Article

Study to determine the efficacy of Clotrimazole 1% cream for the treatment of onychomycosis in association with the mechanical reduction of the nail plate

Authors:
To read the full-text of this research, you can request a copy directly from the author.

Abstract

Onychomycosis is invasion of the nail by dermatophytes yeasts and moulds [Calderon RA, Hay RJ. Fungicidal activity of human neutrophils and monocytes on dermatophyte fungi Tri. Quinckeanum and Tri. Rubrum. Immunology 1986;61:289–95; Degreef H. Onychomycosis. Br J Clin Pract Syn Suppl 1990;71:91–7; Zaias N. Clinical manifestations of onychomycosis. Clin Exp Dermatol 1992;17(1):6–7]. Causative organisms include T. rubrum and T. mentagrophytes. Fungi invade the distal and lateral under surfaces of the nail. The prevalence of onychomycosis approximates to 5–10% of the population and is increasing significantly in recent years [Stutz A. Allylamine derivatives—a new class of active substances in antifungal chemotherapy. Angew Chem 1987;2:320–8].Clotrimazole 1% cream is the most commonly prescribed topical antifungal agent in the United Kingdom although its use on nails has not been widely documented. Past inefficiencies may be due to the thickness of the nail plate. The mechanical reduction of the nail minimises the nail as a barrier to the absorption of the cream and increases the permeability of the nail plate.Subjects were ambulant and healthy with no systemic medication, no past history of anti-fungal agents and an ankle-brachial index indicating sufficient circulation for healing to occur. The infecting organism was identified by microscopy and culture. A total of ninety-two infected nails were isolated over a four-year period. The age range was 60–78 years. Nails were drilled every 14 days by the same operator and the area of infection mapped. Clotrimazole 1% cream was applied twice daily during the trial period and the percentage clearance rate was recorded. After 12 weeks there was an average improvement of 96.2% with the infection in 80% nails completely resolved.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the author.

... Both treatments produced comparable improvement in nail appearance and comparable patient subjective symptom improvement ( Table 2). In an open, noncomparative trial [31], 26 patients (92 nails) were treated with 1 % clotrimazole twice daily for 12 weeks, with mechanical thinning every 2 weeks. At 12 weeks, all nails showed improved appearance, with 99.3 % of the infected area of lesser toes cleared and 96.2 % of the infected area of hallux toes cleared. ...
... In the case of ciclopirox, weekly application may increase compliance with efficacy similar to that seen with daily or 3/2/1 application; weekly application of amorolfine is standard. Most studies in this review selected one target nail to monitor for efficacy outcomes, while treating all affected or all nails; however, four open noncomparative studies did not [24,29,31,41]. Target nail selection at baseline is recommended, as well as treatment of all additional infected nails, in an effort to eliminate a potential source of reinfection. ...
Article
Background Managing toenail onychomycosis with topical treatments is challenging. It is difficult for topical medication to penetrate the nail plate, and this is reflected in lower cure rates with topical treatment than with oral treatment. However, oral medications may not be suitable for some patients, because of drug interactions; therefore, topical treatments are critical in managing the disease in certain patient populations. Objective This paper reviews the quality and content of the scientific literature on topical treatments for toenail onychomycosis. Methods PubMed, Ovid (Medline and Embase), Scopus, Cochrane library, and clinicaltrials.gov databases were searched for original clinical reports of topical monotherapy for microscopy and/or culture-confirmed toenail onychomycosis in adults. Studies were evaluated using an onychomycosis study quality scale, which was based on the CONSORT guidelines. Results Twenty-five publications (28 studies) were identified and met the inclusion criteria. Thirteen studies scored high ratings on the quality scale. These were randomized controlled trials or randomized comparative trials. Low-quality studies were nonrandomized, open studies that prevented statistical analysis. Most studies reported clinical and mycological cure. The most variation was observed with reporting outcomes of clinical improvement. Amorolfine, ciclopirox, tavaborole, and efinaconazole produced clinical and mycological cure in patients with mild to moderate toenail onychomycosis (
... Since this anionic form corresponds to the compound the present fungal growth quantification method is aimed at detecting (the liberated 4-MUF from 4-MUF-NAG by NAGase), the higher yield of fluorescence allows for a detection of smaller amounts of compound, and increase the detection limits of analysis. Its antimicrobial activity may be reduced by interaction with nonionic surfactants (Liebert, 1990;Kurup et al., 1995;Paulus, 2004;Sweetman, 2009;Regulska et al., 2010;SUBSPORT, 2013) Antimicrobial activity tends to be microbistatic unstable in aqueous solutions (Budavari, 1996;Paulus, 2004;Suhr and Nielsen, 2004;Stopforth et al., 2005;McDonnell, 2007;Shibamoto and Bjeldanes, 2009;Sweetman, 2009;Reda, 2011;Lopes et al., 2012;Fraise et al., 2013) Pharmaceutical (Budavari, 1996;Davies, 2006;Sweetman, 2009;Meloun et al., 2010) V. Appendix V ...
