Topical Ciclopirox Olamine Research Articles

Comparison of the Efficacy of Terbinafine versus and Co-Administration of Terbinafine and Fluconazole in Patients of Tinea Corporis

Background: Dermatophytosis management is difficult in Bangladesh, and there have been reports of systemic antifungals being used at greater doses. However, there have been numerous reports of increased treatment failures with terbinafine at standard dosage, consequently we performed this study to compare the efficacy and safety of terbinafine at high dose with terbinafine fluconazole at 150mg weekly dose. In both arms, topical ciclopirox olamine was used. Objectives: The aim of the study was to compare of the efficacy of terbinafine versus and co-administration of terbinafine and fluconazole in patients of tinea corporis. Methods: This was randomized, open label, comparative study where 80 patients with tinea corporis et cruris infection were included. Patients were either prescribed terbinafine 250mg twice a day or Terbinafine 250mg daily and Fluconazole 150mg weekly. Efficacy was assessed based on complete, clinical and mycological cure rate. Safety was assessed by evaluating adverse events and monitoring liver function of patients. Results: Total 80 patients completed the study with 40 in each group. 81.5% patients achieved complete cure in Terbinafine and Fluconazole group compared to 73.9% patients in Terbinafine group. At the end of 6 weeks, there was a statistically significant improvement (p value<0.05) in the total symptom score (erythema, scaling, and pruritus) in Terbinafine as well as in terbinafine and fluconazole compared to baseline. None of the patients showed any significant side effect in both groups. No changes in liver function were observed in both the groups. Conclusion: This study shows that the high dose of terbinafine and Co-administration of standard dose of terbinafine fluconazole along with CPO is effective and safe in management of tinea corporis et cruris.

Effectiveness and safety of Ciclopirox Olamine compared to that of Luliconazole in management of patients with multi-site dermatophytosis on background itraconazole therapy

Wide spread, inappropriate use of antifungal drugs in dermatophytosis has resulted in rise in minimum inhibitory concentration (MIC) values and reduced response. Hence there is a need for a different antifungal with a novel mechanism of action.This was an open-label, randomised, prospective, interventional, comparative, double-arm study. The patients were treated with either topical ciclopirox olamine or luliconazole twice daily for 6 weeks. All the patients were taking oral itraconazole 100mg twice daily for 4 weeks. Effectiveness endpoints were percentage of patients achieving complete cure, clinical cure and mycological cure at the end of the treatment period from baseline. Safety was assessed by analyzing the AEs and monitoring of liver function tests. 92 patients were included in the study. 44 and 43 patients completed the study in ciclopirox and luliconazole group respectively. 84.09%, 88.63% and 86.36% patients achieved ccomplete, clinical and mycological cure rate in ciclopirox group respectively. 83.72%, 88.37% and 86.04% patients achieved complete, clinical and mycological in luliconazole group respectively. 10.63% patients in the Ciclopirox group and 10.86% in the Luliconazole group reported one or more drug related AE. Nausea, skin rash, head ache and vomiting were AEs reported. The results of this study prove that Ciclopirox is novel antifungal agent which is efficacious and safe in the management of dermatophytosis.

Comparative evaluation of efficacy and safety of terbinafine and itraconazole in the management of tinea corporis et cruris

The management of dermatophytosis is challenging in India and there are reports of using systemic antifungals at higher doses. But there are multiple reports of increased treatment failures with terbinafine at standard dosage as well, hence we conducted this study to compare efficacy and safety of high dose of terbinafine with itraconazole at standard dose. Topical ciclopirox olamine was used in both arms.This was randomized, open label, comparative study where 80 patients with tinea corporis et cruris infection were included. Patients were either prescribed terbinafine 250mg twice a day or itraconazole 100mg twice a day for 4 weeks. Efficacy was assessed based on complete, clinical and mycological cure rate. Safety was assessed by evaluating adverse events and monitoring liver function of patients.Total 76 patients completed the study with 38 in each group. 81.5% patients achieved complete cure in terbinafine group compared to 76.31% patients in itraconazole group. At the end of six weeks, there was a statistically significant improvement (p value<0.05) in the total symptom score (erythema, scaling, and pruritus) in Group I as well as in Group II compared to baseline. None of the patients showed any significant side effect in both Itraconazole and Terbinafine groups. No changes in liver function were observed in both the groups. This study shows that the high dose of terbinafine in combination with topical ciclopirox is effective and safe in management of tinea corporis et cruris.

