in the treatment of cutaneous leishmaniasis.
                To compare the efficacy of intralesional injections of ZS 2% with those of MA in the treatment of cutaneous leishmaniasis.
                This was a prospective, double-blind, case-control clinical study. 104 patients with typical lesions of acute cutaneous leishmaniasis (ACL) were included. The duration of treatment was 6 weeks. Improvement was evaluated by clinical examination and direct smear.
                The study was completed in only 66 patients: 35 patients received MA and 31 received ZS. The cure rates were 60% for MA and 83.8% for ZS. After the second and fourth weeks, the efficacy of treatment with ZS was higher than that with MA (p < 0.01), but after 6 weeks no significant differences were observed between the two groups (p > 0.05).
                On the basis of this trial and despite the high number of drop-outs, we consider that the intralesional injection of ZS 2% is an alternative treatment in ACL.
                Copyright 2004 S. Karger AG, Basel The antimycotic efficacy of Naftifine was compared with that of placebo in a double-blind randomized trial in 60 patients with Tinea pedum proved by culture and microscopic examination. Naftifine was significantly superior to placebo concerning the number of mycologically cured patients as well as the clinical response to therapy. At the end of the study all patients were cured by Naftifine, whereas no patient of the placebo group showed an improvement. A double-blind, randomized trial was undertaken in Guatemala to determine the therapeutic efficacy of an ointment for the treatment of cutaneous leishmaniasis that contained 15% paromomycin and 12% methylbenzethonium chloride and that was applied twice a day for 20 days. The treatment group included 35 patients, and the placebo group included 33 patients. The initial clinical response rate (13 weeks after completing the treatment) was 91.4% in the treatment group and 39.4% in the placebo group. The final clinical response rate at the 12-month follow-up examination was 85.7% (31 of 35) in the treatment group and 39.4% (13 of 33) in the placebo group (P < or = 0.001). In general, the treatment was well tolerated and was never interrupted because of adverse effects. The number of adverse effects reported in the placebo group was lower than in the treatment group (16 events versus 30 events). All adverse effects reported by patients disappeared within 1 week of completing the treatment. Our findings show that the combination of paromomycin with methylbenzethonium chloride for 20 days is a good alternative for antimonial treatments of cutaneous leishmaniasis in Guatemala. The classic agent for cutaneous leishmaniasis is pentavalent antimony. However, there are no reports of the efficacy of antimony versus placebo or of the efficacy of any alternative therapy versus either antimony or placebo. In the present report, the oral antifungal agent ketoconazole (600 mg/day for 28 days) was compared to a recommended regimen of intramuscular Pentostam (20 mg antimony/kg, with a maximum of 850 mg antimony/day, for 20 days) in a randomized study of the treatment of Panamanian cutaneous leishmaniasis due to Leishmania braziliensis panamensis. A separate group of patients with this disease was administered placebo.
                Ketoconazole clinically cured 16 of 21 (76%) patients. The lesions on nine patients healed by 1 month after therapy, and the lesions healed by 3 months after therapy on the other seven patients. Side effects were limited to a 27% incidence of mild, reversible hepatocellular enzyme elevation and an asymptomatic, reversible, approximately 70% decrease in serum testosterone in all patients. Pentostam cured 13 of 19 (68%) patients; the lesions on seven patients healed by the end of therapy, and the lesions on four other patients healed by 1 month after the end of therapy. Side effects were a 47% incidence of mild, reversible hepatocellular enzyme elevation and the morbidity due to 20 intramuscular injections in almost all patients. The placebo group of 11 patients had a 0% cure rate. By 1 month after therapy, all placebo-treated patients demonstrated new lesions or one lesion that was 23% to 875% larger than before therapy.
                Both ketoconazole and Pentostam were more effective than placebo against L. braziliensis panamensis cutaneous leishmaniasis. Oral ketoconazole is comparable in efficacy to this parenteral Pentostam regimen and can be recommended as initial treatment for this disease. To evaluate the efficacy and safety of fluconazole for prevention of fungal infections.
                A randomized, placebo-controlled, double-blind, multicenter trial.
                Adults (257) undergoing chemotherapy for acute leukemia.
                Patients were randomly assigned to receive either fluconazole (400 mg orally once daily or 200 mg intravenously every 12 hours) or placebo. The study drug was started at initiation of chemotherapy and continued until recovery of neutrophil count, development of proven or suspected invasive fungal infection, or the occurrence of a drug-related toxicity.