Thesis
Full-text available
Great part of the History of mankind is registered in the form of documents or works of art on paper support. Paper can be deteriorated due to physical, chemical and biological agents. Within microorganisms, fungi are the major paper biodeteriogens. Throughout history, several toxic methods have been used to prevent and stop fungal deterioration on paper based materials. More recently, a growing concern about environmental and health issues has led to the research on new antifungal alternatives, with lower toxicity. However, the existent antifungal methods and compounds still have drawbacks in terms of efficacy, health hazards, damaging effects on paper, or lack of thorough testing. In this context, the present thesis focused on testing and developing accessible antifungal treatments with low toxicity, which could prevent the long term paper deterioration. The selection of antifungal compounds was made taking into account the results from a literature review on antifungals used on paper conservation, a survey to paper conservators, and a review of antifungals used in cosmetics and pharmaceutical industries, having as a basic premise their low toxicity. Aspergillus niger, Chaetomium globosum, Cladosporium cladosporioides, Penicillium chrysogenum and Penicillium corylophilum were selected as test fungal species. Fungal growth on paper was evaluated by measuring colonization areas and biomass dry weight determination. A formulation containing parabens and calcium propionate (PBs+CP) presented the best antifungal activity on paper samples, followed by a formulation containing clotrimazole and calcium hydroxide nanoparticles (CLT+NPs), and ultimately 70% ethanol (70%EtOH). Before application on cultural heritage materials, conservation treatments have to be thoroughly tested to assess if they can cause any damage on the treated materials in the short and long term. The effects of the tested formulations on paper were evaluated in terms of pH, colourimetry, folding endurance and molecular alterations, using moist heat artificial ageing. Besides plain paper, paper previously biodeteriorated by A. niger was tested in order to evaluate the potential of each compound to prevent further deterioration caused by fungal metabolites. The obtained results on biodeteriorated samples illustrate how tremendously damaging the products excreted by fungi can be in the long term. PBs+CP formulation was the only one capable of preventing long term acidification, loss of folding endurance, and discoloration caused by fungal metabolites, but on the other hand, on plain samples, this formulation caused paper discoloration. CLT+NPs formulation significantly prevented the acidification and loss of folding endurance, although causing a minor discoloration on paper at a long term. 70%EtOH had a mild positive impact in the chemical stabilization of paper and did not cause any paper discoloration. The information provided in this thesis contributes to a deeper understanding on safer options for preventing and treating paper deterioration by fungi and opens the way for further research in this challenging field of heritage conservation.
... Onychomycosis is the most common disorders of nail plate and bed. It is caused by dermatophytes such as Trychophyton mentagrophytes and Trychophyton rubrum in up to 90% of cases, but can also be due to other fungi such as yeasts or molds (Davies, 2006). Physiologically, dermatophytes could get into the keratin layer to grow up and to replicate (Ghannoum et al., 2010). ...
Article
Full-text available
Onychomycosis is a fungal infection of nail unit that is caused by dermatophytes. Oral Terbinafine hydrochloride (TBF-HCl) is being used for the treatment of onychomycosis since 24 years. The side effects caused by the systemic application and limitations of topical administration of this drug regarding the diffusion through nail lead to the development of a new formulation based on, TBF-HCl-loaded liposome. The newly obtained film formulations were prepared and characterized via several parameters, such as physical appearance, drug content, thickness, bioadhesive properties and tensile strength. In vitro and ex vivo permeation studies were performed to select an optimum film formulation for antifungal activity to show the efficiency of formulations regarding the treatment of onychomycosis. The in vitro release percentages of drug were found 71.6 ± 3.28, 54.4 ± 4.26, 56.1 ± 7.48 and 46.0 ± 2.43 for liposome loaded pullulan films (LI-P, LII-P) and liposome loaded Eudragit films (LI-E, LII-E), respectively. The accumulated drug in the nail plates were found 31.16 ± 4.22, 24.81 ± 5.35, 8.17 ± 1.81 and 8.92 ± 3.37 for LI-P, LII-P, LI-E and LII-E, respectively, which within therapeutic range for all film formulations. The accumulated drug in the nail plate was found within therapeutic range for all film formulations. The efficacy of the selected TBF-HCl-loaded liposome film formulation was compared with TBF-HCl-loaded liposome, ethosome, liposome poloxamer gel and ethosome chitosan gel formulations. It was found that TBF-HCl-loaded liposome film formulation had better antifungal activity on fungal nails which make this liposome film formulation promising for ungual therapy of fungal nail infection.
