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

Nenoff, P.; Verma, Shyam; Ebert, Andreas; Süß, Anke; Fischer, E; Auerswald, Elke; Dessoi, Stephanie; Hofmann, W; Schmidt, Simone; Neubert, Kathrin; Renner, Regina; Sohl, Sirius; Hradetzky, Uta; Krusche, U; Wenzel, Hans-Christian; Staginnus, Annegret; Schaller, Jörg; Müller, Valentina Laura; Tauer, Christiane; Gebhardt, M.; Schubert, Katja; Almustafa, Zaid Z; Stadler, Rudolf; Fuchs, Andrea; Sitaru, Cassian; Retzlaff, Carsten; Overbeck, Cora; Neumann, Thomas; Kerschnitzki, Anette; Krause, Stephan; Schaller, Martin; Walker, Britta; Walther, Thomas; Köhler, Lars; Albrecht, Manuela; Willing, Ursula; Monod, Michel; Salamin, Karine; Burmester, Anke; Koch, Daniela; Krüger, Constanze; Uhrlaß, Silke

doi:10.3390/jof6040207

Cited by 97 publications

(183 citation statements)

References 36 publications

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“…10 The emergence of terbinafine resistance in dermatophytes has been observed in Iran, Japan, and Europe which can lead to epidemics or extensive infections. 10 , 14 , 15 The present study also focused on the susceptibility profile of olorofim on the varied spectrum of non- marneffei species of Penicillium and Talaromyces, causative agents of rare invasive fungal diseases. Notably, species of Penicillium and Talaromyces are known for their inherent resistance to azoles and amphotericin B.…”

Section: Discussionmentioning

confidence: 99%

In vitroactivity of the novel antifungal olorofim against dermatophytes and opportunistic moulds includingPenicilliumandTalaromycesspecies

Singh

Meis

et al. 2021

Journal of Antimicrobial Chemotherapy

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Objectives Olorofim is a novel antifungal agent with in vitro activity against Aspergillus and other opportunistic moulds. We investigated the in vitro activity of olorofim against a range of filamentous fungi comprising isolates of Aspergillus species, Scedosporium species, Alternaria alternata, dermatophytes, including terbinafine- and multidrug-resistant Trichophyton species, and Penicillium/Talaromyces species originating from patients in North India. Methods Antifungal susceptibility of olorofim was tested against 241 mould isolates of Penicillium/Talaromyces species, Trichophyton species, A. fumigatus and cryptic Aspergillus species, Scedosporium species, and Alternaria alternata using CLSI broth microdilution. The comparators were five systemic azoles, amphotericin B, terbinafine, and luliconazole. Results Overall, olorofim showed highly potent in vitro activity against dermatophytes and opportunistic moulds (MIC range of 0.004–0.125 mg/L) except for Alternaria alternata. Penicillium, and Talaromyces species and Trichophyton species exhibited a low geometric mean (GM) MIC (GM 0.027 mg/L and 0.015 mg/L, respectively) of olorofim. Importantly, a 2–12 dilution step decrease in in vitro activity of olorofim as compared with azoles was observed against Penicillium and Talaromyces. Notably, olorofim displayed potent in vitro activity against Trichophyton isolates including terbinafine-resistant and azole-resistant Trichophyton mentagrophytes/interdigitale with a modal MIC value of 0.008 mg/L. Further, azole-resistant A. fumigatus isolates harbouring mutations in azole target Cyp51A genes and several cryptic aspergilli displayed low MICs (range 0.004–0.03 mg/L) of olorofim. However, no in vitro activity of olorofim against Alternaria alternata was observed. Conclusions The potent in vitro activity of olorofim against drug-resistant dermatophytes and opportunistic moulds is promising, warranting evaluation of the clinical utility of olorofim.

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Section: Discussionmentioning

confidence: 99%

In vitroactivity of the novel antifungal olorofim against dermatophytes and opportunistic moulds includingPenicilliumandTalaromycesspecies

Singh

Meis

et al. 2021

Journal of Antimicrobial Chemotherapy

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“…We aim to comprehensively cover various aspects of the current epidemic-like scenario of dermatophytosis in India. The disease has attained a significant magnitude and is now being observed in other distant nations as well 1,2 often as an extensive and difficult to treat entity with diverse morphology. Recalcitrant superficial dermatophytosis has the potential to become a public health issue in many parts of the world if we do not make an active attempt to understand it in its entirety, take timely measures, and involve public health agencies and the World Health Organization.…”

Section: Introductionmentioning

confidence: 99%

The unprecedented epidemic-like scenario of dermatophytosis in India: I. Epidemiology, risk factors and clinical features

Verma¹,

Panda²,

Nenoff³

et al. 2021

IJDVL

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Dermatophytosis has attained unprecedented dimensions in recent years in India. Its clinical presentation is now multifarious, often with atypical morphology, severe forms and unusually extensive disease in all age groups. We hesitate to call it an epidemic owing to the lack of population-based prevalence surveys. In this part of the review, we discuss the epidemiology and clinical features of this contemporary problem. While the epidemiology is marked by a stark increase in the number of chronic, relapsing and recurrent cases, the clinical distribution is marked by a disproportionate rise in the number of cases with tinea corporis and cruris, cases presenting with the involvement of extensive areas, and tinea faciei.

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“…Similarly, T. mentagrophytes was divided into different genetic types. Type VIII isolates (from India) showed a high level of terbinafine resistance [ 104 ].…”

Section: Intrinsic Resistance Detectionmentioning

confidence: 99%

Molecular Markers of Antifungal Resistance: Potential Uses in Routine Practice and Future Perspectives

García‐Effrón

2021

JoF

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Antifungal susceptibility testing (AST) has come to establish itself as a mandatory routine in clinical practice. At the same time, the mycological diagnosis seems to have headed in the direction of non-culture-based methodologies. The downside of these developments is that the strains that cause these infections are not able to be studied for their sensitivity to antifungals. Therefore, at present, the mycological diagnosis is correctly based on laboratory evidence, but the antifungal treatment is undergoing a growing tendency to revert back to being empirical, as it was in the last century. One of the explored options to circumvent these problems is to couple non-cultured based diagnostics with molecular-based detection of intrinsically resistant organisms and the identification of molecular mechanisms of resistance (secondary resistance). The aim of this work is to review the available molecular tools for antifungal resistance detection, their limitations, and their advantages. A comprehensive description of commercially available and in-house methods is included. In addition, gaps in the development of these molecular technologies are discussed.

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

Cited by 97 publications

References 36 publications

In vitroactivity of the novel antifungal olorofim against dermatophytes and opportunistic moulds includingPenicilliumandTalaromycesspecies

In vitroactivity of the novel antifungal olorofim against dermatophytes and opportunistic moulds includingPenicilliumandTalaromycesspecies

The unprecedented epidemic-like scenario of dermatophytosis in India: I. Epidemiology, risk factors and clinical features

Molecular Markers of Antifungal Resistance: Potential Uses in Routine Practice and Future Perspectives

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