Multi‐drug resistant dermatophyte infections in Western Sydney: A retrospective case series

Dear Editor,

Resistant dermatophyte infections are a growing international issue in dermatology. Reports from India and Japan have identified high rates of terbinafine resistant Trichophyton interdigitale species. ¹ , ² Furthermore, resistance appears to be an emerging worldwide problem with 17 European countries demonstrating antifungal resistance in multiple dermatophyte species, most commonly Trichophyton rubrum, Microsporum canis and Trichophyton mentagrophytes (11 strains specified as genotype VIII [Indian strain]), but also cases of resistance in Trichophyton tonsurans, Microsporum audouinii, T. interdigitale, Trichophyton verrucosum, Trichophyton violaceum and Nannizzia gypsea (formerly known as M. gypseum). ³ To this date, there have been no published reports of dermatophyte antifungal resistance in an Australian dermatology setting.

We present a retrospective case series of patients with dermatophyte infections in an outpatient dermatology clinic setting in Western Sydney. Eligibility criteria included clinical diagnosis of superficial cutaneous dermatophyte infection and clinical and/or mycological resistance to first‐line antifungal therapies. There were no exclusion criteria.

We identified 10 cases over a 12‐month period of T. interdigitale infection demonstrating clinical or mycological resistance to a number of topical and systemic therapies (Figure 1). All cases were of tinea corporis, cruris or faceii and none included cases of majocchi's granuloma or tinea incognito. The average disease duration was 9.1 months, ranging from 2–24 months. In this series all resistant cases confirmed T. interdigitale on culture. In all cultured specimens submitted for testing, intermediate resistance to terbinafine was reported. However, all of these cases showed clinical resistance to treatment with topical and/or oral formulations of terbinafine (Table 1). Two cases demonstrated mycological resistance to fluconazole (Figure 2). Interestingly, one case demonstrated mycological resistance to itraconazole, however, itraconazole at an increased dose of 200 mg twice daily for 8 weeks resulted in successful treatment in this case (Table 1). All 10 cases were resolved with oral itraconazole twice daily at doses ranging between 100–400 mg daily. Treatment course durations of itraconazole were between 4 and 8 weeks to achieve clinical clearance.

FIGURE 1.

Number of patients clinically resistant to topical or oral treatment. *Clinical is resistance defined as ongoing or worsening of dermatophyte infection after receiving the treatment course.

TABLE 1.

Mycological results and treatments of resistant tinea infections in a Western Sydney population

Clinical presentation	Organism on microscopy and culture	Fungal culture sensitivity results*	Agent of successful treatment#
Tinea corporis	T. interdigitale	Terbinafine I itraconazole S miconazole S nystatin S clotrimazole S	Itraconazole 100 mg BD 6 weeks
Tinea corporis	T. interdigitale	Terbinafine I itraconazole S	Itraconazole 100 mg BD 6 weeks
Tinea corporis	T. interdigitale	Terbinafine I fluconazole R itraconazole S	Itraconazole 100 mg BD 6 weeks
Tinea faciei	T. interdigitale	Sensitivity requested, not performed	Itraconazole 100 mg BD 6 weeks
Tinea cruris, tinea faciei	T. interdigitale	Terbinafine I itraconazole R fluconazole R	Itraconazole 200 mg BD 8 weeks
Tinea cruris	T. interdigitale	–	Itraconazole 200 mg BD 8 weeks
Tinea faciei	T. interdigitale	–	Itraconazole 200 mg BD 12 weeks
Tinea corporis, tinea faciei	T. interdigitale	Terbinafine I itraconazole S miconazole S clotrimazole S	Itraconazole 200 mg BD 4 weeks
Tinea corporis, tinea faciei	T. interdigitale	Sensitivity requested, not performed	Itraconazole 200 mg BD 4 weeks
Tinea cruris, tinea manuum	T. interdigitale	–	Itraconazole 200 mg BD 4 weeks

Note: *I, intermediate; S, sensitive; R, resistant, ^#BD, twice daily, resistant and intermediate results are bolded.

FIGURE 2.

Patients with Trichophyton interdigitale demonstrating intermediate or resistant results on mycological sensitivity testing

Our results demonstrate the presence of allylaline and azole‐resistant dermatophyte strains in Western Sydney. Our experience highlights the importance of testing for microscopy, culture and sensitivity for patients with cutaneous dermatophyte infections who are not responding to conventional treatments. Currently, antifungal sensitivity testing is not routinely performed on fungal cultures and we propose this would be helpful in directing therapy and identifying resistance issues. Availability and cost are important barriers to dermatophyte sensitivity testing in Australia. Sensitivity testing for dermatophytes is infrequently performed, lacks standardisation and of significant cost. Other options include Rapid polymerase chain reaction methods for specific gene mutations in resistant organisms. ⁴ Although possible, until these tests become widely available for all known resistant organisms, they also have limitations.

Tinea infections due to resistant strains are frequently extensive and longstanding. This has a deleterious effect on the quality of life and poses a financial burden for affected patients. It also allows for further expansion of resistant disease into the community. Knowledge of dermatophyte resistance as well as access to adequate testing and treatment is a matter of importance to the Australian population.

CONFLICT OF INTEREST

Dr Chelsea Jones works as a sub‐investigator on clinical trials sponsored by Eli Lilly, Dermira, Leo Pharma, Pfizer, Galderma and Bristol Myers Squibb and has received a scholarship from Eli Lilly to attend a conference. Dr Bruno Blaya Alvarez is on the current Australasian Journal of Dermatology editorial board. The authors have no other conflicts of interest to declare.

ETHICS APPROVAL

Ethics approval was granted from the University of Sydney.