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To the Editor:
Historically, commonly available antifungal medications have been effective for treating dermatophytosis (tinea). However, recent tinea outbreaks caused by Trichophyton indotineae—a dermatophyte often resistant to terbinafine and sometimes to other antifungals—have been reported in South Asia, Europe, the Middle East, Southeast Asia, and Australia.1-5
Three confirmed cases of T indotineae dermatophytosis in the United States were reported in 2023 in New York3,6; a fourth confirmed case was reported in 2024 in Pennsylvania.7 Post hoc laboratory testing of fungal isolates in New York in 2022 and 2023 identified an additional 11 cases.8 We present a case of extensive multidrug-resistant tinea caused by T indotineae in a man in California.
An otherwise healthy 65-year-old man who had traveled to Europe in the past 3 months presented to his primary care physician with a widespread pruritic rash (Figure 1). He was treated with 2 weeks of oral terbinafine 250 mg/d and topical medicines, including clotrimazole cream 1%, fluocinonide ointment 0.05%, and clobetasol ointment 0.05% without improvement. Subsequently, 2 weeks of oral griseofulvin microsize 500 mg/d also proved ineffective. An antibody test was negative for HIV. His hemoglobin A1c was 6.2% (reference range, ≤5.6%). The patient was referred to dermatology.
Erythematous plaques—many scaly throughout and some annular with central clearing—were present on the arms, legs, and torso as well as in the groin. Honey crust was present on some plaques on the leg. A potassium hydroxide preparation showed abundant fungal hyphae. Material for fungal and bacterial cultures was collected. The patient was treated again with oral terbinafine 250 mg/d, an oral prednisone taper starting at 60 mg/d for a presumed id reaction, and various oral antihistamines for pruritus; all were ineffective. A bacterial culture showed only mixed skin flora. Oral fluconazole 200 mg/d was prescribed. A skin biopsy specimen showed compact orthokeratosis and parakeratosis of the stratum corneum with few neutrophils and focal pustule formation (Figure 2). Superficial perivascular inflammation, including lymphocytes, histiocytes, and few neutrophils, was present. A periodic acid–Schiff stain showed fungal hyphae in the stratum corneum and a hair follicle (Figure 3). After approximately 2 weeks, mold was identified in the fungal culture. Approximately 2 weeks thereafter, the organism was reported as Trichophyton species.
The rash did not improve; resistance to terbinafine, griseofulvin, and fluconazole was suspected clinically. The fungal isolate was sent to a reference laboratory (University of Texas Health Science Center, San Antonio). Meanwhile, oral itraconazole 200 mg twice daily and ketoconazole cream 2% were prescribed; the rash began to improve. A serum itraconazole trough level obtained 4 days after treatment initiation was 0.5 μg/mL (reference range, ≥0.6 μg/mL). The evening itraconazole dose was increased to 300 mg; a subsequent trough level was 0.8 μg/mL.
Approximately 1 month after the fungal isolate was sent to the reference laboratory, T indotineae was confirmed based on polymerase chain reaction (PCR) testing of internal transcribed spacer region sequences. Minimum inhibitory concentrations (MICs) obtained through antifungal susceptibility testing (AFST) were reported for fluconazole (8 μg/mL), griseofulvin (2 μg/mL), itraconazole (≤0.03 μg/mL), posaconazole (≤0.03 μg/mL), terbinafine (≥2 μg/mL), and voriconazole (0.125 μg/mL).
Approximately 7 weeks after itraconazole and ketoconazole were started, the rash had completely resolved. Nearly 8 months later (at the time this article was written), the rash had not recurred.
We report a unique case of T indotineae in a patient residing in California. Post hoc laboratory testing of dermatophyte isolates sent to the University of Texas reference laboratory identified terbinafine-resistant T indotineae specimens from the United States and Canada dating to 2017; clinical characteristics of patients from whom those isolates were obtained were unavailable.9
Trichophyton indotineae dermatophytosis typically is more extensive, inflamed, and pruritic, as well as likely more contagious, than tinea caused by other dermatophytes.5 Previously called Trichophyton mentagrophytes genotype VIII when first isolated in 2017, the pathogen was renamed T indotineae in 2020 after important genetic differences were discovered between it and other T mentagrophytes species.5 The emergence of T indotineae has been attributed to concomitant use of topical steroids and antifungals,5,10 inappropriate prescribing of antifungals,5 and nonadherence to antifungal treatment.5
Likely risk factors for T indotineae infection include suboptimal hygiene, overcrowded conditions, hot and humid environments, and tight-fitting synthetic clothing.4 Transmission from family members appears common,5 especially when fomites are shared.4 A case reported in Pennsylvania likely was acquired through sexual contact.7 Travel to South Asia has been associated with acquisition of T indotineae infection,3,5-7 though our patient and some others had not traveled there.3,8 It is not clear whether immunosuppression and diabetes mellitus are associated with T indotineae infection.4,5,8Trichophyton indotineae also can affect animals,11 though zoonotic transmission has not been reported.4
Not all T indotineae isolates are resistant to one or more antifungals; furthermore, antifungal resistance in other dermatophyte species has been reported.5 Terbinafine resistance in T indotineae is conferred by mutations in the gene encoding squalene epoxidase, which helps synthesize ergosterol—a component of the cell membrane in fungi.2,4,5,12 Although clinical cut-points for MIC obtained by AFST are not well established, T indotineae MICs for terbinafine of 0.5 μg/mL or more correlate with resistance.9 Resistance to azoles has been linked to overexpression of transporter genes, which increase azole efflux from cells, as well as to mutations in the gene encoding lanosterol 14α demethylase.4,12,13
Potassium hydroxide preparations and fungal cultures cannot differentiate T indotineae from other dermatophytes that typically cause tinea.5,14 Histopathologic findings in our case were no different than those of non–T indotineae dermatophytes. Only molecular testing using PCR assays to sequence internal transcribed spacer genes can confirm T indotineae infection. However, PCR assays and AFST are not available in many US laboratories.5 Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry has shown promise in distinguishing T indotineae from other dermatophytes, though its clinical use is limited and it cannot assess terbinafine sensitivity.15,16 Clinicians in the United States who want to test specimens from cases suspicious for T indotineae infection should contact their local or state health department or the Centers for Disease Control and Prevention for assistance.3,5
Systemic treatment typically is necessary for T indotineae infection.5 Combinations of oral and topical azoles have been used, as well as topical ciclopirox, amorolfine (not available in the United States), and luliconazole.1,5,17-21
Itraconazole has emerged as the treatment of choice for T indotineae tinea, typically at 200 mg/d and often for courses of more than 3 months.5 Testing for serum itraconazole trough levels, as done for our patient, typically is not recommended. Clinicians should counsel patients to take itraconazole with high-fat foods and an acidic beverage to increase bioavailability.5 Potential adverse effects of itraconazole include heart failure and numerous drug-drug interactions.5,22 Patients with T indotineae dermatophytosis should avoid sharing personal belongings and having skin-to-skin contact of affected areas with others.4
Dermatologists who suspect T indotineae infection should work with public health agencies that can assist with testing and undertake infection surveillance, prevention, and control.5,23 Challenges to diagnosing and managing T indotineae infection include lack of awareness among dermatology providers, the need for specialized laboratory testing to confirm infection, lack of established clinical cut-points for MICs from AFST, the need for longer duration of treatment vs what is needed for typical tinea, and potential challenges with insurance coverage for testing and treatment. Empiric treatment with itraconazole should be considered when terbinafine-resistant dermatophytosis is suspected or when terbinafine-resistant T indotineae infection is confirmed.
