Combination of surgical avulsion and topical therapy for single nail onychomycosis: a randomized controlled trial

BACKGROUND: Conventional therapy of onychomycosis is prolonged and often frustrating, which is why combination therapy involving topical, oral and surgical measures has been advocated as the treatment of choice. There are no controlled studies evaluating the efficacy of nail avulsion followed by topical antifungal therapy. OBJECTIVES: To evaluate the efficacy of combined surgical and topical therapy for onychomycosis. METHODS: Forty patients with single nail onychomycosis [28 with distal and lateral subungual onychomycosis, seven with total dystrophic onychomycosis (TDO) and five with proximal subungual onychomycosis] were randomly assigned to four treatment groups. Each group received avulsion of the involved nail, followed by ketoconazole 2% cream without (group I) or with occlusion (group II), or oxiconazole 1% cream without (group III) or with occlusion (group IV). Topical therapies were applied twice daily. The patients were reviewed monthly and treatment was continued until the regrowth of completely normal nail (mycologically negative). In cured cases, further monthly review was carried out for at least 6 months, without any form of therapy. At each visit direct microscopic examination was repeated. RESULTS: There was a high dropout rate, with seven patients (group I), six patients (group II), six patients (group III) and eight patients (group IV) completing the treatment protocol. Out of these, mycological cure was achieved in three (43%) patients in group I, four (67%) in group II, two (33%) in group III and six (75%) in group IV. All the cases of TDO failed to respond to this therapy. Overall, 15 of 27 (56%) patients were cured with this approach. On further follow up, recurrence of onychomycosis was recorded in two patients in group I. No side-effects or long-term complications of the nail avulsion were encountered. Important limitations encountered in the present study included a small sample size, a high dropout rate (32%) and poor patient compliance. CONCLUSIONS: Contrary to earlier reports, surgical nail avulsion with topical antifungal agents was not found to be a very encouraging modality for the treatment of onychomycosis. Both oxiconazole and ketoconazole delivered comparable results. Occlusion improved the treatment outcome, although the difference was not statistically significant. As a subtype, TDO showed poorest response. Surgical nail avulsion followed by topical antifungal therapy cannot be generally recommended for the treatment of onychomycosis.     

Labeled use of efinaconazole topical solution 10% in treating onychomycosis in children and a review of the management of pediatric onychomycosis

Onychomycosis is a difficult to treat condition whose prevalence is increasing. Until recently, there was no FDA approved antifungal agent for the treatment of onychomycosis in children. Although systemic antifungal agents are effective, their use is restricted by the potential adverse events and drug‐drug interactions. There is evidence regarding the safety and efficacy of topical antifungal agents for pediatric onychomycosis. We have summarized the results of a recently published study using efinaconazole topical solution 10% to treat onychomycosis in children and discuss management of pediatric onychomycosis. In a multicenter, open‐label phase 4 study, efinaconazole 10% solution was applied topically once daily in children aged 6 to 16 years with mild to severe, culture positive, distal and lateral subungual onychomycosis. Treatment was for 48 weeks with a follow‐up at week 52. Pharmacokinetics was performed in a subset of patients. There were 62 patients enrolled in the study. At week 52, the efficacy was mycological cure rate 65% and complete cure rate 40%. All treatment‐emergent adverse events (TEAE) were mild to moderate in severity with none resulting in study discontinuation. The only treatment‐related TEAE was ingrown toenail. Efinaconazole was detected at low levels in plasma. Efinaconazole topical solution 10% is effective and safe in treating onychomycosis in children age 6 to 16 years and was recently FDA‐approved for this indication. The on‐label use of other topical agents, tavaborole solution 5% and ciclopirox nail lacquer solution 8% is reviewed. We also briefly discuss the use of oral agents, terbinafine, itraconazole, and fluconazole in pediatric onychomycosis.     