... Analysis of its content revealed a total of 32 dermatological related papers. Of these 14 were published by medics and focussed primarily on skin tumours and common foot infections [52][53][54][55][56][57][58][59][60][61][62][63][64][65] whilst podiatry lead author papers focused on mycoses [66][67][68][69][70][71], wart infections [72][73][74], electrosurgery [75,76] and epidemiology [77]. Interestingly, other single papers by Podiatrists focused on less commonly encountered dermatological conditions [78][79][80][81][82]. Three papers were investigations into the pathology of corns and callus [83][84][85]. ...
Article
Full-text available
Background Although dermatology, as a medical subject, has been a facet of the training and education of podiatrists for many years, it is, arguably, only in recent years that the speciality of podiatric dermatology has emerged within the profession. Some indication of this gradual development may be identified through a content analysis of the podiatric literature in the UK, spanning a 21 year timeframe. Method 6 key professional journals were selected for content analysis in order to provide a picture of the emergence and development of podiatric dermatology over a period extending from 1989 to 2010. Both syntactical and thematic unitization were deployed in the analysis, revealing both manifest and latent content. Categories were devised using a prior coding, a codebook produced to define relevant concepts and category characteristics, and the coding scheme subject to an assessment of reliability. Results 1611 units appeared in the 6 journals across a 21 year timeframe. 88% (n = 1417) occurred in one journal (Podiatry Now and its predecessors). Modal categories within all journals included course adverts (n = 673), commercial adverts (n = 562) and articles by podiatrists (n = 133). There was an overall rise from 40 per annum in 1989, to over 100 in 2010. A wider range of dermatological topics were addressed, ranging from fungal nail infections to melanoma. Conclusions It is evident from this analysis that there has been an increasing focus on dermatology as a topic within the main podiatric journals in the UK over the last 21 years, primarily reflecting a rise in commercial advertising and an increase in academic dermatology related publications. Whilst earlier publications tended to focus on warts and fungal infections, more recent publications address a broader spectrum of topics. Changes in prescribing rights may be relevant to these findings, as may the enhanced professional and regulatory body requirements on continuing professional development.
Article
Superficial fungal infections are among the most widespread diseases known to man. They target parts of the body as diverse in form and function as the skin, the nail, the buccal cavity, the eye and the vagina. Fungistatic azole drugs, that is, imidazole- and triazole-containing compounds (e.g. miconazole and itraconazole, respectively), have been the mainstay of antifungal therapy for many years. The polyene nystatin is effective in treating Candida infections but is inactive against cutaneous dermatophytes. The advent of the fungicidal allylamines (e.g. terbinafine) and their congeners (e.g. butenafine) has improved treatment options: the course of therapy is shorter and cure rates higher with fungicidal drugs. Other newer agents include the echinocandins (e.g. caspofungin) that are primarily intended for systemic administration but which may have a role in topical therapy. In order to elicit a pharmacologic response following topical administration, these agents must enter into and diffuse across the target biologic tissues, which have distinct architectures and compositions depending on their function. The rate and extent of transport will depend on the interplay between the drug’s molecular properties and the characteristics of the biologic tissue. The drug may also interact with specific proteins or other membrane components. These interactions can prolong residence time and therapeutic effect; for example, azoles have an affinity for keratin (as do dermatophytes, their therapeutic target). Drug properties that increase permeability across a given membrane may render the molecule less effective at another biologic tissue; for example, the stratum corneum is a lipidic barrier, whereas the keratin-rich nail contains 10-fold less lipid and is perhaps best viewed as a hydrogel with very low lipid content. Consequently, both offer very different environments and drug delivery challenges compared with the oral and vaginal mucosae. In light of this, it is clear that formulation design and optimization are key steps in increasing the therapeutic efficacy of topical antifungal therapy. Furthermore, the formulation, which is the primary interface with the membrane, must not only be optimized with respect to the drug but also be compatible with the biologic tissue. Thus, developing effective formulations for topical therapy is a complex task. In this review, we provide a brief description of newer approaches in topical antifungal drug development and present a survey of recent work.
