Extensive Dermatophytosis Caused by Terbinafine-Resistant Trichophyton indotineae, France.
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ABSTRACT:
SUBMITTER: Jabet A
PROVIDER: S-EPMC8714191 | biostudies-literature | 2022 Jan
REPOSITORIES: biostudies-literature
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Extensive Dermatophytosis Caused by Terbinafine-Resistant Trichophyton indotineae, France.
Jabet Arnaud A Brun Sophie S Normand Anne-Cecile AC Imbert Sebastien S Akhoundi Mohammad M Dannaoui Eric E Audiffred Laeticia L Chasset Francois F Izri Arezki A Laroche Liliane L Piarroux Renaud R Bachmeyer Claude C Hennequin Christophe C Sabater Alicia Moreno AM
Emerging infectious diseases 20220101 1
Extensive dermatophytosis caused by terbinafine-resistant Trichophyton indotineae harboring Phe397Leu and Leu393Ser substitutions in the squalene epoxidase enzyme was diagnosed in France. Analysis of internal transcribed spacer sequences revealed the wide spread of this species in Asia and Europe. Detection of T. indotineae in animals suggests their possible role as reservoirs. ...[more]
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Project description:Several prolonged and significant outbreaks of dermatophytosis caused by Trichophyton indotineae, a new emerging terbinafine-resistant species, have been ongoing in India in recent years, and have since spread to various countries outside Asia. Miltefosine, an alkylphosphocholine, is the most recently approved drug for the treatment of both visceral and cutaneous leishmaniasis. Miltefosine in vitro activity against terbinafine-resistant and susceptible T. mentagrophytes/T. interdigitale species complex, including T. indotineae, is limited. The current study aimed to assess miltefosine's in vitro activity against dermatophyte isolates, which are the most common causes of dermatophytosis. Miltefosine, terbinafine, butenafine, tolnaftate, and itraconazole susceptibility testing was performed using Clinical and Laboratory Standards Institute broth microdilution methods (CLSI M38-A3) against 40 terbinafine-resistant T. indotineae isolates and 40 terbinafine-susceptible T. mentagrophytes/T. interdigitale species complex isolates. Miltefosine had MIC ranges of 0.063-0.5 µg/mL and 0.125-0.25 µg/mL against both terbinafine-resistant and susceptible isolates. In terbinafine-resistant isolates, the MIC50 and MIC90 were 0.125 µg/mL and 0.25 µg/mL, respectively, and 0.25 µg/mL in susceptible isolates. Miltefosine had statistically significant differences in MIC results when compared to other antifungal agents (p-value 0.05) in terbinafine-resistant strains. Accordingly, the findings suggest that miltefosine has a potential activity for treating infections caused by terbinafine-resistant T. indotineae. However, further studies are needed to determine how well this in vitro activity translates into in vivo efficacy.
| S-EPMC10146699 | biostudies-literature
Project description:Dermatophytes are common causes of skin, hair, and nail infections in humans. The most common species causing infections in humans are Trichophyton rubrum, Trichophyton mentagrophytes, and Trichophyton interdigitale. Outbreaks of recalcitrant dermatophytosis have been reported in parts of South Asia, including those caused by a hypervirulent and resistant species, Trichophyton indotineae. We evaluated the antifungal susceptibility profiles of dermatophytes received by our laboratory from institutions across North America between 2021 and 2022 and performed species identification for isolates deemed to demonstrate in vitro resistance. Susceptibility testing was performed by CLSI broth microdilution methods, and species identification was performed by DNA sequence analysis. During this 2-year period, 271 dermatophyte isolates were included, the majority of which demonstrated low MIC values for terbinafine (geometric mean [GM] and modal MIC, 0.031 μg/mL and 0.008 μg/mL, respectively) and the azoles itraconazole, posaconazole, and voriconazole (0.035 to 0.049 μg/mL and ≤0.03 μg/mL). However, 18.6% of the isolates tested were resistant to terbinafine (MIC ≥ 0.5 μg/mL), including 21 T. rubrum and 21 T. indotineae isolates. These isolates were received from several different states in the United States and two provinces in Canada. In contrast, resistance to itraconazole was relatively rare. We also searched our laboratory database for earlier isolates that were resistant to terbinafine and identified 3 additional T. indotineae isolates, the earliest of which was from 2017. These results demonstrate that terbinafine resistance in dermatophytes was relatively common over this 2-year period and that T. indotineae is present in multiple areas in North America. Continued surveillance is warranted.