Fifth toenail clinical response to systemic antifungal therapy is not a marker of successful therapy for other toenails with onychomycosis

BACKGROUND: Onychodystrophy is a major manifestation of onychomycosis. However, nail trauma may also result in onychodystrophy. The fifth toenail, due to its location, suffers repeated friction/pressure trauma from shoes. OBJECTIVE: To test the hypothesis that treatment failure of fifth toenail onychomycosis is not a marker of treatment failure of other toenails with onychomycosis. METHODS: Fifty patients who had fifth toenail deformity (with or without onychomycosis) and onychomycosis of the other toenails were treated with oral terbinafine, 250 mg/day, for 4 months. RESULTS: Forty-three patients completed the study. Before the study, 26/43 (61%) had callus lateral to the fifth toe (suggesting mechanical pressure in that area). Twenty-one/43 (49%) of the fifth toenails had onychomycosis. At the end of the treatment period, only 4/21 (19%) of the fifth toenails (with initial onychomycosis), compared with 12/21 (57%) of the other toenails, were completely cured (CC). Out of the whole group (n=43), the clinical cure rate of the fifth toenail was 4/43 (9%) and for the other toenails, 20/43 (47%) (P<0.05). The mycological cure rates were 11/21 (52%) for the fifth toenail and 25/43 (58%) for the other toenails. Callus lateral to the fifth toe was associated with a poor clinical result (P<0.01). CONCLUSIONS: Clinical improvement of the fifth toenail after systemic antifungal therapy is less favourable and does not correspond with the clinical cure of the other toenails, mostly because of mechanical factors. Therefore, patients should be told to adjust their expectations as to the visual results of their antifungal treatment.     

Onychomycosis Does Not Always Require Systemic Treatment for Cure: A Trial Using Topical Therapy

Standard teaching dictates that systemic therapy is required for treatment of onychomycosis. It is unknown whether topical antifungal therapy is effective for pediatric nail infections. This prospective, randomized, double‐blind, vehicle‐controlled study was conducted in the Pediatric Dermatology Research Unit at Rady Children's Hospital to determine whether topical antifungal therapy is efficacious for pediatric onychomycosis. Forty patients ages 2 to 16 years with nonmatrix onychomycosis were randomized 1:3 to ciclopirox lacquer or vehicle lacquer. Ciclopirox lacquer or vehicle was applied daily for 32 weeks, with weekly removal of the lacquer and mechanical trimming. Those with poor response were crossed over to active drug at week 12. Thirty‐seven patients completed the 32‐week study, and follow‐up data were collected 1 year after completion of the study from 24 patients. Mycologic cure, effective treatment, and complete cure were assessed, as well as adverse events and effect on quality of life. Mycologic cure was 70% in the treated group and 20% in the vehicle arm (p = 0.03) at week 12. At end of the study (week 32), 77% of treated patients achieved mycologic cure and 71% effective treatment, compared with 22% of the control group. Ninety‐two percent of those who were cured and followed for 1 year remained clear. Topical antifungal lacquer (ciclopirox) can be an effective option for children with nonmatrix onychomycosis. Pediatric onychomycosis does not always require systemic therapy and responds better to topical therapy than does adult disease.     

Toenail abnormalities and onychomycosis in chronic venous insufficiency of the legs: should we treat?

Background Toenail manifestations of chronic venous insufficiency (CVI) may often mimic the nail changes of onychomycosis. The current study aims to determine the frequency of toenails deformations in patients with CVI, onychomycosis prevalence among deformed toenails and the outcome of itraconazole treatment. Methods Patients with clinical evidence of (CVI) were enrolled. All patients with toenails deformations and proven onychomycosis were treated by itraconazole pulse therapy for 4 months and then followed‐up for additional 5 to 6 months. Results Forty‐four patients with CVI entered the study. Thirty‐seven patients (84%) had nail deformations; 28 of 37 patients (75%) had onychomycosis; and 24 patients completed the follow‐up period. Total cure was achieved in 6 of 24 patients (25%), and 14 patients (58%) had no improvement. Patients’ age and CVI duration were significantly correlated to onychomycosis cure rate. Conclusions Nail deformations are more prevalent in CVI patients (84%) then in the general elderly population, and 75% of affected nails had also onychomycosis. In these patients, itraconazole achieved only 25% total cure rate compared with the 60% to 70% cure rate commonly cited in the literature, probably due to irreversible nail deformity caused by the CVI and due to the thickened nail that prevented penetrance of itraconazole into the nail plate. Therefore, before antifungal treatment is started for onychomycosis in patients with CVI, especially in older patients, the caregiver must stress out that the final outcome might not be as desirable as in pure onychomycosis patients.     