Article
Full-text available
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.
Article
This article summarizes the diseases of the nail caused by fungi. The clinical appearance of the diseases are the key to understanding their causes. Therapy is updated. Specifically discussed are distal subungual onychomycosis, white superficial onychomycosis, proximal subungual onychomycosis, and onychomycosis in chronic mucocutaneous candidiasis.
Article
Fungal infections (mycoses) are found throughout the world. Only a few structural classes of compounds currently satisfy the demands of modern chemotherapy in their treatment; hence, the quest for new types of active substances is of major scientific and therapeutic importance. The first representative of a new class of substances–the allylamine derivatives–namely naftifine ((E)-N-methyl-N-(1-naphthylmethyl)-3-phenylallylamine) was discovered by accident and has recently become commercially available as a topical antimycotic. The exploration of structure-activity relationships on the basis of naftifine and new synthetic strategies led to the discovery of the currently most active compound of this type, terbinafine, the first pharmaceutical agent to contain a (E)-1, 3-enyne structural element. Terbinafine exhibits considerably higher activity than the original “lead” structure naftifine both in vitro and in vivo; it is also up to one order of magnitude more effective than standard preparations in various chemotherapeutic animal tests after topical or oral administration. According to clinical experience gained so far, terbinafine is well tolerated and shows promising activity against various types of mycoses. Allylamines act as potent, selective inhibitors of fungal squalene epoxidase via a novel mechanism, which, unlike in the case of other inhibitors of steroid biosynthesis, does not depend on cytochrome P450.
Article
Superficial fungal infections are chronic and recurring conditions. Tinea capitis is a scalp infection, primarily affecting prepubescent children. Ringworm infections, such as tinea corporis and tinea cruris, involve the glabrous skin. Tinea nigra is a rare mycotic infection that may be related to travel abroad. Piedra, black or white, is limited to the hair shaft without involvement of the adjacent skin. Pityriasis (tinea) versicolor and seborrheic dermatitis are dermatoses associated with yeasts of the genus Malassezia that affect the lipid-rich areas of the body. The taxonomy of the Malassezia yeasts has been revised to include nine species, eight of which have been recovered from humans. Tinea pedis, an infection of the feet and toes, is one of the most common forms of dermatophytosis. Onychomycosis is a fungal infection affecting the nail bed and nail plate; it may be chronic and can be difficult to treat. In instances where the superficial fungal infection is severe or chronic, an oral antifungal agent should be considered. Terbinafine, itraconazole, and fluconazole are oral antifungals that are effective in the treatment of superficial mycoses.
Article
Trichophyton rubrum caused 72.9% of the cases of dermatophytosis observed in a sample of caucasoids from Philadelphia. Tinea pedis was found in 84% of the female and male patients with dermatophytosis. Tinea manuum occurred with equal frequency in both sexes whereas tinea unguium was more prevalent in females. Tinea cruris occurred almost exclusively in males. Infections of two or more anatomical sites were observed more frequently in males. The data are compared with those reported by Rosman (1966) from a similar study done in Copenhagen.
Article
Onychomycosis is common worldwide, about 10% of all dermatomycosis being fungal infections of the nails.1 Up until now no satisfactory topical treatment has been available. Therefore, the development of any new antifungal gives rise to high expectations with regard to its effectiveness in onychomycosis. Amorolfine is a phenylpropyl morpholine derivative which has been found to be more effective than imidazole derivatives and polyene antibiotics both in vitro and in experimental infections against dermatophytes and yeasts.2,3 Amorolfine possesses two properties which give rise to hopes that it may be used to treat onychomycosis. First, it is effective at low concentrations,2 and secondly, studies of in-vitro penetration on human nails show the presence of amorolfine in sufficient concentrations in the nail plate and the nail bed to give fungistatic and fungicidal levels.4 Furthermore, the persistence of amorolfine in the subungual keratin for 7 days5 would allow physicians to reduce the frequency of application. Two different lacquer formulations, one methylene chloride-based and the other ethanol based, were developed as vehicles for amorolfine for treating onychomycosis with one or two applications per week. This study was carried out in order to test the bioequivalence of the two different lacquer formulations and to see whether the antifungal activity of amorolfine in the subungual area would last longer than 7 days, as shown in a previous study.5 The measurement of the antifungal activity in the subungual area will be taken as one of the criteria for penetration of amorolfine through the human nail.