| S-EPMC10446870 | biostudies-literature
Project description:Trichophyton indotineae is an emerging fungal pathogen capable of causing extensive recalcitrant dermatophytosis exacerbated by frequently retained terbinafine resistance. Cases of dermatophytosis due to T. indotineae have increased dramatically in India in recent years. Other countries have reported imported infection cases, causing public health concerns over the potential global spread of this drug-resistant pathogen. We describe T. indotineae from 47 clinical cases in Ontario, Canada, from 2014 to 2023, based on 50 isolates received by the provincial public health laboratory. Although detected in Ontario as early as 2014, cases increased sharply in 2022-2023. The majority of cases were found in 20 to 64-year-olds (83.0%). Cases from 2022 to 2023 were noted in only 8 of 34 public health units, clustering in large urban centers. Based on genomic epidemiology, Ontario isolates were genetically similar to isolates from other countries. Neither temporal nor geographic clustering based on country or public health unit was observed, suggesting Ontario cases represented recent introductions from endemic regions, although limited local transmission cannot be ruled out. Genome diversity (4.4 × 10-6) was extremely low, consistent with the hypothesized recent emergence and clonal population structure of T. indotineae. Most (71.4%) cases were terbinafine-resistant, with isolates exhibiting either the L393F/L393S (n = 3) or F397L (n = 27) squalene epoxidase substitution. Decreased susceptibility to itraconazole or voriconazole was found among 23.7% of isolates and was frequently associated with CYP51B gene duplication. Terbinafine-resistant T. indotineae infections are escalating in Ontario, meriting enhanced laboratory detection methods and public health efforts to increase the awareness of recalcitrant dermatophytoses in order to promptly initiate appropriate treatment and control transmission.IMPORTANCECases of dermatophytosis caused by emerging pathogen Trichophyton indotineae are increasing worldwide. Many are resistant to first-line treatment option terbinafine, resulting in difficult-to-treat cases. We describe the emergence of cases of T. indotineae infections in Ontario, Canada. The incidence in primarily urban centers increased dramatically in 2022-2023, with a large percentage of isolates resistant to terbinafine. Decreased susceptibility to azoles was also observed for some isolates, raising concern over the potential evolution of multi-drug resistance. Ontario T. indotineae isolates were genetically similar to those from disparate locales worldwide, signifying the global nature of this public health concern. Together with other reports, this study serves to raise public health awareness to promote better laboratory detection procedures, prompt appropriate treatment of recalcitrant dermatophytoses, and inform infection prevention and control measures.
| S-EPMC11784349 | biostudies-literature
Project description:A 26-year-old male patient referred to our center with a history of extremely itchy crusted skin lesions in his groins for one year. Moreover, his friend, a 25-year-old male, also developed similar lesions in the groin after using the shared pool, whose condition also did not improve with similar treatment. A regular mycology test (direct and culture test) was performed, as well as molecular examination. The antifungal susceptibility assay to terbinafine, itraconazole, posaconazole, fluconazole, and voriconazole was conducted according to the Clinical and Laboratory Standards Institute M38 third ed. The sequencing study identified T. tonsurans as the causative organism in both patients. The abovementioned organism isolated from both patients displayed resistance against terbinafine and fluconazole (MIC ≥ 4 µg/ml and MIC ≥ 8 µg/ml, respectively). Moreover, the susceptibility of both subjects to posaconazole (0.313 µg/ml), voriconazole (0.25-0.0625 µg/ml), and (1 µg/ml) itraconazole increased. The present report aimed to emphasize the increase in antifungal resistance and a demand for antifungal stewardship, to control this public health threat.
| S-EPMC8677411 | biostudies-literature
Project description:We describe a case of tinea genitalis in an immunocompetent woman in Pennsylvania, USA. Infection was caused by Trichophyton indotineae potentially acquired through sexual contact. The fungus was resistant to terbinafine (first-line antifungal) but improved with itraconazole. Clinicians should be aware of T. indotineae as a potential cause of antifungal-resistant genital lesions.
| S-EPMC10977831 | biostudies-literature
Project description:In immunosuppressed patients, dermatophytosis can be more invasive, affecting the dermis and subcutaneous tissues. The authors describe the cases of two patients with kidney and heart transplanted, respectively, that developed a deep dermatophytosis caused by Trichophyton rubrum, confirmed by culture and DNA sequencing. Both patients had concomitant onychomycosis, and both were treated with itraconazole for about two months, which was interrupted due to pharmacological interactions with the immunosuppressive drugs and switched to terbinafine, leading to clinical resolution within four months. Deep dermatophytosis should be considered when dealing with immunocompromised patients, especially when a superficial dermatophytosis is present. Oral treatment is necessary and terbinafine is a preferable option in solid organ transplant recipients because it has less pharmacological interactions.
| S-EPMC9073306 | biostudies-literature
Project description:The emerging pathogen Trichophyton indotineae, often resistant to terbinafine (TRB), is known to cause severe dermatophytoses such as tinea corporis and tinea cruris. In order to achieve successful treatment for these infections, insight in the resistance profile of T. indotineae strains and rapid, reliable identification is necessary. In this research, a screening medium was tested on T. indotineae strains (n = 20) as an indication tool of TRB resistance. The obtained results were confirmed by antifungal susceptibility testing (AST) for TRB following the in vitro broth microdilution reference method. Additionally, AST was performed for eight other antifungal drugs: fluconazole, itraconazole, voriconazole, ketoconazole, griseofulvin, ciclopirox olamine, naftifine and amorolfine. Forty-five percent of the strains were confirmed to be resistant to terbinafine. The TRB resistant strains showed elevated minimal inhibitory concentration values for naftifine and amorolfine as well. DNA sequencing of the squalene epoxidase-encoding gene showed that TRB resistance was a consequence of missense point mutations in this gene, which led to amino acid substitutions F397L or L393F. MALDI-TOF MS was used as a quick, accurate identification tool for T. indotineae, as it can be challenging to distinguish it from closely related species such as Trichophyton mentagrophytes or Trichophyton interdigitale using morphological characteristics. While MALDI-TOF MS could reliably identify ≥ 95% of the T. indotineae strains (depending on the spectral library), it could not be used to successfully distinguish TRB susceptible from TRB resistant strains.