Ciclopirox nail lacquer for the treatment of onychomycosis: An open non-comparative study

Onychomycosis is a relatively common disease accounting for up to 50% of all nail disorders. Topical treatment, although less effective than systemic, is usually preferred by patients. Topical antifungal nail lacquers have been formulated to provide better delivery of the antifungal agent to the nail unit. The purpose of this research is to evaluate the efficacy and safety of ciclopirox nail lacquer in the treatment of onychomycosis. Patients suffering from distal and lateral subungual toenail onychomycosis (DLSO) and lateral subungual onychomycosis (LSO) were treated by ciclopirox nail lacquer once daily for 9 months. Every week the nail lacquer was removed using acetone. Clinical nail status, KOH examination and mycological culture were recorded by the same investigator at 0, 3, 6 and 9 months. Thirty-six patients completed the 9-month regimen. Trichophyton rubrum was the most common pathogen. At the end of the study, good improvement to complete cure was observed in 13 patients (36%), 12 patients showed only mild to moderate improvement and 11 patients (31%) had no clinical improvement. No adverse effects were noted throughout the treatment period. Ciclopirox nail lacquer seems to be slightly more effective than other topical modalities and could be used in patients who cannot or do not want systemic treatment.     

A method for the determination of drug effectiveness in onychomycosis: Trials with ketoconazole and griseofulvin ultramicrosize

A new method for assessing drug effectiveness in onychomycosis is presented. It is based on the clinical experience when three systemic antifungal drugs (griseofulvin, thiabendazole, and ketoconazole) are used against onychomycosis. These drugs act clinically as a barrier to the invasion of the fungus toward the proximal areas of the nail plate. A monthly quantity of normal nail plate should be produced by a given subject after the administration of an effective dose of the antifungal being tested. This quantity is best measured at monthly intervals, and this in fact reflects the normal monthly nail plate growth for the individual. Although there is a slight variation among individuals, most normal healthy subjects grow 1.5 to 2 mm of nail plate per month from their large toenails and 3 to 4 mm of nail plate per month from their fingernails. Utilizing this quantitative system, ketoconazole and griseofulvin ultramicrosize were compared in the treatment of distal subungual onychomycosis by Trichophyton rubrum. In a double-blind study, sixteen patients were treated. It appears that both griseofulvin and ketoconazole can eradicate the episode of onychomycosis. One-year use of a topical antifungal cream after clinical cure of onychomycosis prevented reinfection in the 12-month follow-up period. The use of ketoconazole in long-term therapy may result in serious side effects and should be considered carefully prior to treatment.     

Efficacy and safety of luliconazole 5% nail solution for the treatment of onychomycosis: A multicenter,double‐blind,randomized phase III study

Onychomycosis is a highly prevalent and intractable disease. The first‐line treatment agents are oral preparations, but an effective topical medication has long been desired. The objective was to investigate the efficacy and safety of luliconazole 5% nail solution, an imidazole antifungal agent, for the treatment of patients with onychomycosis. A multicenter, double‐blind, randomized phase III study was conducted in Japanese patients with distal lateral subungual onychomycosis affecting the great toenails, with 20–50% clinical involvement. Patients were randomized (2:1) to luliconazole or vehicle once daily for 48 weeks. The primary end‐point was the complete cure rate (clinical cure [0% clinical involvement of the nail] plus mycological cure [negative results on direct microscopy]). The adverse event incidence was monitored to evaluate safety. The complete cure rate significantly favored luliconazole (14.9%, 29/194 subjects) versus vehicle (5.1%, 5/99) (P = 0.012). Similarly, the negative direct microscopy rate was significantly higher with luliconazole (45.4%, 79/174) than with vehicle (31.2%, 29/93) (P = 0.026). There were no serious adverse drug reactions. We conclude that once daily topical luliconazole 5% nail solution demonstrated clinical efficacy and was confirmed to be well tolerated.     