Article
We have reached a stage whereby many of the superficial mycoses are treatable with short courses of antifungal drugs. However, the minimum duration of therapy has still not been well defined and there remain some mycoses which do not respond to conventional therapy. It may be possible to introduce more radical approaches to therapy such as the single-dose oral or topical therapy for tinea pedis or short-duration therapy for onychomycosis. Amongst these options, topical therapies still have a part to play in the management of onychomycosis, and the role of amorolfine in this respect is of potential value. The ability of the drug to produce lasting remissions after short courses of treatment is also of great interest. Last, but not least, amorolfine has an in-vitro spectrum of activity which covers some of the less common cutaneous pathogens, and hence it may prove of benefit in those infections for which treatment at present is limited.
Article
Human peripheral polymorphonuclear neutrophils exhibited potent cytotoxic activity against the dermatophyte fungi Tricophyton quinckeanum and T. rubrum as assessed by inhibition of fungal replication in Sabouraud's agar. Monocytes also showed cytotoxic activity, but this was less pronounced than that of neutrophils, while lymphocytes had no toxic effect. Cytotoxicity showed a linear relationship to the target cell:effector cell ratio, with significant killing detected at a ratio of one neutrophil to one fungal cell. Fungal killing was optimal at incubation times of 2-24 hr for T. rubrum and 2-48 hr for T. quinckeanum. Thereafter, neutrophils were unable to prevent fungal replication while remaining viable. cytotoxicity was markedly reduced by sodium azide, an agent that inhibits haem enzymes, and by catalase, but not by heat-inactivated catalase or superoxide dismutase. The fungicidal activity of neutrophils and monocytes was greatly increased by stimulation with phorbol myristate acetate (PMA) or with concanavalin A (Con A) compounds known to stimulate the secretion of lysosomal enzymes and the production of highly reactive oxygen intermediates. The cytotoxic activity of monocytes to T. quinckeanum, but not to T. rubrum, was also increased by Con A treatment. Neutrophil and monocyte phagocytosis of dermatophytes was demonstrated by electron microscopy studies. Disrupted T. quinckeanum and T. rubrum germlings were identified in the cytoplasm of the phagocytic cells, and similarly disruption of hyphae surrounded, but not engulfed, by neutrophils was also observed. These studies suggest that phagocytosis and/or oxidative products of the respiratory burst of neutrophils and monocytes may be implicated in the killing of dermatophytes in vivo.
Article
Onychomycosis is defined as the infection of the nail unit by fungi. The terms tinea ungium and nail ringworm were used as synonyms when onychomycosis was thought to be produced exclusively by dermatophytic fungi. Today, however, nondermatophytic fungi and yeast, as well as dermatophytes, are known to be agents of onychomysis. The terms mentioned above should be discouraged since they bring confusion to the medical literature. The more precise terms dermatophytic, nondermatophytic and yeast onychomycosis are recommended.
Article
Currently used antifungal drugs are distinct in terms of spectrum of activity, potency, therapeutic index, development of resistance, and mode of use. An important factor in the usefulnesss of a compound is the mechanism by which it attacks the structure and function of the fungal cell. The target organelles have been established for most antifungal drugs. Polyenes bind irreversibly to cell membranes. Alteration of the permeability of these structures precedes metabolic disruption and cell death. Griseofulvin deteriorates spindle and cytoplasmic microtubules, influencing cell division and outgrowth of hyphal tips. Flucytosine is deaminated to 5-fluorouracil, which is then phosphorylated and incorporated into RNA; protein synthesis is consequently impaired. A mechanism of action via inhibition of DNA synthesis is an alternative explanation. The imidazole derivatives inhibit the biosynthesis of ergosterol, the main sterol in membranes of fungi. These agents also affect the synthesis of triglycerides and phospholipids. Changes in oxidative and peroxidative enzyme activities, leading to an intracellular buildup of toxic concentrations of hydrogen peroxide, may contribute to the observed deterioration of subcellular organelles and to cell necrosis. The imidazole derivatives inhibit the transformation of blastospores of Candida albicans into the invasive mycelial form. This inhibition probably facilitates the task of host defense cells and may be the principal factor leading to clearance of infection.
Article
The purpose of this article is to review the pharmacologic properties of two newer agents, itraconazole and terbinafine, and to assess their clinical efficacy in onychomycosis. Both drugs are effective in treating infections caused by dermatophytes. Itraconazole appears to be more efficacious in infections caused by Candida species. The improved effectiveness of these agents is probably related to their rapid penetration into the nails and prolonged bioavailability at the site of infection.
