Treatment review articles usually focus on recently investigated drugs. However, these new drugs are sometimes of little use in routine clinical practice because they are not first-line options. In Spain, as in the rest of Europe, the most common mycoses are pityriasis versicolor,1 the various clinical forms of dermatophytosis,2–4 and candidiasis. In this review of current treatments, we focus on these 3 groups of mycoses and their first-line treatments.

Our aim is to answer several questions: Are any new treatments available for superficial mycoses? Are new treatments needed, or are the conventional treatments adequate? And finally, do we make good use of the available resources, or do we need to be more efficient in our treatment of superficial mycoses?

What is needed, we believe, is not merely a list of recently developed treatments but a review of ways to improve clinical outcomes through the proper use of conventional drugs. We also believe that costs can be reduced without sacrificing outcome quality.

We draw on our personal experience as well as evidence from 3 types of publications: experimental research, clinical trials, and pharmacoeconomic studies.

In routine clinical practice, the treatment of superficial mycoses with antifungals differs from that of infections treated with antibiotic therapy in that susceptibility testing is only useful in infections caused by Candida organisms.5,6 In the case of other yeasts, such as Malassezia7 and dermatophytes,8 susceptibility tests are difficult to perform, poorly standardized, and purely of academic interest.

Since the appearance of griseofulvin and the polyenes in the 1950s, the pharmacopeia for superficial mycoses has seen the addition of topical treatments, such as the azoles, ciclopirox, and amorolfine as well as the oral triazoles and allylamines. Around 60 new antifungal substances are currently being investigated. These include new formulations and semisynthetic derivatives of polyenes and amphotericin, new peptides such as echinocandins and aerothricines, and novel substances such as amino acids, sordarins, macrolides, terpenes, saponins, and flavans.9,10 Although many of these drugs have been tested against dermatophytes in the laboratory, the specialized products that have been brought to market are expensive and are not indicated for superficial mycoses, except in extreme cases or in a hypothetical future.11

Moreover, despite the large number of clinical trials of antifungal agents conducted over recent decades, we found that the meta-analyses on this topic include a strikingly small number of trials, suggesting a lack of homogeneity in the methodologies used.12–14 Review articles on this subject therefore invariably conclude by indicating that further studies are needed in the field of superficial mycoses.15

A similar situation can be seen in pharmacoeconomic studies on antifungal agents. The results of these studies vary greatly depending on their objectives (cost-effectiveness, cost-utility, cost-benefit), the sponsoring institution (public body or private company), time frame and geographic scope, type of cost evaluated (only the drug or the entire medical intervention), and outcome (cure or disease-free days).16 Pharmacoeconomic studies identify, one way or another, the least expensive treatment, but they do not clearly demonstrate the importance of choosing the least expensive option.17

We requested data from the Spanish Ministry of Health for 2001, a year in which a complete census of Spain's population was conducted (Table 1). According to the data provided, 1 package of topical antifungal agent was used for every 4 people and 1 package of oral antifungal agent was used for every 24 people in the country in 2001. Although a more in-depth analysis is warranted,17 these data clearly suggest that antifungal agents are being overused in Spain.

Recent studies of superficial mycoses have focused primarily on the best use of known resources,18 and on the search for efficacy enhancers, such as adjuvant therapies, for both topical and oral treatments.19,20

Like the use of occlusive dressings, mentioned above, the use of switch therapy can significantly reduce the duration of systemic antifungal treatment. Switch therapy is particularly useful in elderly, immunodeficient, or polymedicated patients with onychomycosis or extensive mycosis of the terminal hair or glabrous skin. In switch therapy, topical antifungal treatment is initiated prior to the start of oral treatment.13,18–20,29

In patients with onychomycosis, the following procedure is recommended. Specimens should be obtained for direct examination and culture and a topical antifungal lacquer, to be applied once daily for 1 month, should be prescribed. After 1 month, depending on the results of the direct examination and culture, oral treatment may be initiated. Topical treatment should be enhanced by using fomentations or hand or foot baths to increase the permeability of the nail plate.29,30,37,38

The use of imidazole shampoo for at least 15 days prior to the start of a 7-day regimen of oral itraconazole can be effective against mycoses affecting hair-bearing areas as well as extensive pityriasis versicolor.20

In ringworm of the scalp, griseofulvin should be used at high doses for 6 weeks. The response rate increases considerably with the addition of fomentations and topical imidazole in a cream, solution, or shampoo.20,24 Noninflammatory trichophytic tineas in adults are treated with a continuous 1-month regimen of oral terbinafine plus the topical treatment described above (Table 2).24

The most effective topical monotherapies for tineas, inflammatory or not, affecting hairless, glabrous, and inguinal skin in young adults are terbinafine and ciclopirox, while the least expensive are tolnaftate and undecylenic acid, both available in various presentations. However, we believe that topical azoles should be the first-line treatment because their efficacy is similar to that of terbinafine and ciclopirox but they are less expensive (Table 2). In order to increase drug penetration and effectiveness, shorten treatment duration, and prevent recurrence, the use of occlusive dressings, fomentations, and hand and foot baths is essential.20

As noted above, combination therapy with an azole and a topical corticosteroid is especially useful at the start of treatment against inflammatory ringworm, in the event of a Herxheimer reaction,31 and in patients who, on completion of treatment, present eczematous or irritative symptoms.20

Switch therapy is the first-line treatment approach in onychomycosis.9,13 The drugs used in a switch therapy regimen can be administered in different sequences, with little impact on the final efficacy but large variations in cost. It is important to focus not on the cost of treating a single patient but on the expenditure of a large group of doctors over many years. Table 3 shows the final cost for 500 000 patients of 2 regimens of similar efficacy, 1 significantly less expensive than the other.39

Another approach that reduces the cost of treating onychomycosis is oral pulse therapy, a method first used in the 1960s with griseofulvin.40,41 At present, pulse therapy with terbinafine is considered to be similar to continuous therapy in terms of efficacy and safety. The recommended regimens range from 500mg daily for the first week of each month for 3 months42 to 500mg daily for the first and third months of a 3-month regimen.43

Various topical response enhancers aimed at reducing the need for oral therapy in onychomycosis have been proposed.30 This group includes substances that enhance the penetration of the topical treatment into the nail, such as urea, urea hydrogen peroxide, salicylic acid, thioglycolic acid, acetylcysteine, 2-mercaptoethanol, 2-nonyl-1,3-dioxolane, keratinases, and phosphoric acid.29 Other methods used to increase nail penetration include abrasion of the nail surface by mechanical means or low-powered laser, total nail avulsion by laser, and conventional surgical avulsion.29,44

Recent studies have found no association between surgical avulsion and subsequent problems with nail regrowth, and no differences between total and partial avulsion.38,44 Outcomes improved, however, when surgical avulsion was accompanied by topical occlusive treatment until the nail had regrown completely. Overall, surgical avulsion was found to have similar efficacy to, and no advantage over, medical treatments.38,44

One of the most promising treatment options is photodynamic therapy. This technique is effective against mucocutaneous candidiasis,45–47 onychomycosis caused by Trichophyton rubrum,48–51 and extensive folliculitis caused by Pityrosporon organisms.52 The results of photodynamic therapy have, however, been less promising in cases of tinea cruris.53 We therefore believe that further studies are needed to determine dosages and treatment regimens.

Other alternatives for treating onychomycosis, such as boosted treatments54,55 and iontophoresis, are still in the experimental stage.56,57

In summary, we consider that the expenditure on topical and systemic antifungal agents in Spain is very high. Moreover, we believe that, in most cases, the proper use of conventional drugs makes the use of more expensive drugs unnecessary. In the case of onychomycosis, we believe that the use of the recommended switch therapy could lead to considerable savings.

The authors declare that they have no conflicts of interest.