Efficacy of long‐term treatment with efinaconazole 10% solution in patients with onychomycosis,including severe cases: A multicenter,single‐arm study

We evaluated the efficacy of efinaconazole 10% topical solution in long‐term use, for up to 72 weeks, for onychomycosis, including severe cases. Among 605 participants, 219 patients diagnosed as having onychomycosis were evaluated for the efficacy of efinaconazole. The treatment success rate (<10% clinical involvement of the target toenail) at the final assessment time point was 56.6%, the complete cure rate was 31.1% and the mycological cure rate was 61.6%, all of which increased over time, demonstrating that continuous application contributed to the improvement of cure rate. Even in severe cases, reduction of the affected nail area was observed, showing the potential efficacy of the treatment. Responses to a quality of life questionnaire among patients with onychomycosis, OnyCOE‐t, suggested that efinaconazole treatment improved the patients’ quality of life. The incidence of adverse drug reaction in the patients eligible for the assessment was 6.3%, and this developed only in the administration site in all cases. No systemic adverse event was observed. In addition, no increase in the incidence of adverse drug reaction due to long‐term use was found. Efinaconazole therapy was proved to exhibit excellent balance between efficacy and safety, and thus may serve as a useful treatment option for onychomycosis.     

Intermittent Therapy with Terbinafine for Dermatophyte Toe-Onychomycosis: A New Approach

Terbinafine, an orally active antifungal agent of the allylamine class, is effective in the treatment of dermatophyte onycomycosis. Its pharmacologic and pharmacokinetic properties give strong support to the possibility that intermittent treatment courses may be equally effective in onychomycosis in general. The present randomized and controlled study was carried out to determine whether intermittent therapy with terbinafine was effective in dermatophyte toe-onychomycosis. Sixty patients with mycologically proven toenail dermatophyte onychomycosis were included in the study. Patients were equally allocated to treatment groups in a random manner. Group 1 was given 250 mg/day of terbinafine for 3 months. Group 2 was given 500 mg/day of terbinafine for 7 days during the first week of each month for 3 months. Nails were examined clinically and mycologically at monthly intervals. All patients were followed up for 48 weeks after starting the treatment. Of the patients who entered the study, 24 in Group I and 23 in Group 2 were evaluable for efficacy. At the end of the follow-up period, the cure rate (negative microscopy and culture) was 79.2% in Group 1 and 73.9% in Group 2; this difference was not significant (p: 0.79). The results indicate that intermittent therapy with terbinafine is as effective as 3-month treatment in dermatophyte toe-onychomycosis.     

A questionnaire study on the management of onychomycosis: a Canadian perspective

Background Onychomycosis of the toenails is a condition that responds poorly to griseofulvin. The introduction of terbinafine in Canada in May 1993 resulted in a marked shift in the choice of treatment for pedal onychomycosis. Methods A questionnaire survey was carried out in 1996 among Canadian dermatologists regarding the management of onychomycosis. Results There were 160 respondents from the roughly 350 practicing dermatologists. The dermatologists saw 8 ± 0.6 patients per week (average ± standard error (SE)) with suspected or diagnosed onychomycosis, with 5 ± 0.5 patients per week consulting the dermatologists for the first time. Most dermatologists performed mycological testing prior to starting treatment for onychomycosis. The management options for onychomycosis (mean ± SE) were oral systemic antifungal therapy 51 ± 3%, no therapy 31 ± 3%, and nondrug therapy 9 ± 2%. The majority of dermatologists (83%) used terbinafine as first-line therapy if, indeed, they used oral antifungal agents. In contrast, griseofulvin and ketoconazole were used as first-line therapy in 5% and 1% of cases, respectively. In Canada, there are no monitoring requirements when using oral terbinafine for onychomycosis. Therefore, it is not surprising that only 30% of dermatologists performed monitoring with terbinafine. In contrast, the frequency of monitoring with griseofulvin and ketoconazole was 40% and 80%, respectively. The subset of dermatologists who reported monitoring carried it out in only a fraction of their patients: 47%, 53%, and 83% for terbinafine, griseofulvin, and ketoconazole, respectively. Therefore, the overall number of patients in whom regular monitoring was performed was 14.1%, 21.2%, and 71.4% for terbinafine, griseofulvin, and ketoconazole, respectively. The perceived cure rates with terbinafine and griseofulvin (mean ± SE) were 83.7 ± 1% and 41 ± 3.1%, respectively. Conclusions In May 1996, within three years of the introduction of terbinafine to Canada, this agent has become the drug of choice for the treatment of pedal onychomycosis (at the time of the survey neither itraconazole or fluconazole were approved for onychomycosis). Terbinafine has been found to be very effective and safe, and only a minority of dermatologists perform regular monitoring with this drug.     