                Fungal colonization, proven superficial or invasive fungal infection, empiric antifungal therapy with amphotericin B, drug-related side effects, and mortality.
                Fluconazole decreased fungal colonization (83 of 122 [68%] placebo patients compared with 34 of 119 [29%] fluconazole patients colonized at end of prophylaxis, P < 0.001) and proven fungal infections (27 of 132 [21%] placebo patients compared with 11 of 123 [9%] fluconazole patients infected, P = 0.02). Superficial fungal infections occurred in 20 of 132 (15%) placebo patients but in only 7 of 123 (6%) fluconazole patients (P = 0.01), whereas invasive fungal infections developed in 10 of 132 (8%) placebo patients and in 5 of 123 (4%) fluconazole patients (P = 0.3). Fluconazole was especially effective in eliminating colonization and infection by Candida species other than Candida krusei (66 of 122 [64%] placebo patients colonized at end of prophylaxis compared with 11 of 119 [9%] fluconazole patients, P < 0.001; 22 of 132 [17%] placebo patients infected compared with 7 of 123 [6%] fluconazole patients, P = 0.005). Aspergillus infections were infrequent in both fluconazole (3 cases) and placebo groups (3 cases). The use of amphotericin B, the incidence of drug-related side effects, and overall mortality were similar in both study groups.
                Prophylactic fluconazole prevents colonization and superficial infections by Candida species other than Candida krusei in patients undergoing chemotherapy for acute leukemia and is well tolerated. Fluconazole could not be clearly shown to be effective for preventing invasive fungal infections, reducing the use of amphotericin B, or decreasing the number of deaths. Some of the views contrasting the beneficial and toxic effects of antimicrobials upon wound healing remain controversial.
                To assess the clinical relevance of histological findings following antimicrobial applications on chronic leg ulcers.
                The present study was performed in three parallel groups of 17 patients suffering from at least 2 similar chronic leg ulcers. Clinical planimetric assessments were performed before and after 3 and 6 weeks of treatment using hydrocolloid dressings. In addition, 1 ulcer in each patient received applications of povidone-iodine (PVP-I), silver sulfadiazine or chlorhexidine digluconate. Histological examinations were made at inclusion and after the 6-week therapy. Time to healing was also recorded.
                At entry in the study, fibroblasts, macrophages, neutrophils and vessels were abundant in the ulcers. In addition, focal necrotizing vasculitis was related to the microbiological load. Compared to the control lesions, both the healing rate and time to healing of the leg ulcers showed a modest improvement at the sites receiving silver sulfadiazine (2-7%) or chlorhexidine digluconate (-1 to 5%). By contrast, PVP-I increased significantly the healing rate (4-18%, p < 0.01), and time to healing was reduced by 2-9 weeks (p < 0.01). The 3 antimicrobials decreased the bacterial density, and the vascular margination and migration of inflammatory cells, thus abating the vasculitic changes. PVP-I applications did not alter the microvessels and did not significantly reduce the density in dendrocytes and fibroblasts. By contrast, both silver sulfadiazine and chorhexidine digluconate appeared to alter the superficial microsvasculature including the dendrocyte population.
                Although topical antimicrobials may apparently achieve almost similar activity on the bacterial load inside chronic leg ulcers, the toxicity upon host cells was different among these agents. PVP-I appeared to be an efficient compound in these respects exhibiting a positive and relevant clinical effect.
                Copyright 2002 S. Karger AG, Basel Fungal infection is a frequent and often fatal complication in patients undergoing remission induction therapy for acute leukemia. Although candidiasis is the most common infection, mold infections are increasing in frequency. Fluconazole (FLU) is a new antifungal agent that has been used successfully to treat Candida infections and has modest activity against aspergillosis in animal models. Subtherapeutic doses of amphotericin B (AMB) have been considered effective as prophylaxis in these patients. This study was designed to compare the efficacy and toxicity of these agents as antifungal prophylaxis.
                Adults with acute leukemia undergoing remission induction chemotherapy randomly were assigned to receive antifungal prophylaxis with AMB (0.5 mg/kg three times weekly) or FLU (400 mg daily). Trimethoprim-sulfamethoxazole was administered as an antibacterial prophylaxis. Prophylaxis was continued until the patient achieved complete remission or was treated for 8 weeks without antileukemic response. Prophylaxis was discontinued if the patient experienced a possible or proven fungal infection or a serious toxicity.