Spread of Terbinafine-Resistant Trichophyton mentagrophytes Type VIII (India) in Germany-"The Tip of the Iceberg?"

Chronic recalcitrant dermatophytoses, due to Trichophyton (T.) mentagrophytes Type VIII are on the rise in India and are noteworthy for their predominance. It would not be wrong to assume that travel and migration would be responsible for the spread of T. mentagrophytes Type VIII from India, with many strains resistant to terbinafine, to other parts of the world. From September 2016 until March 2020, a total of 29 strains of T. mentagrophytes Type VIII (India) were isolated. All patients were residents of Germany: 12 females, 15 males and the gender of the remaining two was not assignable. Patients originated from India (11), Pakistan (two), Bangladesh (one), Iraq (two), Bahrain (one), Libya (one) and other unspecified countries (10). At least two patients were German-born residents. Most samples (21) were collected in 2019 and 2020. All 29 T. mentagrophytes isolates were sequenced (internal transcribed spacer (ITS) and translation elongation factor 1-α gene (TEF1-α)). All were identified as genotype VIII (India) of T. mentagrophytes. In vitro resistance testing revealed 13/29 strains (45%) to be terbinafine-resistant with minimum inhibitory concentration (MIC) breakpoints ≥0.2 µg/mL. The remaining 16 strains (55%) were terbinafine-sensitive. Point mutation analysis revealed that 10/13 resistant strains exhibited Phe397Leu amino acid substitution of squalene epoxidase (SQLE), indicative for in vitro resistance to terbinafine. Two resistant strains showed combined Phe397Leu and Ala448Thr amino acid substitutions, and one strain a single Leu393Phe amino acid substitution. Out of 16 terbinafine-sensitive strains, in eight Ala448Thr, and in one Ala448Thr +, new Val444 Ile amino acid substitutions were detected. Resistance to both itraconazole and voriconazole was observed in three out of 13 analyzed strains. Treatment included topical ciclopirox olamine plus topical miconazole or sertaconazole. Oral itraconazole 200 mg twice daily for four to eight weeks was found to be adequate. Terbinafine-resistant T. mentagrophytes Type VIII are being increasingly isolated. In Germany, transmission of T. mentagrophytes Type VIII from the Indian subcontinent to Europe should be viewed as a significant public health issue.

Candida glabrata

Chronic recurrent vulvovaginal candidiasis caused by Candida glabrata is still rare in comparison to C. albicans infection, but therapy remains more difficult. Standard agents as fluconazole or itraconazole often fail, as well as the newer systemic triazoles like voriconazole or posaconazole. Micafungin is a new echinocandin drug with a wide antifungal spectrum including rare Candida species. No clinical trials with micafungin in chronic recurrent vulvovaginal candidiasis have been undertaken. We present the initial results employing a new therapy regimen consisting of micafungin in combination with topical ciclopirox olamine. All 14 patients with chronic recurrent vulvovaginal candidiasis caused by C. glabrata were treated successfully.

Two cases of tinea caused by Microsporum gyeum and their pathogenic analysis

Two patients were admitted to the hospital for 2-month history of pruritic eruptions on the forehead and 2-week history of pruritie eruptions on the leg, respectively. Both patients had a history of pet contact. Topical application of glucocorticoids did not work well. Dermatological examination revealed a patch measuring 5 cm ×6 cm on the forehead of one patient and a patch measuring 2 cm × 3 cm on the leg of the other patient. Both patches were surrounded by red papules and scaling. Microscopic examination of skin scales revealed hyphae and chain-like spores, and culture of skin scales grew Microsporum gyeum. Both the isolates of Microsporum gyeum were sensitive to ketoconazole, miconazole, bifonazole, terbinafine, and voriconazole. Both patients were healed after treatment with oral terbinafine and topical ciclopirox olamine.

