Update on Efficacy of Treatments for Cutaneous Candidiasis

 The only commercially available oral therapy with evidence-based support for systemic efficacy in cutaneous candidiasis is fluconazole, according to a review of topical and systemic treatments.

In an article published in the European Academy of Dermatology and Venereology, the authors evaluated findings on 19 systemic and topical therapies from a total of 44 studies conducted during a 52-year period. The researchers stated that despite the numerous studies, the evidence regarding topical therapy for cutaneous candidiasis is inadequate.

They reported that the most studied of the available topical therapies for cutaneous candidiasis, clotrimazole, nystatin, and miconazole, all provided similar efficacy with relatively mild adverse effects (AEs). The cure rates with these 3 agents ranged from 73% to 100% across 35 randomized controlled trials and 7 prospective trials. In head-to-head trials, other classes of agents, including amphotericin-B, ciclopirox, sulconazole, haloprogin, bifonazole, flucytosine, and mupirocin demonstrated similar efficacy compared with clotrimazole, nystatin, and miconazole. In other studies, treatment with oxiconazole, eberconazole, bifonazole, and sertaconazole resulted in complete cure rates in 90% for cutaneous candidiasis, although these results were not from comparative trials against clotrimazole, nystatin, or miconazole. In the only comparative study, the complete cure rate for eberconazole was inferior to that of clotrimazole (50% vs 73%).

The review included analysis of 4 studies of systemic therapies in 179 patients (adolescents and adults) treated with fluconazole, ketoconazole, or terbinafine. Fluconazole 150 mg/week or 50 mg/day for 2 to 4 weeks demonstrated complete cure rates of 82% to 100%, comparable to those of high-dose oral ketoconazole 200 mg/day or topical clotrimazole given twice daily.

Weekly fluconazole treatment was associated with a range of AEs, including headache, rash, and abnormal liver function. AEs were reported in 17% of patients in 1 study and in lesser percentages in other studies. Side effects of terbinafine 500 mg/day for 4 weeks included nausea, headache, and urticaria in 5% of patients. AEs with ketoconazole were the most pronounced and included erythema, nausea, vomiting, bloody diarrhea, and vertigo in a small percentage of patients, as well as elevations in basophil count and liver enzyme level. Because of potential liver damage, treatment with oral ketoconazole has been restricted globally since 2013.

The heterogeneity of studies available for review was considered the main limitation to relevant meta-analysis and pointed to the need for “further investigations in order to evaluate new treatment options,” the investigators wrote.

The investigators pointed to increasing resistance to antifungal therapies as a compelling rationale for the use of combinations to enhance their effects. Studies evaluating antifungal therapies in combination with either high- or low-potency corticosteroids showed efficacy comparable to nystatin alone, and improved efficacy over corticosteroids alone. However, combinations of antimicrobial agents and strong corticosteroid therapies also failed to show improvement over basic antifungal therapy and seemed to lack sufficient anti-inflammatory effects.

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Reference

Taudorf EH, Jemec GBE, Hay RJ, Saunte DML. Cutaneous candidiasis – an evidence-based review of topical and systemic treatments to inform clinical practice. J Eur Acad Dermatol Venereol. 2019;33(10):1863-1873.