| S-EPMC10940462 | biostudies-literature
Project description:Background/Objectives: Dermatophytosis due to Trichophyton (T.) indotineae has spread worldwide, and the acquisition of new drug resistances is making this threat challenging to face. We report four cases of dermatophytosis caused by T. indotineae and perform a systematic review of case reports to explore the most relevant clinical and demographic features and the treatment patterns of this infection. Methods: A literature search, using the PubMed database and following PRISMA guidelines, was performed up to the 6th of December 2024. Articles were included if written in English and presented in the form of case reports/series involving human subjects, with detailed information and T. indotineae infection confirmed by internal transcribed spacer sequencing. Results: Initially, 255 records were identified, and 30 articles were finally selected, including 64 patients, mainly from the Asian continent. Most patients were healthy and/or immunocompetent (65.52%), and the mean disease duration suggested long-lasting lesions. At least two different body sites were generally involved, with a predilection for lower body areas (groins included), as also observed in our patients (all from South Asia). Review results indicated itraconazole as the most commonly prescribed final medication. Treatment with itraconazole led to complete remission in three of our patients (one patient was lost to follow-up). Conclusions: T. indotineae infection should be suspected in case of extensive and/or recalcitrant dermatophytosis, especially in patients with a travel history to Asian countries. Further research is needed to develop rapid, inexpensive, and accurate techniques for the identification of T. indotineae and drug-resistant strains and to define the optimal preventive and treatment strategies.
| S-EPMC11856467 | biostudies-literature
Project description:In the current study, we report the genome sequence of two different clinical isolates from India, Trichophyton indotineae UCMS-IGIB-CI12 and Trichophyton indotineae UCMS-IGIB-CI14. The resulting genome assembly achieved a 143-fold coverage in 824 contigs for T. indotineae UCMS-IGIB-CI12 and a 136-fold coverage in 904 contigs for T. indotineae UCMS-IGIB-CI14. Both the clinical isolates contain a c.1342G>A mutation corresponding to Ala448Thr amino acid substitution in erg1 and exhibit an intermittent drug response to terbinafine. Comparative genomics analysis with available genomes of Trichophyton interdigitale/Trichophyton mentagrophytes species complex revealed a similar genome architecture and identified large number of genes associated with virulence and pathogenicity, namely, lipases, proteases, LysM domain-containing factors, carbon metabolism enzymes and cytochrome P450 enzymes, in all the genomes. An analysis of single amino acid polymorphisms (SAPs) in the protein sequences of subtilisin and lipase enzyme families identified a higher frequency of SAPs in functionally important proteins, Sub3 and Sub6 and their possible use in multilocus phylogenetic analysis of T. interdigitale/T. mentagrophytes species complex. The whole genome sequences of T. indotineae clinical isolates provided in this report will, hence, serve as a key reference point for investigation of clinical strains and emerging drug resistance among dermatophytes originating from different parts of the world.
| S-EPMC8353060 | biostudies-literature
Project description:Trichophyton indotineae is an emerging dermatophyte species that plays a relevant role in human healthcare. It has been associated with severe chronic skin infections and a high level of terbinafine resistance. T. indotineae is endemic to India, Iran, and Iraq but several cases have been reported in Europe, recently. In this manuscript, the authors report the first clinical description of a tinea corporis and onychomycosis due to T. indotineae. The patient was a 42-year-old female from India that has lived in Umbria (Central Italy) for the last two years. Firstly, a dermatological examination suggested dermatophytosis: mycology isolation from cultures and macro- and microscopical features identified the colonies as belonging to the T. mentagrophytes/T. interdigitale species complex. Subsequently, ITS1/ITS4 end-point PCR and Sanger sequencing identified the strain as T. indotineae. Lastly, a DermaGenius® Resistance Multiplex real-time PCR assay was carried out, targeting the mutations in the SQLE gene to establish terbinafine resistance or susceptibility of the strain. The melting curve observed was compatible with wild-type positive control, identifying the strain as T. indotineae terbinafine-sensitive. An oral terbinafine treatment was associated with a topical ciclopirox nail solution, resulting in remission in its clinical manifestation. On 3 July 2023, the local Prevention Service notified the case to the Ministry of Health that then reported the information at national and international levels.
| S-EPMC10532841 | biostudies-literature