When First-Line Fails: The Rising Threat of Treatment-Resistant Dermatoses

The emergence of Trichophyton indotineae is not just a story about a single dermatophyte: it is a warning about what can occur when a pathogen outpaces clinician awareness, infrastructure, and the treatment armamentarium.

Trichophyton indotineae, also referred to as T. indotineae, represents a newly identified dermatophyte species with evidence of a spread from the Indian subcontinent to many countries around the world, including Europe and the US.1 It is a notable cause of the severe, highly contagious, and often antifungal-resistant skin infection known as ringworm.2

The dermatophyte itself, T. indotineae, has been identified as genotype VIII within the T. mentagrophytes/T. interdigitale species complex via Internal Transcribed Spacer (ITS) region sequencing of ribosomal DNA, first described in 2019.1

T. indotineae is a type of fungi requiring keratin to grow and infecting patients’ hair, skin, and nails. The dermatophyte has also attained near-epidemic prevalence on the Indian subcontinent, displacing formerly prevalent dermatophyte species in this location. It is also emerging in the US, representing a notable problem for dermatologists and clinicians of all types.2

The dermatophyte’s spread is notable as it is attributable to 2 significant issues faced by dermatologists: misdiagnosis and treatment resistance. This set of compounding issues was discussed in a set of interviews with the HCPLive team and a pair of clinicians, both of whose research has contributed to the medical community’s increasing awareness of the spread of treatment-resistant skin infections.

The experts were Avrom S. Caplan, MD, an assistant professor of dermatology in the Ronald O. Perelman Department of Dermatology at the NYU Grossman School of Medicine, and Ananta Khurana, MD, DNB, from the Department of Dermatology at the Atal Bihari Vajpayee Institute of Medical Sciences (ABVIMS) and Dr. Ram Manohar Lohia (RML) Hospital in New Delhi, India.

Through a combination of recent data and these experts’ insights, this feature explores the rise of treatment-resistant dermatoses across the world, centering on T. Indotineae as a key example, as well as what clinicians need to understand about treatment resistance and why it matters.

"It is something which everyone has to know and understand, before it becomes endemic in more regions of the world,” Khurana expressed. Caplan concurred, noting the dermatophyte has been hiding in plain sight for longer than the medical community has realized.

Recognizing Infection, Clinical Presentation, and Red Flags

Dermatophytoses impact approximately 25% of the global population, according to research authored in part by Caplan.4 Dermatophytes are made up of over 30 species of common and contagious filamentous fungi known to invade keratinized tissues and lead to superficial infections.

Consequently, clinicians, and especially dermatologists, may have to focus more deeply on infections such as these, keeping both antifungal resistance and misdiagnosis in mind as the issue becomes more visible around the world.

“If we're not aware as clinicians of the potential that someone might have this particular dermatophyte, we might be fooled into thinking they have a different dermatologic condition, such as eczema or psoriasis, and then the patient might have a delay in treatment,” Caplan noted in his interview.

T. indotineae is now documented in about 40 countries across multiple continents, according to Khurana, and its spread has been strongly linked to travel and migration patterns.2,3 Cases in the US have been confirmed in multiple states, with 9 of 11 patients identified in a 2023 cohort study having reported prior travel to Bangladesh.2 Diagnostic delays were also observed, ranging from 3 - 42 months in this study.

The dermatophyte causes inflammatory, intensely itchy, commonly widespread dermatophytosis impacting those with the condition in their groin, gluteal region, trunk, and face. Patients of all ages and genders can be affected.

"The kind of extent of infection we see in patients now was not so common before,” Khurana said. “And a lot of patients come with very prominent facial involvement, face, neck, and extension into the scalp."

In the Morbidity and Mortality Weekly Report by the US Centers for Disease Control and Prevention (CDC), the highly transmissible infection is characterized by inflamed, widespread, pruritic plaques on the body, known as tinea corporis.5 Plaques are found in the pubic region, crural fold, the adjacent thigh, or face.