Toenail infection byCladophialophora boppii

Cladophialophora boppii is a black yeast-like fungus that up to now has been only rarely described as a cause of human infection and whose role as a pathogen was not established despite its repeated isolation and genetic identification in these reports. Here we report the first case of a verified toenail infection caused by this fungus in a woman without any systemic disease or evidence of immunodeficiency. Identical dark molds were isolated from the same toenail at three points of time. Species identification was performed by scrutinizing the isolates morphologic, physiologic and genetic characteristics which resulted in their identification as Cladophialophora boppii. Oral treatment with terbinafin plus topical ciclopiroxolamine was effective.

The repositioning of the anti-fungal agent ciclopirox olamine as a novel therapeutic agent for the treatment of haematologic malignancy

6-Cyclohexyl-1-hydroxy-4-methyl-2(1H)-pyridone (ciclopirox) and specifically its olamine salt 6-cyclohexyl-1-hydroxy-4-methyl-2(1H)-pyridone 2-aminoethanol salt (ciclopirox olamine) are anti-fungal agents currently used for the treatment of mild to moderate cutaneous fungal infection. Our objective is to comment on the opportunity to rapidly reposition ciclopirox and its olamine for the treatment of haematologic malignancy by leveraging its prior published toxicology and pharmacology data. Ciclopirox olamine chelates intracellular iron and displays preclinical efficacy in the treatment of haematologic malignancy. Currently, an ongoing study is evaluating topical ciclopirox olamine for the treatment of cervical cancer. Doses of ciclopirox olaine required for a systemic anti-cancer effect appear pharmacologically achievable. However, caution is required as at the highest doses tested in animal toxicology studies, irreversible cardiac degeneration was observed. The existing pharmacology and toxicology data suggest that systemic ciclopirox olamine could be repositioned as a new investigational anti-cancer agent. The available pharmacology and toxicology data should aid in the design of phase I clinical trials of this agent in patients with refractory haematologic malignancies.

Treatment of chronic vulvovaginal candidiasis with posaconazole and ciclopiroxolamine

Therapy of chronic recurrent vulvovaginal can- didiasis (VVC) caused by Candida glabrata is still rare in comparison to C. albicans infection, but therapy remains more difficult. Combination therapy with topical antifungals may improve therapy outcome, but still standard agents as fluconazole or itraconazole often fail. Posaconazole is a new systemic triazole with a wide antifungal spectrum including rare Candida species. Up to now, no clinical trials with posa- conazole in chronic recurrent VVC have been undertaken. Here, first results of the application of a new therapy regimen consisting of oral posaconazole in combination with topical ciclopiroxolamine are presented. 15 patients with chronic recurrent VVC caused by C. glabrata have been treated. 14 of these patients experienced successful therapy, clinical and mycological cure 30 days after begin of therapy has been observed. Long-term results are promising, as in 4 patients clinical and mycologic cure persists for more than 1 year up to now.

Topical treatments for fungal infections of the skin and nails of the foot.

