Combination Antifungal Therapy for Onychomycosis

Abstract

Onychomycosis is a fungal infection of the nail unit including the nail matrix, the nail bed and the nail plate by both dermatophyte and non-dermatophyte agents. It is disturbs not only cosmetic disfigurement, but also it may have an impact on patients’ emotional, social and occupational functioning, finally affecting the overall quality of life. The incidence rate tends to increase, management of onychomycosis is still challenging. Important problems regarding antifungal monotherapy have experienced many failures and recurrences. In general, pharmacological approaches for onychomycosis can be topical or oral antifungal. Antifungal monotherapies often lead to failure treatment, also high incidence of recurrence. One strategy for this problem is a combination antifungal therapy. In vitro studies show the synergistic effect of using combination two antifungals (both oral antifungal or combination topical and oral antifungal), hence it is mycologically or clinically expected to increase the success rate of onychomycosis therapy. This review tries to evaluate the previous study exploring the effectiveness of antifungal combination therapies on onychomycosis. Two oral antifungals usually used are terbinafine as fungicidal agent and itraconazole as fungistatic agent. There is combination between topical and oral antifungal such as itraconazole or terbinafine with amorolfine or ciclopirox, also other combination like griseofulvin and amorolfone or tioconazole. All the combination therapies show better result than monotherapy alone, but it is still difficult to conclude whether antifungal combinations in onychomycosis will increase effectiveness due to variations in therapeutic duration, result definition, and statistical evaluation on existing studies. Further research is required with longer duration of observation, uniform patient criteria and definition of success, random control and blinding to minimize bias.

In Vitro Combination Effect of Topical and Oral Anti-Onychomycosis Drugs on Trichophyton rubrum and Trichophyton interdigitale

“…The failure rate of oral antifungal therapy for onychomycosis is 20%, with a high recurrence rate of 10–53% [ 8 , 9 , 10 , 11 , 12 ]. Some factors also contributing to unsuccessful therapy are the patient’s susceptibility, pattern of resistant fungal growth, presence of fungal dormant spores in the nail, low bioavailability of the drug, and lack of drug penetration into the nail [ 8 , 9 , 13 ]. Therefore, many treatment methods have been introduced to overcome the limitations of onychomycosis therapy, including a combination of oral and topical antifungals or a combination of two oral antifungals [ 8 , 14 ].…”

“…Some factors also contributing to unsuccessful therapy are the patient’s susceptibility, pattern of resistant fungal growth, presence of fungal dormant spores in the nail, low bioavailability of the drug, and lack of drug penetration into the nail [ 8 , 9 , 13 ]. Therefore, many treatment methods have been introduced to overcome the limitations of onychomycosis therapy, including a combination of oral and topical antifungals or a combination of two oral antifungals [ 8 , 14 ]. In addition, because the elimination half-life of orally administered terbinafine and itraconazole from nails is long, ranging from 24 to 156 day and 32 to 147 days, respectively [ 15 ], switch therapy involving switching from oral to topical treatment may also be worth considering.…”

“…Therefore, combination therapy involves two-way penetration of the nail bed by oral drugs and of the nail plate by topical drugs, providing a higher cure rate compared to that provided by each monotherapy, presumably because of a synergistic antifungal effect and diffusion of the two drugs at an effective concentration in the nail. Moreover, combination therapy with oral (terbinafine and itraconazole) and topical (amorolfine and ciclopirox) antifungals has been shown to lead to improvement in mycological and clinical outcomes, reduced therapy duration, and minimized risk of side effects due to systemic treatment [ 8 , 9 , 14 , 17 ].…”

“…The failure rate of oral antifungal therapy for onychomycosis is 20%, with a high recurrence rate of 10-53% [8][9][10][11][12]. Some factors also contributing to unsuccessful therapy are the patient's susceptibility, pattern of resistant fungal growth, presence of fungal dormant spores in the nail, low bioavailability of the drug, and lack of drug penetration into the nail [8,9,13].…”

Preliminary Study on Antifungal Mechanism of Aqueous Extract of Cnidium monnieri Against Trichophyton rubrum

“…In addition, several complications, such as bacterial superinfection, may occur ( Monod et al, 2019 ). The causes of unsuccessful treatment also include the susceptibility of the patients, the growth patterns of the drug-resistant fungus, the presence of dormant fungal spores in the affected area, the low bioavailability of drugs, and poor drug penetration ( Evans, 2001 ; Vora et al, 2014 ; Khamidah and Ervianti, 2018 ).…”