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Review of antifungal therapy, part II: Treatment rationale, including specific patient populations.
J Dermatolog Treat. 2008; 19(3): 168-75
Baran R, Hay RJ, Garduno JI
This portion of the antifungal review focuses on treatment rationale and suggestions, including special populations such as the elderly, children, and pregnant and immunocompromised individuals. In elderly individuals, the pathogen may be associated with certain comorbidities; treatment should begin with local treatments such as debridement (mechanical or chemical) and a topical. In children, the pathogen most commonly isolated is Trichophyton rubrum. Children should be examined for concomitant tinea and treatment options can begin with a chemical debridement (non-painful) and a topical, with non-responders being treated with combination therapy as in adults. It is suggested that blood tests are monitored at baseline and every 4-8 weeks in children on systemic therapy. Terbinafine is the only systemic in category B and local therapies should be the primary treatment modalities in pregnancy. Prevalence of onychomycosis is high in immunocompromised patients with higher relapse rates after treatment. The same fungal infections that are seen in healthy populations are usually represented in the immunocompromised host. There is a stepwise approach that is suggested in the treatment of onychomycosis. Before treatment, several factors should be determined, which include risk for failure and compliance issues. Strategies for therapy include monotherapy, combination therapy, supplemental therapy, and intermittent therapy. Topical monotherapy is effective in early distal nail disease and for the prevention of reinfection of the cured nail. Combination therapy is an appropriate progression of therapy for patients who failed monotherapy or are at risk for failure. Combined therapies are shown to increase cure rates. Mechanical interventions are essential in reducing fungal burdens to allow other modalities to penetrate, especially in dermatophytomas and onycholysis.
Subacute cutaneous lupus erythematosus induced by terbinafine: case report and review of literature.
J Dtsch Dermatol Ges. 2008 Jun 17;
Lorentz K, Booken N, Goerdt S, Goebeler M
Systemic lupus erythematosus and subacute cutaneous lupus erythematosus (SCLE) occasionally evolve as adverse reactions to a large variety of chemically different drugs. We here report on a 76-year-old woman who developed SCLE within 10 days after initiation of oral terbinafine. Analysis of the 27 cases of terbinafine-induced SCLE in the literature revealed that this disorder has been reported 6 times more often in females than in males. Skin lesions evolved on average around 7 weeks after starting the drug. In 79% of the cases ANA could be detected while antibodies against Ro/SS-A and La/SS-B were found in 86% and 39%, respectively. Remarkably, anti-histone antibodies were present in only 29%. In all cases terbinafine-induced SCLE resolved after discontinuation of the triggering agent. Systemic treatment with anti-malarials and/or corticosteroids does not appear to be mandatory.
In vitro antifungal drug susceptibilities of dermatophytes microconidia and arthroconidia.
J Antimicrob Chemother. 2008 Jun 13;
Coelho LM, Aquino-Ferreira R, Maffei CM, Martinez-Rossi NM
Objectives Arthroconidia have been considered as the primary cause of infection by dermatophytes. However, the in vitro antifungal testing evaluates the responses mainly of microconidia or hyphae, and dermatophytes in vivo often produce arthroconidia, a cellular structure presumably more resistant to antifungals. The aim of this study was to compare the in vitro susceptibility of microconidia and arthroconidia of Trichophyton rubrum, Trichophyton tonsurans and Trichophyton equinum to griseofulvin, itraconazole, terbinafine, fluconazole, amphotericin B and hygromycin B. Methods Microconidia and arthroconidia were produced in vitro, and their susceptibility to each drug was evaluated by assessing the CLSI M38-A broth microdilution method. Results Arthroconidia of all strains analysed appeared to be more resistant to fluconazole, griseofulvin and itraconazole than microconidia. The MIC of terbinafine was the same for microconidia and arthroconidia for all strains, and the MIC of amphotericin B for microconidia and arthroconidia was the same for isolates of T. equinum and T. tonsurans, but differed for T. rubrum. Finally, the level of resistance of microconidia for all strains towards the antibiotic hygromycin B was from 25 to 400 mg/L. Conclusions The difference in the susceptibility between microconidia and arthroconidia depends on the drug and on the strain, and may be one of the causes of therapeutic failure. Also, the level of resistance to the antibiotic hygromycin B presented by microconidia of these isolates will allow the use of hygromycin resistance as a dominant marker in fungal transformation procedures in future studies of gene function.
Common tinea infections in children.