Article
To compare the efficacy and safety of terbinafine 1% cream and clotrimazole 1% cream in the treatment of tinea pedis. Multicentre, double blind parallel group study. 32 general practices and one hospital. 256 patients with mycologically confirmed tinea pedis. Of the 211 patients evaluable, 107 were randomised to terbinafine (75 male, 32 female; mean (range) age 40 (12-81) years) and 104 to clotrimazole (79 male, 25 female; mean (range) age 36 (12-71) years). Terbinafine 1% cream applied twice daily for one week and inert cream applied twice daily for the next three weeks. Clotrimazole 1% cream applied twice daily for four weeks. Mycological cure (negative results on microscopy and culture) and effective treatment (mycological cure plus no or minimal signs and symptoms) measured at weeks 1, 2, 3, 4, and 6. At week four rates of mycological cure were 93.5% for terbinafine and 73.1% for clotrimazole (p = 0.0001); and at week six 97.2% for terbinafine and 83.7% for clotrimazole (p = 0.001). Rates of effective treatment at week 4 were 89.7% for terbinafine and 58.7% for clotrimazole (p = 0.0001); and 89.7% for terbinafine and 73.1% for clotrimazole (p = 0.002) at week 6. These results indicate that a one week course of terbinafine 1% cream is more effective in the treatment of tinea pedis than a four week course of clotrimazole 1% cream, both in terms of mycological cure and effective treatment.
Article
Terbinafine is an orally and topically active allylamine antifungal drug which is an effective and well tolerated therapy for a wide range of superficial dermatophyte infections. In contrast to most other commonly prescribed antifungal agents, terbinafine is fungicidal in vitro and possesses improved pharmacokinetic properties with respect to drug penetration into nail tissue following oral administration. These properties enable terbinafine to achieve high success rates with shortened therapy regimens in the treatment of dermatophyte skin infections and onychomycosis. Pharmacoeconomic analyses have shown that oral terbinafine, with its higher rates of clinical efficacy and lower rates of relapse/reinfection, is less costly and more cost effective than oral griseofulvin, ketoconazole and itraconazole when used as initial therapy in the treatment of onychomycosis. However, some points regarding the clinical efficacy of itraconazole relative to terbinafine and the drug treatment regimens used in these studies need further clarification. In the management of tinea pedis, a cost analysis suggested that initial therapy with terbinafine 1% cream was more costly than initial therapy with miconazole, oxiconazole or clotrimazole. However, in cost-effectiveness studies, terbinafine had a lower cost per disease-free day than ciclopirox, clotrimazole, ketoconazole and miconazole in the treatment of dermatophyte skin infections. In conclusion, available clinical and pharmacoeconomic data support the use of topical terbinafine as first-line treatment of dermatophyte skin infections unless the acquisition cost of terbinafine is markedly greater than that of alternative topical antifungal agents. Oral terbinafine can be recommended as a cost-effective first-line treatment, preferable to oral griseofulvin, ketoconazole and itraconazole, in patients with dermatophyte onychomycosis.
Article
Fungal infections may be difficult to treat for several reasons. It is important to obtain the correct diagnosis, and select the appropriate antifungal agent and route. General considerations that may be associated with recurrent infections are, a genetic predisposition and suboptimal bioavailability of drug, resulting in insufficient concentration at the target site. The aetiologic organism, the severity of disease, other coexisting diseases, concomitant drug intake, and the presence of fungal infection at other sites are some factors that determine the choice of antifungal therapy and its route of administration, oral vs. topical lacquer. Local factors such as the thickness of the nail, presence of lateral onychomycosis, longitudinal spike, dermatophytoma and severe onycholysis are some factors that may determine the choice of secondary measures such as mechanical or topical treatment. Booster or supplemental therapy may be of benefit when the response to initial treatment is poorer than expected and unlikely to result in complete response. Steps should be taken to reduce the possibility of recurrence once cure has been achieved.
Article
Dermatophytes are fungi that require keratin for growth. These fungi can cause superficial infections of the skin, hair, and nails. Dermatophytes are spread by direct contact from other people (anthropophilic organisms), animals (zoophilic organisms), and soil (geophilic organisms), as well as indirectly from fomites. Dermatophyte infections can be readily diagnosed based on the history, physical examination, and potassium hydroxide (KOH) microscopy. Diagnosis occasionally requires Wood's lamp examination and fungal culture or histologic examination. Topical therapy is used for most dermatophyte infections. Cure rates are higher and treatment courses are shorter with topical fungicidal allylamines than with fungistatic azoles. Oral therapy is preferred for tinea capitis, tinea barbae, and onychomycosis. Orally administered griseofulvin remains the standard treatment for tinea capitis. Topical treatment of onychomycosis with ciclopirox nail lacquer has a low cure rate. For onychomycosis, "pulse" oral therapy with the newer imidazoles (itraconazole or fluconazole) or allylamines (terbinafine) is considerably less expensive than continuous treatment but has a somewhat lower mycologic cure rate. The diagnosis of onychomycosis should be confirmed by KOH microscopy, culture, or histologic examination before therapy is initiated, because of the expense, duration, and potential adverse effects of treatment.
