Combined oral antifungals overcome drug resistance in kids

Skin infections

By Geir O'Rourke

8 Nov 2023

Combination oral antifungal therapy can successfully control monotherapy resistant fungal infections in children as well as adults, say the authors of an Australian case series.

Based on the seven cases presented, they suggest terbinafine and azole antifungals do not appear to have any cross reactivity and are safe and well-tolerated, with no side effects reported.

Patients in the study ranged from three to 17 years of age and included two cases of tinea capitis and five of onychomycosis, all of which had failed appropriate single-agent oral antifungal medications for an appropriate duration.

Five were then given a combination of terbinafine and itraconazole (Sporanox), while the remainder used terbinafine and fluconazole over durations ranging from six weeks to four months.

With no known recurrence and no adverse effects, these combinations were a success in each case, the researchers reported in Australasian Journal of Dermatology (link here’).

“The use of combination oral antifungal therapy may be superior to a single agent in the treatment of recalcitrant cutaneous fungal infections in paediatric patients where clinical resistance is presumed,” they wrote.

“We suggest that it is a reasonable option that if clinical clearance of fungal infection has not occurred with a single agent over an appropriate time frame, combining oral antifungals is the next step in management.”

While successful use of combined antifungals had previously been described in adults, this was among the first reports in paediatric patients, stressed the authors, from Box Hill Hospital and the Royal Children’s Hospital, Melbourne.

As a result, randomised controlled studies in this population were still needed to support their use in clinical practice, according to the authors.

In addition, the use of combination of therapy “makes it difficult” to attribute side effects, even though none were observed in the seven cases, they said.

“Although not performed in this study, antifungal resistance testing is available in Australia and may be considered in the management of recalcitrant fungal infections,” the authors said.

Beyond that, they noted there were potential problems associated with combination therapy, including drug reactivity, organ toxicity and the risk of increasing superinfection with inappropriate use.

Therefore, combination antifungal treatment “should only be considered for use after single-agent treatment failure,” they added.

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