Am Fam Physician. 2008 May 15; 77(10): 1415-20
Andrews MD, Burns M
The common dermatophyte genera Trichophyton, Microsporum, and Epidermophyton are major causes of superficial fungal infections in children. These infections (e.g., tinea corporis, pedis, cruris, and unguium) are typically acquired directly from contact with infected humans or animals or indirectly from exposure to contaminated soil or fomites. A diagnosis usually can be made with a focused history, physical examination, and potassium hydroxide microscopy. Occasionally, Wood's lamp examination, fungal culture, or histologic tissue examination is required. Most tinea infections can be managed with topical therapies; oral treatment is reserved for tinea capitis, severe tinea pedis, and tinea unguium. Topical therapy with fungicidal allylamines may have slightly higher cure rates and shorter treatment courses than with fungistatic azoles. Although oral griseofulvin has been the standard treatment for tinea capitis, newer oral antifungal agents such as terbinafine, itraconazole, and fluconazole are effective, safe, and have shorter treatment courses.
Br J Dermatol. 2008 May 28;
Ghannoum MA, Wraith LA, Cai B, Nyirady J, Isham N
Background Our group, in collaboration with seven other laboratories, has recently developed a method to determine the susceptibility of dermatophytes. Objectives The objective of this study was to determine the terbinafine susceptibility profile of dermatophyte isolates obtained from patients with tinea capitis enrolled in two large worldwide clinical trials and to investigate whether these susceptibilities differ by geographical location. Methods Susceptibilities were determined according to the Clinical and Laboratory Standards Institute M38-A2 standard. Results From a total of 978 baseline dermatophyte isolates, we selected 301 isolates at random. These included: Trichophyton tonsurans (n = 125), Microsporum canis (n = 94), T. violaceum (n = 63) and M. audouinii (n = 19). The terbinafine minimum inhibitory concentration (MIC) range was 0.001-0.25 mug mL(-1), while MIC(50) and MIC(90) ranged between 0.002 and 0.125 mug mL(-1) and 0.03 and 0.25 mug mL(-1), respectively, for all species tested. MIC(50) and MIC(90) varied by individual species; however, there was no difference in terbinafine MIC among the different species isolated from U.S. and non-U.S. sites. Conclusion Terbinafine demonstrates potent antifungal activity against dermatophyte isolates obtained from patients with tinea capitis worldwide.
Skin Pharmacol Physiol. 2008 May 29; 21(4): 203-210
Schafer-Korting M, Schoellmann C, Korting HC
Terbinafine, a synthetic allylamine, exerts fungicidal activity against dermatophytes, the causative pathogens of tinea pedis. As proven in numerous clinical trials, tinea pedis can be effectively and safely treated by topical terbinafine. In fact, a 1-week application of terbinafine 1% cream eradicated fungal pathogens at least as effectively as 4-week treatment courses with topical azole derivative antifungals and showed lower relapse rates. A new innovative single-application formulation of terbinafine 1% in a film-forming solution produces a high concentration gradient on the skin surface and enables a prolonged (up to 13 days) exposure of the skin to terbinafine. High drug penetration into the skin results in an otherwise not obtained drug reservoir in the horny layer, the location of dermatophytes in tinea pedis. Although azole antimycotics can also effectively penetrate into the horny layer of the skin, short-term therapy might not be feasible due to its primarily fungistatic activity against dermatophytes. Thus, we conclude that the high efficacy of short-term treatment with terbinafine in patients with tinea pedis is possible due to its fungicidal activity coupled with a distinct reservoir formation in the upper layers of the epidermis.
Mycoses. 2008 May 21;
Ghannoum MA, Long L, Pfister WR
Currently available topical antifungals are often not satisfactory for the treatment of nail infections, because of the inability to penetrate the nail plate. Terbinafine HCl nail solution is a novel antifungal formulation containing a nail penetration enhancer dodecyl-2-N,N-dimethylaminopropionate hydrochloride (DDAIP HCl, trade name NexACT((R))-88). In this study, we used a guinea pig model of Trichophyton mentagrophytes dermatophytosis and evaluated the clinical and mycological efficacy of different terbinafine HCl nail solutions (TNS) formulated with or without DDAIP HCl. Ciclopirox (8%) nail lacquer (Penlac((R))), the only Food and Drug Administration approved topical treatment for onychomycosis, was used as a comparator. Following the IACUC Guidelines, the skin of male albino guinea pigs was abraded under anaesthesia. Each animal was infected with T. mentagrophytes ATCC 24953 (cell suspension containing 1 x 10(7) conidia). The experimental animals were divided into 11 groups (five animals per group) and tested with the following formulations: vehicle control, 0.5% DDAIP HCl, 1%, 5% and 10% TNS (without DDAIP HCl), 1% TNS with 0.5%, 2.5% and 5.0% DDAIP HCl, 5% and 10% TNS with 0.5% DDAIP HCl, 8% ciclopirox nail lacquer and an untreated control group. Evaluation of clinical and mycological efficacy was performed 72 h after completion of a 7-day treatment regimen. Skin biopsy samples were processed for histopathological examination. The infected untreated control guinea pigs showed patches of hair loss and ulcerated or scaly skin and fungal invasion of hair roots. The vehicle and 0.5% DDAIP HCl treated groups showed minimal clinical efficacy (only 11% and 5%, respectively). In contrast, all three concentrations of TNS (1%, 5% and 10% terbinafine HCl) formulated with or without 0.5% DDAIP HCl showed 100% mycological efficacy by the hair root invasion test. Clinical efficacy of the 5% and 10% TNS improved with addition of 0.5% DDAIP HCl (47.4% and 73.8% vs. 68.4% and 89.5%, respectively). In addition, no fungal elements were detected in the treated guinea pig skin. All formulations of TNS resulted in a higher clinical and mycological efficacy compared with the 8% ciclopirox nail lacquer (P = 0.0444). In conclusion, TNS containing 1%, 5% and 10% terbinafine HCl formulated with and without DDAIP HCl demonstrated high antifungal efficacy in experimental dermatophytosis. Addition of 0.5% DDAIP HCl to 5% and 10% TNS significantly enhanced the clinical and mycological efficacy of these formulations which were superior compared with the 8% ciclopirox nail lacquer. Evaluation of the 1%, 5% and 10% TNS in clinical trials for the treatment of dermatophytosis and onychomycosis is warranted.