Article
These guidelines for management of onychomycosis have been prepared for dermatologists on behalf of the British Association of Dermatologists. They present evidence-based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of epidemiological aspects, diagnosis and investigation.
Article
Combination therapy is one way of improving the cure rate of onychomycosis. The LION Study examined the efficacies of terbinafine and itraconazole. The Icelandic cohort of the study reported that after 5 years only 46% of the terbinafine-treated patients and 13% of the itraconazole-treated patients were still disease-free, suggesting that relapses and reinfections were common in the long term treatment of onychomycosis with monotherapy. Combination therapy is a well-established principle in mycology; the current strategy involves the combination of oral and topical antifungal treatments. A number of specific drug combinations have proved to be useful in the treatment of onychomycosis: tioconazole and griseofulvin, amorolfine and griseofulvin, amorolfine and terbinafine, and amorolfine and itraconazole. However, comparison of the combination trials can be difficult because of the short duration of some of the studies and variation in global cure rates. Although it is necessary to consider these factors it is clear that combination therapy offers advantages when compared with monotherapy. Combination therapy can be administered sequentially or in parallel. Parallel therapy is recommended for patients who are likely to fail therapy (e.g. patients with diabetes), whereas sequential therapy is recommended for patients who show a poor response to initial treatment.
Article
The treatment of onychomycosis has improved in recent years and many patients can now expect a complete and lasting cure. However, for up to 25% of patients, persistent disease remains a problem, thus presenting a particular challenge to the clinician. For these patients, it is obviously important to ensure that a correct diagnosis of onychomycosis has been made, as misdiagnosis will inevitably jeopardize the perception of therapeutic effectiveness. Although onychomycosis accounts for about 50% of all nail diseases seen by physicians, nonfungal causes of similar symptoms include repeated trauma, psoriasis, lichen planus, local tumours vascular disorders and inflammatory diseases. Predisposing factors that contribute to a poor response to topical and/or oral therapy include the presence of a very thick nail, extensive involvement of the entire nail unit, lateral nail disease and yellow spikes. However, poor penetration of systemic agents to the centre of infection, or the inability of topical agents to diffuse between the surface of the nail plate and the active disease below, probably contributes to this.
Article
Superficial white onychomycosis (SWO) is a distinct pattern of fungal nail invasion, which is usually treated with topical antifungals. This paper presents a case of SWO with deep penetration and records other similar cases. The clues to deep invasion of the nail plate are twofold: an inability to clear the discoloration by scraping the nail and a clinical involvement of the nail plate in the proximal nailfold area. Histology of the nail keratin will confirm deep penetration beyond the superficial layers of the nail plate. In the light of this finding the authors propose a further subdivision of SWO to reflect previously unrecognized variants with therapeutic implications into: (i) the classical SWO type; (ii) the dual invasion of the nail plate, superficial and ventral; and (iii) the pseudo-SWO with deep fungal invasion of the nail plate. This subdivision of SWO allows the clinician to treat the patient appropriately using topical antifungals when the disease is restricted to the dorsum of the nail. Systemic drugs either in isolation or in combination with topical treatment are mandatory when deep penetration or ventral fungal invasion are observed.
Article
The purpose of this investigation was to study the physico-chemical properties of hot-melt extruded films containing ketoconazole and to determine the influence of 'nail etching' on film bioadhesion and drug permeability for the assessment of topical onychomycosis therapies. Hot-melt extrusion (HME) was used to prepare films containing 20% w/w ketoconazole. Ketoconazole 0.125% gel was also prepared using Carbopol 974P NF. Films were processed at a temperature range of 115-120 degrees C utilizing a Killion extruder (KLB-100), and were evaluated for post-extrusion drug content, content uniformity, bioadhesion, thermal behavior and nail drug permeation. The extruded films demonstrated excellent content uniformity and post-processing drug content. Tensile and peel tests were recorded to determine the bioadhesive profiles. In this study, work of adhesion and peak adhesive force determinations using the peel tests provided more sensitive results for evaluating the bioadhesivity of the HME films than the tensile tests. The in vitro permeability profiles have demonstrated, that nail samples treated with an 'etchant' demonstrated a significant increase in drug permeability compared to control. Differential scanning calorimetry (DSC) thermograms indicated that ketoconazole was in solid solution within the HME films. These findings are encouraging for the future design and formulation of novel drug delivery systems for the topical treatment of onychomycosis.