Efficacy and safety of fosravuconazole L‐lysine ethanolate,a novel oral triazole antifungal agent,for the treatment of onychomycosis: A multicenter,double‐blind,randomized phase III study

Fosravuconazole L‐lysine ethanolate (F‐RVCZ) is a prodrug of ravuconazole, a novel triazole antifungal agent, exerting broad and potent antifungal activity. The efficacy and safety of F‐RVCZ, compared with a placebo, were investigated in a multicenter, double‐blind, randomized study of Japanese onychomycosis patients with 25% or more clinical involvement of the target toenail. Subjects (n = 153) were randomly assigned to receive F‐RVCZ (100 mg RVCZ, n = 101) or placebo (n = 52) p.o. once daily for 12 weeks. The primary end‐point was the rate of complete cure (clinical cure [0% clinical involvement of the target toenail] plus mycological cure [negative potassium hydroxide examination]) at week 48 (36‐week post‐treatment visit). Secondary end‐points were changes over time in the efficacy and mycological effect of F‐RVCZ. Safety was also evaluated. The complete cure rate at week 48 was significantly higher with F‐RVCZ (59.4%, 60/101) than the placebo (5.8%, 3/52) in the full analysis set (P < 0.001). The mycological cure rate at week 48 was also significantly higher with F‐RVCZ (82.0%, 73/89) than the placebo (20.0%, 10/50, P < 0.001). Regarding safety, adverse events were observed in 83.2% (84/101) and 80.8% (42/52), and adverse drug reactions (ADR) in 23.8% (24/101) and 3.8% (2/52) of F‐RVCZ and placebo subjects, respectively. ADR were mild to moderate in severity, with none being serious. F‐RVCZ (equivalent to 100 mg ravuconazole) administrated once daily for 12 weeks was more effective than placebo and tolerable in patients with onychomycosis, suggesting it to be a promising drug for onychomycosis treatment.     

Long-term effectiveness of treatment with terbinafine vs itraconazole in onychomycosis: a 5-year blinded prospective follow-up study

OBJECTIVE: To examine long-term cure and relapse rates after treatment with continuous terbinafine and intermittent itraconazole in onychomycosis. DESIGN: Long-term prospective follow-up study. SETTING: Three centers in Iceland. SUBJECTS: The study population comprised 151 patients aged 18 to 75 years with a clinical and mycological diagnosis of dermatophyte toenail onychomycosis. INTERVENTIONS: In a double-blind, double-dummy study, patients were randomized to receive either terbinafine (250 mg/d) for 12 or 16 weeks or itraconazole (400 mg/d) for 1 week in every 4 for 12 or 16 weeks (first intervention). Patients who did not achieve clinical cure at month 18 or experienced relapse or reinfection were offered an additional course of terbinafine (second intervention). MAIN OUTCOME MEASURES: The primary efficacy criterion was mycological cure, defined as negative results on microscopy and culture at the end of follow-up and no requirement of second intervention treatment. Secondary efficacy criteria included clinical cure without second intervention treatment and mycological and clinical relapse rates. RESULTS: Median duration of follow-up was 54 months. At the end of the study, mycological cure without second intervention treatment was found in 34 (46%) of the 74 terbinafine-treated subjects and 10 (13%) of the 77 itraconazole-treated subjects (P<.001). Mycological and clinical relapse rates were significantly higher in itraconazole vs terbinafine-treated patients (53% vs 23% and 48% vs 21%, respectively). Of the 72 patients who received subsequent terbinafine treatment, 63 (88%) achieved mycological cure and 55 (76%) achieved clinical cure. CONCLUSION: In the treatment of onychomycosis, continuous terbinafine provided superior long-term mycological and clinical efficacy and lower rates of mycological and clinical relapse compared with intermittent itraconazole.     