"One of the things I hear from patients most is how itchy it is,” Caplan added. “It can be sort of maddeningly itchy, and it can be pretty widespread across the body."

The diagnosis of resulting tinea infections poses a challenge, given their similar appearance to other conditions with comparable lesions. Researchers have noted eczema’s similar appearance to tinea corporis and alopecia areata’s similarity to tinea capitis, for example.6

Caplan noted the importance of looking into t. Indotineae as a possibility, noting additional exploration may be needed when “someone has been treated for eczema or psoriasis for quite some time, and it's not getting better, and then we start to pick up some more clinical clues.”

Additionally, both Khurana and Caplan urged attention if a family member has the infection or if a patient has traveled to a country in which the dermatophyte is widespread.

Research has suggested that culture and physiological characteristics of the infection cannot confirm identification at the species level.6 Such a situation, therefore, could require species-level confirmation via molecular methods.

The Resistance Picture: What Clinicians Should Understand

One of the biggest concerns surrounding the spread of T. indotineae is the dermatophyte’s resistance to terbinafine, an antifungal commonly known by the brand name Lamisil. Terbinafine is typically the first-line treatment for tinea.

“There had been actually articles before, in the early 2000s, which said that it is very unlikely that dermatophytes will ever become resistant to terbinafine, because the mode of action of that resistance in acquiring a single gene mutation in the target enzyme would be a very rare occurrence,” Khurana explained.

Khurana noted it had been established that dermatophytes would not have the ability to resist antifungal drugs such as terbinafine. She pointed to the well-documented observation that the dermatophyte is, in fact, developing resistance.2

Those who are resistant to terbinafine are often treated next with oral itraconazole. However, data has suggested T. indotineae is often resistant to azole antifungals such as itraconazole and fluconazole.7 Its use as an alternative option has seen success, but questions about resistance remain.

"If we are actually seeing terbinafine resistance and itraconazole resistance, that's really worrisome,” Caplan noted. “Now there's a lot of debate and discussion about whether we're actually seeing itraconazole resistance or not. But talking to colleagues anecdotally, it sounds like there are some countries where people are now reaching for other antifungals beyond itraconazole to treat this infection."

Published data suggest T. indotineae carries predominantly in vitro genetic resistance to terbinafine through point mutations in the enzyme squalene epoxidase (SQLE).3 There is also no established clinical breakpoint for antifungal treatment of dermatophytes. Additionally, in vitro antifungal susceptibility tests (AFST) do not necessarily correspond to patients’ clinical responses, leading to additional treatment issues.

In the current treatment landscape, there is still a lack of consensus on the most impactful therapeutic approach for infections resulting from T. indotineae, including antifungal agents, duration of treatment, dosing regimens, and infection control measures needed to diminish continued dermatophyte transmission.4

Adapting Treatment Strategies and Looking to the Future

Knowledge about how to confront treatment-resistant dermatophytes is increasingly becoming necessary for clinicians. When it comes to addressing suspected or confirmed T. indotineae, both Khurana are in agreement: shifting to itraconazole directly rather than defaulting to terbinafine may be warranted.

While terbinafine at higher-than-standard doses retains utility and has data supporting its utilization, the pair noted it may not fully overcome resistance and should be reserved for select cases or where itraconazole is contraindicated.

Another important aspect worth considering is counseling patients on their duration of treatment. Khurana urged caution to clinicians who might assume itraconazole failures are immediate evidence of treatment resistance.

“Currently, the organism is sensitive to itraconazole, and clinically, itraconazole does work well,” Khurana said. “Mostly when the patients say they have taken itraconazole and not responded, it's mostly to do with compliance with the long treatment durations, or if a good formulation has not been used."

Caplan echoed this sentiment, pointing to the need for close follow-up to confirm not only patients’ initial response to treatment, but also their level of clearance. He highlighted the value of ensuring patients have consistent access to their medication and are taking it correctly.