Review of antifungal therapy and the severity index for assessing onychomycosis: part I.
J Dermatolog Treat. 2008; 19(2): 72-81
Baran R, Hay RJ, Garduno JI
This review outlines recent data on treatment modalities and outcomes with antifungal therapy in onychomycosis. Included are topical, mechanical, chemical and systemic treatments or a combination thereof. Topical treatments, or transungual drug delivery systems (TUDDS), including ciclopirox and amorolfine were shown to be effective if used alone for mild-moderate nail involvement. Specifically, superficial white onychomycosis (SWO) restricted to the dorsum of the nail plate and moderate distal lateral subungual onychomycosis (DLSO). Mechanical treatments were mostly effective as adjuncts to topical therapy which include nail avulsion and abrasion. In particular, partial nail avulsion aids topical therapy in DLSO and partial subungual onychomycosis for a more effective therapy. Chemical avulsion is a painless method of debridement which uses a keratinolysis formula that is effective only in limited and early disease. Systemic therapies have been shown to be effective with terbinafine and itraconazole is suggested as being the most cost-effective therapy. Systemic therapies require consideration of side effects and monitoring by both patient and physician prior to treatment application. An effective suggestion is the use of a topical with debridement for mild-moderate onychomycosis and systemic (terbinafine) plus topical for severe onychomycosis. Most treatment modalities will require long-term use from 3 to 9 months to be most effective, with strategies presented in Part II of this review.
J Dtsch Dermatol Ges. 2008 May 7;
Korting HC, Schöllmann C
Itraconazole is an antifungal drug from the triazole group with distinct in vitro activity against dermatophytes,yeasts and some molds. Itraconazole has a primarily fungistatic activity. Itraconazole accumulates in the stratum corneum and in nail material due to its high affinity to keratin,as well as in sebum and vaginal mucosa. Together with terbinafine and fluconazole, itraconazole belongs to the modern highly effective systemic antifungal drugs with a favorable risk-benefit ratio and for this reason is a preferred therapy option for fungal infections of skin,nails and mucous membranes.Compared to terbinafine in the treatment of fingernail and toenail fungal infections,itraconazole offers the advantage of a broad antifungal spectrum and better effectiveness against onychomycosis caused by yeasts yet appears inferior with regard to the more common dermatophyte infections. Itraconazole constitutes an important therapy option,along with fluconazole,terbinafine,ketoconazole and griseofulvin, for the treatment of dermatophyte infections of glabrous skin (tinea pedis, tinea manuum,tinea corporis and tinea cruris) in adults following unsuccessful topical therapy. In the oral therapy of tinea capitis,itraconazole plays an especially important role,in particular for disease caused by Microsporum canis (for children, however, only off-label use is feasible currently). In the treatment of oropharyngeal candidiasis,candidiasis of the skin and vulvovaginal candidiasis, itraconazole and fluconazole are the preferred treatment options in cases in which topical therapy has proven unsuccessful.
Update in Antifungal Therapy of Dermatophytosis.
Mycopathologia. 2008 May 14;
Gupta AK, Cooper EA
Treatment of dermatophyte infection involves primarily oral and/or topical formulations of azoles or allylamines, particularly itraconazole and terbinafine. Topical medications applied once or twice daily are the primary treatment indicated for tinea corporis/cruris, and tinea pedis/manuum. Use of oral antifungals may be practical where the tinea involvement is extensive or chronic, or where application of a topical is not feasible. For tinea unguium (onychomycosis) and tinea capitis, oral therapies are the primary treatments provided. Recently, topical amorolfine and ciclopirox formulations have been approved for use in milder onychomycosis cases, and their role in the treatment of the different clinical forms of onychomycosis is currently being defined. Relapse of infection remains a problem, particularly with tinea pedis/unguium. Appropriate follow-up duration and education of patients on proper foot hygiene are also important components in providing effective therapy.