Effects of foot care intervention including nail drilling combined with topical antifungal application in diabetic patients with onychomycosis

We performed periodical foot care intervention including nail drilling combined with topical antifungal application for 6 months or more in 24 diabetic patients with onychomycosis who were not receiving oral antifungals, and evaluated its effects. The type of onychomycosis was superficial white onychomycosis (SWO) in eight patients, and distal-lateral subungual onychomycosis (DLSO) in 16. The state of onychomycosis was evaluated according to the Scoring Clinical Index for Onychomycosis (SCIO). Of the eight patients with SWO, none showed aggravation of the onychomycosis state, and two were cured 6 months after the initiation of intervention and two after 1 year (total of four patients, 50%). In the patients with DLSO, the SCIO score was 18.1 +/- 6.5 before intervention but significantly decreased to 14.6 +/- 6.6 6 months after intervention. In 12 patients who we were able to consecutively follow up for 1 year, the SCIO score also significantly decreased compared with the score before intervention. Thus, foot care intervention including nail drilling combined with topical antifungal application had effects on onychomycosis and achieved cure in some patients with SWO. In addition, intervention increased patients' awareness of foot care, showing educational effects. Therefore, foot care intervention including nail drilling may be useful.     

Onychomycosis: current treatment and future challenges

Onychomycosis is a fungal infection of the nails, more often of the toenails. It is a common condition, with an estimated overall prevalence of 3–10% in European populations. Dermatophytes, especially Trichophyton rubrum and Trichophyton mentagrophytes , are the usual pathogens. Some 50% of infected patients fail to seek medical advice. Medically confirmed onychomycosis should be treated. This recommendation is based on several disease-specific considerations: cosmetic and functional disability, lack of spontaneous remission, impairment of health and wellbeing in elderly patients and the need to reduce contamination in communal bathing places. Current treatments for onychomycosis include oral antifungal agents such as terbinafine (Lamisil^®) and itraconazole (Sporanox^®). They offer significantly improved rates of cure, shorter treatment regimens and a lower level of adverse events than was previously the case. Comparative studies have shown that terbinafine is more effective than griseofulvin, fluconazole or itraconazole in the treatment of this condition, providing a cure rate of 70–80% and an excellent tolerability profile. Terbinafine is also the most cost-effective agent. However, several problems remain that will provide future challenges in the treatment of onychomycosis, not least the consistent treatment failure rate of 20%. In many of these cases, surgery may need to precede drug therapy in order to maximise the prospects of clinical and mycological cure. In addition, duration of treatment also needs to be more closely adjusted to the individual case by prior identification of severity and extent of toenail infection, and combined oral and topical therapy also requires further investigation.     

Usefulness of itraconazole for sporotrichosis in Japan: study of three cases and literature comparison of therapeutic effects before and after release on the market

Potassium iodide, itraconazole (ITCZ), and terbinafine are widely known as oral antifungal agents for the treatment of sporotrichosis. Although potassium iodide has been used as the antifungal agent of first choice in Japan due to its high efficacy, its use is not covered by the health insurance programs. In this report, we present the disease course of 3 patients with sporotrichosis in which ITCZ was remarkably effective. By reviewing cases reported in the past, we found sufficient therapeutic effects of ITCZ against sporotrichosis. We also conducted a simple comparison of the efficacy of ITCZ in clinical trials with that of its post-market release; finding the latter to be lower. This seems to be attributable to the problem of compliance or the administration method.     