Fungal infections of the feet normally occur in the outermost layer of the skin (epidermis). The skin between the toes is a frequent site of infection which can cause pain and itchiness. Fungal infections of the nail (onychomycosis) can affect the entire nail plate. To assess the effects of topical treatments in successfully treating (rate of treatment failure) fungal infections of the skin of the feet and toenails and in preventing recurrence. We searched the Cochrane Skin Group Specialised Register (January 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2005), MEDLINE and EMBASE (from inception to January 2005). We screened the Science Citation Index, BIOSIS, CAB - Health and Healthstar, CINAHL DARE, NHS Economic Evaluation Database and EconLit (March 2005). Bibliographies were searched. Randomised controlled trials (RCTs) using participants who had mycologically diagnosed fungal infections of the skin and nails of the foot. Two authors independently summarised the included trials and appraised their quality of reporting using a structured data extraction tool. Of the 144 identified papers, 67 trials met the inclusion criteria. Placebo-controlled trials yielded the following pooled risk ratios (RR) of treatment failure for skin infections: allylamines RR 0.33 (95% CI 0.24 to 0.44); azoles RR 0.30 (95% CI 0.20 to 0.45); ciclopiroxolamine RR 0.27 (95% CI 0.11 to 0.66); tolnaftate RR 0.19 (95% CI 0.08 to 0.44); butenafine RR 0.33 (95% CI 0.24 to 0.45); undecanoates RR 0.29 (95% CI 0.12 - 0.70). Meta-analysis of 11 trials comparing allylamines and azoles showed a risk ratio of treatment failure RR 0.63 (95% CI 0.42 to 0.94) in favour of allylamines. Evidence for the management of topical treatments for infections of the toenails is sparser. There is some evidence that ciclopiroxolamine and butenafine are both effective but they both need to be applied daily for prolonged periods (at least 1 year). The 6 trials of nail infections provided evidence that topical ciclopiroxolamine has poor cure rates and that amorolfine might be substantially more effective but more research is required. 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.

Trichophytic Majocchi granuloma mimicking Kaposi sarcoma

A 68-year-old man presented with a one month history of painful blue-red papules and nodules on an erythematous base on the top of his feet, as well as dystrophic toenails. He had undergone renal transplantation six months previously for membranous glomerulonephritis, and was immunosuppressed with tacrolimus 3 g, mycophenolate mofetil 1500 mg and prednisolone 5 mg daily. His tacrolimus level was 29.8 ng/ml (expected level 6-8 ng/ml). Even though the cutaneous lesions strongly suggested Kaposi sarcoma, the histological examination revealed a dermal abscess in which hyphae and spores were seen with PAS staining. ELISA-PCR of the biopsy identified Trichophyton rubrum, which was also grown on culture of the biopsy tissue. The diagnosis of Majocchi granuloma secondary to excessive immunosuppression was made. Systemic treatment with terbinafine 250 mg per day and topical ciclopirox olamine completely cured the granulomatous skin lesions, and later the nails.

An open randomized comparative study to test the efficacy and safety of oral terbinafine pulse as a monotherapy and in combination with topical ciclopirox olamine 8% or topical amorolfine hydrochloride 5% in the treatment of onychomycosis

Onychomycosis is a fungal infection of nails caused by dermatophytes, yeasts and molds. To study the efficacy and safety of oral terbinafine pulse as a monotherapy and in combination with topical ciclopirox olamine 8% or topical amorolfine hydrochloride 5% in onychomycosis. A clinical comparative study was undertaken on 96 Patients of onychomycosis during the period between August 2005 to July 2006. Forty-eight patients were randomly assigned in group A to receive oral terbinafine 250 mg, one tablet twice daily for seven days every month (pulse therapy); 24 patients in group B to receive oral terbinafine pulse therapy plus topical ciclopirox olamine 8% to be applied once daily at night on all affected nails; and 24 patients in group C to receive oral terbinafine pulse therapy plus topical amorolfine hydrochloride 5% to be applied once weekly at night on all the affected nails. The treatment was continued for four months. The patients were evaluated at four weekly intervals till sixteen weeks and then at 24 and 36 weeks. We observed clinical cure in 71.73, 82.60 and 73.91% patients in groups A, B and C, respectively; Mycological cure rates against dematophytes were 88.9, 88.9 and 85.7 in groups A, B and C, respectively. The yeast mycological cure rates were 66.7, 100 and 50 in groups A, B and C, respectively. In the case of nondermatophytes, the overall response was poor: one out of two cases (50%) responded in group A, while one case each in group B and group C did not respond at all. Terbinafine pulse therapy is effective and safe alternative in treatment of onychomycosis due to dermatophytes; and combination therapy with topical ciclopirox or amorolfine do not show any significant difference in efficacy in comparison to monotherapy with oral terbinafine.