When considering what follows itraconazole, both experts believe the answer is not escalation. Third-generation azoles such as posaconazole and voriconazole must be preserved for invasive and systemic fungal infections. Implementing them for widespread community tinea would be both clinically inappropriate and could be seen as a failure of stewardship.

The experts noted the antifungal pipeline is limited, with very few new treatments in development. This, they suggested, means clinicians should resist their impulse to move to other drugs out of frustration or uncertainty.

“We don't have a lot of antifungals in the pipeline, and so we need to preserve what we have,” Caplan explained. “Also, we need to think about what's called antifungal stewardship, [which means] not using antifungals inappropriately, so that we're not contributing to any potential resistance."

Overall, Khurana and Caplan are 2 of many experts who have pointed to the explosion of antifungal-resistant dermatophyte infections as an alarming global health issue.8 In the interest of preventing such easily transmissable infections, clinicians may wish to maintain a high level of awareness of resistant dermatophyte infections.

Additionally, the maintenance of the aforementioned antifungal stewardship measures may be critical for stemming the tide of these infections. Dermatologists may be in a position to lead efforts in the coming years to prevent the rising spread of treatment-resistant dermatophytes in the US and around the world.

References

1. Uhrlaß S, Verma SB, Gräser Y, Rezaei-Matehkolaei A, Hatami M, Schaller M, Nenoff P. Trichophyton indotineae-An Emerging Pathogen Causing Recalcitrant Dermatophytoses in India and Worldwide-A Multidimensional Perspective. J Fungi (Basel). 2022 Jul 21;8(7):757. doi: 10.3390/jof8070757. PMID: 35887512; PMCID: PMC9323571.

2. Tamer F, Polat M. Evaluation of Clinical Studies of Patients With Dermatophyte Infections Caused by Trichophyton indotineae: Treatment Response and Resistance to Antifungal Medications. Dermatol Pract Concept. 2025 Oct 1;15(4):e20255517. doi: 10.5826/dpc.1504a5517. PMID: 41236241; PMCID: PMC12615080.

3. Caplan AS, Todd GC, Zhu Y, et al. Clinical Course, Antifungal Susceptibility, and Genomic Sequencing of Trichophyton indotineae. JAMA Dermatol. 2024;160(7):701–709. doi:10.1001/jamadermatol.2024.1126.

4. Dellière S, Jabet A, Abdolrasouli A. Current and emerging issues in dermatophyte infections. PLoS Pathog. 2024 Jun 13;20(6):e1012258. doi: 10.1371/journal.ppat.1012258. PMID: 38870096; PMCID: PMC11175395.

5. Caplan AS, Chaturvedi S, Zhu Y, et al. Notes from the Field: First Reported U.S. Cases of Tinea Caused by Trichophyton indotineae — New York City, December 2021–March 2023. MMWR Morb Mortal Wkly Rep 2023;72:536–537. DOI: http://dx.doi.org/10.15585/mmwr.mm7219a4.

6. Marbaniang YV, Leto D, Almohri H, Hasan MR. Treatment and diagnostic challenges associated with the novel and rapidly emerging antifungal-resistant dermatophyte, Trichophyton indotineae. J Clin Microbiol. 2025 Jun 11;63(6):e0140724. doi: 10.1128/jcm.01407-24. Epub 2025 Jun 11. PMID: 40497720; PMCID: PMC12153305.

7. Hui ST, Gifford H, Rhodes J. Emerging Antifungal Resistance in Fungal Pathogens. Curr Clin Microbiol Rep. 2024;11(2):43-50. doi: 10.1007/s40588-024-00219-8. Epub 2024 Mar 18. PMID: 38725545; PMCID: PMC11076205.

8. Hill RC, Caplan AS, Elewski B, Gold JAW, Lockhart SR, Smith DJ, Lipner SR. Expert Panel Review of Skin and Hair Dermatophytoses in an Era of Antifungal Resistance. Am J Clin Dermatol. 2024 May;25(3):359-389. doi: 10.1007/s40257-024-00848-1. Epub 2024 Mar 18. PMID: 38494575; PMCID: PMC11201321.