Acknowledgments—Jeremy Gold, MD; Dallas J. Smith, PharmD; and Shawn Lockhart, PhD, all of the Centers for Disease Control and Prevention, Mycotic Diseases Branch (Atlanta, Georgia), provided helpful comments to the authors in preparing the manuscript of this article.
- Uhrlaß S, Verma SB, Gräser Y, al. Trichophyton indotineae—an emerging pathogen causing recalcitrant dermatophytoses in India and worldwide—a multidimensional perspective. J Fungi (Basel). 2022;8:757. doi:10.3390/jof8070757
- Jabet A, Brun S, Normand A-C, et al. Extensive dermatophytosis caused by terbinafine-resistant Trichophyton indotineae, France. Emerg Infect Dis. 2022;28:229-233. doi:10.3201/eid2801.210883
- 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:10.15585/mmwr.mm7219a4
- Jabet A, Normand A-C, Brun S, et al. Trichophyton indotineae, from epidemiology to therapeutic. J Mycol Med. 2023;33:101383. doi:10.1016/j.mycmed.2023.101383
- Hill RC, Caplan AS, Elewski B, et al. Expert panel review of skin and hair dermatophytoses in an era of antifungal resistance. Am J Clin Dermatol. 2024;25:359-389. doi:10.1007/s40257-024-00848-1
- Caplan AS, Zakhem GA, Pomeranz MK. Trichophyton mentagrophytes internal transcribed spacer genotype VIII. JAMA Dermatol. 2023;159:1130. doi:10.1001/jamadermatol.2023.2645
- Spivack S, Gold JAW, Lockhart SR, et al. Potential sexual transmission of antifungal-resistant Trichophyton indotineae. Emerg Infect Dis. 2024;30:807-809. doi:10.3201/eid3004.240115
- Caplan AS, Todd GC, Zhu Y, et al. Clinical course, antifungal susceptibility, and genomic sequencing of Trichophyton indotineae. JAMA Dermatol. Published online May 15, 2024. doi:10.1001/jamadermatol.2024.1126
- Cañete-Gibas CF, Mele J, Patterson HP, et al. Terbinafine-resistant dermatophytes and the presence of Trichophyton indotineae in North America. J Clin Microbiol. 2023;61:e0056223. doi:10.1128/jcm.00562-23
- Gupta AK, Venkataraman M, Hall DC, et al. The emergence of Trichophyton indotineae: implications for clinical practice. Int J Dermatol. 2023;62:857-861.
- Oladzad V, Nasrollahi Omran A, Haghani I, et al. Multi-drug resistance Trichophyton indotineae in a stray dog. Res Vet Sci. 2024;166:105105. doi:10.1016/j.rvsc.2023.105105
- Martinez-Rossi NM, Bitencourt TA, Peres NTA, et al. Dermatophyte resistance to antifungal drugs: mechanisms and prospectus. Front Microbiol. 2018;9:1108. doi:10.3389/fmicb.2018.01108
- Sacheli R, Hayette MP. Antifungal resistance in dermatophytes: genetic considerations, clinical presentations and alternative therapies. J Fungi (Basel). 2021;711:983. doi:10.3390/jof7110983
- Gupta AK, Cooper EA. Dermatophytosis (tinea) and other superficial fungal infections. In: Hospenthal DR, Rinaldi MG, eds. Diagnosis and Treatment of Human Mycoses. Humana Press; 2008:355-381.
- Normand A-C, Moreno-Sabater A, Jabet A, et al. MALDI-TOF mass spectrometry online identification of Trichophyton indotineae using the MSI-2 application. J Fungi (Basel). 2022;8:1103. doi:10.3390/jof8101103
- De Paepe R, Normand A-C, Uhrlaß S, et al. Resistance profile, terbinafine resistance screening and MALDI-TOF MS identification of the emerging pathogen Trichophyton indotineae. Mycopathologia. 2024;189:29. doi:10.1007/s11046-024-00835-4
- Rajagopalan M, Inamadar A, Mittal A, et al. Expert consensus on the management of dermatophytosis in India (ECTODERM India). BMC Dermatol. 2018;18:6. doi:10.1186/s12895-018-0073-1
- Verma SB, Panda S, Nenoff P, et al. The unprecedented epidemic-like scenario of dermatophytosis in India: III. Antifungal resistance and treatment options. Indian J Dermatol Venereol Leprol. 2021;87:468-482. doi:10.25259/IJDVL_303_20
- Shaw D, Singh S, Dogra S, et al. MIC and upper limit of wild-type distribution for 13 antifungal agents against a Trichophyton mentagrophytes–Trichophyton interdigitale complex of Indian origin. Antimicrob Agents Chemother. 2020;64:E01964-19. doi:10.1128/AAC.01964-19
- Burmester A, Hipler U-C, Uhrlaß S, et al. Indian Trichophyton mentagrophytes squalene epoxidase erg1 double mutants show high proportion of combined fluconazole and terbinafine resistance. Mycoses. 2020;63:1175-1180. doi:10.1111/myc.13150
- Khurana A, Agarwal A, Agrawal D, et al. Effect of different itraconazole dosing regimens on cure rates, treatment duration, safety, and relapse rates in adult patients with tinea corporis/cruris: a randomized clinical trial. JAMA Dermatol. 2022;158:1269-1278. doi:10.1001/jamadermatol.2022.3745
- Itraconazole capsule. DailyMed [Internet]. Updated June 3, 2024. Accessed June 19, 2024. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=2ab38a8a-3708-4b97-9f7f-8e554a15348d
- Bui TS, Katz KA. Resistant Trichophyton indotineae dermatophytosis—an emerging pandemic, now in the US. JAMA Dermatol. Published online May 15, 2024. doi:10.1001/jamadermatol.2024.1125
To the Editor:
Historically, commonly available antifungal medications have been effective for treating dermatophytosis (tinea). However, recent tinea outbreaks caused by Trichophyton indotineae—a dermatophyte often resistant to terbinafine and sometimes to other antifungals—have been reported in South Asia, Europe, the Middle East, Southeast Asia, and Australia.1-5
Three confirmed cases of T indotineae dermatophytosis in the United States were reported in 2023 in New York3,6; a fourth confirmed case was reported in 2024 in Pennsylvania.7 Post hoc laboratory testing of fungal isolates in New York in 2022 and 2023 identified an additional 11 cases.8 We present a case of extensive multidrug-resistant tinea caused by T indotineae in a man in California.
An otherwise healthy 65-year-old man who had traveled to Europe in the past 3 months presented to his primary care physician with a widespread pruritic rash (Figure 1). He was treated with 2 weeks of oral terbinafine 250 mg/d and topical medicines, including clotrimazole cream 1%, fluocinonide ointment 0.05%, and clobetasol ointment 0.05% without improvement. Subsequently, 2 weeks of oral griseofulvin microsize 500 mg/d also proved ineffective. An antibody test was negative for HIV. His hemoglobin A1c was 6.2% (reference range, ≤5.6%). The patient was referred to dermatology.