Perniosis‐like tinea corporis caused by Trichophyton verrucosum in cold‐exposed individuals

Trichophyton verrucosum is a zoophilic infectious agent causing 98% of the dermatophytic infections of cattle. Transmission to humans has, until recently, been rare. One reason for an increase of infection in humans and animals seems to be the decrease in immunisation of cattle. We report on three cases of pertinent human infections with disseminated, sharply defined, bluish red, partly oedematous nodules and plaques in particular not only on the thighs, but also on the trunk and arms. Two of our patients work with farm animals. The third one works as an assistant in a butcher shop, but lives on a cow farm. All three patients are often exposed to the cold. In all three cases T. verrucosum was detected by culture. Tinea corporis was histologically confirmed in two patients. Based on the microbiological results, we began a combined systemic and local antimycotic therapy with fluconazole 50 mg day(-1) in two patients, itraconazole 100 mg day(-1) in one patient p.o. combined with topical ciclopiroxolamine. All patients were cured. Dermatophytosis caused by T. verrucosum can, under certain circumstances, such as frequent exposure to cold or a long-term corticosteroid therapy, mimic the characteristic clinical picture of perniosis, as we demonstrate here.

Efficacy of ciclopiroxolamine 1% cream in onychomycosis and tinea pedis

Ciclopiroxolamine is now under use as an antifungal agent for about a decade. Its activity is well-known in moderate climates, but there is a lack of knowledge on the activity in tropical and subtropical areas. 49 patients suffering from onychomycosis (42) and/or tinea pedis (33) were enrolled in a clinical trial in Taiwan. The patients received ciclopiroxolamine 1% cream 2-3 times a day for 3 to 24 month. In addition, infected nails were filed to facilitate drug penetration. In onychomycosis, 14% of the patients were cured and another 36% improved. One patient relapsed after 10 months. Cure was achieved more easily, if there were only modest alterations of the nail plate. With respect to tinea pedis the results were more favourable, the cure rate was 42%, another 45% of the patients improved. Following this dosage regimen, side effects did not occur. The results show onychomycosis to be highly resistant to antifungal therapy, perhaps even more as compared to tinea pedis in temperate climates. The good tolerability favours topical ciclopiroxolamine for this recalcitrant disease.

Onychomycosis and AIDS: Treatment with Topical Ciclopirox Olamine

Onychomycosis and AIDS: Treatment with Topical Ciclopirox Olamine

Hendersonula toruloidea infection: successful response of onychomycosis to nail avulsion and topical ciclopiroxolamine

The exotic mould Hendersonula toruloidea may occasionally produce a ringwormlike, non-inflammatory, therapy-resistant mycosis of the skin and nails simulating chronic dermatophytosis. We report on a 30-year-old Nigerian male who, after two years´ sojourn in Sweden, developed finger-nail dystrophy and mild scaling of the palm and sole skin due to H. toruloidea infection. Nail avulsion followed by long-term occlusive application of ciclopiroxolamine cleared the onychomycosis, whereas the sole and palm infection was resistant to ciclopiroxolamine and glutaraldehyde treatment.

Ciclopirox olamine 1% cream. A preliminary review of its antimicrobial activity and therapeutic use.

Ciclopirox olamine is a substituted pyridone antimycotic, unrelated to the imidazole derivatives, with activity against a broad spectrum of dermatophytes, yeasts, actinomycetes, molds, other fungi, and a variety of Gram-positive and Gram-negative bacteria. The efficacy of ciclopirox olamine cream has been demonstrated in open and placebo-controlled studies in patients with superficial dermatophyte or yeast infections, and in double-blind comparative trials in patients with dermatomycoses, topical ciclopirox olamine was comparable to or better than clotrimazole in efficacy and caused a similar number of side effects. Ciclopirox olamine penetrates through fingernails and in preliminary studies has been successfully used in onychomycoses. However, further studies are needed to establish the role of ciclopirox in the treatment of onychomycoses and dermatomycoses relative to that of the more recently introduced antigungal agents.