Correlation of invitro susceptibility based on MICs and SQLE mutations with clinical response to terbinafine in patients with tinea corporis/cruris

Khurana, Ananta; Masih, Aradhana; Chowdhary, Anuradha; Sardana, Kabir; Borker, Sagar; Gupta, Aastha; Gautam, R. K.; Sharma, Pankaj; Jain, Dhruv

doi:10.1101/326603

Cited by 5 publications

(9 citation statements)

References 38 publications

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“…There are some indications of a lack of in vivo correlation of in vitro resistance in dermatophytosis [ 35 ]. On the other hand, it was demonstrated that the odds of achieving a cure with terbinafine MIC < 1 µg/mL strains were 2.5 times the odds of achieving a cure with strains exhibiting MIC ≥ 1 µg/mL, suggesting a good in vitro and in vivo correlation [ 36 ]. Further studies are recommended to understand this complex problem of the in vitro/in vivo discordance.…”

Section: Discussionmentioning

confidence: 99%

Spread of Terbinafine-Resistant Trichophyton mentagrophytes Type VIII (India) in Germany–“The Tip of the Iceberg?”

Nenoff¹,

Verma²,

Ebert

et al. 2020

JoF

127

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Chronic recalcitrant dermatophytoses, due to Trichophyton (T.) mentagrophytes Type VIII are on the rise in India and are noteworthy for their predominance. It would not be wrong to assume that travel and migration would be responsible for the spread of T. mentagrophytes Type VIII from India, with many strains resistant to terbinafine, to other parts of the world. From September 2016 until March 2020, a total of 29 strains of T. mentagrophytes Type VIII (India) were isolated. All patients were residents of Germany: 12 females, 15 males and the gender of the remaining two was not assignable. Patients originated from India (11), Pakistan (two), Bangladesh (one), Iraq (two), Bahrain (one), Libya (one) and other unspecified countries (10). At least two patients were German-born residents. Most samples (21) were collected in 2019 and 2020. All 29 T. mentagrophytes isolates were sequenced (internal transcribed spacer (ITS) and translation elongation factor 1-α gene (TEF1-α)). All were identified as genotype VIII (India) of T. mentagrophytes. In vitro resistance testing revealed 13/29 strains (45%) to be terbinafine-resistant with minimum inhibitory concentration (MIC) breakpoints ≥0.2 µg/mL. The remaining 16 strains (55%) were terbinafine-sensitive. Point mutation analysis revealed that 10/13 resistant strains exhibited Phe397Leu amino acid substitution of squalene epoxidase (SQLE), indicative for in vitro resistance to terbinafine. Two resistant strains showed combined Phe397Leu and Ala448Thr amino acid substitutions, and one strain a single Leu393Phe amino acid substitution. Out of 16 terbinafine-sensitive strains, in eight Ala448Thr, and in one Ala448Thr +, new Val444 Ile amino acid substitutions were detected. Resistance to both itraconazole and voriconazole was observed in three out of 13 analyzed strains. Treatment included topical ciclopirox olamine plus topical miconazole or sertaconazole. Oral itraconazole 200 mg twice daily for four to eight weeks was found to be adequate. Terbinafine-resistant T. mentagrophytes Type VIII are being increasingly isolated. In Germany, transmission of T. mentagrophytes Type VIII from the Indian subcontinent to Europe should be viewed as a significant public health issue.

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Section: Discussionmentioning

confidence: 99%

Spread of Terbinafine-Resistant Trichophyton mentagrophytes Type VIII (India) in Germany–“The Tip of the Iceberg?”