                Overall, 58% of the 36 patients assigned to AMB successfully completed prophylaxis compared with 80% of the 41 patients assigned to FLU (< 0.05). Proven, probable, or possible fungal infections occurred in 31% and 17% of the patients, respectively. The risk of discontinuing prophylaxis due to fungal infection or toxicity increased with time in the study and was significantly greater for AMB (P = 0.02).
                At the dose used in this study, AMB was no more effective and was more toxic than FLU for prophylaxis of fungal infections in patients undergoing remission induction chemotherapy for acute leukemia. Cutaneous leishmaniasis is a common disease in Iran, particularly in Kerman province. It usually occurs via the bite of an infected sandfly.
                One hundred and fifty patients suffering from cutaneous leishmaniasis were included in this study in Kerman. The patients were randomly divided into three groups. They were matched with regard to age, sex, duration of the disease, and type, number, and site of the lesions. For each group, one of the following therapeutic methods was applied: (i) oral allopurinol (15 mg/kg/day) for 3 weeks; (ii) intramuscular injection of Glucantime (30 mg/kg/day), corresponding to 8 mg/kg/day of pentavalent antimony, for 2 weeks; (iii) combined therapy. The lesions were re-examined at the end of treatment and 2 and 4 weeks later. The response to treatment was graded as excellent (reduction in the size of the lesion by at least 80% or complete clearance), good (reduction in the size of the lesion by 50%), and poor (minimal or no change in the lesion).
                The overall results indicated that 18% of patients showed excellent response, 6% good response, and 76% poor response in the first group. In the second group, 24% of patients showed excellent response, 6% good response, and 70% poor response. In the third group, 46% of patients showed excellent response, 8% good response, and 46% poor response.
                The results obtained by the three therapeutic methods indicated that combined therapy with allopurinol plus Glucantime was much more effective than that obtained by each of the two drugs when used alone (P < 0.05). A wide variety of generalists and specialists treat locally infected ingrown toenails, with perhaps the most common treatment regimen including resection of the nail border coupled with oral antibiotics.
                To determine whether oral antibiotic therapy is beneficial as an adjunct to the phenol chemical matrixectomy in the treatment of infected ingrown toenails.
                We prospectively enrolled healthy patients with infected ingrown toenails. Each patient was randomly assigned to 1 of 3 groups that received either 1 week of antibiotics and a chemical matrixectomy simultaneously (group 1), antibiotics for 1 week and then a matrixectomy (group 2), or a matrixectomy alone (group 3).
                Institutional ambulatory outpatient clinic.
                Fifty-four healthy patients with infected ingrown toenails were studied. Patients with immunocompromised states, peripheral vascular disease, or cellulitis proximal to the hallux interphalangeal joint were excluded. Groups were age matched for comparison.
                Mean healing times for groups 1, 2, and 3 were 1.9, 2.3, and 2.0 weeks, respectively. Subjects receiving antibiotics and a simultaneous chemical matrixectomy (group 1) healed significantly sooner than those receiving a 1-week course of antibiotics followed by a matrixectomy (group 2). There was not a significant difference in healing time between those that received a chemical matrixectomy alone (group 3) and those that received a matrixectomy coupled with a course of oral antibiotics (group 1).
                The use of oral antibiotics as an adjunctive therapy in treating ingrown toenails does not play a role in decreasing the healing time or postprocedure morbidity. In a placebo-controlled double-blind study the prophylactic value of oral systemic treatment with the antimycotic agent miconazole was assessed in 30 highly predisposed patients receiving intensive cytostatic chemotherapy because of haematological malignancies. Patients colonized with Candida before treatment were not freed from this micro-organism by miconazole treatment. However, only 3 out of 6 initially non-colonized miconazole-treated patients became colonized during the study, against 10 out of 10 placebo-treated patients (p = 0.036). Seven out of 15 patients in the placebo group developed clinical mycosis, against only two out of 15 in the miconazole group. The miconazole-treated patients remained clinically free of mycosis for 252 out of 264 treatment days, while the placebo-treated patients remained free of mycosis for only 263 out or 338 treatment days (p = 0.0001). The results indicate that systemic miconazole treatment protects highly predisposed patients from colonization with Candida and prevents or postpones clinically established candidosis. A double-blind trial of 2% miconazole in a cream and in a powder base and of the respective vehicles was done in a group of forty-five young sportsmen regularly training and using the showers in a gymnasium. After 4 weeks treatment, the mycological cure rate using the active preparation was 60% compared to 24% for the placebo (P less than 0-05). To evaluate the efficacy of topical (1%) and systemic itraconazole against common fungi such as Aspergillus and other filamentous fungi that cause mycotic corneal ulcer.
                A prospective randomised, controlled study was done in 54 clinically suspected cases of fungal keratitis of which 44 were culture proven. Half the cases (n=27) with superficial involvement were treated with only topical itraconazole (1%) and the other half were treated with both topical and systemic itraconazole.
                Aspergillus, Penicillium and Fusarium were the most common fungi isolated. The ulcer resolved in 42 eyes (77%) and 12 eyes (23%) did not respond well to treatment. Four of 12 non-responding eyes were caused by Fusarium species.
                Itraconazole, given either topically or systemically, is effective in treating mycotic corneal ulcers. To investigate the prevention and therapy of fungal infection in patients with severe acute pancreatitis (SAP).
                Seventy patients with SAP admitted from Jan. 1998 to Dec. 2002 were randomly divided into garlicin prevention group, fluconazole (low dosage) prevention group and control group. The incidence of fungal infection, the fungal clearance and mortality after treatment were compared.
                The incidence of fungal infection in garlicin group and fluconazole group was lower than that in control group (16% vs 30%, P<0.05 and 9% vs 30%, P<0.01, respectively). Amphotericin B or therapy-dose fluconazole had effects on patients with fungal infection in garlicin group and control group, but had no effects on patients with fungal infection in fluconzole group.
                Prophylactic dosage of antifungal agents (garlicin or low dosage fluconazole) can reduce the incidence of fungal infection in patients with SAP. But once fungal infection occurs, amphotericin B should be used as early as possible if fluconazole is not effective. Topical steroids are the first choice for the treatment of oral lichen planus (OLP). Antifungal drugs are often employed together with them, to prevent secondary oral candidosis, although it has been suggested anecdotally that they can also be beneficial for OLP itself.
                To compare the effect of clobetasol propionate with and without a topical antifungal drug (miconazole) on the symptoms and extension of OLP.
                A randomized, parallel, double-blind trial was conducted at the Unit of Oral Medicine and Pathology of the University of Milan. Thirty-five outpatients with histologically proven OLP were randomly assigned to receive either clobetasol propionate and miconazole, or clobetasol propionate and placebo for 6 weeks. Primary outcomes included symptoms and extension of lesions; adverse effects were also recorded.
                All the patients who concluded the study (30 of 35) showed clinical and subjective improvement within 3 weeks. The addition of miconazole did not affect in a significant way the signs and symptoms of OLP. No cases of clinical candidosis were seen in the patients taking miconazole, while one-third (five of 15) of the placebo group were affected.
                Although effective in preventing iatrogenic candidosis, the addition of miconazole to topical steroid treatment does not improve the efficacy of the therapy. The safety and effectiveness of oral terbinafine, 125 mg twice daily, and griseofulvin, 250 mg twice daily, in patients with moccasin-type tinea pedis were examined in a double-blind randomized trial. At the end of the 6-week treatment period, both a clinical and mycologic cure or a mycologic cure with minimal signs of infection was noted in 12 (75%) of the 16 terbinafine-treated patients compared with only 3 (27%) of the 12 patients treated with griseofulvin. The overall response rate 2 weeks after the completion of treatment was 88% in the terbinafine-treated group and 45% in the griseofulvin-treated group. When contacted again 6 to 15 months after completion of the study, 94% of the terbinafine-treated patients reported sustained clearing of tinea pedis, and 88% of those with nail involvement at the time of treatment reported improvement. In contrast, tinea pedis remained cured in only 30% of the patients who had received griseofulvin, and onychomycosis improved in only 14%. Several small studies have indicated that the systemic administration of pentoxifylline may accelerate healing of venous leg ulcers. The goal of this study was to further evaluate these findings in a larger scale placebo controlled trial and to explore the effect of the dose of pentoxifylline on healing. The study used a prospective, randomized, double-blind, parallel group placebo controlled design in a multicenter outpatient setting. Patients with one or more venous ulcer were enrolled, with all patients receiving standardized compression bandaging for treatment for their ulcers. Patients were also randomized to receive either pentoxifylline 400 mg, pentoxifylline 800 mg (two 400 mg tablets), or placebo tablets three times a day for up to 24 weeks. The main outcome measure was time to complete healing of all leg ulcers, using life table analysis. The study was completed as planned in 131 patients. Patients receiving 800 mg three times a day of pentoxifylline healed faster than placebo (p = 0.043, Wilcoxon test). The median time to complete healing was 100, 83, and 71 days for placebo, pentoxifylline 400 mg, and pentoxifylline 800 mg three times a day, respectively. Over half of all patients were ulcer free at week 16 (placebo) and at week 12 in both pentoxifylline groups. Whereas the placebo group had only achieved complete healing in half of the cases by week 16, all of the subjects remaining in the group receiving the high dose of pentoxifylline had healed completely. Treatment with pentoxifylline was well tolerated with similar drop-out rates in all three treatment groups. Complete wound closure occurred at least 4 weeks earlier in the majority of patients treated with pentoxifylline by comparison to placebo. A higher dose of pentoxifylline (800 mg three times a day) was more effective than the lower dose. We conclude that pentoxifylline is effective in accelerating healing of leg ulcers. To evaluate the efficacy of topical 1% voriconazole versus 5% natamycin in treatment of fungal corneal ulcers.