Erythematous plaques—many scaly throughout and some annular with central clearing—were present on the arms, legs, and torso as well as in the groin. Honey crust was present on some plaques on the leg. A potassium hydroxide preparation showed abundant fungal hyphae. Material for fungal and bacterial cultures was collected. The patient was treated again with oral terbinafine 250 mg/d, an oral prednisone taper starting at 60 mg/d for a presumed id reaction, and various oral antihistamines for pruritus; all were ineffective. A bacterial culture showed only mixed skin flora. Oral fluconazole 200 mg/d was prescribed. A skin biopsy specimen showed compact orthokeratosis and parakeratosis of the stratum corneum with few neutrophils and focal pustule formation (Figure 2). Superficial perivascular inflammation, including lymphocytes, histiocytes, and few neutrophils, was present. A periodic acid–Schiff stain showed fungal hyphae in the stratum corneum and a hair follicle (Figure 3). After approximately 2 weeks, mold was identified in the fungal culture. Approximately 2 weeks thereafter, the organism was reported as Trichophyton species.
The rash did not improve; resistance to terbinafine, griseofulvin, and fluconazole was suspected clinically. The fungal isolate was sent to a reference laboratory (University of Texas Health Science Center, San Antonio). Meanwhile, oral itraconazole 200 mg twice daily and ketoconazole cream 2% were prescribed; the rash began to improve. A serum itraconazole trough level obtained 4 days after treatment initiation was 0.5 μg/mL (reference range, ≥0.6 μg/mL). The evening itraconazole dose was increased to 300 mg; a subsequent trough level was 0.8 μg/mL.
Approximately 1 month after the fungal isolate was sent to the reference laboratory, T indotineae was confirmed based on polymerase chain reaction (PCR) testing of internal transcribed spacer region sequences. Minimum inhibitory concentrations (MICs) obtained through antifungal susceptibility testing (AFST) were reported for fluconazole (8 μg/mL), griseofulvin (2 μg/mL), itraconazole (≤0.03 μg/mL), posaconazole (≤0.03 μg/mL), terbinafine (≥2 μg/mL), and voriconazole (0.125 μg/mL).
Approximately 7 weeks after itraconazole and ketoconazole were started, the rash had completely resolved. Nearly 8 months later (at the time this article was written), the rash had not recurred.
We report a unique case of T indotineae in a patient residing in California. Post hoc laboratory testing of dermatophyte isolates sent to the University of Texas reference laboratory identified terbinafine-resistant T indotineae specimens from the United States and Canada dating to 2017; clinical characteristics of patients from whom those isolates were obtained were unavailable.9
Trichophyton indotineae dermatophytosis typically is more extensive, inflamed, and pruritic, as well as likely more contagious, than tinea caused by other dermatophytes.5 Previously called Trichophyton mentagrophytes genotype VIII when first isolated in 2017, the pathogen was renamed T indotineae in 2020 after important genetic differences were discovered between it and other T mentagrophytes species.5 The emergence of T indotineae has been attributed to concomitant use of topical steroids and antifungals,5,10 inappropriate prescribing of antifungals,5 and nonadherence to antifungal treatment.5
Likely risk factors for T indotineae infection include suboptimal hygiene, overcrowded conditions, hot and humid environments, and tight-fitting synthetic clothing.4 Transmission from family members appears common,5 especially when fomites are shared.4 A case reported in Pennsylvania likely was acquired through sexual contact.7 Travel to South Asia has been associated with acquisition of T indotineae infection,3,5-7 though our patient and some others had not traveled there.3,8 It is not clear whether immunosuppression and diabetes mellitus are associated with T indotineae infection.4,5,8Trichophyton indotineae also can affect animals,11 though zoonotic transmission has not been reported.4
Not all T indotineae isolates are resistant to one or more antifungals; furthermore, antifungal resistance in other dermatophyte species has been reported.5 Terbinafine resistance in T indotineae is conferred by mutations in the gene encoding squalene epoxidase, which helps synthesize ergosterol—a component of the cell membrane in fungi.2,4,5,12 Although clinical cut-points for MIC obtained by AFST are not well established, T indotineae MICs for terbinafine of 0.5 μg/mL or more correlate with resistance.9 Resistance to azoles has been linked to overexpression of transporter genes, which increase azole efflux from cells, as well as to mutations in the gene encoding lanosterol 14α demethylase.4,12,13
Potassium hydroxide preparations and fungal cultures cannot differentiate T indotineae from other dermatophytes that typically cause tinea.5,14 Histopathologic findings in our case were no different than those of non–T indotineae dermatophytes. Only molecular testing using PCR assays to sequence internal transcribed spacer genes can confirm T indotineae infection. However, PCR assays and AFST are not available in many US laboratories.5 Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry has shown promise in distinguishing T indotineae from other dermatophytes, though its clinical use is limited and it cannot assess terbinafine sensitivity.15,16 Clinicians in the United States who want to test specimens from cases suspicious for T indotineae infection should contact their local or state health department or the Centers for Disease Control and Prevention for assistance.3,5
Systemic treatment typically is necessary for T indotineae infection.5 Combinations of oral and topical azoles have been used, as well as topical ciclopirox, amorolfine (not available in the United States), and luliconazole.1,5,17-21
Itraconazole has emerged as the treatment of choice for T indotineae tinea, typically at 200 mg/d and often for courses of more than 3 months.5 Testing for serum itraconazole trough levels, as done for our patient, typically is not recommended. Clinicians should counsel patients to take itraconazole with high-fat foods and an acidic beverage to increase bioavailability.5 Potential adverse effects of itraconazole include heart failure and numerous drug-drug interactions.5,22 Patients with T indotineae dermatophytosis should avoid sharing personal belongings and having skin-to-skin contact of affected areas with others.4
Dermatologists who suspect T indotineae infection should work with public health agencies that can assist with testing and undertake infection surveillance, prevention, and control.5,23 Challenges to diagnosing and managing T indotineae infection include lack of awareness among dermatology providers, the need for specialized laboratory testing to confirm infection, lack of established clinical cut-points for MICs from AFST, the need for longer duration of treatment vs what is needed for typical tinea, and potential challenges with insurance coverage for testing and treatment. Empiric treatment with itraconazole should be considered when terbinafine-resistant dermatophytosis is suspected or when terbinafine-resistant T indotineae infection is confirmed.
Acknowledgments—Jeremy Gold, MD; Dallas J. Smith, PharmD; and Shawn Lockhart, PhD, all of the Centers for Disease Control and Prevention, Mycotic Diseases Branch (Atlanta, Georgia), provided helpful comments to the authors in preparing the manuscript of this article.
To the Editor:
Historically, commonly available antifungal medications have been effective for treating dermatophytosis (tinea). However, recent tinea outbreaks caused by Trichophyton indotineae—a dermatophyte often resistant to terbinafine and sometimes to other antifungals—have been reported in South Asia, Europe, the Middle East, Southeast Asia, and Australia.1-5
Three confirmed cases of T indotineae dermatophytosis in the United States were reported in 2023 in New York3,6; a fourth confirmed case was reported in 2024 in Pennsylvania.7 Post hoc laboratory testing of fungal isolates in New York in 2022 and 2023 identified an additional 11 cases.8 We present a case of extensive multidrug-resistant tinea caused by T indotineae in a man in California.
An otherwise healthy 65-year-old man who had traveled to Europe in the past 3 months presented to his primary care physician with a widespread pruritic rash (Figure 1). He was treated with 2 weeks of oral terbinafine 250 mg/d and topical medicines, including clotrimazole cream 1%, fluocinonide ointment 0.05%, and clobetasol ointment 0.05% without improvement. Subsequently, 2 weeks of oral griseofulvin microsize 500 mg/d also proved ineffective. An antibody test was negative for HIV. His hemoglobin A1c was 6.2% (reference range, ≤5.6%). The patient was referred to dermatology.
Erythematous plaques—many scaly throughout and some annular with central clearing—were present on the arms, legs, and torso as well as in the groin. Honey crust was present on some plaques on the leg. A potassium hydroxide preparation showed abundant fungal hyphae. Material for fungal and bacterial cultures was collected. The patient was treated again with oral terbinafine 250 mg/d, an oral prednisone taper starting at 60 mg/d for a presumed id reaction, and various oral antihistamines for pruritus; all were ineffective. A bacterial culture showed only mixed skin flora. Oral fluconazole 200 mg/d was prescribed. A skin biopsy specimen showed compact orthokeratosis and parakeratosis of the stratum corneum with few neutrophils and focal pustule formation (Figure 2). Superficial perivascular inflammation, including lymphocytes, histiocytes, and few neutrophils, was present. A periodic acid–Schiff stain showed fungal hyphae in the stratum corneum and a hair follicle (Figure 3). After approximately 2 weeks, mold was identified in the fungal culture. Approximately 2 weeks thereafter, the organism was reported as Trichophyton species.
The rash did not improve; resistance to terbinafine, griseofulvin, and fluconazole was suspected clinically. The fungal isolate was sent to a reference laboratory (University of Texas Health Science Center, San Antonio). Meanwhile, oral itraconazole 200 mg twice daily and ketoconazole cream 2% were prescribed; the rash began to improve. A serum itraconazole trough level obtained 4 days after treatment initiation was 0.5 μg/mL (reference range, ≥0.6 μg/mL). The evening itraconazole dose was increased to 300 mg; a subsequent trough level was 0.8 μg/mL.
Approximately 1 month after the fungal isolate was sent to the reference laboratory, T indotineae was confirmed based on polymerase chain reaction (PCR) testing of internal transcribed spacer region sequences. Minimum inhibitory concentrations (MICs) obtained through antifungal susceptibility testing (AFST) were reported for fluconazole (8 μg/mL), griseofulvin (2 μg/mL), itraconazole (≤0.03 μg/mL), posaconazole (≤0.03 μg/mL), terbinafine (≥2 μg/mL), and voriconazole (0.125 μg/mL).
Approximately 7 weeks after itraconazole and ketoconazole were started, the rash had completely resolved. Nearly 8 months later (at the time this article was written), the rash had not recurred.
We report a unique case of T indotineae in a patient residing in California. Post hoc laboratory testing of dermatophyte isolates sent to the University of Texas reference laboratory identified terbinafine-resistant T indotineae specimens from the United States and Canada dating to 2017; clinical characteristics of patients from whom those isolates were obtained were unavailable.9
Trichophyton indotineae dermatophytosis typically is more extensive, inflamed, and pruritic, as well as likely more contagious, than tinea caused by other dermatophytes.5 Previously called Trichophyton mentagrophytes genotype VIII when first isolated in 2017, the pathogen was renamed T indotineae in 2020 after important genetic differences were discovered between it and other T mentagrophytes species.5 The emergence of T indotineae has been attributed to concomitant use of topical steroids and antifungals,5,10 inappropriate prescribing of antifungals,5 and nonadherence to antifungal treatment.5
Likely risk factors for T indotineae infection include suboptimal hygiene, overcrowded conditions, hot and humid environments, and tight-fitting synthetic clothing.4 Transmission from family members appears common,5 especially when fomites are shared.4 A case reported in Pennsylvania likely was acquired through sexual contact.7 Travel to South Asia has been associated with acquisition of T indotineae infection,3,5-7 though our patient and some others had not traveled there.3,8 It is not clear whether immunosuppression and diabetes mellitus are associated with T indotineae infection.4,5,8Trichophyton indotineae also can affect animals,11 though zoonotic transmission has not been reported.4
Not all T indotineae isolates are resistant to one or more antifungals; furthermore, antifungal resistance in other dermatophyte species has been reported.5 Terbinafine resistance in T indotineae is conferred by mutations in the gene encoding squalene epoxidase, which helps synthesize ergosterol—a component of the cell membrane in fungi.2,4,5,12 Although clinical cut-points for MIC obtained by AFST are not well established, T indotineae MICs for terbinafine of 0.5 μg/mL or more correlate with resistance.9 Resistance to azoles has been linked to overexpression of transporter genes, which increase azole efflux from cells, as well as to mutations in the gene encoding lanosterol 14α demethylase.4,12,13
Potassium hydroxide preparations and fungal cultures cannot differentiate T indotineae from other dermatophytes that typically cause tinea.5,14 Histopathologic findings in our case were no different than those of non–T indotineae dermatophytes. Only molecular testing using PCR assays to sequence internal transcribed spacer genes can confirm T indotineae infection. However, PCR assays and AFST are not available in many US laboratories.5 Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry has shown promise in distinguishing T indotineae from other dermatophytes, though its clinical use is limited and it cannot assess terbinafine sensitivity.15,16 Clinicians in the United States who want to test specimens from cases suspicious for T indotineae infection should contact their local or state health department or the Centers for Disease Control and Prevention for assistance.3,5
Systemic treatment typically is necessary for T indotineae infection.5 Combinations of oral and topical azoles have been used, as well as topical ciclopirox, amorolfine (not available in the United States), and luliconazole.1,5,17-21
Itraconazole has emerged as the treatment of choice for T indotineae tinea, typically at 200 mg/d and often for courses of more than 3 months.5 Testing for serum itraconazole trough levels, as done for our patient, typically is not recommended. Clinicians should counsel patients to take itraconazole with high-fat foods and an acidic beverage to increase bioavailability.5 Potential adverse effects of itraconazole include heart failure and numerous drug-drug interactions.5,22 Patients with T indotineae dermatophytosis should avoid sharing personal belongings and having skin-to-skin contact of affected areas with others.4
Dermatologists who suspect T indotineae infection should work with public health agencies that can assist with testing and undertake infection surveillance, prevention, and control.5,23 Challenges to diagnosing and managing T indotineae infection include lack of awareness among dermatology providers, the need for specialized laboratory testing to confirm infection, lack of established clinical cut-points for MICs from AFST, the need for longer duration of treatment vs what is needed for typical tinea, and potential challenges with insurance coverage for testing and treatment. Empiric treatment with itraconazole should be considered when terbinafine-resistant dermatophytosis is suspected or when terbinafine-resistant T indotineae infection is confirmed.
Acknowledgments—Jeremy Gold, MD; Dallas J. Smith, PharmD; and Shawn Lockhart, PhD, all of the Centers for Disease Control and Prevention, Mycotic Diseases Branch (Atlanta, Georgia), provided helpful comments to the authors in preparing the manuscript of this article.
- Uhrlaß S, Verma SB, Gräser Y, al. Trichophyton indotineae—an emerging pathogen causing recalcitrant dermatophytoses in India and worldwide—a multidimensional perspective. J Fungi (Basel). 2022;8:757. doi:10.3390/jof8070757
- Jabet A, Brun S, Normand A-C, et al. Extensive dermatophytosis caused by terbinafine-resistant Trichophyton indotineae, France. Emerg Infect Dis. 2022;28:229-233. doi:10.3201/eid2801.210883
- 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:10.15585/mmwr.mm7219a4
- Jabet A, Normand A-C, Brun S, et al. Trichophyton indotineae, from epidemiology to therapeutic. J Mycol Med. 2023;33:101383. doi:10.1016/j.mycmed.2023.101383
- Hill RC, Caplan AS, Elewski B, et al. Expert panel review of skin and hair dermatophytoses in an era of antifungal resistance. Am J Clin Dermatol. 2024;25:359-389. doi:10.1007/s40257-024-00848-1
- Caplan AS, Zakhem GA, Pomeranz MK. Trichophyton mentagrophytes internal transcribed spacer genotype VIII. JAMA Dermatol. 2023;159:1130. doi:10.1001/jamadermatol.2023.2645
- Spivack S, Gold JAW, Lockhart SR, et al. Potential sexual transmission of antifungal-resistant Trichophyton indotineae. Emerg Infect Dis. 2024;30:807-809. doi:10.3201/eid3004.240115
- Caplan AS, Todd GC, Zhu Y, et al. Clinical course, antifungal susceptibility, and genomic sequencing of Trichophyton indotineae. JAMA Dermatol. Published online May 15, 2024. doi:10.1001/jamadermatol.2024.1126
- Cañete-Gibas CF, Mele J, Patterson HP, et al. Terbinafine-resistant dermatophytes and the presence of Trichophyton indotineae in North America. J Clin Microbiol. 2023;61:e0056223. doi:10.1128/jcm.00562-23
- Gupta AK, Venkataraman M, Hall DC, et al. The emergence of Trichophyton indotineae: implications for clinical practice. Int J Dermatol. 2023;62:857-861.
- Oladzad V, Nasrollahi Omran A, Haghani I, et al. Multi-drug resistance Trichophyton indotineae in a stray dog. Res Vet Sci. 2024;166:105105. doi:10.1016/j.rvsc.2023.105105
- Martinez-Rossi NM, Bitencourt TA, Peres NTA, et al. Dermatophyte resistance to antifungal drugs: mechanisms and prospectus. Front Microbiol. 2018;9:1108. doi:10.3389/fmicb.2018.01108
- Sacheli R, Hayette MP. Antifungal resistance in dermatophytes: genetic considerations, clinical presentations and alternative therapies. J Fungi (Basel). 2021;711:983. doi:10.3390/jof7110983
- Gupta AK, Cooper EA. Dermatophytosis (tinea) and other superficial fungal infections. In: Hospenthal DR, Rinaldi MG, eds. Diagnosis and Treatment of Human Mycoses. Humana Press; 2008:355-381.
- Normand A-C, Moreno-Sabater A, Jabet A, et al. MALDI-TOF mass spectrometry online identification of Trichophyton indotineae using the MSI-2 application. J Fungi (Basel). 2022;8:1103. doi:10.3390/jof8101103
- De Paepe R, Normand A-C, Uhrlaß S, et al. Resistance profile, terbinafine resistance screening and MALDI-TOF MS identification of the emerging pathogen Trichophyton indotineae. Mycopathologia. 2024;189:29. doi:10.1007/s11046-024-00835-4
- Rajagopalan M, Inamadar A, Mittal A, et al. Expert consensus on the management of dermatophytosis in India (ECTODERM India). BMC Dermatol. 2018;18:6. doi:10.1186/s12895-018-0073-1
- Verma SB, Panda S, Nenoff P, et al. The unprecedented epidemic-like scenario of dermatophytosis in India: III. Antifungal resistance and treatment options. Indian J Dermatol Venereol Leprol. 2021;87:468-482. doi:10.25259/IJDVL_303_20
- Shaw D, Singh S, Dogra S, et al. MIC and upper limit of wild-type distribution for 13 antifungal agents against a Trichophyton mentagrophytes–Trichophyton interdigitale complex of Indian origin. Antimicrob Agents Chemother. 2020;64:E01964-19. doi:10.1128/AAC.01964-19
- Burmester A, Hipler U-C, Uhrlaß S, et al. Indian Trichophyton mentagrophytes squalene epoxidase erg1 double mutants show high proportion of combined fluconazole and terbinafine resistance. Mycoses. 2020;63:1175-1180. doi:10.1111/myc.13150
- Khurana A, Agarwal A, Agrawal D, et al. Effect of different itraconazole dosing regimens on cure rates, treatment duration, safety, and relapse rates in adult patients with tinea corporis/cruris: a randomized clinical trial. JAMA Dermatol. 2022;158:1269-1278. doi:10.1001/jamadermatol.2022.3745
- Itraconazole capsule. DailyMed [Internet]. Updated June 3, 2024. Accessed June 19, 2024. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=2ab38a8a-3708-4b97-9f7f-8e554a15348d
- Bui TS, Katz KA. Resistant Trichophyton indotineae dermatophytosis—an emerging pandemic, now in the US. JAMA Dermatol. Published online May 15, 2024. doi:10.1001/jamadermatol.2024.1125
- Uhrlaß S, Verma SB, Gräser Y, al. Trichophyton indotineae—an emerging pathogen causing recalcitrant dermatophytoses in India and worldwide—a multidimensional perspective. J Fungi (Basel). 2022;8:757. doi:10.3390/jof8070757
- Jabet A, Brun S, Normand A-C, et al. Extensive dermatophytosis caused by terbinafine-resistant Trichophyton indotineae, France. Emerg Infect Dis. 2022;28:229-233. doi:10.3201/eid2801.210883
- 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:10.15585/mmwr.mm7219a4
- Jabet A, Normand A-C, Brun S, et al. Trichophyton indotineae, from epidemiology to therapeutic. J Mycol Med. 2023;33:101383. doi:10.1016/j.mycmed.2023.101383
- Hill RC, Caplan AS, Elewski B, et al. Expert panel review of skin and hair dermatophytoses in an era of antifungal resistance. Am J Clin Dermatol. 2024;25:359-389. doi:10.1007/s40257-024-00848-1
- Caplan AS, Zakhem GA, Pomeranz MK. Trichophyton mentagrophytes internal transcribed spacer genotype VIII. JAMA Dermatol. 2023;159:1130. doi:10.1001/jamadermatol.2023.2645
- Spivack S, Gold JAW, Lockhart SR, et al. Potential sexual transmission of antifungal-resistant Trichophyton indotineae. Emerg Infect Dis. 2024;30:807-809. doi:10.3201/eid3004.240115
- Caplan AS, Todd GC, Zhu Y, et al. Clinical course, antifungal susceptibility, and genomic sequencing of Trichophyton indotineae. JAMA Dermatol. Published online May 15, 2024. doi:10.1001/jamadermatol.2024.1126
- Cañete-Gibas CF, Mele J, Patterson HP, et al. Terbinafine-resistant dermatophytes and the presence of Trichophyton indotineae in North America. J Clin Microbiol. 2023;61:e0056223. doi:10.1128/jcm.00562-23
- Gupta AK, Venkataraman M, Hall DC, et al. The emergence of Trichophyton indotineae: implications for clinical practice. Int J Dermatol. 2023;62:857-861.
- Oladzad V, Nasrollahi Omran A, Haghani I, et al. Multi-drug resistance Trichophyton indotineae in a stray dog. Res Vet Sci. 2024;166:105105. doi:10.1016/j.rvsc.2023.105105
- Martinez-Rossi NM, Bitencourt TA, Peres NTA, et al. Dermatophyte resistance to antifungal drugs: mechanisms and prospectus. Front Microbiol. 2018;9:1108. doi:10.3389/fmicb.2018.01108
- Sacheli R, Hayette MP. Antifungal resistance in dermatophytes: genetic considerations, clinical presentations and alternative therapies. J Fungi (Basel). 2021;711:983. doi:10.3390/jof7110983
- Gupta AK, Cooper EA. Dermatophytosis (tinea) and other superficial fungal infections. In: Hospenthal DR, Rinaldi MG, eds. Diagnosis and Treatment of Human Mycoses. Humana Press; 2008:355-381.
- Normand A-C, Moreno-Sabater A, Jabet A, et al. MALDI-TOF mass spectrometry online identification of Trichophyton indotineae using the MSI-2 application. J Fungi (Basel). 2022;8:1103. doi:10.3390/jof8101103
- De Paepe R, Normand A-C, Uhrlaß S, et al. Resistance profile, terbinafine resistance screening and MALDI-TOF MS identification of the emerging pathogen Trichophyton indotineae. Mycopathologia. 2024;189:29. doi:10.1007/s11046-024-00835-4
- Rajagopalan M, Inamadar A, Mittal A, et al. Expert consensus on the management of dermatophytosis in India (ECTODERM India). BMC Dermatol. 2018;18:6. doi:10.1186/s12895-018-0073-1
- Verma SB, Panda S, Nenoff P, et al. The unprecedented epidemic-like scenario of dermatophytosis in India: III. Antifungal resistance and treatment options. Indian J Dermatol Venereol Leprol. 2021;87:468-482. doi:10.25259/IJDVL_303_20
- Shaw D, Singh S, Dogra S, et al. MIC and upper limit of wild-type distribution for 13 antifungal agents against a Trichophyton mentagrophytes–Trichophyton interdigitale complex of Indian origin. Antimicrob Agents Chemother. 2020;64:E01964-19. doi:10.1128/AAC.01964-19
- Burmester A, Hipler U-C, Uhrlaß S, et al. Indian Trichophyton mentagrophytes squalene epoxidase erg1 double mutants show high proportion of combined fluconazole and terbinafine resistance. Mycoses. 2020;63:1175-1180. doi:10.1111/myc.13150
- Khurana A, Agarwal A, Agrawal D, et al. Effect of different itraconazole dosing regimens on cure rates, treatment duration, safety, and relapse rates in adult patients with tinea corporis/cruris: a randomized clinical trial. JAMA Dermatol. 2022;158:1269-1278. doi:10.1001/jamadermatol.2022.3745
- Itraconazole capsule. DailyMed [Internet]. Updated June 3, 2024. Accessed June 19, 2024. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=2ab38a8a-3708-4b97-9f7f-8e554a15348d
- Bui TS, Katz KA. Resistant Trichophyton indotineae dermatophytosis—an emerging pandemic, now in the US. JAMA Dermatol. Published online May 15, 2024. doi:10.1001/jamadermatol.2024.1125
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<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>Bui trichophyton</fileName> <TBEID>0C02F977.SIG</TBEID> <TBUniqueIdentifier>NJ_0C02F977</TBUniqueIdentifier> <newsOrJournal>Journal</newsOrJournal> <publisherName>Frontline Medical Communications Inc.</publisherName> <storyname>Case Letter</storyname> <articleType>1</articleType> <TBLocation>Copyfitting-CT</TBLocation> <QCDate/> <firstPublished>20240625T155242</firstPublished> <LastPublished>20240625T155243</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20240625T155242</CMSDate> <articleSource/> <facebookInfo/> <meetingNumber/> <byline>Toan S. Bui, BS</byline> <bylineText>Toan S. Bui, BS; Jessica B. Chan, MD; Kenneth A. Katz, MD, MSc, MSCE</bylineText> <bylineFull>Toan S. Bui, BS</bylineFull> <bylineTitleText/> <USOrGlobal/> <wireDocType/> <newsDocType/> <journalDocType/> <linkLabel/> <pageRange>E20-E23</pageRange> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:"> <name/> <rightsInfo> <copyrightHolder> <name/> </copyrightHolder> <copyrightNotice/> </rightsInfo> </provider> <abstract/> <metaDescription>To the Editor:Historically, commonly available antifungal medications have been effective for treating dermatophytosis (tinea). However, recent tinea outbreaks </metaDescription> <articlePDF/> <teaserImage/> <title>Extensive Multidrug-Resistant Dermatophytosis From Trichophyton indotineae</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear>2024</pubPubdateYear> <pubPubdateMonth>June</pubPubdateMonth> <pubPubdateDay/> <pubVolume>113</pubVolume> <pubNumber>6</pubNumber> <wireChannels/> <primaryCMSID/> <CMSIDs> <CMSID>2307</CMSID> <CMSID>2159</CMSID> </CMSIDs> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>CT</publicationCode> <pubIssueName>June 2024</pubIssueName> <pubArticleType>Departments | 2159</pubArticleType> <pubTopics/> <pubCategories/> <pubSections> <pubSection>Case Letter | 2307<pubSubsection/></pubSection> </pubSections> <journalTitle>Cutis</journalTitle> <journalFullTitle>Cutis</journalFullTitle> <copyrightStatement>Copyright 2015 Frontline Medical Communications Inc., Parsippany, NJ, USA. All rights reserved.</copyrightStatement> </publicationData> </publications_g> <publications> <term canonical="true">12</term> </publications> <sections> <term canonical="true">44</term> </sections> <topics> <term canonical="true">234</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Extensive Multidrug-Resistant Dermatophytosis From Trichophyton indotineae</title> <deck/> </itemMeta> <itemContent> <p>To the Editor:<br/><br/>Historically, commonly available antifungal medications have been effective for treating dermatophytosis (tinea). However, recent tinea outbreaks caused by <i>Trichophyton indotineae</i>—a dermatophyte often resistant to terbinafine and sometimes to other antifungals—have been reported in South Asia, Europe, the Middle East, Southeast Asia, and Australia.<sup>1-5</sup> </p> <p>Three confirmed cases of <i>T indotineae</i> dermatophytosis in the United States were reported in 2023 in New York<sup>3,6</sup>; a fourth confirmed case was reported in 2024 in Pennsylvania.<sup>7</sup> Post hoc laboratory testing of fungal isolates in New York in 2022 and 2023 identified an additional 11 cases.<sup>8</sup> We present a case of extensive multidrug-resistant tinea caused by <span class="Iitalic">T indotineae</span> in a man in California.<br/><br/>An otherwise healthy 65-year-old man who had traveled to Europe in the past 3 months presented to his primary care physician with a widespread pruritic rash (Figure 1). He was treated with 2 weeks of oral terbinafine 250 mg/d and topical medicines, including clotrimazole cream 1%, fluocinonide ointment 0.05%, and clobetasol ointment 0.05% without improvement. Subsequently, 2 weeks of oral griseofulvin microsize 500 mg/d also proved ineffective. An antibody test was negative for HIV. His hemoglobin A<sub>1c</sub> was 6.2% (reference range, ≤5.6%). The patient was referred to dermatology.<br/><br/>Erythematous plaques—many scaly throughout and some annular with central clearing—were present on the arms, legs, and torso as well as in the groin. Honey crust was present on some plaques on the leg. A potassium hydroxide preparation showed abundant fungal hyphae. Material for fungal and bacterial cultures was collected. The patient was treated again with oral terbinafine 250 mg/d, an oral prednisone taper starting at 60 mg/d for a presumed id reaction, and various oral antihistamines for pruritus; all were ineffective. A bacterial culture showed only mixed skin flora. Oral fluconazole 200 mg/d was prescribed. A skin biopsy specimen showed compact orthokeratosis and parakeratosis of the stratum corneum with few neutrophils and focal pustule formation (Figure 2). Superficial perivascular inflammation, including lymphocytes, histiocytes, and few neutrophils, was present. A periodic acid–Schiff stain showed fungal hyphae in the stratum corneum and a hair follicle (Figure 3). After approximately 2 weeks, mold was identified in the fungal culture. Approximately 2 weeks thereafter, the organism was reported as <span class="Iitalic">Trichophyton</span><i> </i>species. <br/><br/>The rash did not improve; resistance to terbinafine, griseofulvin, and fluconazole was suspected clinically. The fungal isolate was sent to a reference laboratory (University of Texas Health Science Center, San Antonio). Meanwhile, oral itraconazole 200 mg twice daily and ketoconazole cream 2% were prescribed; the rash began to improve. A serum itraconazole trough level obtained 4 days after treatment initiation was 0.5 <span class="body">μ</span>g/mL (reference range, ≥0.6 <span class="body">μ</span>g/mL). The evening itraconazole dose was increased to 300 mg; a subsequent trough level was 0.8<span class="body"> </span><span class="body">μ</span>g/mL. <br/><br/>Approximately 1 month after the fungal isolate was sent to the reference laboratory, <span class="Iitalic">T indotineae</span><i> </i>was confirmed based on polymerase chain reaction (PCR) testing of internal transcribed spacer region sequences. Minimum inhibitory concentrations (MICs) obtained through antifungal susceptibility testing (AFST) were reported for fluconazole (8 <span class="body">μ</span>g/mL), griseofulvin (2 <span class="body">μ</span>g/mL), itraconazole (≤0.03 <span class="body">μ</span>g/mL), posaconazole (≤0.03 <span class="body">μ</span>g/mL), terbinafine (≥2 <span class="body">μ</span>g/mL), and voriconazole (0.125 <span class="body">μ</span>g/mL). <br/><br/>Approximately 7 weeks after itraconazole and ketoconazole were started, the rash had completely resolved. Nearly 8 months later (at the time this article was written), the rash had not recurred. <br/><br/>We report a unique case of <span class="Iitalic">T indotineae</span> in a patient residing in California. Post hoc laboratory testing of dermatophyte isolates sent to the University of Texas reference laboratory identified terbinafine-resistant <span class="Iitalic">T indotineae</span> specimens from the United States and Canada dating to 2017; clinical characteristics of patients from whom those isolates were obtained were unavailable.<sup>9<br/><br/></sup><span class="Iitalic">Trichophyton indotineae</span> dermatophytosis typically is more extensive, inflamed, and pruritic, as well as likely more contagious, than tinea caused by other dermatophytes.<sup>5</sup> Previously called <span class="Iitalic">Trichophyton mentagrophytes </span>genotype VIII when first isolated in 2017, the pathogen was renamed <span class="Iitalic">T indotineae</span> in 2020 after important genetic differences were discovered between it and other <span class="Iitalic">T mentagrophytes</span> species.<sup>5</sup> The emergence of <span class="Iitalic">T indotineae </span>has<i> </i>been attributed to concomitant use of topical steroids and antifungals,<sup>5,10</sup> inappropriate prescribing of antifungals,<sup>5</sup> and nonadherence to antifungal treatment.<sup>5</sup> <br/><br/>Likely risk factors for <span class="Iitalic">T indotineae</span> infection include suboptimal hygiene, overcrowded conditions, hot and humid environments, and tight-fitting synthetic clothing.<sup>4</sup> Transmission from family members appears common,<sup>5</sup> especially when fomites are shared.<sup>4</sup> A case reported in Pennsylvania likely was acquired through sexual contact.<sup>7</sup> Travel to South Asia has been associated with acquisition of <span class="Iitalic">T indotineae</span> infection,<sup>3,5-7</sup> though our patient and some others had not traveled there.<sup>3,8</sup> It is not clear whether immunosuppression and diabetes mellitus are associated with<span class="Iitalic"> T indotineae </span>infection.<sup>4,5,8</sup> <span class="Iitalic">Trichophyton indotineae</span> also can affect animals,<sup>11</sup> though zoonotic transmission has not been reported.<sup>4<br/><br/></sup>Not all<span class="Iitalic"> T indotineae</span> isolates are resistant to one or more antifungals; furthermore, antifungal resistance in other dermatophyte species has been reported.<sup>5</sup> Terbinafine resistance in <span class="Iitalic">T indotineae</span> is conferred by mutations in the gene encoding squalene epoxidase, which helps synthesize ergosterol—a component of the cell membrane in fungi.<sup>2,4,5,12</sup> Although clinical cut-points for MIC obtained by AFST are not well established, <span class="Iitalic">T indotineae</span> MICs for terbinafine of 0.5 <span class="body">μ</span>g/mL or more correlate with resistance.<sup>9</sup> Resistance to azoles has been linked to overexpression of transporter genes, which increase azole efflux from cells, as well as to mutations in the gene encoding lanosterol 14<span class="body">α</span> demethylase.<sup>4,12,13</sup> <br/><br/>Potassium hydroxide preparations and fungal cultures cannot differentiate <span class="Iitalic">T indotineae</span> from other dermatophytes that typically cause tinea.<sup>5,14</sup> Histopathologic findings in our case were no different than those of non–<span class="Iitalic">T indotineae</span> dermatophytes. Only molecular testing using PCR assays to sequence internal transcribed spacer genes can confirm <span class="Iitalic">T indotineae</span> infection. However, PCR assays and AFST are not available in many US laboratories.<sup>5</sup> Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry has shown promise in distinguishing <span class="Iitalic">T indotineae</span> from other dermatophytes, though its clinical use is limited and it cannot assess terbinafine sensitivity.<sup>15,16</sup> Clinicians in the United States who want to test specimens from cases suspicious for <span class="Iitalic">T indotineae</span> infection should contact their local or state health department or the Centers for Disease Control and Prevention for assistance.<sup>3,5</sup> <br/><br/>Systemic treatment typically is necessary for <span class="Iitalic">T indotineae</span> infection.<sup>5</sup> Combinations of oral and topical azoles have been used, as well as topical ciclopirox, amorolfine (not available in the United States), and luliconazole.<sup>1,5,17-21 <br/><br/></sup>Itraconazole has emerged as the treatment of choice for<span class="Iitalic"> T indotineae</span> tinea, typically at 200 mg/d and often for courses of more than 3 months.<sup>5</sup> Testing for serum itraconazole trough levels, as done for our patient, typically is not recommended. Clinicians should counsel patients to take itraconazole with high-fat foods and an acidic beverage to increase bioavailability.<sup>5</sup> Potential adverse effects of itraconazole include heart failure and numerous drug-drug interactions.<sup>5,22</sup> Patients with <span class="Iitalic">T indotineae</span> dermatophytosis should avoid sharing personal belongings and having skin-to-skin contact of affected areas with others.<sup>4 <br/><br/></sup>Dermatologists who suspect <span class="Iitalic">T indotineae</span> infection should work with public health agencies that can assist with testing and undertake infection surveillance, prevention, and control.<sup>5,23</sup> Challenges to diagnosing and managing <span class="Iitalic">T indotineae</span> infection include lack of awareness among dermatology providers, the need for specialized laboratory testing to confirm infection, lack of established clinical cut-points for MICs from AFST, the need for longer duration of treatment vs what is needed for typical tinea, and potential challenges with insurance coverage for testing and treatment. Empiric treatment with itraconazole should be considered when terbinafine-resistant dermatophytosis is suspected or when terbinafine-resistant <span class="Iitalic">T indotineae</span> infection is confirmed. </p> <p><i>Acknowledgments</i>—Jeremy Gold, MD; Dallas J. Smith, PharmD; and Shawn Lockhart, PhD, all of the Centers for Disease Control and Prevention, Mycotic Diseases Branch (Atlanta, Georgia), provided helpful comments to the authors in preparing the manuscript of this article. </p> <h2>REFERENCES</h2> <p class="reference"> 1. Uhrlaß S, Verma SB, Gräser Y, al. <i>Trichophyton indotineae</i>—an emerging pathogen causing recalcitrant dermatophytoses in India and worldwide—a multidimensional perspective. <i>J Fungi (Basel)</i>. 2022;8:757. <span class="citation-doi">doi:10.3390/jof8070757<br/><br/></span> 2. Jabet A, Brun S, Normand A-C, et al. Extensive dermatophytosis caused by terbinafine-resistant <i>Trichophyton indotineae</i>, France. <i>Emerg Infect Dis</i>. 2022;28:229-233. <span class="citation-doi">doi:10.3201/eid2801.210883<br/><br/></span> 3. Caplan AS, Chaturvedi S, Zhu Y, et al. Notes from the field. First reported U.S. cases of tinea caused by <i>Trichophyton indotineae</i>—New York City, December 2021-March 2023. <i>MMWR Morb Mortal Wkly Rep</i>. 2023;72:536-537. doi:10.15585/mmwr.mm7219a4 <br/><br/> 4. Jabet A, Normand A-C, Brun S, et al. <i>Trichophyton indotineae</i>, from epidemiology to therapeutic. <i>J Mycol Med</i>. 2023;33:101383. doi:10.1016/j.mycmed.2023.101383<br/><br/> 5. Hill RC, Caplan AS, Elewski B, et al. Expert panel review of skin and hair dermatophytoses in an era of antifungal resistance. <i>Am J Clin Dermatol</i>. 2024;25:359-389. <span class="citation-doi">doi:10.1007/s40257-024-00848-1<br/><br/></span> 6. Caplan AS, Zakhem GA, Pomeranz MK. <i>Trichophyton mentagrophytes</i> internal transcribed spacer genotype VIII. <i>JAMA Dermatol.</i> 2023;159:1130. doi:10.1001/jamadermatol.2023.2645 <br/><br/> 7. Spivack S, Gold JAW, Lockhart SR, et al. Potential sexual transmission of antifungal-resistant <i>Trichophyton indotineae</i>. <i>Emerg Infect Dis</i>. 2024;30:807-809. <span class="citation-doi">doi:10.3201/eid3004.240115<br/><br/></span> 8. Caplan AS, Todd GC, Zhu Y, et al. Clinical course, antifungal susceptibility, and genomic sequencing of <i>Trichophyton indotineae</i>. <i>JAMA Dermatol</i>. Published online May 15, 2024. doi:10.1001/jamadermatol.2024.1126<br/><br/> 9. Cañete-Gibas CF, Mele J, Patterson HP, et al. Terbinafine-resistant dermatophytes and the presence of <i>Trichophyton indotineae</i> in North America. <i>J Clin Microbiol</i>. 2023;61:e0056223. doi:10.1128/jcm.00562-23 <br/><br/>10. Gupta AK, Venkataraman M, Hall DC, et al. The emergence of <i>Trichophyton indotineae</i>: implications for clinical practice. <i>Int J Dermatol</i>. 2023;62:857-861. <br/><br/>11. Oladzad V, Nasrollahi Omran A, Haghani I, et al. Multi-drug resistance <i>Trichophyton indotineae</i> in a stray dog. <i>Res Vet Sci</i>. 2024;166:105105. doi:10.1016/j.rvsc.2023.105105 <br/><br/>12. Martinez-Rossi NM, Bitencourt TA, Peres NTA, et al. Dermatophyte resistance to antifungal drugs: mechanisms and prospectus. <i>Front Microbiol</i>. 2018;9:1108. <span class="citation-doi">doi:10.3389/fmicb.2018.01108</span></p> <p class="reference">13. Sacheli R, Hayette MP. Antifungal resistance in dermatophytes: genetic considerations, clinical presentations and alternative therapies. <i>J Fungi (Basel)</i>. 2021;711:983. <span class="citation-doi">doi:10.3390/jof7110983</span> <br/><br/>14. Gupta AK, Cooper EA. Dermatophytosis (tinea) and other superficial fungal infections. In: Hospenthal DR, Rinaldi MG, eds. <i>Diagnosis and Treatment of Human Mycoses</i>. Humana Press; 2008:355-381.<br/><br/>15. Normand A-C, Moreno-Sabater A, Jabet A, et al. MALDI-TOF mass spectrometry online identification of <i>Trichophyton indotineae</i> using the MSI-2 application. <i>J Fungi (Basel)</i>. 2022;8:1103. <span class="citation-doi">doi:10.3390/jof8101103<br/><br/></span>16. De Paepe R, Normand A-C, Uhrlaß S, et al. Resistance profile, terbinafine resistance screening and MALDI-TOF MS identification of the emerging pathogen <i>Trichophyton indotineae</i>. <i>Mycopathologia</i>. 2024;189:29. doi:10.1007/s11046-024-00835-4<br/><br/>17. Rajagopalan M, Inamadar A, Mittal A, et al. Expert consensus on the management of dermatophytosis in India (ECTODERM India). <i>BMC Dermatol</i>. 2018;18:6. <span class="citation-doi">doi:10.1186/s12895-018-0073-1<br/><br/></span>18. Verma SB, Panda S, Nenoff P, et al. 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Practice Points
- Trichophyton indotineae can cause extensive dermatophytosis that often is resistant to terbinafine and in some cases to other antifungals.
- Only molecular testing, which is not widely available, can distinguish T indotineae from other dermatophytes.
- Suspected or confirmed cases of T indotineae dermatophytosis should be reported to public health agencies to provide assistance with testing, as well as surveillance, prevention, and control of infection.