Nenoff¹,

Verma²,

Ebert

et al. 2020

JoF

127

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“…Recent studies have demonstrated emerging predominance of Trichophyton mentagrophytes as the causative organism in such cases . We have noticed that in some of these studies the causative agent of the chronic, relapsing dermatophytosis outbreak in India has been described as Trichophyton interdigitale . In our opinion, it is very likely that these T interdigitale strains isolated in Delhi and Chennai in India are, in fact, strains more closely related to the neotype of T mentagrophytes and are not strains of T interdigitale .…”

Section: Introductionmentioning

confidence: 87%

“…[4][5][6] We have noticed that in some of these studies the causative agent of the chronic, relapsing dermatophytosis outbreak in India has been described as Trichophyton interdigitale. [7][8][9] In our opinion, it is very likely that these T interdigitale strains isolated in Delhi and Chennai in India are, in fact, strains more closely related to the neotype of T mentagrophytes and are not strains of T interdigitale. 10 We therefore wish to underscore the importance of a common nomenclature of species in accordance with the new taxonomy of dermatophytes.…”

mentioning

confidence: 99%

The current Indian epidemic of superficial dermatophytosis due toTrichophyton mentagrophytes—A molecular study

Nenoff¹,

Verma²,

Vasani³

et al. 2019

Mycoses

188

216

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Summary The disease burden of chronic‐relapsing and therapy‐refractory superficial dermatophytosis dramatically increased in India within the past 5‐6 years. In order to evaluate the prevalence of this trend, 201 skin scrapings were collected from patients from all parts of India and were tested for dermatophytes using both fungal culture and a PCR‐ELISA directly performed with native skin scrapings. Fungal culture material was identified by genomic Sanger sequencing of the internal transcribed spacer (ITS) region and the translation elongation factor (TEF)‐1α gene. In total, 149 (74.13%) out of the 201 samples showed a dermatophyte‐positive culture result. Out of this, 138 (92.62%) samples were identified as Trichophyton (T.) mentagrophytes and 11 (7.38%) as Trichophyton rubrum. The PCR‐ELISA revealed similar results: 162 out of 201 (80.56%) samples were dermatophyte‐positive showing 151 (93.21%) T mentagrophytes‐ and 11 (6.79%) T rubrum‐positive samples. In this study, we show for the first time a dramatic Indian‐wide switch from T rubrum to T mentagrophytes. Additionally, sequencing revealed a solely occurring T mentagrophytes “Indian ITS genotype” that might be disseminated Indian‐wide due to the widespread abuse of topical clobetasol and other steroid molecules mixed with antifungal and antibacterial agents.

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“…We would also like to highlight that keeping pets is a rarity in India. Only two of the 64 tinea corporis/cruris patients, reported by Khurana et al had pets at home, and these were also apparently uninfected. Thus, to propose that a zoophilic species is the cause of the Indian epidemic is implausible.…”

Section: Introductionmentioning

confidence: 92%

“…There is also a rampant spread within families including young children and infants presenting with widespread tinea corporis/cruris has been commonly noticed (Figure C). In the study by Khurana et al 54.6% patients had an infected family member. We would also like to highlight that keeping pets is a rarity in India.…”

Section: Introductionmentioning

confidence: 99%

Perspectives on misidentification of Trichophyton interdigitale/Trichophyton mentagrophytes using internal transcribed spacer region sequencing: Urgent need to update the sequence database

Chowdhary

Singh

et al. 2018

Mycoses

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Summary The taxonomy of the dermatophytes has been revisited using a novel multilocus phylogenetic approach, and several neotypes and reference strains have been assigned for Trichophyton species. Single gene sequencing, that is the ITS region, for identification of highly related species T. mentagrophytes/T. interdigitale, warrant reassessment. The sequence database (Westerdijk and NCBI) needs to be updated as several incorrect/obsolete entries of reference and neotype strains of T. interdigitale/T. mentagrophytes hampers correct identification of this complex.

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Correlation of invitro susceptibility based on MICs and SQLE mutations with clinical response to terbinafine in patients with tinea corporis/cruris

Cited by 5 publications

References 38 publications

Spread of Terbinafine-Resistant Trichophyton mentagrophytes Type VIII (India) in Germany–“The Tip of the Iceberg?”

Spread of Terbinafine-Resistant Trichophyton mentagrophytes Type VIII (India) in Germany–“The Tip of the Iceberg?”

The current Indian epidemic of superficial dermatophytosis due toTrichophyton mentagrophytes—A molecular study

Perspectives on misidentification of Trichophyton interdigitale/Trichophyton mentagrophytes using internal transcribed spacer region sequencing: Urgent need to update the sequence database

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