                A prospective, randomized pilot study in a tertiary care hospital.
                Thirty patients of microbiologically proven fungal keratitis divided randomly in two groups of 15 patients each.
                Two groups were treated with either 5% natamycin (group A) or 1% voriconazole (group B) topically as a primary treatment for fungal keratitis. The mean size, depth of infiltrate and LogMAR visual acuity at presentation were comparable in both groups (P > 0.05). Patients were followed up for minimum of 10 weeks or till complete resolution of ulcer, whichever was later. Cultures to identify the causative organisms were performed.
                Time of resolution of the ulcer.
                Twenty-nine of the total 30 patients showed complete resolution. Average time of resolution and gain in LogMAR visual acuity was 24.3 days and 1.12 in group A and 27.2 days and 0.77 in group B. These were comparable in the two groups (P > 0.05%). Aspergillus spp. (40%) and Curvularia spp. (30.0%) were found to be most common isolates.
                Topical 1% voriconazole was found to be safe and effective drug in primary management of fungal keratitis, its efficacy matching conventional natamycin. There was no added advantage of using topical 1% voriconazole over topical natamycin as primary treatment in fungal keratitis.
                © 2011 The Authors. Clinical and Experimental Ophthalmology © 2011 Royal Australian and New Zealand College of Ophthalmologists. Fluconazole is a new orally absorbed antifungal azole which is effective in the treatment of mucosal and systemic infections caused by Candida, cryptococci and other fungi. In view of its favourable efficacy, safety and pharmacokinetic profile it was considered appropriate to evaluate its use prophylactically in patients undergoing a period of neutropenia. Two hundred and forty-eight patients receiving chemotherapy and/or bone marrow transplantation for the treatment of acute leukaemia, lymphoma or aplastic anaemia, and expected to be rendered temporarily neutropenic, have been entered into an ongoing multicentre comparative clinical study to compare the prophylactic efficacy of 50 mg daily oral fluconazole with that of widely used regimens of oral polyenes. The incidence of suspected fungal infection was less in the fluconazole group (27%) than in the polyene group (45%), the difference being statistically significant (P less than 0.05). Only one of the suspected infections in the fluconazole group was confirmed mycologically compared with 17 in the polyene group. Fluconazole prophylaxis was well tolerated and it therefore offers a promising new approach to the management of fungal infection in the neutropenic patient. Further studies are warranted to define the optimum dosage for use in this situation. Whereas certain oral antifungal azoles are well documented to have activity against leishmania, data on the efficacy of fluconazole for leishmaniasis are limited. We conducted a controlled trial in Saudi Arabia of fluconazole for the treatment of cutaneous leishmaniasis caused by Leishmania major.
                This randomized, double-blind, placebo-controlled trial assessed the efficacy of oral fluconazole, in a dose of 200 mg daily for six weeks, in the treatment of parasitologically confirmed cutaneous leishmaniasis. The primary outcome measure was the time to the complete healing of all lesions.
                A total of 106 patients were assigned to receive fluconazole, and 103 patients were assigned to receive placebo. Follow-up data were available for 80 and 65 patients, respectively. At the three-month follow-up, healing of lesions was complete for 63 of the 80 patients in the fluconazole group (79 percent) and 22 of the 65 patients in the placebo group (34 percent; relative risk of complete healing, 2.33 [95 percent confidence interval, 1.63 to 3.33]). According to an intention-to-treat analysis, the rates of healing were 59 percent and 22 percent, respectively (relative risk, 2.76 [95 percent confidence interval, 1.84 to 4.12]). Sodium stibogluconate was offered to 11 patients in the fluconazole group who returned for follow-up (14 percent) and 33 of those in the placebo group (51 percent) in whom oral treatment was judged to have failed. According to a Kaplan-Meier analysis, the time to healing was shorter for the fluconazole group (median, 8.5 weeks, as compared with 11.2 weeks in the placebo group; P<0.001 by the log-rank test). Side effects were mild and similar in both groups.