Article
Superficial fungal infections are common, especially onychomycosis, dermatophytoses, and superficial Candida infections. Most superficial fungal infections are treated with topical antifungal agents unless the infection covers an extensive area or is resistant to initial therapy. Onychomycosis often requires systemic therapy with griseofulvin, itraconazole, or terbinafine. The objective of this review is to provide the practicing dermatologist with the recommended available therapy for the treatment of common superficial fungal infections.
Article
In order to assess the safety and efficacy of once-weekly fluconazole orally (100, 150, or 300 mg) with once-a-day topical application of 1% ketoconazole cream in the treatment of onychomycosis in Japan, 121 patients were assigned to one of three fluconazole dosages (100, 150, or 300 mg) and took fluconazole orally, once weekly, for 12 months or until a complete cure was achieved. In addition, once-a-day topical ketoconazole cream was applied. At each weekly visit, adverse events were investigated and the length of the diseased nails was measured. Treatment efficacy was assessed 12 months after discontinuation of fluconazole using the following scale: cured, markedly improved, improved, slightly improved, no change. Mycological cure was assessed using KOH wet mount and fungus culture. The results showed that the numbers of patients achieving marked improvement or better were 38/68 (55%), 13/22 (60%), and 21/31 (67%) for the 100 mg, 150 mg, and 300 mg groups, respectively. There was no significant difference between any two groups. The duration of fluconazole therapy was the longest for patients in the 100 mg group. None of the patients reported adverse effects. These findings led to the conclusion that once-weekly fluconazole with once-a-day application of topical ketoconazole cream appears safe and effective for treating onychomycosis. The dosage of 150 mg once weekly for 6 months was recommended, considering both effectiveness and economy.
Article
Onychomycosis is a relatively common disease accounting for up to 50% of all nail disorders and its prevalence rises with age. As onychomycosis is an important medical disorder affecting both patient's health and quality of life, it requires prompt and effective treatment. Topical antifungal nail lacquers have been formulated to provide efficient delivery to the nail unit. As both amorolfine and ciclopirox have proved useful as monotherapy for onychomycosis that does not involve the nail matrix area, the purpose of this article is to check if, when combined with oral agents, the effectiveness and scope of treatment can be improved further. Combining data for mycological cure with clinical success (nail morphology) provides a more exacting efficacy measure. Clinical investigations have shown that the combination of oral therapies with antifungal nail lacquer can confer considerable advantage over monotherapy with either drug type. The improved effectiveness and economic advantages of combined topical/oral therapies benefit both patients and health providers; these treatment regimens therefore have an important role to play in the modern management of onychomycosis.
Article
Antifungal agents are beneficial in the treatment of onychomycosis in the general population, as well as in children, the elderly, and immunocompromised individuals. Special patient populations can be more difficult to treat due to such factors as drug interactions with concomitant medications, adverse events, and poor compliance. In addition, there is limited information about the use of antifungal agents in special populations, e.g., children. The pros and cons of oral and topical antifungal agents are discussed, with focus on special patient populations. We searched MedLine (1966 to April 2003) for clinical studies evaluating the efficacy of oral and topical antifungal agents to treat onychomycosis. The key words used in conjunction with "onychomycosis" include: "terbinafine," "itraconazole," "fluconazole," "amorolfine nail lacquer," "ciclopirox nail lacquer," "HIV," "transplant patients," "diabetes," "children," and "elderly." Studies were excluded if published in a language other than English. Studies have shown that antifungal agents can be of benefit in treating the elderly, children, and immunocompromised individuals (e.g., transplant patients, Down's patients, HIV patients, and diabetics) with onychomycosis. The treatment modality of onychomycosis in special patient populations should take into account the clinical presentation of the onychomycosis, the causative organism, patient and physician preference, the concomitant medications that the patient is on, and the potential for adverse events for that patient if antifungal therapy is undertaken.
Treatment of onychomycosis
  • Ryder Je Gupta Ak
  • Skinner
Gupta AK, Ryder JE, Skinner AR. Treatment of onychomycosis. J Cutan Med Surg 2004;8(1):25–30.
Drug watch: safety concerns in two antifungals
Treatment of onychomycosis
  • Gupta