Itraconazole pulse therapy for onychomycosis and dermatomycoses: An overview

Background: Itraconazole is a broad-spectrum antifungal agent that has been used to treat dermatomycosis and onychomycosis using continuous therapy. More recently the drug has been used as pulse dosing. Objective: Our purpose was to review the studies in which itraconazole pulse therapy (PT) has been administered in the management of dermatomycoses. Results: For tinea pedis and manuum, the recommended dosage is itraconazole 200 mg twice daily for 1 week (n = 220). A clinical response and mycologic cure rate of 90% ± 4% and 76% ± 6%, respectively, has been obtained. For tinea corporis/cruris, itraconazole 200 mg/day for 1 week (n = 354) resulted in a clinical response and mycologic cure rate of 90% ± 4% and 77% ± 6%, respectively. When three pulses of itraconazole are used to treat toenail onychomycosis (n = 1389), the clinical cure rate, clinical response, and mycologic cure rate at follow-up 12 months after the start of therapy were 58% ± 10%, 82% ± 3%, and 77% ± 5%, respectively. With two pulses for onychomycosis of the fingernails, the clinical cure rate, clinical response, and mycologic cure rate at follow-up, 9 months after the start of therapy, were 78% ± 10%, 89% ± 6%, and 87% ± 8%, respectively. Conclusion: Itraconazole PT is effective and safe in the treatment of tinea pedis/manuum, tinea corporis/cruris, and onychomycosis. (J Am Acad Dermatol 1997;37:969-74.)     

The topical treatment of onychomycosis using a new combined urea/imidazole preparation

Forty-two patients with mycologically proven onychomycosis involving 48 nails were treated topically with a paste formulation of 1% bifonazole and 40% urea following one of two treatment regimens. The results using the most effective regimen (Regimen 2), which involved daily application of the medication for 1 week, produced a mycological cure rate of 62–5% at 12 weeks, reduced to 46% at follow-up at 24 weeks. These results compare favourably with those obtained by long-term systemic treatment with griseofulvin. Such topical treatment ought to be considered as an alternative in onychomycosis especially that of the toenails.     

Prognostic factors of mycological cure following treatment of onychomycosis with oral antifungal agents

BACKGROUND: There is considerable literature on the efficacy and safety of various drugs used in treating onychomycosis; however, little information is available regarding prognostic factors which may be associated with non-response to conventional treatment. OBJECTIVES: To identify parameters influencing mycological cure at 72 weeks following treatment of toenail onychomycosis with oral antifungal agents. METHODS: Univariate and multivariate logistic regression analysis from a randomized double-blind controlled trial including 496 patients with toenail onychomycosis caused by dermatophytes. RESULTS: Baseline parameters including patient's age, gender, weight, number of toenails involved, percentage of nail involvement, duration of infection, history of previous treatment were not associated with mycological cure. In the multivariate prognostic factor analysis based on factors assessed at week 12, positive mycological culture at 12 weeks [odds ratio (OR): 0.583; 95% confidence interval (CI): 0.370-0.918] was negatively associated with mycological cure at 72 weeks. Similarly, in the multivariate prognostic factor analysis based on factors assessed at week 24, positive direct microscopy at 24 weeks (OR: 0.373; 95% CI: 0.211-0.659) and mycological culture at 24 weeks (OR: 0.293; 95% CI: 0.168-0.513) were negatively associated with mycological cure at 72 weeks. CONCLUSIONS: Mycological culture at 12 and 24 weeks and direct microscopic examination at 24 weeks can help in early identification of patients failing to respond to conventional oral antifungal treatment.     

The use of 40% urea cream in the treatment of moccasin tinea pedis

Moccasin tinea pedis is a chronic dermatophyte infection of the foot that is recalcitrant to topical antifungal therapy. Furthermore, most patients with moccasin tinea pedis also have onychomycosis, thus adding to the recalcitrant nature of the infection. The topical antifungals used as sole therapy are generally ineffective because the scale on the plantar surface impedes or limits the absorption of the antifungal agent. The aim of this study was to evaluate the efficacy of 40% urea cream as an adjunct to topical antifungals in the treatment of moccasin tinea pedis. Patients with untreated moccasin tinea pedis were selected from the general dermatology clinic. The diagnosis of moccasin tinea pedis was made clinically and confirmed with a potassium hydroxide test or a positive fungal culture. A total of 12 patients with moccasin tinea pedis were treated with 40% urea cream once daily and ciclopirox cream twice daily. Patients then were evaluated after 2 to 3 weeks of treatment for the presence of erythema, scaling, and pruritus. After 2 to 3 weeks, a 100% cure rate was achieved in the 12 patients treated with topical 40% urea cream and ciclopirox cream concomitantly.