                A six-week course of oral fluconazole is a safe and useful treatment for cutaneous leishmaniasis caused by L. major. Although pentavalent antimonials are often used in the first-line treatment of cutaneous leishmaniasis (CL), they have several adverse effects. Intralesional administration of antimonials and other antileishmanial drugs can be painful. In the present, double-blind, randomized study, to determine if topical treatment with paromomycin is effective in the treatment of CL, 35 cases of CL were treated, twice daily for 30 days, with a commercial skin-care lotion containing 10% urea (the placebo) and another 30 were similarly treated with the same lotion to which paromomycin sulphate had been added (to give a concentration of 15%). Each case was assessed clinically 7, 14, 21 and 30 days after treatment began, and parasitologically 30 and 60 days after the initiation of treatment. Five (17%) and five (17%) of the cases treated with paromomycin showed complete healing, with the apparent clearance of amastigotes from their lesions, 30 and 60 days after treatment began, respectively. At the same time-points, however, the lesions on six (17%) and seven (20%) of the cases in the placebo group, respectively, also appeared to have healed completely. Ointment containing 15% paromomycin therefore appears ineffective in the treatment of CL, at least when applied twice daily for 30 days to the lesions of cases from an endemic area of Isfahan, Iran. We determined the efficacy of the combination of the topical formulation 15% paromomycin sulfate/12% methylbenzethonium chloride (MBCL) and a short course (7 days) of parenteral meglumine antimonate (pentavalent antimony [Sb]) as treatment of American cutaneous leishmaniasis in Colombian patients. Patients were randomly assigned in unequal allocation (2:1:1:1) to group 1 (topical paromomycin/MBCL plus injectable Sb for 7 days), group 2 (topical placebo plus injectable Sb for 7 days), group 3 (topical paromomycin/MBCL plus injectable Sb for 3 days), and group 4 (injectable Sb for 20 days). Cure was defined as complete reepithelialization of all lesions without relapse. Cure rates among groups were as follows: 58% (34 of 59), group 1; 53% (16 of 30), group 2; 20% (6 of 30), group 3; and 84% (26 of 31), group 4. Seventy-one percent of the organisms identified to the species level were Leishmania braziliensis panamensis. We conclude that 10 days of therapy with paromomycin/MBCL does not augment the response of cutaneous leishmaniasis (predominately due to L. braziliensis panamensis) to a short course of treatment with meglumine antimonate. Liposomal amphotericin (AmBisome) 2 mg/kg three times weekly was compared with placebo as prophylaxis against fungal infection in patients undergoing chemotherapy or bone marrow transplantation (BMT) for haematological malignancies. Prophylaxis began on day 1 of chemotherapy and continued until neutrophils regenerated or infection was suspected. Of 161 evaluable patients, 74 received AmBisome and 87 received placebo. Proven fungal infections developed in no patients on AmBisome and in three on placebo (3.4%) (P = NS). Suspected fungal infections requiring intervention with systemic antifungal therapy (usually amphotericin B) occurred in 31 patients on AmBisome (42%) and in 40 on placebo (46%) (P = NS). Suspected deep-seated infections developed in 21 (28.3%) and 31 (35.6%) patients, respectively (P = NS). Time to develop a suspected or proven deep-seated infection showed a trend in favour of AmBisome (P = 0.11). Fifty patients had fungal colonisation (48 with Candida spp, two with Aspergillus spp) of at least one body site during prophylaxis; 15 patients while receiving AmBisome (20%) and 35 while on placebo (40%) (P < 0.01). Time to colonisation was significantly delayed in the group receiving AmBisome (P < 0.05). Treatment-related toxicity was modest and no additional toxicity was observed in patients receiving AmBisome. AmBisome 2 mg/kg three times weekly is safe and reduces fungal colonisation in patients receiving intensive chemotherapy or BMT. However, despite encouraging trends, prophylactic AmBisome did not lead to a significant reduction in fungal infection or in requirement for systemic antifungal therapy.
Placebo-controlled trials of allylamines and azoles for athlete's foot consistently produce much higher percentages of cure than placebo. Allylamines cure slightly more infections than azoles and are now available OTC. Further research into the effectiveness of antifungal agents for nail infections is required.