Antifungal treatment may cause DNA strain type switching in onychomycosis




Although DNA strain type switches are known to be a natural occurrence in patients with onychomycosis, increases in strain type switching that follow treatment failure could be an antifungal-induced response, according to the results of a study published in the British Journal of Dermatology.

“The dermatophyte Trichophyton rubrum is responsible for the majority (~80%) of [onychomycosis] cases, many of which frequently relapse after successful antifungal treatment,” noted the study authors, led by Dr. Aditya K. Gupta of the University of Toronto. Despite several previous studies of various facets related to onychomycosis, “data outlining onychomycosis infections of T. rubrum with DNA strain type, treatments, outcome and geographical location are still warranted,” they added (Br. J. Dermatol. 2015;172:74-80).

© Metin Cengiz Bar??/Thinkstock

Dr. Gupta and his associates examined 50 adults infected with T. rubrum, determined via analysis of toenail specimens from onychomycosis patients in southwest Ontario. The patients were divided into cohorts based on the treatment they received: oral terbinafine, laser, or placebo (no terbinafine and no laser). Typing of DNA strains was done only in culture-positive samples before and after treatment, leaving a study population of six in the terbinafine group, nine in the laser group, and eight in the placebo group.

Half of the terbinafine subjects were prescribed oral terbinafine 250 mg/day for 12 weeks, while the other three received oral terbinafine 250 mg/day pulse therapy at on/off intervals of 2 weeks up to 12 weeks.

The investigators also used three DNA strains known to be common in Europe for comparison and found that six distinct strains, labeled A-F, accounted for 94% of the T. rubrum strains – these strains corresponded to the European ones. However, three other strains (6% of strains) were found that investigators concluded were native to North America.

Strain type switching occurred in five (83%) of the terbinafine subjects, five (56%) of the laser cohort subjects, and two (25%) of those in the placebo cohort. Roughly half of the type switches noted in the terbinafine cohort were associated with mycological cures and were followed by relapse shortly thereafter. Dr. Gupta and his associates also found that all DNA strains in this cohort were susceptible to terbinafine while in vitro. Strain types in the laser and placebo cohorts did not show any signs of intermittent cures.

The patients were sampled at intervals of 0, 12, 24, 36, 48, 60, and 72 weeks of treatment, and T. rubrum DNA strain types were determined at week 0 (n = 6) and week 48 (n = 1) or 72 (n = 5). Patients in the laser cohort were treated at weeks 0, 8, and 16 and sampled at weeks 0, 8, 16, 24, and 48, with T. rubrum DNA strain types determined at week 0 (n = 9) and week 24 (n = 5) or 48 (n = 4). Finally, placebo patients were sampled at the same regularity as those in the laser cohort, with T. rubrum DNA strain types determined at week 0 (n = 8) and week 24 (n = 1) or 48 (n = 7), they reported.

“The T. rubrum DNA strain type switches observed in ongoing infections among all treatment groups could be attributed to microevolution or coinfections of DNA strains,” the researchers noted. “The presence of coinfecting T. rubrum DNA strains that flux with environmental conditions or local niches could account for the DNA strain type switches observed in all treatment groups, where only the relatively stable types are able to propagate in culture,” they added.

Dr. Gupta and his associates did not disclose any source of funding or any relevant conflicts of interest.

Next Article: