Regional Differences in Antifungal Susceptibility of the Prevalent Dermatophyte Trichophyton rubrum

Y Jiang,A M S Al-Hatmi,Z Wan,R Li,B Zhang,Z Shang,P E Verweij,W Luo,G S De Hoog,S A Ahmed,Y Song

doi:10.1007/s11046-020-00515-z

Abstract

In vitro susceptibility testing for Trichophyton rubrum has shown resistance to terbinafine, azoles and amorolfine, locally, but epidemiological cutoffs are not available. In order to assess the appropriateness of current first-line antifungal treatment for T. rubrum in China, we characterized antifungal susceptibility patterns of Chinese T. rubrum strains to nine antifungals and also described the upper limits of wild-type (WT) minimal inhibitory concentrations (MIC) (UL-WT) based on our study and another six studies published during the last decades. Sixty-two clinical isolates originating from seven provinces in China were identified as T. rubrum sensu stricto; all Chinese strains showed low MICs to eight out of nine antifungal drugs. Terbinafine (TBF) showed the lowest MICs of all antifungal classes tested in both the Chinese and global groups, with a 97.5% UL-WT MIC-value of 0.03 mg/L. No non-WT isolates were observed for TBF in China, but were reported in 18.5% of the global group. Our study indicated that TBF was still the most active drug for Chinese T. rubrum isolates, and all strains were within the WT-population. TBF therefore remains recommended for primary therapy to dermatophytosis caused by T. rubrum in China now, but regular surveillance of dermatophytes and antifungal susceptibility is recommended.

Highlights

Trichophyton rubrum has been among the most prevalent dermatophytes causing tinea pedis and tinea unguium since the early twenty-first century [1]
This study showed that the systemic antifungal drug terbinafine, first-line drug for dermatophytosis, had lost its in vitro activity in most parts in India [19]
In order to investigate potential trends in drug resistance of T. rubrum, we reviewed available minimal inhibitory concentrations (MIC) values from published literature and describe wild-type (WT) MIC distributions of nine drugs for T. rubrum according to the criteria used by Clinical and Laboratory Standards Institute (CLSI)

Summary

Introduction

Trichophyton rubrum has been among the most prevalent dermatophytes causing tinea pedis and tinea unguium since the early twenty-first century [1]. The global predominance of T. rubrum suggests that this species has a significantly higher capacity of transmission than other anthropophilic dermatophytes [2]. As confirmed by wholegenome sequencing [3], that T. rubrum is clonal with a highly conserved gene content, low levels of variation, and little evidence of recombination. One of the main characteristics promoting global spread is the low virulence of T. rubrum [8]. Hardly noticeable cutaneous infections with transmission via skin scales released from mild hyperkeratosis does not interfere with transmissionenhancing interaction of human hosts. Infections only are more serious in CARD9-deficient patients or in those with dysfunctional cellular immunity, e.g., with cirrhosis, AIDS, hematological malignancies or solid organ transplants [9,10,11]

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Conclusion