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Dermatophyte Infections YVONNE M Postgraduate Medical Journal (September 1979) 55, 605-607 Postgrad Med J: first published as 10.1136/pgmj.55.647.605 on 1 September 1979. Downloaded from Dermatophyte infections YVONNE M. CLAYTON Ph.D. Institute of Dermatology, St John's Hospitalfor Diseases of the Skin, Lisle Street, London WC2H 7BJ Summary skin. This broad spectrum of activity is also shown The newer antifungal agents, clotrimazole, miconazole by the imidazole derivatives, clotrimazole, micon- and haloprogin are considered for their efficacy and azole and econazole, all of which are available as acceptability, and are compared with other topical topical agents for the treatment of superficial fungal agents used for the treatment of dermatophyte infec- infections of the skin. These imidazoles also show tions of the skin. activity against some Gram-positive bacteria so that they may also be used for the treatment of eryth- THE dermatophytes are a closely related group of rasma. This broad spectrum of activity may be of fungi that cause infections of the keratinized tissues particular value when facilities for laboratory - the stratum corneum of the skin, hair and nails. mycological diagnosis are not readily available. Protected by copyright. The keratin is colonized but there is no penetration Many open and controlled comparative clinical of the epidermal layers composed of living cells. A investigations have been carried out to try to deter- wide variety of clinical conditions is produced mine whether one topical agent is likely to be more depending on the site of the infection and on the effective or more acceptable than another. Variations species of fungus responsible. The choice of treat- in the type of infection, causative fungus, length of ment may well be dictated by either or both of these treatment, numbers of patients and different factors. Topical therapy alone will usually be methods of assessing results make comparisons of successful in eradicating lesions of the glabrous skin, reports of such studies difficult. However, a few although widespread and chronic infections, par- examples are given to show that the more recently ticularly those caused by Trichophyton rubrum, and introduced imidazoles and haloprogin appear to be the more severe types of granulomatous lesions as efficient as other topical agents in current use. produced by T. verrucosum and other fungi of Keczkes, Leighton and Good (1975), in a study of animal origin may require systemic therapy. Sys- 41 patients with dermatophyte infections of the temic therapy is essential for infections of the nails skin, compared 4 weeks' topical application of and hair. tolnaftate with a similar period of clotrimazole A wide variety of topical preparations are in use therapy. They found that, as judged by negative http://pmj.bmj.com/ for the treatment of dermatophyte infections. Whit- culture results, tolnaftate produced a cure rate of field's ointment (benzoic acid compound ointment) 93°/ compared with 95°/ for the group of patients is still widely used in the U.K. It is effective and treated with clotrimazole. In a double-blind trial inexpensive but may be irritant particularly on raw comparing Whitfield's ointment with clotrimazole and tender skin. Tolnaftate was one of the first cream, Clayton and Connor (1973) found that after synthetic chemical agents to show antifungal activity 4 weeks' therapy 88% of the patients in each treat- when used topically. It is effective against skin ment group were cured as assessed by negative on October 2, 2021 by guest. infections and only very few toxic or hypersensitivity culture results. In a similarly conducted trial com- reactions to it have been reported. Pecilocin is the paring 4 weeks of treatment with clotrimazole or only clinically available antibiotic, apart from griseo- with miconazole, 790 of patients treated with fulvin, effective against dermatophytes but, unlike clotrimazole were found to be mycologically free griseofulvin, it can only be used topically. from infection compared with 83°% of those treated Haloprogin, an iodinated trichlorophenol com- with miconazole (Clayton and Knight, 1976). This pound, is one of the newer synthetic antifungal difference was not statistically significant. Another agents available for topical use. It differs from the 3 clinical study comparing haloprogin with miconazole compounds mentioned above in that it is not only recorded no significant superiority for either com- effective for dermatophyte infections but also for pound when cure was assessed by negative culture pityriasis versicolor and Candida infections of the results (Clayton et al., 1979). 0032-5473/79/0900-0605$02.00 () 1979 The Fellowship of Postgraduate Medicine 606 Yvonne M. Clayton Postgrad Med J: first published as 10.1136/pgmj.55.647.605 on 1 September 1979. Downloaded from A controlled study on the comparative efficacy of was shown by Haller and Plempel (1978) to be very tolnaftate and haloprogin in tinea pedis (Carter, similar, the majority of strains being inhibited at 1972) found that when cure was assessed by negative concentrations of 4 mg/l or less. The ability to laboratory findings, haloprogin gave a significantly penetrate into the skin shown by the imidazoles so higher cure rate than did tolnaftate. This difference that even in the lower layers of the epidermis con- was not revealed by the less objective clinical obser- centrations are obtained which are > the minimal vations on improvement. The more accurate assess- inhibitory values found in vitro, accounts for their ment of cure by mycological results compared to success in eliminating the causative fungus. clinical judgement alone was also noted by Keczkes The acceptability of the preparation will also play et al. (1975). Only about 50°/ of the patients an important part in ensuring that it is used cor- receiving tolnaftate or clotrimazole appeared to be rectly and regularly. The majority of the topical clinically cured, whilst over 90°Y in each treatment agents now in use are non-staining and odourless. group were free from infection as judged by negative The irritant properties of Whitfield's ointment have culture results. already been mentioned. Tolnaftate appears rela- Relapse, or re-infection, still remains a problem in tively free from any side effects and this also applies the treatment of dermatophyte infections. The to the imidazoles. Transient burning and irritation follow-up period in many studies is too short to mostly occurring immediately after application and determine whether one antifungal compound is only during the first few days of treatment have been superior to another in completely eradicating the noted by a few patients using clotrimazole and causative fungus. miconazole. Reports of sensitization to these com- The possibility of the development of resistance pounds are uncommon. by the fungus to the drug being used for treatment Although there are now many effective antifungal should be considered. In a clinical trial comparing drugs available for topical therapy, griseofulvin the topical use of clotrimazole and miconazole, all still remains the most important therapeutic agent Protected by copyright. strains of fungi isolated were tested before therapy in the systemic treatment of dermatophyte infections was started for their sensitivity to the drugs (Clayton, and is specific for them. It is effective against all 1976). Any fungi isolated during treatment were dermatophytes and is readily absorbed when given similarly assessed for their sensitivity to these com- by mouth. Long courses of therapy are almost pounds (Table 1). None of the strains isolated at any invariably well tolerated and side effects are rare. stage during therapy had developed resistance to The dosage of griseofulvin for adults is generally 500 mg to one g daily and the length of treatment is TABLE 1. Sensitivity pattern of 53 strains of Trichophyton determined largely by the site involved. Scalp rubrum isolated from patients during a trial comparing infections usually require 4 to 8 weeks' therapy, clotrimazole with miconazole whilst nail infections need several months of treat- No. of weeks' treatment ment. Finger nails may be free from infection after 6 to 12 months of therapy, but the control of toe nail 0 2 4 infections is far less certain requiring in many cases Minimal inhibitory concentration Site (mg/I) over one year's continuous treatment, even then the relapse rate is very high. The development of in vitro http://pmj.bmj.com/ Clotrimazole resistance to this antibiotic by fungi has not been Toe webs 0-75 0 75 shown to be a cause of treatment failure. Sole 0 75 0-75 - Hand 0-18 - 037 The search for new and more effective antifungal Miconazole agents for use both topically and systemically will Toe webs 0 75 - 0-37 continue. These infections are still among the com- Sole 0 37 0-75 075 monest fungal diseases encountered in medical Hand 0-75 0-75 - practice. There exists a range of antifungal drugs available for their treatment, which have been shown on October 2, 2021 by guest. either clotrimazole or miconazole. The emergence of to be effective both by their in vitro activity and as resistant strains of dermatophytes during treatment assessed by clinical studies. Patients' acceptance of with the imidazoles or other antifungal compounds such factors as the length of treatment and the form used topically has not yet been reported. in which the compound is introduced may, however, The efficacy of a topical agent will depend on a ultimately decide which drug is most successful. high activity in vitro against the dermatophytes and on its ability to penetrate the skin so that an adequate concentration of the drug reaches the infecting References CARTER, V.H. (1972) A controlled study of haloprogin and fungus. The in vitro inhibitory effect on dermato- tolnaftate in tinea pedis. Current Therapeutic Research, 14, phytes of the imidazoles, tolnaftate and haloprogin 307. Dermatophyte infections 607 Postgrad Med J: first published as 10.1136/pgmj.55.647.605 on 1 September 1979.
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